Therapeutic drug monitoring of caffeine in preterm infants: Could saliva be an alternative to serum?

PubMed

Chaabane, Amel; Chioukh, Fatma Z; Chadli, Zohra; Ben Fredj, Nadia; Ben Ameur, Karim; Ben Hmida, Hayet; Boughattas, Naceur A; Monastiri, Kamel; Aouam, Karim

2017-12-01

Evaluate whether saliva could be a useful alternative to serum for routine therapeutic drug monitoring of caffeine in preterm infants using the enzyme multiplied immunoassay technique (EMIT) assay. We conducted a prospective study including preterm infants (less than 34 weeks' amenorrhea) admitted to the intensive care and neonatal medicine department. All infants received 5, 10, 15, 20 and 25mg/kg/day of citrate caffeine intravenously from the first to the fifth day of birth, respectively. For each patient, two concomitant blood and saliva samples corresponding to the trough concentrations were collected 24hours after each caffeine dose. The caffeine concentrations were determined using the EMIT ® 2000 caffeine assay. Thirteen preterm infants were included. The saliva and the serum caffeine concentration increased proportionally to the administered dose. Saliva and serum kinetics were comparable and the saliva caffeine concentrations were correlated to the serum ones (r 2 =0.76). Saliva caffeine monitoring by EMIT is a valid, useful and safe alternative to serum in preterm infants. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

Caffeinated beverage intake and reproductive hormones among premenopausal women in the BioCycle Study.

PubMed

Schliep, Karen C; Schisterman, Enrique F; Mumford, Sunni L; Pollack, Anna Z; Zhang, Cuilin; Ye, Aijun; Stanford, Joseph B; Hammoud, Ahmad O; Porucznik, Christina A; Wactawski-Wende, Jean

2012-02-01

Caffeinated beverages are widely consumed among women of reproductive age, but their association with reproductive hormones, and whether race modifies any such associations, is not well understood. We assessed the relation between caffeine and caffeinated beverage intake and reproductive hormones in healthy premenopausal women and evaluated the potential effect modification by race. Participants (n = 259) were followed for up to 2 menstrual cycles and provided fasting blood specimens for hormonal assessment at up to 8 visits per cycle and four 24-h dietary recalls per cycle. Weighted linear mixed models and nonlinear mixed models with harmonic terms were used to estimate associations between caffeine and hormone concentrations, adjusted for age, adiposity, physical activity, energy and alcohol intakes, and perceived stress. On the basis of a priori assumptions, an interaction between race and caffeine was tested, and stratified results are presented. Caffeine intake ≥200 mg/d was inversely associated with free estradiol concentrations among white women (β = -0.15; 95% CI: -0.26, -0.05) and positively associated among Asian women (β = 0.61; 95% CI: 0.31, 0.92). Caffeinated soda intake and green tea intake ≥1 cup/d (1 cup = 240 mL) were positively associated with free estradiol concentrations among all races: β = 0.14 (95% CI: 0.06, 0.22) and β = 0.26 (95% CI: 0.07, 0.45), respectively. Moderate consumption of caffeine was associated with reduced estradiol concentrations among white women, whereas caffeinated soda and green tea intakes were associated with increased estradiol concentrations among all races. Further research is warranted on the association between caffeine and caffeinated beverages and reproductive hormones and whether these relations differ by race.

Caffeinated beverage intake and reproductive hormones among premenopausal women in the BioCycle Study123

PubMed Central

Schisterman, Enrique F; Mumford, Sunni L; Pollack, Anna Z; Zhang, Cuilin; Ye, Aijun; Stanford, Joseph B; Hammoud, Ahmad O; Porucznik, Christina A; Wactawski-Wende, Jean

2012-01-01

Background: Caffeinated beverages are widely consumed among women of reproductive age, but their association with reproductive hormones, and whether race modifies any such associations, is not well understood. Objective: We assessed the relation between caffeine and caffeinated beverage intake and reproductive hormones in healthy premenopausal women and evaluated the potential effect modification by race. Design: Participants (n = 259) were followed for up to 2 menstrual cycles and provided fasting blood specimens for hormonal assessment at up to 8 visits per cycle and four 24-h dietary recalls per cycle. Weighted linear mixed models and nonlinear mixed models with harmonic terms were used to estimate associations between caffeine and hormone concentrations, adjusted for age, adiposity, physical activity, energy and alcohol intakes, and perceived stress. On the basis of a priori assumptions, an interaction between race and caffeine was tested, and stratified results are presented. Results: Caffeine intake ≥200 mg/d was inversely associated with free estradiol concentrations among white women (β = −0.15; 95% CI: −0.26, −0.05) and positively associated among Asian women (β = 0.61; 95% CI: 0.31, 0.92). Caffeinated soda intake and green tea intake ≥1 cup/d (1 cup = 240 mL) were positively associated with free estradiol concentrations among all races: β = 0.14 (95% CI: 0.06, 0.22) and β = 0.26 (95% CI: 0.07, 0.45), respectively. Conclusions: Moderate consumption of caffeine was associated with reduced estradiol concentrations among white women, whereas caffeinated soda and green tea intakes were associated with increased estradiol concentrations among all races. Further research is warranted on the association between caffeine and caffeinated beverages and reproductive hormones and whether these relations differ by race. PMID:22237060

Modeling caffeine concentrations with the Stanford Caffeine Questionnaire: preliminary evidence for an interaction of chronotype with the effects of caffeine on sleep.

PubMed

Nova, Philip; Hernandez, Beatriz; Ptolemy, Adam S; Zeitzer, Jamie M

2012-04-01

To examine the validity of a novel caffeine intake questionnaire and to examine the effects of caffeine on sleep in college students. One-week, ad libitum behavior of 50 university students (28 female, 22 male; aged 20.9 ± 1.78 years) was examined with sleep logs, wrist actigraphy, and a novel daily questionnaire assessing caffeine intake at different times of day. Saliva samples were collected for caffeine assessment (questionnaire validation) and DNA extraction, and for analysis of a single nucleotide polymorphism in the adenosine receptor 2A (ADORA2A) gene. The caffeine questionnaire was able to accurately predict salivary concentrations of caffeine (R(2) = 0.41, P<0.001). Estimations of integrated salivary caffeine concentration during sleep were correlated with wake after sleep onset (WASO) most strongly in morning-type individuals (R(2) = 0.49; P<0.001, ANOVA), less so in intermediate chronotypes (R(2) = 0.16; P<0.001, ANOVA), and not significantly in evening-types (R(2) = 0.00098; P = 0.13, ANOVA). Using multivariate modeling methods we found that the ADORA2A genotype did not moderate the effects of caffeine on WASO, but did independently alter WASO such that those with the CC genotype had nearly three-times as much WASO as those with CT or TT. Our questionnaire was able to accurately predict salivary caffeine concentrations and helped to describe a novel relationship between the effects of caffeine on sleep and genotype and chronotype. Published by Elsevier B.V.

Caffeine Inhibits Fluid Secretion by Interlobular Ducts From Guinea Pig Pancreas.

PubMed

Mochimaru, Yuka; Yamamoto, Akiko; Nakakuki, Miyuki; Yamaguchi, Makoto; Taniguchi, Ituka; Ishiguro, Hiroshi

2017-04-01

Caffeine is contained in coffee, tea, and numerous beverages and foods. We examined the direct effects of caffeine on the physiological function of pancreatic duct cells by using interlobular duct segments isolated from guinea pig pancreas. The rate of fluid secretion was continuously measured by monitoring the luminal volume of isolated duct segments. Changes in intracellular Ca concentration ([Ca]i) were estimated by microfluorometry in ducts loaded with Fura-2. Both secretin-stimulated and acetylcholine (ACh)-stimulated fluid secretions were substantially and reversibly inhibited by relatively low concentrations of caffeine as low as 0.03 mM relevant to blood levels after ingestion of caffeine-containing beverages. Caffeine inhibited ACh-induced elevation of [Ca]i and secretin-induced fluctuation of [Ca]i. Caffeine abolished thapsigargin-induced intracellular Ca release but did not affect the entry of extracellular Ca. Caffeine (0.05 mM) abolished ethanol (1 mM)-induced fluid hypersecretion in secretin-stimulated pancreatic duct. Low concentrations of caffeine directly inhibit pancreatic ductal fluid secretion stimulated by secretin or ACh and also ethanol-induced fluid hypersecretion. The inhibition by caffeine seems to be mediated by the blockade of intracellular Ca mobilization. Daily intake of caffeine may reduce the volume of pancreatic juice secretion.

The effect of caffeine as an ergogenic aid in anaerobic exercise.

PubMed

Woolf, Kathleen; Bidwell, Wendy K; Carlson, Amanda G

2008-08-01

The study examined caffeine (5 mg/kg body weight) vs. placebo during anaerobic exercise. Eighteen male athletes (24.1+/-5.8 yr; BMI 26.4+/-2.2 kg/m2) completed a leg press, chest press, and Wingate test. During the caffeine trial, more total weight was lifted with the chest press, and a greater peak power was obtained during the Wingate test. No differences were observed between treatments for the leg press and average power, minimum power, and power drop (Wingate test). There was a significant treatment main effect found for postexercise glucose and insulin concentrations; higher concentrations were found in the caffeine trial. A significant interaction effect (treatment and time) was found for cortisol and glucose concentrations; both increased with caffeine and decreased with placebo. Postexercise systolic blood pressure was significantly higher during the caffeine trial. No differences were found between treatments for serum free-fatty-acid concentrations, plasma lactate concentrations, serum cortisol concentrations, heart rate, and rating of perceived exertion. Thus, a moderate dose of caffeine resulted in more total weight lifted for the chest press and a greater peak power attained during the Wingate test in competitive athletes.

Distribution of caffeine levels in urine in different sports in relation to doping control before and after the removal of caffeine from the WADA doping list.

PubMed

Van Thuyne, W; Delbeke, F T

2006-09-01

Caffeine concentrations were measured in the urine of 4633 athletes tested for doping control in the Ghent Doping Control Laboratory in 2004. Determination of these concentrations was done using an alkaline extraction with a mixture of dichloromethane and methanol (9 : 1; v/v) followed by high performance liquid chromatography and ultraviolet detection (HPLC-UV). The method was validated according to ISO 17 025 standards (International Organisation for Standardisation). Quantification was done by using a linear calibration curve in the range from 0 to 20 microg/ml. The limit of quantification (LOQ) was 0.10 microg/ml. Because the results were not normally distributed, transformation of the data was done to evaluate the difference in detected concentrations in several sports. This resulted in an overall average concentration of 1.12 +/- 2.68 microg/ml. Comparison of the most frequently tested sports in 2004 demonstrated that caffeine concentrations in samples originating from power lifters are significantly higher in comparison to urines taken in other sports. Also, a significant difference between caffeine concentrations found in cycling and concentrations found in other sports, including athletics and some ball sports, was observed. A comparison was made between results obtained in 2004 and results obtained before the removal of caffeine from the WADA (World Anti-Doping Agency) doping list indicating that average caffeine concentrations decreased after the withdrawal of caffeine from the list of prohibited substances. The overall percentage of positive samples between the two periods remained the same although the percentage of positive samples noticed in cycling increased after the removal of caffeine from the doping list.

Influence of caffeine consumption on 7,12-dimethylbenz(a)anthracene-induced mammary gland tumorigenesis in female rats fed a chemically defined diet containing standard and high levels of unsaturated fat.

PubMed

Welsch, C W; DeHoog, J V

1988-04-15

The effect of caffeine (430-500 mg/liter of drinking water) on the initiation and promotion phases of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary gland tumorigenesis in female Sprague-Dawley rats fed a chemically defined diet containing standard (5%) or high (20%) levels of fat (corn oil) was examined. In the initiation studies, caffeine and the standard or high fat diet treatments were provided for 34 days, from 24-29 days of age to 58-63 days of age. Three days prior to termination of caffeine-fat diet treatments, each rat received a single dose of DMBA. In the promotion studies, caffeine and the standard or high fat diets were provided commencing 3 days after a single dose of DMBA (at 56-61 days of age) and until termination of the study. Caffeine consumption, during the initiation phase significantly (P less than 0.05) reduced mammary carcinoma multiplicity (number of tumors/rat), in rats fed either a standard or high fat diet. In the promotion studies, prolonged consumption of caffeine in rats fed either a standard or high fat diet did not significantly effect mammary carcinoma multiplicity. In the early stages of promotion, an apparent increase in mammary carcinoma multiplicity was observed; this increase in mammary carcinoma multiplicity did not, however, reach the 5% level of statistical probability. When caffeine was administered during both the initiation and promotion phases, no significant effect on mammary carcinoma multiplicity was observed. Treatment of rats during the initiation or promotion phases with caffeinated coffee (via drinking water) mimicked the mammary tumor modulating activities of caffeine. Decaffeinated coffee consumption did not effect either the initiation or promotion phases of this tumorigenic process. In both the initiation and promotion studies, caffeine and/or coffee consumption did not significantly affect the incidence of mammary carcinomas (percentage of rats bearing mammary carcinomas) or the mean latency period of mammary tumor appearance. Thus, in female rats fed a chemically defined standard or high fat diet, caffeine consumption can significantly influence chemical carcinogenesis of the mammary gland; an effect that is dependent upon the duration and time-span of caffeine administration.

Sequential updating of a new dynamic pharmacokinetic model for caffeine in premature neonates.

PubMed

Micallef, Sandrine; Amzal, Billy; Bach, Véronique; Chardon, Karen; Tourneux, Pierre; Bois, Frédéric Y

2007-01-01

Caffeine treatment is widely used in nursing care to reduce the risk of apnoea in premature neonates. To check the therapeutic efficacy of the treatment against apnoea, caffeine concentration in blood is an important indicator. The present study was aimed at building a pharmacokinetic model as a basis for a medical decision support tool. In the proposed model, time dependence of physiological parameters is introduced to describe rapid growth of neonates. To take into account the large variability in the population, the pharmacokinetic model is embedded in a population structure. The whole model is inferred within a Bayesian framework. To update caffeine concentration predictions as data of an incoming patient are collected, we propose a fast method that can be used in a medical context. This involves the sequential updating of model parameters (at individual and population levels) via a stochastic particle algorithm. Our model provides better predictions than the ones obtained with models previously published. We show, through an example, that sequential updating improves predictions of caffeine concentration in blood (reduce bias and length of credibility intervals). The update of the pharmacokinetic model using body mass and caffeine concentration data is studied. It shows how informative caffeine concentration data are in contrast to body mass data. This study provides the methodological basis to predict caffeine concentration in blood, after a given treatment if data are collected on the treated neonate.

Caffeine in an Urbanized Estuary: Past and Present Influence ...

EPA Pesticide Factsheets

Caffeine has been identified by previous research as a potential tracer of sanitary wastewater. To further assess the utility of caffeine as a tracer of wastewater sources, samples from 25 sites throughout Boston Harbor were collected and analyzed for caffeine by LC-MS/MS. Caffeine concentrations in Boston Harbor ranged from 15 ng/L in the outer harbor to a high of 185 ng/L in the inner harbor; mean concentrations and median concentrations were 51 ng/L were 33 ng/L respectively. These data were visualized by a simple inverse distance weighting model to improve the understanding of transport and fate dynamics of wastewater derived contaminants. Elevated concentrations of caffeine in the inner harbor during the sampling period were determined to be the result of a combined sewage overflow (CSO) event as well as illicit discharge of sanitary sewage into municipal storm drains. A comparison of contemporary results to data from 1998 to 1999 shows significant reductions in caffeine levels within the harbor. For instance, concentrations were reduced by a factor of approximately 20 at the site of the former wastewater effluent discharge outfall in Boston Harbor. Lower present-day concentrations throughout the harbor were attributed to the relocation of effluent discharge from within the harbor to Massachusetts Bay, and a reduction in the number and discharge volume of CSOs. Spatial distributions of caffeine identified CSOs as the major contemporary source of con

Caffeine dependence in rats: effects of exposure duration and concentration.

PubMed

Dingle, Rachel N; Dreumont-Boudreau, Sarah E; Lolordo, Vincent M

2008-09-03

Groups of rats were chronically exposed to a 1.0-g/L caffeine solution for 5, 10, 15 or 20 days. Upon removal of caffeine, rats were given brief exposure to a novel flavour CS (withdrawal CS) followed by 12 days of plain water and then brief exposure to a second flavour CS (neutral CS). Only rats exposed to 20 days of caffeine strongly preferred the neutral CS to the withdrawal CS in a 2-bottle test. In Experiment 2, groups of rats were chronically exposed to caffeine at one of four concentrations (1.0, 0.5, 0.25, or 0.125 g/L) for 21 days, after which withdrawal and neutral CSs were established. Only rats that drank the highest caffeine concentration, 1.0 g/L, preferred the neutral CS to the withdrawal CS. This suggests that long exposure to a strong caffeine solution is required in order to induce dependence in rats such that a CS associated with the withdrawal of caffeine becomes avoided.

Human coffee drinking: manipulation of concentration and caffeine dose.

PubMed Central

Griffiths, R R; Bigelow, G E; Liebson, I A; O'Keeffe, M; O'Leary, D; Russ, N

1986-01-01

In a residential research ward coffee drinking was studied in 9 volunteer human subjects with histories of heavy coffee drinking. A series of five experiments was undertaken to characterize adlibitum coffee consumption and to investigate the effects of manipulating coffee concentration, caffeine dose per cup, and caffeine preloads prior to coffee drinking. Manipulations were double-blind and scheduled in randomized sequences across days. When cups of coffee were freely available, coffee drinking tended to be rather regularly spaced during the day with intercup intervals becoming progressively longer throughout the day; experimental manipulations showed that this lengthening of intercup intervals was not due to accumulating caffeine levels. Number of cups of coffee consumed was an inverted U-shaped function of both coffee concentration and caffeine dose per cup; however, coffee-concentration and dose-per-cup manipulations did not produce similar effects on other measures of coffee drinking (intercup interval, time to drink a cup, within-day distribution of cups). Caffeine preload produced dose-related decreases in number of cups consumed. As a whole, these experiments provide some limited evidence for both the suppressive and the reinforcing effects of caffeine on coffee consumption. Examination of total daily coffee and caffeine intake across experiments, however, provides no evidence for precise regulation (i.e., titration) of coffee or caffeine intake. PMID:3958660

Response Surface Optimization for Decaffeination and Theophylline Production by Fusarium solani.

PubMed

Nanjundaiah, Shwetha; Bhatt, Praveena; Rastogi, Navin Kumar; Thakur, Munna Singh

2016-01-01

Coffee processing industries generate caffeine-containing waste that needs to be treated and decaffeinated before being disposed. Five fungal isolates obtained on caffeine-containing mineral media were tested for their ability to utilize caffeine at high concentrations. An isolate identified as Fusarium solani could utilize caffeine as a sole source of carbon and nitrogen up to 5 g/l and could degrade it to an extent of 30-53 % in 120 h. Sucrose that was added as an auxiliary substrate (5 g/l) enhanced the biodecaffeination of caffeine to 88 % in 96 h. The addition of co- substrate (sucrose) not only resulted in higher biodecaffeination efficiency, but also reduced the incubation period from the initial 120 to 96 h. Theophylline and 3-methyl xanthine were obtained as the major metabolites of decaffeination at 96 and 120 h, respectively. Response surface methodology used to optimize the process parameters for maximum biodecaffeination as well as theophylline production showed that a pH of 5.8, temperature of 24 °C and inoculum size of 4.8 × 10(5) spores/ml have resulted in a complete biodecaffeination of caffeine as well as the production of theophylline with a yield of 33 % (w/w). Results thus show that a viable and sustainable process can be developed for the detoxification of caffeine along with the recovery of theophylline, a commercially important chemical.

The effects of low and moderate doses of caffeine supplementation on upper and lower body maximal voluntary concentric and eccentric muscle force.

PubMed

Tallis, Jason; Yavuz, Harley C M

2018-03-01

Despite the growing quantity of literature exploring the effect of caffeine on muscular strength, there is a dearth of data that directly explores differences in erogenicity between upper and lower body musculature and the dose-response effect. The present study sought to investigate the effects of low and moderate doses of caffeine on the maximal voluntary strength of the elbow flexors and knee extensors. Ten nonspecifically strength-trained, recreationally active participants (aged 21 ± 0.3 years) completed the study. Using a randomised, counterbalanced, and double-blind approach, isokinetic concentric and eccentric strength was measured at 60 and 180°/s following administration of a placebo, 3 mg·kg -1 body mass caffeine, and 6 mg·kg -1 body mass caffeine. There was no effect of caffeine on the maximal voluntary concentric and eccentric strength of the elbow flexors, or the eccentric strength of the knee extensors. Both 3 and 6 mg·kg -1 body mass caffeine caused a significant increase in peak concentric force of the knee extensors at 180°/s. No difference was apparent between the 2 concentrations. Only 6 mg·kg -1 body mass caused an increase in peak concentric force during repeated contractions. The results infer that the effective caffeine concentration to evoke improved muscle performance may be related to muscle mass and contraction type. The present work indicates that a relatively low dose of caffeine treatment may be effective for improving lower body muscular strength, but may have little benefit for the strength of major muscular groups of the upper body.

Caffeine content of beverages as consumed.

PubMed Central

Gilbert, R. M.; Marshman, J. A.; Schwieder, M.; Berg, R.

1976-01-01

Quantitative analysis of beverages prepared at home by staff of the Addiction Research Foundation revealed a lower and much more variable caffeine content of both tea and coffee than had been reported in earlier studies, most of which were based on analysis of laboratory-prepared beverages. Median caffeine concentration of 37 home-prepared samples of tea was 27 mg per cup (range, 8 to 91 mg); for 46 coffee samples the median concentration was 74 mg per cup (range, 29 to 176 mg). If tea and coffee as drunk contain less caffeine than generally supposed, the potency of caffeine may be greater than commonly realized, as may the relative caffeine content of certain commercial preparations, including chocolate and colas. The substantial variation in caffeine content emphasizes the need to establish actual caffeine intake in clinical, epidemiologic and experimental investigations of caffeine effects. PMID:1032351

Serum caffeine concentrations and short-term outcomes in premature infants of ⩽29 weeks of gestation.

PubMed

Alur, P; Bollampalli, V; Bell, T; Hussain, N; Liss, J

2015-06-01

Caffeine is effective in the treatment of apnea of prematurity but it is not well known if the therapeutic concentration of the drug has an impact on other neonatal outcomes such as chronic lung disease (CLD). The aim of this study was to determine if there is an association between caffeine concentrations and the incidence of CLD in premature infants of ⩽29 weeks of gestation. A retrospective chart review of all the infants born ⩽29 weeks of gestation from 2007 to 2011, who survived until discharge or 36 weeks postmenstrual age, was conducted. Caffeine concentrations were obtained weekly on infants getting the drug. Average caffeine concentrations (ACCs) were determined for the duration of caffeine therapy and correlated with CLD, length of stay (LOS), oxygen at discharge (OD), duration of ventilation (DV) and total charges for hospitalization for each patient. Of the 222 eligible infants, 198 met the inclusion criteria. ACC for infants without CLD was 17.0±3.8 μg ml(-1) compared with infants with CLD 14.3±6.1 μg ml(-1) (P<0.001). Infants receiving high ACC (>14.5 μg ml(-1)) had lower incidence of patent ductus arteriosus, lesser number of days on ventilator and oxygen, lesser need for diuretics, lower incidence of CLD, were more likely to go home without supplemental OD and had lower LOS and lower total hospital charges (all differences were significant P<0.05) Multiple logistic regression modeling after adjusting for confounding variables indicated that higher caffeine concentrations were significantly associated with decrease in CLD. Receiver operating curve analysis confirmed a significant predictive ability of caffeine concentration for CLD with a cutoff concentration of 14.5 μg ml(-1) (sensitivity of 42.6 and specificity of 86.8). The AUC (area under the curve) for the prediction of CLD was 0.632 (95% confidence interval 0.56-0.69, P=0.009). Caffeine concentrations >14.5 μg ml(-1) were strongly correlated with reduced CLD in infants born at ⩽29 weeks of gestation. Higher caffeine concentrations were associated with decreased total hospital charges, DV, OD and LOS. Additional randomized trials are needed to confirm these findings, to identify ideal serum concentrations and determine possible long-term neurologic benefits.

Development of the caffeine withdrawal symptom questionnaire: caffeine withdrawal symptoms cluster into 7 factors.

PubMed

Juliano, Laura M; Huntley, Edward D; Harrell, Paul T; Westerman, Ashley T

2012-08-01

Habitual caffeine consumers who abstain from caffeine experience withdrawal symptoms such as headache, fatigue, difficulty concentrating, mood disturbances, and flu-like symptoms (Juliano and Griffiths, 2004). The caffeine withdrawal syndrome has been documented across many experimental studies; however, little is known about how withdrawal symptoms co-vary during a discrete episode. Furthermore, a validated measure of caffeine withdrawal is lacking. To develop, evaluate, and reduce a 23-item measure of caffeine withdrawal symptoms; the Caffeine Withdrawal Symptom Questionnaire (CWSQ), to a set of composite variables. Caffeine consumers (N=213) completed the CWSQ after 16h of caffeine abstinence. A subset of participants also completed the CWSQ during a preceding baseline period and/or after double-blind consumption of caffeinated coffee. Principal components analysis resulted in a solution comprised of 7-factors: (1) Fatigue/drowsiness; (2) Low alertness/difficulty concentrating; (3) Mood disturbances; (4) Low sociability/motivation to work; (5) Nausea/upset stomach; (6) Flu-like feelings; and (7) Headache. With the exception of nausea/upset stomach, the CWSQ total score and individual composite scores were significantly greater during caffeine abstinence relative to both baseline and double-blind consumption of caffeinated coffee, thereby demonstrating sensitivity of the measure. Compared to non-daily coffee consumers, daily consumers had greater increases in total withdrawal, fatigue/drowsiness, low alertness/difficulty concentrating, mood disturbances, and headache. Future directions include replication, assessment on a clinical population, and further examination of psychometric properties of the CWSQ. The CWSQ should facilitate the assessment and diagnosis of caffeine withdrawal and increase our knowledge of the caffeine withdrawal syndrome. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Conductive diamond electrochemical oxidation of caffeine-intensified biologically treated urban wastewater.

PubMed

Martín de Vidales, María J; Millán, María; Sáez, Cristina; Pérez, José F; Rodrigo, Manuel A; Cañizares, Pablo

2015-10-01

In this work, the usefulness of Conductive Diamond Electrochemical Oxidation (CDEO) to degrade caffeine in real urban wastewater matrixes was assessed. The oxidation of actual wastewater intensified with caffeine (from 1 to 100 mg L(-1)) was studied, paying particular attention to the influence of the initial load of caffeine and the differences observed during the treatment of caffeine in synthetic wastewater. The results showed that CDEO is a technology that is capable of efficiently degrading this compound even at very low concentrations and that it can even be completely depleted. Profiles of the ionic species of S (SO4(2-)), N (NH4(+), NO3(-)) and Cl (ClO(-), ClO3(-) and ClO4(-)) were monitored and explained for plausible oxidation mechanisms. It was observed that the efficiency achieved is higher in the treatment of real wastewater than in the oxidation of synthetic wastewater because of the contribution of electrogenerated oxidant species such as hypochlorite. The formation of chlorate and perchlorate during electrochemical processes was observed, and a combined strategy to prevent this important drawback was successfully tested based on the application of low current densities with the simultaneous dosing of hydrogen peroxide. Copyright © 2015 Elsevier Ltd. All rights reserved.

Influence of caffeine and/or coffee consumption on the initiation and promotion phases of 7,12-dimethylbenz(a)anthracene-induced rat mammary gland tumorigenesis.

PubMed

Welsch, C W; DeHoog, J V; O'Connor, D H

1988-04-15

The effect of caffeine and/or coffee consumption (via the drinking water) during the initiation phase and promotion phase of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary gland tumorigenesis in female Sprague-Dawley rats fed a commercial laboratory animal chow was examined. In the initiation studies, DMBA was administered once at 53-55 days of age; caffeine (100-860 mg/liter of drinking water) and/or coffee (moderate or high dose, sole source of drinking water) treatments were for 32 consecutive days, commencing 29 days prior to DMBA treatment and terminating 3 days after DMBA treatment. In the promotion studies, DMBA was administered once at 54-55 days of age; caffeine and/or coffee treatments were daily from 57-58 days of age to termination of experiments (12-21 weeks after carcinogen treatment). In the initiation studies, either moderate (100-400 mg) or high (860 mg) dose levels of caffeine or moderate to high dose levels of caffeinated coffee significantly (P less than 0.05) reduced mammary carcinoma multiplicity (number of tumors/rat). Consumption of high or moderate dose levels of decaffeinated coffee did not significantly alter mammary carcinoma multiplicity. The addition of caffeine to the moderate dose level of decaffeinated coffee resulted in a significant (P less than 0.05) reduction in mammary carcinoma multiplicity. In the promotion studies, prolonged consumption of moderated dose levels of caffeine or moderate or high dose levels of caffeinated coffee or decaffeinated coffee did not significantly effect mammary carcinoma multiplicity. In the early stages of promotion, however, a significant (p less than 0.05) stimulatory effect of caffeine on mammary carcinoma multiplicity was observed; an effect that was temperate and transitory. In both the initiation and promotion studies caffeine and/or coffee consumption did not significantly affect the incidence of mammary carcinomas (percentage of rats bearing mammary carcinomas) or the mean latency period of mammary tumor appearance. These results provide evidence that caffeine and/or caffeinated coffee consumption can significantly influence mammary carcinoma multiplicity in female rats treated with DMBA, an effect that is dependent upon the dose level, duration, and time-span of caffeine administration.

Pharmacokinetic and pharmacodynamic interactions between zolpidem and caffeine.

PubMed

Cysneiros, R M; Farkas, D; Harmatz, J S; von Moltke, L L; Greenblatt, D J

2007-07-01

The kinetic and dynamic interaction of caffeine and zolpidem was evaluated in a double-blind, single-dose, six-way crossover study of 7.5 mg zolpidem (Z) or placebo (P) combined with low-dose caffeine (250 mg), high-dose caffeine (500 mg), or placebo. Caffeine coadministration modestly increased maximum plasma concentration (C(max)) and area under the plasma concentration-time curve of zolpidem by 30-40%, whereas zolpidem did not significantly affect the pharmacokinetics of caffeine or its metabolites. Compared to P+P, Z+P significantly increased sedation, impaired digit-symbol substitution test performance, slowed tapping speed and reaction time, increased EEG relative beta amplitude, and impaired delayed recall. Caffeine partially, but not completely, reversed most pharmacodynamic effects of zolpidem. Thus, caffeine only incompletely reverses zolpidem's sedative and performance-impairing effects, and cannot be considered as an antidote to benzodiazepine agonists.

Contribution of caffeine to the homocysteine-raising effect of coffee: a randomized controlled trial in humans.

PubMed

Verhoef, Petra; Pasman, Wilrike J; Van Vliet, Trinette; Urgert, Rob; Katan, Martijn B

2002-12-01

A high plasma total homocysteine concentration is associated with increased risk of cardiovascular disease. Consumption of unfiltered or filtered coffee raises total homocysteine concentrations in healthy volunteers. The responsible compound, however, is unknown. The objective was to determine whether caffeine explains the homocysteine-raising effect of coffee. Forty-eight subjects aged 19-65 y completed this randomized crossover study with 3 treatments, each lasting 2 wk. Subjects consumed 6 capsules providing 870 mg caffeine/d (test treatment), 0.9 L paper-filtered coffee providing approximately 870 mg caffeine/d, or 6 placebo capsules. Blood samples were drawn fasting and 4 h after consumption of 0.45 L coffee or 3 capsules. The mean fasting plasma homocysteine concentration after the placebo treatment was 9.6 +/- 3.1 micro mol/L. The caffeine and coffee treatments increased fasting homocysteine by 0.4 micro mol/L (95% CI: 0.1, 0.7; P = 0.04), or 5%, and by 0.9 micro mol/L (95% CI: 0.6, 1.2; P = 0.0001), or 11%, respectively, compared with placebo. The increase in homocysteine concentrations 4 h after consumption of 0.45 L coffee relative to consumption of 3 placebo capsules was 19% (P = 0.0001). Caffeine treatment had a much weaker acute effect on homocysteine (4%; P = 0.09). Effects of caffeine were stronger in women than in men, but the effects of coffee did not differ significantly between men and women. Caffeine is partly responsible for the homocysteine-raising effect of coffee. Coffee, but not caffeine, affects homocysteine metabolism within hours after intake, although the effect is still substantial after an overnight fast.

Acute Effects of 24-h Sleep Deprivation on Salivary Cortisol and Testosterone Concentrations and Testosterone to Cortisol Ratio Following Supplementation with Caffeine or Placebo

PubMed Central

DONALD, CIARAN MC; MOORE, JOSS; MCINTYRE, ALAN; CARMODY, KEVIN; DONNE, BERNARD

2017-01-01

Caffeine has become a popular ergogenic aid amongst athletes and usage to improve athletic performance has been well documented. The effect of caffeine on anabolic and catabolic hormones in a sleep-deprived s tate has had little investigation to date. The purpose of the current study was to investigate the potential of caffeine to offset the effects, if any, of short-term sleep deprivation and exercise on an athlete’s testosterone and cortisol concentrations via salivary technique. Eleven competitive male athletes volunteered to be part of this prospective double-blinded study. Three test days were scheduled for each athlete; one non-sleep deprived, one sleep-deprived with caffeine supplementation (6 mg.kg−1) and one sleep-deprived with placebo ingestion. Sleep deprivation was defined as 24-h without sleep. Each test day was composed of 2 aerobic components: a modified Hoff test and a Yo-Yo test. Testosterone and cortisol concentrations were measured via salivary analysis at 4 different time-points; T1 to T4, representing baseline, and pre- and post-aerobic components, respectively. Overall no significant differences were detected comparing the different sleep states for testosterone or cortisol concentrations. A trend existed whereby the sleep-deprived with caffeine ingestion state mirrored the non-sleep deprived state for cortisol concentration. Therefore, caffeine supplementation may have potential benefits for athletes during short-term aerobic exercise when sleep-deprived. An increase in mean testosterone concentration post-aerobic exercise was only observed in the sleep-deprived with caffeine ingestion state. PMID:28479951

Action of caffeine on x-irradiated HeLa cells. IV. Progression delays and enhanced cell killing at high caffeine concentrations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tolmach, L.J.; Busse, P.M.

1980-05-01

The response of x-irradiated and unirradiated HeLa S3 cells to treatment with caffeine at concentrations between 1 and 10 nM has been examined with respect to both delay in progression through the cell generation cycle and enhancement of the expression of potentially lethal x-ray damage. Progression is delayed in a concentration-dependent fashion: the generation time is doubled at about 4 mM. The duration of G/sub 1/ is lengthened, and the rate of DNA synthesis is reduced, although the kinetics are different in the two phases; the rate of DNA synthesis is usually unaffected at 1 or 2 mM, while theremore » is no concentration threshold for the slowing of progression through G/sub 1/. Progression through G/sub 2/ appears to be unaffected by concentrations up to at least 10 mM. Killing of irradiated cells in G/sub 2/ is somewhat greater after treatment with the higher caffeine concentrations than reported previously for 1 mM. Moreover, an additional mode of killing is observed in irradiated G/sub 1/ cells which had been found previously to be only slightly affected by 1 mM caffeine; they suffer extensive killing at concentrations above 5 mM. The time-survival curves for irradiated, caffeine-treated G/sub 1/ and G/sub 2/ cells have characteristically different shapes. The dose-survival curves for cells treated with the higher caffeine concentrations display steeper terminal slopes and narrower shoulders.« less

Early Caffeine Prophylaxis and Risk of Failure of Initial Continuous Positive Airway Pressure in Very Low Birth Weight Infants.

PubMed

Patel, Ravi M; Zimmerman, Kanecia; Carlton, David P; Clark, Reese; Benjamin, Daniel K; Smith, P Brian

2017-11-01

To test the hypothesis that early caffeine treatment on the day of birth, compared with later treatment in very low birth weight (VLBW, <1500 g) infants receiving continuous positive airway pressure (CPAP) therapy, is associated with a decreased risk of CPAP failure in the first week of life. Multicenter, observational cohort study in 366 US neonatal intensive care units. We evaluated inborn, VLBW infants discharged from 2000 to 2014, who received only CPAP therapy without surfactant treatment on day of life (DOL) 0, had a 5-minute Apgar ≥3, and received caffeine in the first week of life. We used multivariable conditional logistic regression to compare the risk of CPAP failure, defined as invasive mechanical ventilation or surfactant therapy on DOL 1-6, by timing of caffeine treatment as either early (initiation on DOL 0) or routine (initiation on DOL 1-6). We identified 11 133 infants; 4528 (41%) received early caffeine and 6605 (59%) received routine caffeine. Median gestational age was lower in the early caffeine group, 29 weeks (25th, 75th percentiles; 28, 30) vs the routine caffeine group, 30 weeks (29, 31); P < 0.001. The incidence of CPAP failure on DOL 1-6 was similar between the early and routine caffeine groups: 22% vs 21%; adjusted OR = 1.05 (95% CI: 0.93, 1.18). Early caffeine treatment on the day of birth was not associated with a decreased risk of CPAP failure in the first week of life for VLBW infants initially treated with CPAP. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of caffeine on the anticonvulsant effects of oxcarbazepine, lamotrigine and tiagabine in a mouse model of generalized tonic-clonic seizures.

PubMed

Chrościńska-Krawczyk, Magdalena; Ratnaraj, Neville; Patsalos, Philip N; Czuczwar, Stanisław J

2009-01-01

Caffeine has been reported to be proconvulsant and to reduce the anticonvulsant efficacy of a variety of antiepileptic drugs (carbamazepine, phenobarbital, phenytoin, valproate and topiramate) in animal models of epilepsy and to increase seizure frequency in patients with epilepsy. Using the mouse maximal electroshock model, the present study was undertaken so as to ascertain whether caffeine affects the anticonvulsant efficacy of the new antiepileptic drugs lamotrigine, oxcarbazepine and tiagabine. The results indicate that neither acute nor chronic caffeine administration (up to 46.2 mg/kg) affected the ED(50) values of oxcarbazepine or lamotrigine against maximal electroshock. Similarly, caffeine did not modify the tiagabine electroconvulsive threshold. Furthermore, caffeine had no effect on oxcarbazepine, lamotrigine and tiagabine associated adverse effects such as impairment of motor coordination (measured by the chimney test) or long-term memory (measured by the passive avoidance task). Concurrent plasma concentration measurements revealed no significant effect on lamotrigine and oxcarbazepine concentrations. For tiagabine, however, chronic caffeine (4 mg/kg) administration was associated with an increase in tiagabine concentrations. In conclusion, caffeine did not impair the anticonvulsant effects of lamotrigine, oxcarbazepine, or tiagabine as assessed by electroconvulsions in mice. Also, caffeine was without effect upon the adverse potential of the studied antiepileptic drugs. Thus caffeine may not necessarily adversely affect the efficacy of all antiepileptic drugs and this is an important observation.

The influence of caffeine on the activity of moclobemide, venlafaxine, bupropion and milnacipran in the forced swim test in mice.

PubMed

Poleszak, Ewa; Szopa, Aleksandra; Wyska, Elżbieta; Wośko, Sylwia; Serefko, Anna; Wlaź, Aleksandra; Pieróg, Mateusz; Wróbel, Andrzej; Wlaź, Piotr

2015-09-01

Worrying data indicate that excessive caffeine intake applies to patients suffering from mental disorders, including depression. It is thus possible to demonstrate the usefulness of caffeine and its derivatives in the treatment of depression. The main goal of the present studywas to evaluate the influence of caffeine (5mg/kg) on the activity of moclobemide (1.5 mg/kg), venlafaxine (1 mg/kg), bupropion (10 mg/kg), and milnacipran (1.25 mg/kg). Moreover, we assessed the influence of caffeine on their serum and brain levels using highperformance liquid chromatography. The experiment was carried out on naïve adult male Albino Swiss mice. Caffeine and tested drugs were administered intraperitoneally. The influence of caffeine on the activity of selected antidepressant drugs was evaluated in forced swim test (FST). Locomotor activity was estimated to verify and exclude false positive/negative results. To assess the influence of caffeine on the levels of studied antidepressant drugs, their concentrations were determined in murine serum and brains using high-performance liquid chromatography. Caffeine potentiated activity of all antidepressants examined in FST and the observed effects were not due to the increase in locomotor activity in the animals. Only in the case of co-administration of caffeine and milnacipran an increased milnacipran concentration in serum was observed without affecting its concentration in the brain. Caffeine potentiates the activity of antidepressant drugs from different chemical groups. The interactions of caffeine with venlafaxine, bupropion and moclobemide occur in pharmacodynamic phase, whereas the interaction of caffeine–milnacipran occurs, at least partially, in pharmacokinetic phase.

Prediction of Caffeine Content in Java Preanger Coffee Beans by NIR Spectroscopy Using PLS and MLR Method

NASA Astrophysics Data System (ADS)

Budiastra, I. W.; Sutrisno; Widyotomo, S.; Ayu, P. C.

2018-05-01

Caffeine is one of important components in coffee that contributes to the coffee beverages flavor. Caffeine concentration in coffee bean is usually determined by chemical method which is time consuming and destructive method. A nondestructive method using NIR spectroscopy was successfully applied to determine the caffeine concentration of Arabica gayo coffee bean. In this study, NIR Spectroscopy was assessed to determine the caffeine concentration of java preanger coffee bean. A hundred samples, each consist of 96 g coffee beans were prepared for reflectance and chemical measurement. Reflectance of the sample was measured by FT-NIR spectrometer in the wavelength of 1000-2500 nm (10000-4000 cm-1) followed by determination of caffeine content using LCMS method. Calibration of NIR spectra and the caffeine content was carried out using PLS and MLR methods. Several spectra data processing was conducted to increase the accuracy of prediction. The result of the study showed that caffeine content could be determined by PLS model using 7 factors and spectra data processing of combination of the first derivative and MSC of spectra absorbance (r = 0.946; CV = 1.54 %; RPD = 2.28). A lower accuracy was obtained by MLR model consisted of three caffeine and other four absorption wavelengths (r = 0.683; CV = 3.31%; RPD = 1.18).

Source-specific sewage pollution detection in urban river waters using pharmaceuticals and personal care products as molecular indicators.

PubMed

Kiguchi, Osamu; Sato, Go; Kobayashi, Takashi

2016-11-01

Source-specific elucidation of domestic sewage pollution caused by various effluent sources in an urban river water, as conducted for this study, demands knowledge of the relation between concentrations of pharmaceuticals and personal care products (PPCPs) as molecular indicators (caffeine, carbamazepine, triclosan) and water quality concentrations of total nitrogen (T-N) and total phosphorous (T-P). River water and wastewater samples from the Asahikawa River Basin in northern Japan were analyzed using derivatization-gas chromatography/mass spectrometry. Caffeine, used as an indicator of domestic sewage in the Asahikawa River Basin, was more ubiquitous than either carbamazepine or triclosan (92-100 %). Its concentration was higher than any target compound used to assess the basin: <4.4-370 ng/L for caffeine, <0.6-3.9 ng/L for carbamazepine, and <1.1-13 ng/L for triclosan. Higher caffeine concentrations detected in wastewater effluents and the strongly positive mutual linear correlation between caffeine and T-N or T-P (R 2  > 0.759) reflect the contribution of septic tank system effluents to the lower Asahikawa River Basin. Results of relative molecular indicators in combination with different molecular indicators (caffeine/carbamazepine and triclosan/carbamazepine) and cluster analysis better reflect the contribution of sewage than results obtained using concentrations of respective molecular indicators and cluster analysis. Relative molecular indicators used with water quality parameters (e.g., caffeine/T-N ratio) in this study provide results more clearly, relatively, and quantitatively than results obtained using molecular indicators alone. Moreover, the caffeine/T-N ratio reflects variations of caffeine flux from effluent sources. These results suggest strongly relative molecular indicators are also useful indicators, reflecting differences in spatial contributions of domestic sources for PPCPs in urban areas.

Metabolic effects of physiological levels of caffeine in myotubes.

PubMed

Schnuck, Jamie K; Gould, Lacey M; Parry, Hailey A; Johnson, Michele A; Gannon, Nicholas P; Sunderland, Kyle L; Vaughan, Roger A

2018-02-01

Caffeine has been shown to stimulate multiple major regulators of cell energetics including AMP-activated protein kinase (AMPK) and Ca 2+ /calmodulin-dependent protein kinase II (CaMKII). Additionally, caffeine induces peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitochondrial biogenesis. While caffeine enhances oxidative metabolism, experimental concentrations often exceed physiologically attainable concentrations through diet. This work measured the effects of low-level caffeine on cellular metabolism and gene expression in myotubes, as well as the dependence of caffeine's effects on the nuclear receptor peroxisome proliferator-activated receptor beta/delta (PPARβ/δ). C2C12 myotubes were treated with various doses of caffeine for up to 24 h. Gene and protein expression were measured via qRT-PCR and Western blot, respectively. Cellular metabolism was determined via oxygen consumption and extracellular acidification rate. Caffeine significantly induced regulators of mitochondrial biogenesis and oxidative metabolism. Mitochondrial staining was suppressed in PPARβ/δ-inhibited cells which was rescued by concurrent caffeine treatment. Caffeine-treated cells also displayed elevated peak oxidative metabolism which was partially abolished following PPARβ/δ inhibition. Similar to past observations, glucose uptake and GLUT4 content were elevated in caffeine-treated cells, however, glycolytic metabolism was unaltered following caffeine treatment. Physiological levels of caffeine appear to enhance cell metabolism through mechanisms partially dependent on PPARβ/δ.

Caffeine and theobromine levels in chocolate couverture and coating products.

PubMed

Ramli, N; Rahman, S; Hassan, O; Mohd Yatim, A; Said, M; Lim, L; Ng, W

2000-03-01

Thirty-two samples of chocolate products were analysed by HPLC for caffeine and theobromine contents. Defatted residues of samples were extracted with 80% aqueous acetone. After extraction into boiling water, the methylxanthines were identified and quantified with the use of μ-Bondapak column and mobile phase of methanol:water:acetic acid (20:79:1). Levels of caffein and theobromine in 32 samples of chocolate products averaged 0.62-1.14 mg/g and 0.026-0.153 mg/g respectively. Mean values for theobromine and caffeine content for chocolate coating were 0.82 and 0.07 mg/g respectively. The chocolate coating made from fat substitute had theobromine and caffeine levels ranging from 0.36-0.70 mg/g and 0.027-0.061 mg/g respectively, with mean values of 0.49 mg theobromine/g and 0.039 mg caffeine/g. In local chocolate, the mean theobromine and caffeine levels respectively were 0.72 mg/g and 0.04 mg/g in milk chocolate, and 0.85 mg/g and 0.06 mg/g in dark chocolate. Meanwhile, for imported chocolate, the mean theobromine and caffeine levels respectively were 1.05 mg/g and 0.12 mg/g in dark chocolate; 0.76 mg/g and 0.04 mg/g in milk chocolate; and 0.74 mg/g and 0.03 mg/g in white chocolate. Compared with the local chocolates, imported chocolates had higher levels of theobromine and caffeine at 1.141 mg/g and 0.1533mg/g. The average theobromine and caffeine concentrations in local chocolate were 0.082mg/g and 0.066mg/g. Theobromine concentration in chocolate samples is within the range of 0.62mg/g-1.141mg/g and the range of caffeine concentration is 0.026mg/g-0.153mg/g respectively. Bittersweet chocolates were found to have higher theobromine and caffeine concentrations than normal sweet chocolates and milk chocolates.

Systematic review of randomised controlled trials of the effects of caffeine or caffeinated drinks on blood glucose concentrations and insulin sensitivity in people with diabetes mellitus.

PubMed

Whitehead, N; White, H

2013-04-01

Compounds other than macronutrients have been shown to influence blood glucose concentrations and insulin sensitivity in people with diabetes, with caffeine being one such substance. The present study systematically reviewed the evidence of the effects of caffeine on blood glucose concentrations and/or insulin sensitivity in people with diabetes. Four databases, including MEDLINE and EMBASE, were searched up to 1 February 2012. Randomised controlled trials (RCTs) investigating the effects of caffeine on blood glucose and/or insulin sensitivity in humans, diagnosed with type I, type II or gestational diabetes mellitus (GDM), were included. Quality assessment and data extraction were conducted and agreed by both authors. Of 253 articles retrieved, nine trials (134 participants) were identified. Trials in people with type II diabetes demonstrated that the ingestion of caffeine (approximately 200-500 mg) significantly increased blood glucose concentrations by 16-28% of the area under the curve (AUC) and insulin concentrations by 19-48% of the AUC when taken prior to a glucose load, at the same time as decreasing insulin sensitivity by 14-37%. In type I diabetes, trials indicated enhanced recognition and a reduced duration of hypoglycaemic episodes following ingestion of 400-500 mg caffeine, without altering glycated haemoglobin. In GDM, a single trial demonstrated that approximately 200 mg of caffeine induced a decrease in insulin sensitivity by 18% and a subsequent increase in blood glucose concentrations by 19% of the AUC. Evidence indicates a negative effect of caffeine intake on blood glucose control in individuals with type II diabetes, as replicated in a single trial in GDM. Larger-scale RCTs of longer duration are needed to determine the effects of timing and dose. Early indications of a reduced duration and an improved awareness of hypoglycaemia in type I diabetes require further confirmation. © 2013 The Authors Journal of Human Nutrition and Dietetics © 2013 The British Dietetic Association Ltd.

Quantitative Analysis by Isotopic Dilution Using Mass Spectroscopy: The Determination of Caffeine by GC-MS.

ERIC Educational Resources Information Center

Hill, Devon W.; And Others

1988-01-01

Describes a laboratory technique for quantitative analysis of caffeine by an isotopic dilution method for coupled gas chromatography-mass spectroscopy. Discusses caffeine analysis and experimental methodology. Lists sample caffeine concentrations found in common products. (MVL)

Quantitative HPLC Analysis of an Analgesic/Caffeine Formulation: Determination of Caffeine

NASA Astrophysics Data System (ADS)

Ferguson, Glenda K.

1998-04-01

A modern high performance liquid chromatography (HPLC) laboratory experiment which entails the separation of acetaminophen, aspirin, and caffeine and the quantitative assay of caffeine in commercial mixtures of these compounds has been developed. Our HPLC protocol resolves these compounds in only three minutes with a straightforward chromatographic apparatus which consists of a C-18 column, an isocratic mobile phase, UV detection at 254 nm, and an integrator; an expensive, sophisticated system is not required. The separation is both repeatable and rapid. Moreover, the experiment can be completed in a single three-hour period. The experiment is appropriate for any chemistry student who has completed a minimum of one year of general chemistry and is ideal for an analytical or instrumental analysis course. The experiment detailed herein involves the determination of caffeine in Goody's Extra Strength Headache Powders, a commercially available medication which contains acetaminophen, aspirin, and caffeine as active ingredients. However, the separation scheme is not limited to this brand of medication nor is it limited to caffeine as the analyte. With only minor procedural modifications, students can simultaneously quantitate all of these compounds in a commercial mixture. In our procedure, students prepare a series of four caffeine standard solutions as well as a solution from a pharmaceutical analgesic/caffeine mixture, chromatographically analyze each solution in quadruplicate, and plot relative average caffeine standard peak area versus concentration. From the mathematical relationship that results, the concentration of caffeine in the commercial formulation is obtained. Finally, the absolute standard deviation of the mean concentration is calculated.

Neocarzinostatin as a probe for DNA protection activity--molecular interaction with caffeine.

PubMed

Chin, Der-Hang; Li, Huang-Hsien; Kuo, Hsiu-Maan; Chao, Pei-Dawn Lee; Liu, Chia-Wen

2012-04-01

Neocarzinostatin (NCS), a potent mutagen and carcinogen, consists of an enediyne prodrug and a protein carrier. It has a unique double role in that it intercalates into DNA and imposes radical-mediated damage after thiol activation. Here we employed NCS as a probe to examine the DNA-protection capability of caffeine, one of common dietary phytochemicals with potential cancer-chemopreventive activity. NCS at the nanomolar concentration range could induce significant single- and double-strand lesions in DNA, but up to 75 ± 5% of such lesions were found to be efficiently inhibited by caffeine. The percentage of inhibition was caffeine-concentration dependent, but was not sensitive to the DNA-lesion types. The well-characterized activation reactions of NCS allowed us to explore the effect of caffeine on the enediyne-generated radicals. Postactivation analyses by chromatographic and mass spectroscopic methods identified a caffeine-quenched enediyne-radical adduct, but the yield was too small to fully account for the large inhibition effect on DNA lesions. The affinity between NCS chromophore and DNA was characterized by a fluorescence-based kinetic method. The drug-DNA intercalation was hampered by caffeine, and the caffeine-induced increases in DNA-drug dissociation constant was caffeine-concentration dependent, suggesting importance of binding affinity in the protection mechanism. Caffeine has been shown to be both an effective free radical scavenger and an intercalation inhibitor. Our results demonstrated that caffeine ingeniously protected DNA against the enediyne-induced damages mainly by inhibiting DNA intercalation beforehand. The direct scavenging of the DNA-bound NCS free radicals by caffeine played only a minor role. Copyright © 2011 Wiley Periodicals, Inc.

Pharmacokinetics of Caffeine in the Lens Capsule/Epithelium After Peroral Intake: A Pilot Randomized Controlled Study.

PubMed

Kronschläger, Martin; Stimpfl, Thomas; Ruiß, Manuel; Hirnschall, Nino; Leisser, Christoph; Findl, Oliver

2018-04-01

To determine the pharmacokinetics of perorally administered caffeine, a widely consumed and potent dietary antioxidant, in the anterior lens capsule and lens epithelial cells, a crucial cell monolayer for cataract development. Bilateral cataract patients were scheduled for cataract surgery with a caffeine abstinence of 1 week before surgery of each eye. At the day of surgery of the second eye patients were administered no drink (0-mg group) or coffee with 60-, 120-, or 180-mg caffeine. After capsulorhexis the lens capsule including lens epithelial cells was transferred to a test tube for analysis of caffeine concentration by gas chromatography-mass spectrometry (GC-MS/MS). Coffee consumption significantly (P < 0.05) increased caffeine levels of the lens capsule/epithelium in the 60-, 120-, and 180-mg group. Caffeine concentrations (caffeine ng/lens capsule/epithelium) measured as difference between 1st and 2nd eye were -0.52 ± 1.16 (0-mg group, n = 7), 1.88 ± 2.02 (60-mg group, n = 8), 2.09 ± 0.67 (120-mg group, n = 9), and 3.68 ± 1.86 (180-mg group, n = 9). The increase constant of caffeine in a linear regression model was estimated as a 95% CI 0.02 ± 0.0046 (degrees of freedom; 25; r = 0.85). Peroral intake of coffee significantly increased caffeine concentrations in the lens capsule and lens epithelial cells in a dose-dependent manner. This information is important for further investigations on preventing cataract.

Induction of sister chromatid exchanges and inhibition of cellular proliferation in vitro. I. Caffeine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guglielmi, G.E.; Vogt, T.F.; Tice, R.R.

1982-01-01

While many agents have been examined for their ability to induce SCE's, complete dose-response information has often been lacking. We have reexamined the ability of one such compound - caffeine - to induce SCEs and also to inhibit cellular proliferation in human peripheral lymphocytes in vitro. An acute exposure to caffeine prior to the DNA synthetic period did not affect either SCE frequency or the rate of cellular proliferation. Chronic exposure to caffeine throughout the culture period lead to both a dose-dependent increase in SCEs (SCE/sub d/ or doubling dose = 2.4 mM; SCE/sub 10/ or the dose capable ofmore » inducing 10 SCE = 1.4 mM) and a dose-dependent inhibition of cellular proliferation (IC/sub 50/ or the 50% inhibition concentration = 2.6 mM). The relative proportion of first generation metaphase cells, an assessment of proliferative inhibiton, increased linearly with increasing caffeine concentrations. However, SCE frequency increased nonlinearly over the same range of caffeine concentrations. Examination of the ratio of nonsymmetrical to symmetrical SCEs in third generation metaphase cells indicated that caffeine induced SCEs in equal frequency in each of three successive generations. The dependency of SCE induction and cellular proliferative inhibition on caffeine's presence during the DNA synthetic period suggests that caffeine may act as an antimetabolite in normal human cells.« less

Dimer excision in Escherichia coli in the presence of caffeine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rothman, R.H.

1980-07-01

The observation that polA1 and recL152 mutations result in both slow pyrimidine dimer excision and large repair patch size leads to the hypothesis that patch size is directly related to the rate of excision. In this study caffeine, a known inhibitor of excision repair, was used to examine the extent of correlation between excision rate and patch size by measuring patch size in the presence of several concentrations of caffeine. Both the rate of excision and the resistance to ultraviolet radiation were reduced with increasing concentrations of caffeine after irradiation. Caffeine also inhibited the rate at which incisions were mademore » and prolonged the time required to rejoin the discontinuities. Patch size, however, was unaffected by caffeine treatment.« less

Shifting the boundaries for early caffeine initiation in neonatal practice: Results of a prospective, multicenter study on very preterm infants with respiratory distress syndrome.

PubMed

Borszewska-Kornacka, Maria Katarzyna; Hożejowski, Roman; Rutkowska, Magdalena; Lauterbach, Ryszard

2017-01-01

There is growing evidence that supports the benefits of early use of caffeine in preterm neonates with RDS; however, no formal recommendations specifying the exact timing of therapy initiation have been provided. We compared neonatal outcomes in infants receiving early (initial dose on the 1st day of life) and late (initial dose on day 2+ of life) caffeine therapy. Using data from a prospective, cohort study, we identified 986 infants ≤32 weeks' gestation with RDS and assessed the timing of caffeine therapy initiation, need for ventilatory support, mortality and incidence of typical complications of prematurity. To adjust for baseline severity, the early and late caffeine groups were propensity score (PS) matched to 286 infants (1:1). Clinical outcomes were compared between the PS-matched groups. Early treatment with caffeine citrate was associated with a significantly reduced need for invasive ventilation (71.3% vs 83.2%; P = 0.0165) and total duration of mechanical ventilation (mean 5 ± 11.1 days vs 10.8 ± 14.6 days; P = 0.0000) and significantly lower odds of intraventricular hemorrhage (IVH) (OR 0.4827; 95% CI 0.2999-0.7787) and patent ductus arteriosus (PDA) (OR 0.5686; 95% CI 0.3395-0.9523). The incidence of bronchopulmonary dysplasia (BPD) (36.4% vs 45.8%) and rates of moderate and severe BPD were not significantly different between the two groups. The mortality rates were comparable between the two groups (8.6% vs 8.5%, P = ns). Early caffeine initiation was associated with a decreased need for invasive ventilatory support and lower incidence of IVH and PDA.

Effects of caffeine on cytoplasmic free Ca2+ concentration in pancreatic beta-cells are mediated by interaction with ATP-sensitive K+ channels and L-type voltage-gated Ca2+ channels but not the ryanodine receptor.

PubMed Central

Islam, M S; Larsson, O; Nilsson, T; Berggren, P O

1995-01-01

In the pancreatic beta-cell, an increase in the cytoplasmic free Ca2+ concentration ([Ca2+]i) by caffeine is believed to indicate mobilization of Ca2+ from intracellular stores, through activation of a ryanodine receptor-like channel. It is not known whether other mechanisms, as well, underlie caffeine-induced changes in [Ca2+]i. We studied the effects of caffeine on [Ca2+]i by using dual-wavelength excitation microfluorimetry in fura-2-loaded beta-cells. In the presence of a non-stimulatory concentration of glucose, caffeine (10-50 mM) consistently increased [Ca2+]i. The effect was completely blocked by omission of extracellular Ca2+ and by blockers of the L-type voltage-gated Ca2+ channel, such as D-600 or nifedipine. Depletion of agonist-sensitive intracellular Ca2+ pools by thapsigargin did not inhibit the stimulatory effect of caffeine on [Ca2+]i. Moreover, this effect of caffeine was not due to an increase in cyclic AMP, since forskolin and 3-isobutyl-1-methylxanthine (IBMX) failed to raise [Ca2+]i in unstimulated beta-cells. In beta-cells, glucose and sulphonylureas increase [Ca2+]i by causing closure of ATP-sensitive K+ channels (KATP channels). Caffeine also caused inhibition of KATP channel activity, as measured in excised inside-out patches. Accordingly, caffeine (> 10 mM) induced insulin release from beta-cells in the presence of a non-stimulatory concentration of glucose (3 mM). Hence, membrane depolarization and opening of voltage-gated L-type Ca2+ channels were the underlying mechanisms whereby the xanthine drug increased [Ca2+]i and induced insulin release. Paradoxically, in glucose-stimulated beta-cells, caffeine (> 10 mM) lowered [Ca2+]i. This effect was due to the fact that caffeine reduced depolarization-induced whole-cell Ca2+ current through the L-type voltage-gated Ca2+ channel in a dose-dependent manner. Lower concentrations of caffeine (2.5-5.0 mM), when added after glucose-stimulated increase in [Ca2+]i, induced fast oscillations in [Ca2+]i. The latter effect was likely to be attributable to the cyclic AMP-elevating action of caffeine, leading to phosphorylation of voltage-gated Ca2+ channels. Hence, in beta-cells, caffeine-induced changes in [Ca2+]i are not due to any interaction with intracellular Ca2+ pools. In these cells, a direct interference with KATP channel- and L-type voltage-gated Ca(2+)-channel activity is the underlying mechanism by which caffeine increases or decreases [Ca2+]i. Images Figure 9 PMID:7702559

Relative contribution of rat cytochrome P450 isoforms to the metabolism of caffeine: the pathway and concentration dependence.

PubMed

Kot, Marta; Daniel, Władysława A

2008-04-01

The aim of the present study was to estimate the relative contribution of rat P450 isoforms to the metabolism of caffeine and to assess the usefulness of caffeine as a marker substance for estimating the activity of P450 in rat liver and its potential for pharmacokinetic interactions in pharmacological experiments. The results obtained using rat cDNA-expressed P450s indicated that 8-hydroxylation was the main oxidation pathway of caffeine (70%) in the rat. CYP1A2 was found to be a key enzyme catalyzing 8-hydroxylation (72%) and substantially contributing to 3-N-demethylation (47%) and 1-N-demethylation (37.5%) at a caffeine concentration of 0.1mM (relevant to "the maximum therapeutic concentration in humans"). Furthermore, CYP2C11 considerably contributed to 3-N-demethylation (31%). The CYP2C subfamily (66%) - mainly CYP2C6 (27%) and CYP2C11 (29%) - played a major role in catalyzing 7-N-demethylation. At higher substrate concentrations, the contribution of CYP1A2 to the metabolism of caffeine decreased in favor of CYP2C11 (N-demethylations) and CYP3A2 (mainly 8-hydroxylation). The obtained results were confirmed with liver microsomes (inhibition and correlation studies). Therefore, caffeine may be used as a marker substance for assessing the activity of CYP1A2 in rats, using 8-hydroxylation (but not 3-N-demethylation-like in humans); moreover, caffeine may also be used to simultaneously, preliminarily estimate the activity of CYP2C using 7-N-demethylation as a marker reaction. Hence caffeine pharmacokinetics in rats may be changed by drugs affecting the activity of CYP1A2 and/or CYP2C, e.g. by some antidepressants.

Caffeine depression of spontaneous activity in rabbit sino-atrial node cells.

PubMed

Satoh, H

1993-05-01

1. Effects of caffeine on the action potentials and the membrane currents in spontaneously beating rabbit sino-atrial (SA) node cells were examined using a two-microelectrode technique. 2. Cumulative administrations of caffeine (1-10 mM) caused a negative chronotropic effect in a concentration-dependent manner, which was not modified by atropine (0.1 microM). At 10 mM, caffeine increased the amplitude and prolonged the duration of action potentials significantly; the other parameters were unaffected. 3. In 3 of 16 preparations, caffeine (5 mM) elicited arrhythmia. At high Ca2+ (8.1 mM), caffeine (5 mM) increased the incidence of arrhythmia. 4. Caffeine (0.5-10 mM) enhanced the slow inward current, but at 10 mM decreased the enhanced peak current by 5 mM. The hyperpolarization-activated inward current was also enhanced by caffeine, but 10 mM caffeine decreased the current peak as compared with that at 5 mM. In addition, caffeine inhibited the delayed rectifying outward current in a concentration-dependent manner, accompanied by a depressed activation curve without any shift in the half-maximum activation voltage. 5. Caffeine elevated the cytoplasmic Ca2+ level in the SA node cells loaded with Ca(2+)-sensitive fluorescent dye (fura-2). 6. These results suggest that caffeine enhances and/or inhibits the ionic currents and elicits arrhythmia due to the induction of cellular calcium overload.

Caffeine-Related Deaths: Manner of Deaths and Categories at Risk.

PubMed

Cappelletti, Simone; Piacentino, Daria; Fineschi, Vittorio; Frati, Paola; Cipolloni, Luigi; Aromatario, Mariarosaria

2018-05-14

Caffeine is the most widely consumed psychoactive compound worldwide. It is mostly found in coffee, tea, energizing drinks and in some drugs. However, it has become really easy to obtain pure caffeine (powder or tablets) on the Internet markets. Mechanisms of action are dose-dependent. Serious toxicities such as seizure and cardiac arrhythmias, seen with caffeine plasma concentrations of 15 mg/L or higher, have caused poisoning or, rarely, death; otherwise concentrations of 3⁻6 mg/kg are considered safe. Caffeine concentrations of 80⁻100 mg/L are considered lethal. The aim of this systematic review, performed following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement for the identification and selection of studies, is to review fatal cases in which caffeine has been recognized as the only cause of death in order to identify potential categories at risk. A total of 92 cases have been identified. These events happened more frequently in infants, psychiatric patients, and athletes. Although caffeine intoxication is relatively uncommon, raising awareness about its lethal consequences could be useful for both clinicians and pathologists to identify possible unrecognized cases and prevent related severe health conditions and deaths.

Caffeine-Related Deaths: Manner of Deaths and Categories at Risk

PubMed Central

Cappelletti, Simone; Piacentino, Daria; Fineschi, Vittorio; Frati, Paola; Cipolloni, Luigi; Aromatario, Mariarosaria

2018-01-01

Caffeine is the most widely consumed psychoactive compound worldwide. It is mostly found in coffee, tea, energizing drinks and in some drugs. However, it has become really easy to obtain pure caffeine (powder or tablets) on the Internet markets. Mechanisms of action are dose-dependent. Serious toxicities such as seizure and cardiac arrhythmias, seen with caffeine plasma concentrations of 15 mg/L or higher, have caused poisoning or, rarely, death; otherwise concentrations of 3–6 mg/kg are considered safe. Caffeine concentrations of 80–100 mg/L are considered lethal. The aim of this systematic review, performed following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement for the identification and selection of studies, is to review fatal cases in which caffeine has been recognized as the only cause of death in order to identify potential categories at risk. A total of 92 cases have been identified. These events happened more frequently in infants, psychiatric patients, and athletes. Although caffeine intoxication is relatively uncommon, raising awareness about its lethal consequences could be useful for both clinicians and pathologists to identify possible unrecognized cases and prevent related severe health conditions and deaths. PMID:29757951

Caffeine inhibition of GLUT1 is dependent on the activation state of the transporter.

PubMed

Gunnink, Leesha K; Busscher, Brianna M; Wodarek, Jeremy A; Rosette, Kylee A; Strohbehn, Lauren E; Looyenga, Brendan D; Louters, Larry L

2017-06-01

Caffeine has been shown to be a robust uncompetitive inhibitor of glucose uptake in erythrocytes. It preferentially binds to the nucleotide-binding site on GLUT1 in its tetrameric form and mimics the inhibitory action of ATP. Here we demonstrate that caffeine is also a dose-dependent, uncompetitive inhibitor of 2-deoxyglucose (2DG) uptake in L929 fibroblasts. The inhibitory effect on 2DG uptake in these cells was reversible with a rapid onset and was additive to the competitive inhibitory effects of glucose itself, confirming that caffeine does not interfere with glucose binding. We also report for the first time that caffeine inhibition was additive to inhibition by curcumin, suggesting distinct binding sites for curcumin and caffeine. In contrast, caffeine inhibition was not additive to that of cytochalasin B, consistent with previous data that reported that these two inhibitors have overlapping binding sites. More importantly, we show that the magnitude of maximal caffeine inhibition in L929 cells is much lower than in erythrocytes (35% compared to 90%). Two epithelial cell lines, HCLE and HK2, have both higher concentrations of GLUT1 and increased basal 2DG uptake (3-4 fold) compared to L929 cells, and subsequently display greater maximal inhibition by caffeine (66-70%). Interestingly, activation of 2DG uptake (3-fold) in L929 cells by glucose deprivation shifted the responsiveness of these cells to caffeine inhibition (35%-70%) without a change in total GLUT1 concentration. These data indicate that the inhibition of caffeine is dependent on the activity state of GLUT1, not merely on the concentration. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Molecular and biochemical characterization of caffeine synthase and purine alkaloid concentration in guarana fruit.

PubMed

Schimpl, Flávia Camila; Kiyota, Eduardo; Mayer, Juliana Lischka Sampaio; Gonçalves, José Francisco de Carvalho; da Silva, José Ferreira; Mazzafera, Paulo

2014-09-01

Guarana seeds have the highest caffeine concentration among plants accumulating purine alkaloids, but in contrast with coffee and tea, practically nothing is known about caffeine metabolism in this Amazonian plant. In this study, the levels of purine alkaloids in tissues of five guarana cultivars were determined. Theobromine was the main alkaloid that accumulated in leaves, stems, inflorescences and pericarps of fruit, while caffeine accumulated in the seeds and reached levels from 3.3% to 5.8%. In all tissues analysed, the alkaloid concentration, whether theobromine or caffeine, was higher in young/immature tissues, then decreasing with plant development/maturation. Caffeine synthase activity was highest in seeds of immature fruit. A nucleotide sequence (PcCS) was assembled with sequences retrieved from the EST database REALGENE using sequences of caffeine synthase from coffee and tea, whose expression was also highest in seeds from immature fruit. The PcCS has 1083bp and the protein sequence has greater similarity and identity with the caffeine synthase from cocoa (BTS1) and tea (TCS1). A recombinant PcCS allowed functional characterization of the enzyme as a bifunctional CS, able to catalyse the methylation of 7-methylxanthine to theobromine (3,7-dimethylxanthine), and theobromine to caffeine (1,3,7-trimethylxanthine), respectively. Among several substrates tested, PcCS showed higher affinity for theobromine, differing from all other caffeine synthases described so far, which have higher affinity for paraxanthine. When compared to previous knowledge on the protein structure of coffee caffeine synthase, the unique substrate affinity of PcCS is probably explained by the amino acid residues found in the active site of the predicted protein. Copyright © 2014 Elsevier Ltd. All rights reserved.

Caffeine controversies.

PubMed

Gentle, Samuel J; Travers, Colm P; Carlo, Waldemar A

2018-04-01

Caffeine use in preterm infants has endured several paradigms: from standard of care to possible neurotoxin to one of the few medications for which there is evidence of bronchopulmonary dysplasia (BPD) risk reduction. The purpose of the review is to analyze this dynamic trajectory and discuss controversies that still remain after decades of caffeine use. Following concerns for caffeine safety in preterm infants, a large randomized controlled trial demonstrated a reduction in BPD and treatment for patent ductus arteriosus. The lower rate of death or neurodevelopmental impairment noted at 18-21 months was not statistically different at later timepoints; however, infants in the caffeine group had lower rates of motor impairment at 11-year follow-up. The time of caffeine therapy initiation is now substantially earlier, and doses used are sometimes higher that previously used, but there are limited data to support these practices. Caffeine therapy for apnea of prematurity (AOP) remains one of the pillars of neonatal care, although more evidence to support dosing and timing of initiation and discontinuation are needed.

Caffeine-induced increase in voluntary activation and strength of the quadriceps muscle during isometric, concentric and eccentric contractions.

PubMed

Behrens, Martin; Mau-Moeller, Anett; Weippert, Matthias; Fuhrmann, Josefin; Wegner, Katharina; Skripitz, Ralf; Bader, Rainer; Bruhn, Sven

2015-05-13

This study investigated effects of caffeine ingestion (8 mg/kg) on maximum voluntary torque (MVT) and voluntary activation of the quadriceps during isometric, concentric and eccentric contractions. Fourteen subjects ingested caffeine and placebo in a randomized, controlled, counterbalanced, double-blind crossover design. Neuromuscular tests were performed before and 1 h after oral caffeine and placebo intake. MVTs were measured and the interpolated twitch technique was applied during isometric, concentric and eccentric contractions to assess voluntary activation. Furthermore, normalized root mean square of the EMG signal was calculated and evoked spinal reflex responses (H-reflex evoked at rest and during weak isometric voluntary contraction) as well as twitch torques were analyzed. Caffeine increased MVT by 26.4 N m (95%CI: 9.3-43.5 N m, P = 0.004), 22.5 N m (95%CI: 3.1-42.0 N m, P = 0.025) and 22.5 N m (95%CI: 2.2-42.7 N m, P = 0.032) for isometric, concentric and eccentric contractions. Strength enhancements were associated with increases in voluntary activation. Explosive voluntary strength and voluntary activation at the onset of contraction were significantly increased following caffeine ingestion. Changes in spinal reflex responses and at the muscle level were not observed. Data suggest that caffeine ingestion induced an acute increase in voluntary activation that was responsible for the increased strength regardless of the contraction mode.

Maternal caffeine intake during pregnancy and risk of fetal growth restriction: a large prospective observational study.

PubMed

2008-11-03

To examine the association of maternal caffeine intake with fetal growth restriction. Prospective longitudinal observational study. Two large UK hospital maternity units. 2635 low risk pregnant women recruited between 8-12 weeks of pregnancy. Investigations Quantification of total caffeine intake from 4 weeks before conception and throughout pregnancy was undertaken with a validated caffeine assessment tool. Caffeine half life (proxy for clearance) was determined by measuring caffeine in saliva after a caffeine challenge. Smoking and alcohol were assessed by self reported status and by measuring salivary cotinine concentrations. Fetal growth restriction, as defined by customised birth weight centile, adjusted for alcohol intake and salivary cotinine concentrations. Caffeine consumption throughout pregnancy was associated with an increased risk of fetal growth restriction (odds ratios 1.2 (95% CI 0.9 to 1.6) for 100-199 mg/day, 1.5 (1.1 to 2.1) for 200-299 mg/day, and 1.4 (1.0 to 2.0) for >300 mg/day compared with <100 mg/day; test for trend P<0.001). Mean caffeine consumption decreased in the first trimester and increased in the third. The association between caffeine and fetal growth restriction was stronger in women with a faster compared to a slower caffeine clearance (test for interaction, P=0.06). Caffeine consumption during pregnancy was associated with an increased risk of fetal growth restriction and this association continued throughout pregnancy. Sensible advice would be to reduce caffeine intake before conception and throughout pregnancy.

Optimizing Caffeine Use and Risk of Bronchopulmonary Dysplasia in Preterm Infants: A Systematic Review, Meta-analysis, and Application of Grading of Recommendations Assessment, Development, and Evaluation Methodology.

PubMed

Pakvasa, Mitali Atul; Saroha, Vivek; Patel, Ravi Mangal

2018-06-01

Caffeine reduces the risk of bronchopulmonary dysplasia (BPD). Optimizing caffeine use could increase therapeutic benefit. We performed a systematic-review and random-effects meta-analysis of studies comparing different timing of initiation and dose of caffeine on the risk of BPD. Earlier initiation, compared to later, was associated with a decreased risk of BPD (5 observational studies; n = 63,049, adjusted OR 0.69; 95% CI 0.64-0.75, GRADE: low quality). High-dose caffeine, compared to standard-dose, was associated with a decreased risk of BPD (3 randomized trials, n = 432, OR 0.65; 95% CI 0.43-0.97; GRADE: low quality). Higher quality evidence is needed to guide optimal caffeine use. Copyright © 2018 Elsevier Inc. All rights reserved.

Comparison of caffeine disposition following administration by oral solution (energy drink) and inspired powder (AeroShot) in human subjects.

PubMed

Laizure, S Casey; Meibohm, Bernd; Nelson, Kembral; Chen, Feng; Hu, Zhe-Yi; Parker, Robert B

2017-12-01

To determine the disposition and effects of caffeine after administration using a new dosage form (AeroShot) that delivers caffeine by inspiration of a fine powder into the oral cavity and compare it to an equivalent dose of an oral solution (energy drink) as the reference standard. Healthy human subjects (n = 17) inspired a 100 mg caffeine dose using the AeroShot device or consumed an energy drink on separate study days. Heart rate, blood pressure and subject assessments of effects were measured over an 8-h period. Plasma concentrations of caffeine and its major metabolites were determined by liquid chromatography-mass spectrometry. Pharmacokinetic, cardiovascular and perceived stimulant effects were compared between AeroShot and energy drink phases using a paired t test and standard bioequivalency analysis. Caffeine disposition was similar after caffeine administration by the AeroShot device and energy drink: peak plasma concentration 1790 and 1939 ng ml -1 , and area under the concentration-time curve (AUC) 15 579 and 17 569 ng ml -1 × h, respectively, but they were not bioequivalent: AeroShot AUC of 80.3% (confidence interval 71.2-104.7%) and peak plasma concentration of 86.3% (confidence interval 62.8-102.8%) compared to the energy drink. Female subjects did have a significantly larger AUC compared to males after consumption of the energy drink. The heart rate and blood pressure were not significantly affected by the 100 mg caffeine dose, and there were no consistently perceived stimulant effects by the subjects using visual analogue scales. Inspiration of caffeine as a fine powder using the AeroShot device produces a similar caffeine profile and effects compared to administration of an oral solution (energy drink). © 2017 The British Pharmacological Society.

Genotoxicity of antiobesity drug orlistat and effect of caffeine intervention: an in vitro study.

PubMed

Chakrabarti, Manoswini; Ghosh, Ilika; Jana, Aditi; Ghosh, Manosij; Mukherjee, Anita

2017-07-01

Obesity is a major global health problem associated with various adverse effects. Pharmacological interventions are often necessary for the management of obesity. Orlistat is an FDA-approved antiobesity drug which is a potent inhibitor of intestinal lipases. In the current study, orlistat was evaluated for its genotoxic potential in human lymphocyte cells in vitro and was compared with that of another antiobesity drug sibutramine, presently withdrawn from market due its undesirable health effects. Caffeine intake may be an additional burden in people using anorectic drugs, therefore, further work is needed to be carried out to evaluate the possible effects of caffeine on orlistat-induced DNA damage. Human lymphocytes were exposed to orlistat (250, 500 and 1000 μg/ml), sibutramine (250, 500 and 1000 μg/ml) and caffeine (25, 50, 75, 100, 125 and 150 μg/ml) to assess their genotoxicity by comet assay in vitro. In addition, lymphocytes were co-incubated with caffeine (50, 75 and 100 μg/ml) and a single concentration of orlistat (250 μg/ml). Orlistat and sibutramine were genotoxic at all concentrations tested, sibutramine being more genotoxic. Caffeine was found to be genotoxic at concentrations 125 μg/ml and above. Co-treatment of orlistat with non-genotoxic concentrations (50, 75 and 100 μg/ml) of caffeine lead to a decrease in DNA damage. Orlistat can induce DNA damage in human lymphocytes in vitro and caffeine was found to reduce orlistat-induced genotoxicity.

The Interaction of Sorbitol with Caffeine in Aqueous Solution

PubMed Central

Tavagnacco, Letizia; Brady, John W.; Cesàro, Attilio

2013-01-01

Molecular dynamics simulations were carried out on a system of caffeine interacting with the sugar alcohol sorbitol. The system examined had a caffeine concentration 0.083 m and a sugar concentration 1.08 m. The trajectories of all molecules in the system were collected over a period of 80 ns and analyzed to determine whether there is any tendency for sorbitol to bind to caffeine, and if so, by what mechanism. The results show that the sorbitol molecules have an affinity for the caffeine molecules and that the binding occurred by the interaction of the aliphatic hydrophobic protons of the sugar with the caffeine face. This intermolecular association via face-to-face stacking, as suggested by simulation studies, is similar to that found for sucrose and for D-glucose, which overwhelmingly exists in the pyranose ring chair form in aqueous solution, as well as for caffeine-caffeine association. The sorbitol molecules, however, exist as relatively extended chains and are, therefore, topologically quite different from the sugars sucrose and glucose. The comparison of the average conformation of sorbitol molecules bound to caffeine with that of molecules in the free state shows a substantial similarity. PMID:24000279

The Interaction of Sorbitol with Caffeine in Aqueous Solution.

PubMed

Tavagnacco, Letizia; Brady, John W; Cesàro, Attilio

2013-09-01

Molecular dynamics simulations were carried out on a system of caffeine interacting with the sugar alcohol sorbitol. The system examined had a caffeine concentration 0.083 m and a sugar concentration 1.08 m. The trajectories of all molecules in the system were collected over a period of 80 ns and analyzed to determine whether there is any tendency for sorbitol to bind to caffeine, and if so, by what mechanism. The results show that the sorbitol molecules have an affinity for the caffeine molecules and that the binding occurred by the interaction of the aliphatic hydrophobic protons of the sugar with the caffeine face. This intermolecular association via face-to-face stacking, as suggested by simulation studies, is similar to that found for sucrose and for D-glucose, which overwhelmingly exists in the pyranose ring chair form in aqueous solution, as well as for caffeine-caffeine association. The sorbitol molecules, however, exist as relatively extended chains and are, therefore, topologically quite different from the sugars sucrose and glucose. The comparison of the average conformation of sorbitol molecules bound to caffeine with that of molecules in the free state shows a substantial similarity.

Effects of Caffeine on Crayfish Muscle Fibers

PubMed Central

Chiarandini, Dante J.; Reuben, John P.; Brandt, Philip W.; Grundfest, Harry

1970-01-01

Contractions are evoked in single muscle fibers of crayfish by intracellular as well as extracellular applications of caffeine. Responses to external applications in concentrations above 2 mM could be induced indefinitely. With concentrations above 5 mM the caffeine-induced responses were highly repeatable. Tensions were transient even when the caffeine remained in the bath. There was no change in resting potential, but during the contraction the effective resistance decreased about 10%. A number of factors (change in pH, Ca, K, and Cl) modified the responses. The time course of the tension was greatly prolonged when the transverse tubular system (TTS) was s swollen and was again shortened when the TTS was caused to shrink. An increased permeability to Ca induced by caffeine was evidenced by the transformation of the normally graded electrical responses to Ca spikes, which are insensitive to tetrodotoxin. The overshoot is a function of both external Ca and caffeine. A 10-fold change in Ca changed the overshoot by 19 mv in the presence of 10 mM caffeine and by 29 mv in 80 mM caffeine. The role of the increased permeability to Ca for caffeine-induced contractions will be analyzed in the accompanying paper. PMID:5443468

Concentration- and age-dependent effects of chronic caffeine on contextual fear conditioning in C57BL/6J mice

PubMed Central

Poole, Rachel L.; Braak, David; Gould, Thomas J.

2015-01-01

Chronic caffeine exerts negligible effects on learning and memory in normal adults, but it is unknown whether this is also true for children and adolescents. The hippocampus, a brain region important for learning and memory, undergoes extensive structural and functional modifications during pre-adolescence and adolescence. As a result, chronic caffeine may have differential effects on hippocampus-dependent learning in pre-adolescents and adolescents compared with adults. Here, we characterized the effects of chronic caffeine and withdrawal from chronic caffeine on hippocampus-dependent (contextual) and hippocampus-independent (cued) fear conditioning in pre-adolescent, adolescent, and adult mice. The results indicate that chronic exposure to caffeine during pre-adolescence and adolescence enhances or impairs contextual conditioning depending on concentration, yet has no effect on cued conditioning. In contrast, withdrawal from chronic caffeine impairs contextual conditioning in pre-adolescent mice only. No changes in learning were seen for adult mice for either the chronic caffeine or withdrawal conditions. These findings support the hypothesis that chronic exposure to caffeine during pre-adolescence and adolescence can alter learning and memory and as changes were only seen in hippocampus-dependent learning, this suggests that the developing hippocampus may be sensitive to the effects of caffeine. PMID:25827925

Caffeine and pharmaceuticals as indicators of waste water contamination in wells

USGS Publications Warehouse

Seiler, R.L.; Zaugg, S.D.; Thomas, J.M.; Howcroft, D.L.

1999-01-01

The presence of caffeine or human pharmaceuticals in ground water with elevated nitrate concentrations can provide a clear, unambiguous indication that domestic waste water is a source of some of the nitrate. Water from domestic, public supply, and monitoring wells in three communities near Reno, Nevada, was sampled to test if caffeine or pharmaceuticals are common, persistent, and mobile enough in the environment that they can be detected in nitrate-contaminated ground water and, thus, can be useful indicators of recharge from domestic waste water. Results of this study indicate that these compounds can be used as indicators of recharge from domestic waste water, although their usefulness is limited because caffeine is apparently nonconservative and the presence of prescription pharmaceuticals is unpredictable. The absence of caffeine or pharmaceuticals in ground water with elevated nitrate concentrations does not demonstrate that the aquifer is free of waste water contamination. Caffeine was detected in ground water samples at concentrations up to 0.23 ??g/L. The human pharmaceuticals chlorpropamide, phensuximide, and carbamazepine also were detected in some samples.

Ca2+-induced Ca2+ Release Phenomena in Mammalian Sympathetic Neurons Are Critically Dependent on the Rate of Rise of Trigger Ca2+

PubMed Central

Hernández-Cruz, Arturo; Escobar, Ariel L.; Jiménez, Nicolás

1997-01-01

The role of ryanodine-sensitive intracellular Ca2+ stores present in nonmuscular cells is not yet completely understood. Here we examine the physiological parameters determining the dynamics of caffeine-induced Ca2+ release in individual fura-2–loaded sympathetic neurons. Two ryanodine-sensitive release components were distinguished: an early, transient release (TR) and a delayed, persistent release (PR). The TR component shows refractoriness, depends on the filling status of the store, and requires caffeine concentrations ≥10 mM. Furthermore, it is selectively suppressed by tetracaine and intracellular BAPTA, which interfere with Ca2+-mediated feedback loops, suggesting that it constitutes a Ca2+-induced Ca2+-release phenomenon. The dynamics of release is markedly affected when Sr2+ substitutes for Ca2+, indicating that Sr2+ release may operate with lower feedback gain than Ca2+ release. Our data indicate that when the initial release occurs at an adequately fast rate, Ca2+ triggers further release, producing a regenerative response, which is interrupted by depletion of releasable Ca2+ and Ca2+-dependent inactivation. A compartmentalized linear diffusion model can reproduce caffeine responses: When the Ca2+ reservoir is full, the rapid initial Ca2+ rise determines a faster occupation of the ryanodine receptor Ca2+ activation site giving rise to a regenerative release. With the store only partially loaded, the slower initial Ca2+ rise allows the inactivating site of the release channel to become occupied nearly as quickly as the activating site, thereby suppressing the initial fast release. The PR component is less dependent on the store's Ca2+ content. This study suggests that transmembrane Ca2+ influx in rat sympathetic neurons does not evoke widespread amplification by CICR because of its inability to raise [Ca2+] near the Ca2+ release channels sufficiently fast to overcome their Ca2+-dependent inactivation. Conversely, caffeine-induced Ca2+ release can undergo considerable amplification especially when Ca2+ stores are full. We propose that the primary function of ryanodine-sensitive stores in neurons and perhaps in other nonmuscular cells, is to emphasize subcellular Ca2+ gradients resulting from agonist-induced intracellular release. The amplification gain is dependent both on the agonist concentration and on the filling status of intracellular Ca2+ stores. PMID:9041445

Nutrition Influences Caffeine-Mediated Sleep Loss in Drosophila.

PubMed

Keebaugh, Erin S; Park, Jin Hong; Su, Chenchen; Yamada, Ryuichi; Ja, William W

2017-11-01

Plant-derived caffeine is regarded as a defensive compound produced to prevent herbivory. Caffeine is generally repellent to insects and often used to study the neurological basis for aversive responses in the model insect, Drosophila melanogaster. Caffeine is also studied for its stimulatory properties where sleep or drowsiness is suppressed across a range of species. Since limiting access to food also inhibits fly sleep-an effect known as starvation-induced sleep suppression-we tested whether aversion to caffeinated food results in reduced nutrient intake and assessed how this might influence fly studies on the stimulatory effects of caffeine. We measured sleep and total consumption during the first 24 hours of exposure to caffeinated diets containing a range of sucrose concentrations to determine the relative influence of caffeine and nutrient ingestion on sleep. Experiments were replicated using three fly strains. Caffeine reduced total consumption and nighttime sleep, but only at intermediate sucrose concentrations. Although sleep can be modeled by an exponential dose response to nutrient intake, caffeine-mediated sleep loss cannot be explained by absolute caffeine or sucrose ingestion alone. Instead, reduced sleep strongly correlates with changes in total consumption due to caffeine. Other bitter compounds phenocopy the effect of caffeine on sleep and food intake. Our results suggest that a major effect of dietary caffeine is on fly feeding behavior. Changes in feeding behavior may drive caffeine-mediated sleep loss. Future studies using psychoactive compounds should consider the potential impact of nutrition when investigating effects on sleep. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Spectroscopic study of surface enhanced Raman scattering of caffeine on borohydride-reduced silver colloids

NASA Astrophysics Data System (ADS)

Chen, Xiaomin; Gu, Huaimin; Shen, Gaoshan; Dong, Xiao; Kang, Jian

2010-06-01

The surface enhanced Raman scattering (SERS) of caffeine on borohydride-reduced silver colloids system under different aqueous solution environment has been studied in this paper. The relative intensity of SERS of caffeine significantly varies with different concentrations of sodium chloride and silver particles. However, at too high or too low concentration of sodium chloride and silver particle, the enhancement of SERS spectra is not evident. The SERS spectra of caffeine suggest that the contribution of the charge transfer mechanism to SERS may be dominant. The chloride ions can significantly enhance the efficiency of SERS, while the enhancement is selective, as the efficiency in charge transfer enhancement is higher than in electromagnetic enhancement. Therefore, it can be concluded that the active site of chloride ion locates on the bond between the caffeine and the silver surface. In addition, the SERS spectra of caffeine on borohydride-reduced and citrate-reduced silver colloids are different, which may be due to different states caffeine adsorbed on silver surface under different silver colloids.

Gender Differences in Subjective and Physiological Responses to Caffeine and the Role of Steroid Hormones

PubMed Central

Ziegler, Amanda M.

2011-01-01

Background We have shown previously that male and female adolescents differ in their responses to caffeine, but to date, the mechanisms underlying these gender differences are unknown. Objective The purpose of this study was to test the hypothesis that differences in circulating steroid hormones mediate gender differences in response to caffeine. Methods Subjective and physiological responses to caffeine were tested in adolescents using a double-blind, placebo controlled, crossover design. Participants were tested every 2 weeks for 8 weeks and received placebo and caffeine (2 mg/kg) twice each. Females were tested with placebo and caffeine in each phase of their menstrual cycle. Salivary concentrations of testosterone, estradiol, and progesterone were also measured. Results Males showed greater positive subjective effects than females. In females, higher levels of estradiol were associated with little or no subjective responses to caffeine, but lower levels of estradiol were associated with negative subjective responses to caffeine relative to placebo. There were gender differences in cardiovascular responses to caffeine, with males showing greater decreases in heart rate after caffeine administration than females, but females showing greater increases in diastolic blood pressure than males after caffeine administration. These gender differences may be related to steroid hormone concentrations. Blood pressure responses to caffeine were lower in males when estradiol was high, but higher in females when estradiol was high. Conclusions When taken together, these findings suggest that males and females differ in their responses to caffeine and that these differences may be mediated by changes in circulating steroid hormones. PMID:24761262

Caffeine-induced increase in voluntary activation and strength of the quadriceps muscle during isometric, concentric and eccentric contractions

PubMed Central

Behrens, Martin; Mau-Moeller, Anett; Weippert, Matthias; Fuhrmann, Josefin; Wegner, Katharina; Skripitz, Ralf; Bader, Rainer; Bruhn, Sven

2015-01-01

This study investigated effects of caffeine ingestion (8 mg/kg) on maximum voluntary torque (MVT) and voluntary activation of the quadriceps during isometric, concentric and eccentric contractions. Fourteen subjects ingested caffeine and placebo in a randomized, controlled, counterbalanced, double-blind crossover design. Neuromuscular tests were performed before and 1 h after oral caffeine and placebo intake. MVTs were measured and the interpolated twitch technique was applied during isometric, concentric and eccentric contractions to assess voluntary activation. Furthermore, normalized root mean square of the EMG signal was calculated and evoked spinal reflex responses (H-reflex evoked at rest and during weak isometric voluntary contraction) as well as twitch torques were analyzed. Caffeine increased MVT by 26.4 N m (95%CI: 9.3-43.5 N m, P = 0.004), 22.5 N m (95%CI: 3.1-42.0 N m, P = 0.025) and 22.5 N m (95%CI: 2.2-42.7 N m, P = 0.032) for isometric, concentric and eccentric contractions. Strength enhancements were associated with increases in voluntary activation. Explosive voluntary strength and voluntary activation at the onset of contraction were significantly increased following caffeine ingestion. Changes in spinal reflex responses and at the muscle level were not observed. Data suggest that caffeine ingestion induced an acute increase in voluntary activation that was responsible for the increased strength regardless of the contraction mode. PMID:25969895

Modification of caffeine-induced injury in Ca2+-free perfused rat hearts. Relationship to the calcium paradox.

PubMed Central

Vander Heide, R. S.; Altschuld, R. A.; Lamka, K. G.; Ganote, C. E.

1986-01-01

The pathogenesis of the calcium paradox has not been established. In calcium-free perfused hearts, caffeine, which releases calcium from the sarcoplasmic reticulum, causes severe myocardial injury, with creatine kinase (CK) release and contraction band necrosis similar in many respects to the calcium paradox. It has been postulated that contracture, initiated by a small rise in intracellular calcium, may cause sarcolemmal injury in both the calcium paradox and caffeine-induced myocardial injury. The present study was initiated to determine whether interventions which modulate caffeine-induced contracture will also correspondingly alter cellular injury. The effects of caffeine dose, procaine, extended calcium-free perfusion, elevated potassium, temperature, and increasing intracellular sodium on caffeine-induced contracture were examined in Langendorff-perfused adult rat hearts. Caffeine-induced contracture at 22 C increased over a dose range of 5-40 mM caffeine. Procaine, which inhibits caffeine-induced calcium release at doses between 5 and 20 mM, progressively reduced contracture caused by addition of 20 mM caffeine at 22 C. Hearts perfused with calcium-free solution containing 16 mM K+ showed a reduction in caffeine-induced contracture. Extended calcium-free perfusion (20 minutes) at temperatures from 18 to 37 C resulted in a progressive reduction of caffeine-induced contracture. Each of these interventions was also found to inhibit caffeine-induced injury at 37 C. Low temperature was found to have complex effects. Hypothermia enhanced caffeine contractures but also protected hearts from cell separations and CK release. Increasing intracellular sodium was found to enhance caffeine-induced contracture at 37 C. There was a direct correlation between measured intracellular sodium levels and the magnitude and duration of caffeine-induced contracture. These results demonstrate a direct correlation between the magnitude of contracture and myocardial injury in calcium-free hearts. It is proposed that contracture is the primary mediator of sarcolemmal membrane injury in hearts with intercalated disks weakened by prior calcium-free perfusion. Images Figure 11 PMID:3706496

Caffeine, an anthropogenic marker for wastewater comtamination of surface waters.

PubMed

Buerge, Ignaz I; Poiger, Thomas; Müller, Markus D; Buser, Hans-Rudolf

2003-02-15

The suitability of caffeine as a chemical marker for surface water pollution by domestic wastewaters was assessed in this study. Caffeine concentrations in influents and effluents of Swiss wastewater treatment plants (WWTPs, 7-73 and 0.03-9.5 microg/L, respectively) indicated an efficient elimination of 81-99.9%. Corresponding loads in untreated wastewater showed small variations when normalized forthe population discharging to the WWTPs (15.8 +/- 3.8 mg person(-1) d(-1)), reflecting a rather constant consumption. WWTP effluent loads were considerably lower (0.06 +/- 0.03 mg person(-1) d(-1)), apart from installations with low sludge age (< or = 5 d, loads up to 4.4 mg person(-1) d(-1)). Despite the efficient removal in most WWTPs, caffeine was ubiquitously found in Swiss lakes and rivers (6-250 ng/ L), except for remote mountain lakes (<2 ng/L; analytical procedure for wastewater and natural waters: SPE, GC-MS-SIM or GC-MS-MS-MRM, internal standard 13C3-labeled caffeine). Caffeine concentrations in lakes correlated with the anthropogenic burden by domestic wastewaters, demonstrating the suitability of caffeine as a marker. A mass balance for Greifensee revealed that approximately 1-4% of the wastewaters had been discharged without treatment, presumably on rainy days when the capacity of WWTPs had been exceeded. For Zürichsee, it could be shown that the monthly inputs of caffeine correlated with precipitation data. The depth- and seasonal-dependent concentrations in this lake were adequately rationalized by a numerical model considering flushing, biodegradation, and indirect photodegradation via HO. radicals as elimination processes and caffeine inputs as fitting variables.

Occurrence and removal of pharmaceuticals and personal care products (PPCPs) in an advanced wastewater reclamation plant.

PubMed

Yang, Xin; Flowers, Riley C; Weinberg, Howard S; Singer, Philip C

2011-10-15

The occurrence of nineteen pharmaceutically active compounds and personal care products was followed monthly for 12 months after various stages of treatment in an advanced wastewater reclamation plant in Gwinnett County, GA, U.S.A. Twenty-four hour composite samples were collected after primary clarification, activated sludge biological treatment, membrane filtration, granular media filtration, granular activated carbon (GAC) adsorption, and ozonation in the wastewater reclamation plant. Compounds were identified and quantified using high performance liquid chromatography/tandem mass spectrometry (LC-MS/MS) and gas chromatography/mass spectrometry (GC-MS) after solid-phase extraction. Standard addition methods were employed to compensate for matrix effects. Sixteen of the targeted compounds were detected in the primary effluent; sulfadimethoxine, doxycycline, and iopromide were not found. Caffeine and acetaminophen were found at the highest concentrations (∼10(5) ng/L), followed by ibuprofen (∼10(4) ng/L), sulfamethoxazole and DEET (∼10(3) ng/L). Most of the other compounds were found at concentrations on the order of hundreds of ng/L. After activated sludge treatment and membrane filtration, the concentrations of caffeine, acetaminophen, ibuprofen, DEET, tetracycline, and 17α-ethynylestradiol (EE2) had decreased by more than 90%. Erythromycin and carbamazepine, which were resistant to biological treatment, were eliminated by 74 and 88%, on average, by GAC. Primidone, DEET, and caffeine were not amenable to adsorption by GAC. Ozonation oxidized most of the remaining compounds by >60%, except for primidone and DEET. Of the initial 16 compounds identified in the primary effluent, only sulfamethoxazole, primidone, caffeine and DEET were frequently detected in the final effluent, but at concentrations on the order of 10-100 ng/L. Removal of the different agents by the various treatment processes was related to the physical-chemical properties of the compounds. Copyright © 2011 Elsevier Ltd. All rights reserved.

Stacking of purines in water: the role of dipolar interactions in caffeine.

PubMed

Tavagnacco, L; Di Fonzo, S; D'Amico, F; Masciovecchio, C; Brady, J W; Cesàro, A

2016-05-11

During the last few decades it has been ascertained that base stacking is one of the major contributions stabilizing nucleic acid conformations. However, the understanding of the nature of the interactions involved in the stacking process remains under debate and it is a subject of theoretical and experimental studies. Structural similarity between purine bases (guanine and adenine) in DNA and the caffeine molecule makes caffeine an excellent model for the purine bases. The present study clearly shows that dipolar interactions play a fundamental role in determining stacking of purine molecules in solution. In order to reach this achievement, polarized ultraviolet Raman resonant scattering experiments have been carried out on caffeine aqueous solutions as a function of concentration and temperature. The investigation pointed out at the aggregation and solvation properties, particularly at elevated temperatures. Kubo-Anderson theory was used as a framework to investigate the non-coincidence effect (NCE) occurring in the totally symmetric breathing modes of the purine rings, and in the bending modes of the methyl groups of caffeine. The NCE concentration dependence shows that caffeine aggregation at 80 °C occurs by planar stacking of the hydrophobic faces. The data clearly indicate that dipolar interactions determine the reorientational motion of the molecules in solution and are the driving force for the stacking of caffeine. In parallel, the observed dephasing times imply a change in caffeine interactions as a function of temperature and concentration. A decrease, at low water content, of the dephasing time for the ring breathing vibration mode indicates that self-association alters the solvation structure that is detectable at low concentration. These results are in agreement with simulation predictions and serve as an important validation of the models used in those calculations.

Molecular Dynamics and Neutron Scattering Studies of Mixed Solutions of Caffeine and Pyridine in Water.

PubMed

Tavagnacco, Letizia; Mason, Philip E; Neilson, George W; Saboungi, Marie-Louise; Cesàro, Attilio; Brady, John W

2018-05-31

Insight into the molecular interactions of homotactic and heterotactic association of caffeine and pyridine in aqueous solution is given on the basis of both experimental and simulation studies. Caffeine is about 5 times more soluble in a 3 m aqueous pyridine solution than it is in pure water (an increase from ∼0.1 m to 0.5 m). At this elevated concentration the system becomes suitable for neutron scattering study. Caffeine-pyridine interactions were studied by neutron scattering and molecular dynamics simulations, allowing a detailed characterization of the spatial and orientational structure of the solution. It was found that while pyridine-caffeine interactions are not as strong as caffeine-caffeine interactions, the pyridine-caffeine interactions still significantly disrupted caffeine-caffeine stacking. The alteration of the caffeine-caffeine stacking, occasioned by the presence of pyridine molecules in solution and the consequent formation of heterotactic interactions, leads to the experimentally detected increase in caffeine solubility.

Make Caffeine Visible: a Fluorescent Caffeine “Traffic Light” Detector

NASA Astrophysics Data System (ADS)

Xu, Wang; Kim, Tae-Hyeong; Zhai, Duanting; Er, Jun Cheng; Zhang, Liyun; Kale, Anup Atul; Agrawalla, Bikram Keshari; Cho, Yoon-Kyoung; Chang, Young-Tae

2013-07-01

Caffeine has attracted abundant attention due to its extensive existence in beverages and medicines. However, to detect it sensitively and conveniently remains a challenge, especially in resource-limited regions. Here we report a novel aqueous phase fluorescent caffeine sensor named Caffeine Orange which exhibits 250-fold fluorescence enhancement upon caffeine activation and high selectivity. Nuclear magnetic resonance spectroscopy and Fourier transform infrared spectroscopy indicate that π-stacking and hydrogen-bonding contribute to their interactions while dynamic light scattering and transmission electron microscopy experiments demonstrate the change of Caffeine Orange ambient environment induces its fluorescence emission. To utilize this probe in real life, we developed a non-toxic caffeine detection kit and tested it for caffeine quantification in various beverages. Naked-eye sensing of various caffeine concentrations was possible based on color changes upon irradiation with a laser pointer. Lastly, we performed the whole system on a microfluidic device to make caffeine detection quick, sensitive and automated.

Simultaneous determination of pentoxifylline, metabolites M1 (lisofylline), M4 and M5, and caffeine in plasma and dried blood spots for pharmacokinetic studies in preterm infants and neonates.

PubMed

Page-Sharp, Madhu; Strunk, Tobias; Salman, Sam; Hibbert, Julie; Patole, Sanjay K; Manning, Laurens; Batty, Kevin T

2017-11-30

Advances in bioanalytical methods are facilitating micro-volume and dried blood spot (DBS) analysis of drugs in biological matrices for pharmacokinetic studies in children and neonates. We sought to develop a UPLC-MS/MS assay for simultaneous measurement of caffeine, pentoxifylline (PTX) and three metabolites of PTX in both plasma and DBS. Caffeine, PTX, the metabolites M1 (lisofylline), M4 and M5, and the internal standards (caffeine-d 9 and PTX-d 6 ) were separated using a Waters Aquity T3 UPLC C 18 column and gradient mobile phase (water-methanol-formic acid). Retention times for caffeine, M5, M4, PTX and M1 were 1.6, 1.7, 1.9, 2.0 and 2.1min, respectively, with a run time of 5min. The precision (≤10%) and accuracy (≤15%) across the concentration range 0.1-50mg/L for caffeine, PTX and the three metabolites in plasma and DBS were within accepted limits, as were the limits of quantification (100μg/L for caffeine and 10μg/L for PTX, M1, M4 and M5). Caffeine, PTX and the metabolites were stable in DBS for >34days at room and refrigerated temperatures. Plasma and DBS samples were obtained from 24 preterm infants recruited into a clinical pharmacokinetic study of PTX. Paired analysis indicated that DBS concentrations were 9% lower than concurrent plasma concentrations for caffeine, 7% lower for PTX (consistent with the blood:plasma ratio) and 13% lower for M1 (lisofylline). The validated UPLC-MS/MS method is suitable for micro-volume plasma and DBS analysis of caffeine, PTX and its metabolites for pharmacokinetic studies in paediatric patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Caffeine Expectancy Questionnaire (CaffEQ): Construction, Psychometric Properties, and Associations with Caffeine Use, Caffeine Dependence, and Other Related Variables

ERIC Educational Resources Information Center

Huntley, Edward D.; Juliano, Laura M.

2012-01-01

Expectancies for drug effects predict drug initiation, use, cessation, and relapse, and may play a causal role in drug effects (i.e., placebo effects). Surprisingly little is known about expectancies for caffeine even though it is the most widely used psychoactive drug in the world. In a series of independent studies, the nature and scope of…

Investigating causal associations between use of nicotine, alcohol, caffeine and cannabis: a two-sample bidirectional Mendelian randomization study.

PubMed

Verweij, Karin J H; Treur, Jorien L; Vink, Jacqueline M

2018-07-01

Epidemiological studies consistently show co-occurrence of use of different addictive substances. Whether these associations are causal or due to overlapping underlying influences remains an important question in addiction research. Methodological advances have made it possible to use published genetic associations to infer causal relationships between phenotypes. In this exploratory study, we used Mendelian randomization (MR) to examine the causality of well-established associations between nicotine, alcohol, caffeine and cannabis use. Two-sample MR was employed to estimate bidirectional causal effects between four addictive substances: nicotine (smoking initiation and cigarettes smoked per day), caffeine (cups of coffee per day), alcohol (units per week) and cannabis (initiation). Based on existing genome-wide association results we selected genetic variants associated with the exposure measure as an instrument to estimate causal effects. Where possible we applied sensitivity analyses (MR-Egger and weighted median) more robust to horizontal pleiotropy. Most MR tests did not reveal causal associations. There was some weak evidence for a causal positive effect of genetically instrumented alcohol use on smoking initiation and of cigarettes per day on caffeine use, but these were not supported by the sensitivity analyses. There was also some suggestive evidence for a positive effect of alcohol use on caffeine use (only with MR-Egger) and smoking initiation on cannabis initiation (only with weighted median). None of the suggestive causal associations survived corrections for multiple testing. Two-sample Mendelian randomization analyses found little evidence for causal relationships between nicotine, alcohol, caffeine and cannabis use. © 2018 Society for the Study of Addiction.

Self-association of caffeine in aqueous solution. Study of dilute solutions by normal and second derivative UV absorption spectroscopy.

NASA Astrophysics Data System (ADS)

Iza, N.; Gil, M.; Montero, J. L.; Morcillo, J.

1988-05-01

The concentration dependence of the spectral parameters of caffeine bands at ˜205 and 273 nm has been studied in aqueous solution by normal and second derivative spectroscopy. The concentration range was 5 x 10 -6 - 5 x 10 -3 M and thirty-five different concentrations were used. Discontinuities in parameter variation of these two bands at ˜7.5 x 10 -5, ˜2 x 10 -4, and ˜1 x 10 -3M were observed as concentration was increased. These "limiting" concentrations define three quite differenciated hyper- or hipochromic effects: the first one can be explained as caffeine-water molecule interaction and the second and third as dimer and (dimer + polymer) stacking, respectively. Apparent self-association constants using the isodesmic model have been obtained K= 160 M -1 (for the second hypochromic effect) and K= 13.6 M -1 (for the third hypochromic effect), for the 273 nm band. It is noteworthy that the three "limiting" concentrations coincide with changes in DNA-caffeine interaction modes (H. Lang , 1976) and biological activity (I.B. Syed , 1976).

Evaluation of Timing and Dosing of Caffeine Citrate in Preterm Neonates for the Prevention of Bronchopulmonary Dysplasia.

PubMed

Shenk, Eleni E; Bondi, Deborah S; Pellerite, Matthew M; Sriram, Sudhir

2018-01-01

The aim of this study was to evaluate the timing and dosing of caffeine therapy in relation to the development of bronchopulmonary dysplasia (BPD). This was a single-center, retrospective cohort study comparing early (days of life 0-2) to late (day of life 3 or greater) caffeine initiation in extremely low birth weight neonates, with a secondary analysis of large (10 mg/kg/day) to small dose (5 mg/kg/day) caffeine. There were 138 patients in the primary timing analysis. The early caffeine group had a lower incidence and reduced odds of the composite outcome of BPD or all-cause mortality, compared with the late caffeine group (64% vs. 88%, respectively; adjusted p < 0.05; adjusted OR 0.36 [95% CI 0.13-0.98]). No statistically significant difference was found between dosing groups (p = 0.29) in the primary outcome; however, there was a lower rate of patent ductus arteriosus requiring treatment (p = 0.05) and decreased likelihood of discharging home on oxygen (p = 0.02) in the large-dose group compared with the small-dose group. Early caffeine initiation significantly decreased the incidence of BPD or all-cause mortality in extremely low birth weight neonates. Patients receiving large-dose caffeine had improved secondary outcomes, although no difference in BPD was noted. Further studies are needed to determine the optimal dosing of caffeine.

Caffeine enhances the speed of the recovery of the hypothalamo-pituitary-adrenocortical axis after chronic prednisolone administration in the rat.

PubMed

Marzouk, H F; Zuyderwijk, J; Uitterlinden, P; van Koetsveld, P; Blijd, J J; Abou-Hashim, E M; el-Kannishy, M H; de Jong, F H; Lamberts, S W

1991-11-01

Chronic administration of corticosteroids results in a suppression of the hypothalamo-pituitary-adrenocortical (HPA) axis. The time course of the recovery of the HPA axis depends on the dose and duration of corticosteroid administration. We investigated the recovery of the HPA axis after 14 days of prednisolone administration to rats at a dose of 2.0 mg/rat/day via the drinking water (188 mumol/l). The in vitro corticosterone production by dispersed adrenal cells in response to increasing concentrations of ACTH had recovered 3 days after stopping prednisolone administration. In parallel the initially suppressed plasma corticosterone concentrations had recovered after 3 days, while the pituitary ACTH content had recovered after 5 days. We investigated the possibility to enhance the speed of the recovery of the HPA axis by the simultaneous administration of two drugs with known CRF-stimulating activity via the drinking water. Caffeine in a dose of 100 mg/kg body weight enhanced the recovery of the prednisolone-suppressed HPA axis significantly. One day after the end of prednisolone administration a significant increase in the adrenal weight, in the corticosterone production by dispersed adrenal cells, as well as in the plasma corticosterone concentrations, and in the pituitary ACTH content was observed in the caffeine-treated rats. Chlorimipramine (20 mg/kg body weight), on the other hand, did not influence the prednisolone-mediated suppression of the HPA axis.(ABSTRACT TRUNCATED AT 250 WORDS)

An analysis of energy-drink toxicity in the National Poison Data System.

PubMed

Seifert, Sara M; Seifert, Steven A; Schaechter, Judy L; Bronstein, Alvin C; Benson, Blaine E; Hershorin, Eugene R; Arheart, Kristopher L; Franco, Vivian I; Lipshultz, Steven E

2013-08-01

Small studies have associated energy drinks-beverages that typically contain high concentrations of caffeine and other stimulants-with serious adverse health events. To assess the incidence and outcomes of toxic exposures to caffeine-containing energy drinks, including caffeinated alcoholic energy drinks, and to evaluate the effect of regulatory actions and educational initiatives on the rates of energy drink exposures. We analyzed all unique cases of energy drink exposures reported to the US National Poison Data System (NPDS) between October 1, 2010 and September 30, 2011. We analyzed only exposures to caffeine-containing energy drinks consumed as a single product ingestion and categorized them as caffeine-containing non-alcoholic, alcoholic, or "unknown" for those with unknown formulations. Non-alcoholic energy drinks were further classified as those containing caffeine from a single source and those containing multiple stimulant additives, such as guarana or yerba mate. The data were analyzed for the demographics and outcomes of exposures (unknown data were not included in the denominator for percentages). The rates of change of energy drink-related calls to poison centers were analyzed before and after major regulatory events. Of 2.3 million calls to the NPDS, 4854 (0.2%) were energy drink-related. The 3192 (65.8%) cases involving energy drinks with unknown additives were excluded. Of 1480 non-alcoholic energy drink cases, 50.7% were children < 6 years old; 76.7% were unintentional; and 60.8% were males. The incidence of moderate to major adverse effects of energy drink-related toxicity was 15.2% and 39.3% for non-alcoholic and alcoholic energy drinks, respectively. Major adverse effects consisted of three cases of seizure, two of non-ventricular dysrhythmia, one ventricular dysrhythmia, and one tachypnea. Of the 182 caffeinated alcoholic energy drink cases, 68.2% were < 20 years old; 76.7% were referred to a health care facility. Educational and legislative initiatives to enhance understanding of the health consequences of energy drink consumption were significantly associated with a decreased rate of energy drink-related cases (p = 0.036). About half the cases of energy drink-related toxicity involved unintentional exposures by children < 6 years old. Educational campaigns and legal restrictions on the sale of energy drinks were associated with decreasing calls to poison centers for energy drink toxicity and are encouraged.

Caffeine Controls Glutamatergic Synaptic Transmission and Pyramidal Neuron Excitability in Human Neocortex

PubMed Central

Kerkhofs, Amber; Xavier, Ana C.; da Silva, Beatriz S.; Canas, Paula M.; Idema, Sander; Baayen, Johannes C.; Ferreira, Samira G.; Cunha, Rodrigo A.; Mansvelder, Huibert D.

2018-01-01

Caffeine is the most widely used psychoactive drug, bolstering attention and normalizing mood and cognition, all functions involving cerebral cortical circuits. Whereas studies in rodents showed that caffeine acts through the antagonism of inhibitory A1 adenosine receptors (A1R), neither the role of A1R nor the impact of caffeine on human cortical neurons is known. We here provide the first characterization of the impact of realistic concentrations of caffeine experienced by moderate coffee drinkers (50 μM) on excitability of pyramidal neurons and excitatory synaptic transmission in the human temporal cortex. Moderate concentrations of caffeine disinhibited several of the inhibitory A1R-mediated effects of adenosine, similar to previous observations in the rodent brain. Thus, caffeine restored the adenosine-induced decrease of both intrinsic membrane excitability and excitatory synaptic transmission in the human pyramidal neurons through antagonism of post-synaptic A1R. Indeed, the A1R-mediated effects of endogenous adenosine were more efficient to inhibit synaptic transmission than neuronal excitability. This was associated with a distinct affinity of caffeine for synaptic versus extra-synaptic human cortical A1R, probably resulting from a different molecular organization of A1R in human cortical synapses. These findings constitute the first neurophysiological description of the impact of caffeine on pyramidal neuron excitability and excitatory synaptic transmission in the human temporal cortex, providing adequate ground for the effects of caffeine on cognition in humans. PMID:29354052

Endothelial Nitric Oxide Mediates Caffeine Antagonism of Alcohol-Induced Cerebral Artery Constriction

PubMed Central

Chang, Jennifer; Fedinec, Alexander L.; Kuntamallappanavar, Guruprasad; Leffler, Charles W.; Bukiya, Anna N.

2016-01-01

Despite preventive education, the combined consumption of alcohol and caffeine (particularly from “energy drinks”) continues to rise. Physiologic perturbations by separate intake of ethanol and caffeine have been widely documented. However, the biologic actions of the alcohol-caffeine combination and their underlying subcellular mechanisms have been scarcely studied. Using intravital microscopy on a closed-cranial window and isolated, pressurized vessels, we investigated the in vivo and in vitro action of ethanol-caffeine mixtures on cerebral arteries from rats and mice, widely recognized models to address cerebrovascular pathophysiology and pharmacology. Caffeine at concentrations found in human circulation after ingestion of one to two cups of coffee (10 µM) antagonized the endothelium-independent constriction of cerebral arteries evoked by ethanol concentrations found in blood during moderate-heavy alcohol intoxication (40–70 mM). Caffeine antagonism against alcohol was similar whether evaluated in vivo or in vitro, suggesting independence of systemic factors and drug metabolism, but required a functional endothelium. Moreover, caffeine protection against alcohol increased nitric oxide (NO•) levels over those found in the presence of ethanol alone, disappeared upon blocking NO• synthase, and could not be detected in pressurized cerebral arteries from endothelial nitric-oxide synthase knockout (eNOS−/−) mice. Finally, incubation of de-endothelialized cerebral arteries with the NO• donor sodium nitroprusside (10 µM) fully restored the protective effect of caffeine. This study demonstrates for the first time that caffeine antagonizes ethanol-induced cerebral artery constriction and identifies endothelial NO• as the critical caffeine effector on smooth muscle targets. Conceivably, situations that perturb endothelial function and/or NO• availability will critically alter caffeine antagonism of alcohol-induced cerebrovascular constriction without significantly disrupting endothelium-independent, alcohol-induced cerebral artery constriction itself. PMID:26555891

Acute stress blocks the caffeine-induced enhancement of contextual memory retrieval in mice.

PubMed

Pierard, Chistophe; Krazem, Ali; Henkous, Nadia; Decorte, Laurence; Béracochéa, Daniel

2015-08-15

This study investigated in mice the dose-effect of caffeine on memory retrieval in non-stress and stress conditions. C57 Bl/6 Jico mice learned two consecutive discriminations (D1 and D2) in a four-hole board which involved either distinct contextual (CSD) or similar contextual (SSD) cues. All mice received an i.p. injection of vehicle or caffeine (8, 16 or 32mg/kg) 30min before the test session. Results showed that in non-stress conditions, the 16mg/kg caffeine dose induced a significant enhancement of D1 performance in CSD but not in SSD. Hence, we studied the effect of an acute stress (electric footshocks) administered 15min before the test session on D1 performance in caffeine-treated mice. Results showed that stress significantly decreased D1 performance in vehicle-treated controls and the memory-enhancing effect induced by the 16mg/kg caffeine dose in non-stress condition is no longer observed. Interestingly, whereas caffeine-treated mice exhibited weaker concentrations of plasma corticosterone as compared to vehicles in non-stress condition, stress significantly increased plasma corticosterone concentrations in caffeine-treated mice which reached similar level to that of controls. Overall, the acute stress blocked both the endocrinological and memory retrieval enhancing effects of caffeine. Copyright © 2015 Elsevier B.V. All rights reserved.

Pharmacokinetic analysis and comparison of caffeine administered rapidly or slowly in coffee chilled or hot versus chilled energy drink in healthy young adults.

PubMed

White, John R; Padowski, Jeannie M; Zhong, Yili; Chen, Gang; Luo, Shaman; Lazarus, Philip; Layton, Matthew E; McPherson, Sterling

2016-01-01

There is a paucity of data describing the impact of type of beverage (coffee versus energy drink), different rates of consumption and different temperature of beverages on the pharmacokinetic disposition of caffeine. Additionally, there is concern that inordinately high levels of caffeine may result from the rapid consumption of cold energy drinks. The objective of this study was to compare the pharmacokinetics of caffeine under various drink temperature, rate of consumption and vehicle (coffee versus energy drink) conditions. Five caffeine (dose = 160 mg) conditions were evaluated in an open-label, group-randomized, crossover fashion. After the administration of each caffeine dose, 10 serial plasma samples were harvested. Caffeine concentration was measured via liquid chromatography-mass spectrometry (LC-MS), and those concentrations were assessed by non-compartmental pharmacokinetic analysis. The calculated mean pharmacokinetic parameters were analyzed statistically by one-way repeated measures analysis of variance (RM ANOVA). If differences were found, each group was compared to the other by all pair-wise multiple comparison. Twenty-four healthy subjects ranging in age from 18 to 30 completed the study. The mean caffeine concentration time profiles were similar with overlapping SDs at all measured time points. The ANOVA revealed significant differences in mean Cmax and Vd ss/F, but no pair-wise comparisons reached statistical significance. No other differences in pharmacokinetic parameters were found. The results of this study are consistent with previous caffeine pharmacokinetic studies and suggest that while rate of consumption, temperature of beverage and vehicle (coffee versus energy drink) may be associated with slightly different pharmacokinetic parameters, the overall impact of these variables is small. This study suggests that caffeine absorption and exposure from coffee and energy drink is similar irrespective of beverage temperature or rate of consumption.

Pharmacokinetic analysis and comparison of caffeine administered rapidly or slowly in coffee chilled or hot versus chilled energy drink in healthy young adults

PubMed Central

White, John R.; Padowski, Jeannie M.; Zhong, Yili; Chen, Gang; Luo, Shaman; Lazarus, Philip; Layton, Matthew E.; McPherson, Sterling

2016-01-01

Abstract Context: There is a paucity of data describing the impact of type of beverage (coffee versus energy drink), different rates of consumption and different temperature of beverages on the pharmacokinetic disposition of caffeine. Additionally, there is concern that inordinately high levels of caffeine may result from the rapid consumption of cold energy drinks. Objective: The objective of this study was to compare the pharmacokinetics of caffeine under various drink temperature, rate of consumption and vehicle (coffee versus energy drink) conditions. Materials: Five caffeine (dose = 160 mg) conditions were evaluated in an open-label, group-randomized, crossover fashion. After the administration of each caffeine dose, 10 serial plasma samples were harvested. Caffeine concentration was measured via liquid chromatography–mass spectrometry (LC–MS), and those concentrations were assessed by non-compartmental pharmacokinetic analysis. The calculated mean pharmacokinetic parameters were analyzed statistically by one-way repeated measures analysis of variance (RM ANOVA). If differences were found, each group was compared to the other by all pair-wise multiple comparison. Results: Twenty-four healthy subjects ranging in age from 18 to 30 completed the study. The mean caffeine concentration time profiles were similar with overlapping SDs at all measured time points. The ANOVA revealed significant differences in mean C max and V d ss/F, but no pair-wise comparisons reached statistical significance. No other differences in pharmacokinetic parameters were found. Discussion: The results of this study are consistent with previous caffeine pharmacokinetic studies and suggest that while rate of consumption, temperature of beverage and vehicle (coffee versus energy drink) may be associated with slightly different pharmacokinetic parameters, the overall impact of these variables is small. Conclusion: This study suggests that caffeine absorption and exposure from coffee and energy drink is similar irrespective of beverage temperature or rate of consumption. PMID:27100333

Effect of decaffeination of coffee or tea on gastro-oesophageal reflux.

PubMed

Wendl, B; Pfeiffer, A; Pehl, C; Schmidt, T; Kaess, H

1994-06-01

Coffee and tea are believed to cause gastro-oesophageal reflux; however, the effects of these beverages and of their major component, caffeine, have not been quantified. The aim of this study was to evaluate gastro-oesophageal reflux induced by coffee and tea before and after a decaffeination process, and to compare it with water and water-containing caffeine. Three-hour ambulatory pH-metry was performed on 16 healthy volunteers, who received 300 ml of (i) regular coffee, decaffeinated coffee or tap water (n = 16), (ii) normal tea, decaffeinated tea, tap water, or coffee adapted to normal tea in caffeine concentration (n = 6), and (iii) caffeine-free and caffeine-containing water (n = 8) together with a standardized breakfast. Regular coffee induced a significant (P < 0.05) gastro-oesophageal reflux compared with tap water and normal tea, which were not different from each other. Decaffeination of coffee significantly (P < 0.05) diminished gastro-oesophageal reflux, whereas decaffeination of tea or addition of caffeine to water had no effect. Coffee adapted to normal tea in caffeine concentration significantly (P < 0.05) increased gastro-oesophageal reflux. Coffee, in contrast to tea, increases gastro-oesophageal reflux, an effect that is less pronounced after decaffeination. Caffeine does not seem to be responsible for gastro-oesophageal reflux which must be attributed to other components of coffee.

High Blood Caffeine Levels in MCI Linked to Lack of Progression to Dementia

PubMed Central

Cao, Chuanhai; Loewenstein, David A.; Lin, Xiaoyang; Zhang, Chi; Wang, Li; Duara, Ranjan; Wu, Yougui; Giannini, Alessandra; Bai, Ge; Cai, Jianfeng; Greig, Maria; Schofield, Elizabeth; Ashok, Raj; Small, Brent; Potter, Huntington; Arendash, Gary W.

2017-01-01

Although both human epidemiologic and animal model studies have suggested that caffeine/coffee protects against Alzheimer’s disease, direct human evidence for this premise has been lacking. In the present case-control study, two separate cohorts consisting of 124 total individuals (65–88 years old) were cognitively assessed and a blood sample taken for caffeine/biomarker analysis. Subjects were then monitored for cognitive status over the ensuing 2–4 year period to determine the extent to which initial plasma caffeine/biomarkers levels would be predictive of changes in cognitive status. Plasma caffeine levels at study onset were substantially lower (−51%) in mild cognitive impairment (MCI) subjects who later progressed to dementia (MCI→DEM) compared to levels in stable MCI subjects (MCI→MCI). Moreover, none of the MCI→DEM subjects had initial blood caffeine levels that were above a critical level of 1200 ng/ml, while half of stable MCI→MCI subjects had blood caffeine levels higher than that critical level. Thus, plasma caffeine levels greater than 1200 ng/ml (≈6 µM) in MCI subjects were associated with no conversion to dementia during the ensuing 2–4 year follow-up period. Among the 11 cytokines measured in plasma, three of them (GCSF, IL-10, and IL-6) were decreased in MCI→DEM subjects, but not in stable MCI→MCI subjects with high plasma caffeine levels. Coffee would appear to be the major or perhaps only source of caffeine for such stable MCI patients. This case-control study provides the first direct evidence that caffeine/coffee intake is associated with a reduced risk of dementia or delayed onset, particularly for those who already have MCI. PMID:22430531

Determination of submicrogram-per-liter concentrations of caffeine in surface water and groundwater samples by solid-phase extraction and liquid chromatography

USGS Publications Warehouse

Burkhardt, M.R.; Soliven, P.P.; Werner, S.L.; Vaught, D.G.

1999-01-01

A method for determining submicrogram-per-liter concentrations of caffeine in surface water and groundwater samples has been developed. Caffeine is extracted from a 1 L water sample with a 0.5 g graphitized carbon-based solid-phase cartridge, eluted with methylene chloride-methanol (80 + 20, v/v), and analyzed by liquid chromatography with photodiode-array detection. The single-operator method detection limit for organic-free water samples was 0.02 ??g/L. Mean recoveries and relative standard deviations were 93 ?? 13% for organicfree water samples fortified at 0.04 ??g/L and 84 ?? 4% for laboratory reagent spikes fortified at 0.5 ??g/L. Environmental concentrations of caffeine ranged from 0.003 to 1.44 ??g/L in surface water samples and from 0.01 to 0.08 ??g/L in groundwater samples.

The role of sorption and biodegradation in the removal of acetaminophen, carbamazepine, caffeine, naproxen and sulfamethoxazole during soil contact: A kinetics study.

PubMed

Martínez-Hernández, Virtudes; Meffe, Raffaella; Herrera López, Sonia; de Bustamante, Irene

2016-07-15

In countries like Spain, where water is a limited resource, reusing effluents from wastewater treatment plants may imply the introduction of incompletely eliminated pollutants into the environment. Therefore, this work identified the role of sorption and biodegradation in attenuating pharmaceutical compounds (acetaminophen, carbamazepine, caffeine, naproxen and sulfamethoxazole) in natural soil. It also determined which sorption and removal ("sorption+biodegradation") kinetics models describe the behaviour of these substances in the water-soil system. Presence of potential transformation products (TPs) as a result of pharmaceuticals biodegradation was also studied. To this end, serial batch-type experiments were performed with a soil:water ratio of 1:4 and an initial pharmaceutical concentration of 100μgL(-1). Despite results are dependent on soil characteristics, they revealed that, for those substances with a higher affinity to the soil used (loamy sand), sorption seems to play a key role during the first 48h of contact with soil, and gives way to biodegradation afterwards. The sorption of the pharmaceuticals studied follows a pseudo second-order kinetics. Caffeine and sulfamethoxazole displayed the fastest initial sorption velocities (h=2055 and h=228μgkg(-1)h(-1), respectively). The removal kinetics experiments, satisfactorily simulated by the first-order kinetics model, indicated the presence of potential microbial adaptation to degradation. Indeed, half-lives decreased from 1.6- to 11.7-fold with respect to initial values. The microbial capacity to degrade sulfamethoxazole could be a matter of concern if bacteria have developed resistance to this antibiotic. Caffeine, acetaminophen and sulfamethoxazole were mitigated to a greater extent, whereas the removal of naproxen and carbamazepine was more limited. The appearance of epoxy-carbamazepine and N4-acetyl-sulfamethoxazole as possible TPs of carbamazepine and sulfamethoxazole, respectively, indicated that biodegradation was incomplete and showed the capacity of soil microbes to transform these substances. Copyright © 2016 Elsevier B.V. All rights reserved.

Development and initial validation of a caffeine craving questionnaire.

PubMed

West, Oliver; Roderique-Davies, Gareth

2008-01-01

Craving for caffeine has received little empirical attention, despite considerable research into the potential for caffeine dependence. The main aim of this study was to develop, and initially validate, a multi-item, multidimensional instrument to measure cravings for caffeine. Participants were 189 caffeine consumers who completed the Questionnaire of Caffeine Cravings, which was based on the Questionnaire of Smoking Urges (QSU), in one of five naturally occurring periods of abstinence; 1-15 min; 16-120 mins; 3-7 h; 12-48 h and +48 h. Exploratory factor analysis suggested a three-factor solution best described the data; Factor 1 reflected strong desires, intentions and positive reinforcement; Factor 2 reflected mild/general positive and negative reinforcement and Factor 3 reflected functional/mood-based negative reinforcement. Significantly higher Factor 1 and Factor 2 scores were recorded for high frequency users; significantly higher Factor 1 and Factor 3 scores were recorded as a function of increased levels of dependence. Duration of abstinence did not significantly effect cravings across all three factors. Regression analyses suggested level of dependence best predicted both current cravings and frequency of daily use. These findings suggest caffeine cravings may be conceptualized multidimensionally and further validates the use of multidimensional, multi-item instruments. Cravings for caffeine may manifest and be detected across varying levels of dependence and, frequency of use and independently of duration of abstinence.

Caffeine and exercise.

PubMed

Paluska, Scott A

2003-08-01

Caffeine is the most commonly consumed drug in the world, and athletes frequently use it as an ergogenic aid. It improves performance and endurance during prolonged, exhaustive exercise. To a lesser degree it also enhances short-term, high-intensity athletic performance. Caffeine improves concentration, reduces fatigue, and enhances alertness. Habitual intake does not diminish caffeine's ergogenic properties. Several mechanisms have been proposed to explain the physiologic effects of caffeine, but adenosine receptor antagonism most likely accounts for the primary mode of action. It is relatively safe and has no known negative performance effects, nor does it cause significant dehydration or electrolyte imbalance during exercise. Routine caffeine consumption may cause tolerance or dependence, and abrupt discontinuation produces irritability, mood shifts, headache, drowsiness, or fatigue. Major sport governing bodies ban excessive use of caffeine, but current monitoring techniques are inadequate, and ethical dilemmas persist regarding caffeine intake by athletes.

Sorption and degradation of wastewater-associated pharmaceuticals and personal care products in agricultural soils and sediment.

PubMed

Zhang, Ting; Wu, Bo; Sun, Na; Ye, Yong; Chen, Huaixia

2013-01-01

Pharmaceuticals and personal care products (PPCPs) have drawn popular concerns recently as an emerging class of aquatic contaminants. In this study, adsorption and degradation of four selected PPCPs, metronidazole, tinidazole, caffeine and chloramphenicol, have been investigated in the laboratory using two agricultural soils in China and sediment from Changjiang River. Adsorption tests using a batch equilibrium method demonstrated that adsorption of all tested chemicals in soils could be well described with Freundlich equation, and their adsorption affinity on soil followed the order of chloramphenicol > caffeine > tinidazole > metronidazole. Generally, higher Kf value was associated with soils which had higher organic matter contents (except for caffeine acid in this study). Degradation of selected PPCPs in soils generally followed first-order exponential decay kinetics, and half-lives ranging from 0.97 to 10.21 d. Sterilization generally decreased the degradation rates, indicating that microbial activity played a significant role in the degradation in soils. The degradation rate constant decreased with increasing initial chemical concentrations in soil, implying that the microbial activity was inhibited with high chemical loading levels.

Degradation of fifteen emerging contaminants at microg L(-1) initial concentrations by mild solar photo-Fenton in MWTP effluents.

PubMed

Klamerth, N; Rizzo, L; Malato, S; Maldonado, Manuel I; Agüera, A; Fernández-Alba, A R

2010-01-01

The degradation of 15 emerging contaminants (ECs) at low concentrations in simulated and real effluent of municipal wastewater treatment plant with photo-Fenton at unchanged pH and Fe=5 mg L(-1) in a pilot-scale solar CPC reactor was studied. The degradation of those 15 compounds (Acetaminophen, Antipyrine, Atrazine, Caffeine, Carbamazepine, Diclofenac, Flumequine, Hydroxybiphenyl, Ibuprofen, Isoproturon, Ketorolac, Ofloxacin, Progesterone, Sulfamethoxazole and Triclosan), each with an initial concentration of 100 microg L(-1), was found to depend on the presence of CO(3)(2-) and HCO(3)(-) (hydroxyl radicals scavengers) and on the type of water (simulated water, simulated effluent wastewater and real effluent wastewater), but is relatively independent of pH, the type of acid used for release of hydroxyl radicals scavengers and the initial H(2)O(2) concentration used. Toxicity tests with Vibrio fisheri showed that degradation of the compounds in real effluent wastewater led to toxicity increase. (c) 2009 Elsevier Ltd. All rights reserved.

Effects of activated aflatoxin B/sub 1/ and caffeine on DNA replicon initiation in HeLa cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cramer, P.; Painter, R.B.

1981-01-01

Afatoxin B/sub 1/ (AFB/sub 1/) is activated by a rat microsomal extract (S-9) to form a product that inhibits DNA synthesis in HeLa cells. At 10/sup -7/ M, AFB/sub 1/ inhibited initiation of replicons, as shown in alkaline sucrose gradient profiles 30 min after incubation with the drug. Ninety minutes later, the profile of treated cells was similar to that of control, but 4 h later there was another effect on replicon initiation. At 10/sup -6/ M, the inhibition of initiation was greater than at 10/sup -7/ M and increased progressively. Four hours after removal of the drug, the gradientmore » profile showed low amounts of radioactivity in all size classes of DNA. When cells were incubated in medium containing caffeine (2 mM) even as late as 60 min after incubation with AFB/sub 1/, the inhibition of replicon initiation was prevented. If caffeine was later removed from the medium, replicon initiation was then inhibited. At 10/sup -7/ M or 10/sup -6/ M, AFB/sub 1/ had little immediate effect on chain elongation, but at 10/sup -5/ M, the gradient profiles showed an accumulation of low molecular weight DNA molecules, with no radioactivity in the region of high molecular weight DNA, owing to a block to chain elongation; this was not affected by caffeine. These results suggest that AFB/sub 1/ induces damage that changes the fonformation of chromatin so that initiation of new replicons cannot occur; in the presence of caffeine this change does not occur and DNA replication is not inhibited.« less

Wake up and smell the coffee. Caffeine, coffee, and the medical consequences.

PubMed Central

Chou, T

1992-01-01

Caffeine is a methylxanthine whose primary biologic effect is antagonism of the adenosine receptor. Its presence in coffee, tea, soda beverages, chocolate, and many prescription and over-the-counter drugs makes it the most commonly consumed stimulant drug. Initially caffeine increases blood pressure, plasma catecholamine levels, plasma renin activity, serum free fatty acid levels, urine production, and gastric acid secretion. Its long-term effects have been more difficult to substantiate. Most of the caffeine consumed in the United States is in coffee, which contains many other chemicals that may have other biologic actions. The consumption of coffee is a self-reinforcing behavior, and caffeine dependence and addiction are common. Coffee and caffeine intake have been linked to many illnesses, but definitive correlations have been difficult to substantiate. Initial trials showing coffee's association with coronary disease and myocardial infarction have been difficult to reproduce and have many confounding variables. Recent studies showing a larger effect over long follow-up periods and with heavy coffee consumption have again brought the question of the role of coffee in disease states to the fore. Caffeine in average dosages does not seem to increase the risk of arrhythmia. At present there is no convincing evidence that caffeine or coffee consumption increases the risk for any solid tumor. The intake of coffee and caffeine has clearly been decreasing in this country over the past two decades, largely brought about by the increasing health consciousness of Americans. Although there have been many studies that hint that the fears of increased disease with coffee drinking may be warranted, many questions have yet to be answered about the health effects of coffee and caffeine use. Images PMID:1441496

Wake up and smell the coffee. Caffeine, coffee, and the medical consequences.

PubMed

Chou, T

1992-11-01

Caffeine is a methylxanthine whose primary biologic effect is antagonism of the adenosine receptor. Its presence in coffee, tea, soda beverages, chocolate, and many prescription and over-the-counter drugs makes it the most commonly consumed stimulant drug. Initially caffeine increases blood pressure, plasma catecholamine levels, plasma renin activity, serum free fatty acid levels, urine production, and gastric acid secretion. Its long-term effects have been more difficult to substantiate. Most of the caffeine consumed in the United States is in coffee, which contains many other chemicals that may have other biologic actions. The consumption of coffee is a self-reinforcing behavior, and caffeine dependence and addiction are common. Coffee and caffeine intake have been linked to many illnesses, but definitive correlations have been difficult to substantiate. Initial trials showing coffee's association with coronary disease and myocardial infarction have been difficult to reproduce and have many confounding variables. Recent studies showing a larger effect over long follow-up periods and with heavy coffee consumption have again brought the question of the role of coffee in disease states to the fore. Caffeine in average dosages does not seem to increase the risk of arrhythmia. At present there is no convincing evidence that caffeine or coffee consumption increases the risk for any solid tumor. The intake of coffee and caffeine has clearly been decreasing in this country over the past two decades, largely brought about by the increasing health consciousness of Americans. Although there have been many studies that hint that the fears of increased disease with coffee drinking may be warranted, many questions have yet to be answered about the health effects of coffee and caffeine use.

Designed polar cosolvent-modified supercritical CO2 removing caffeine from and retaining catechins in green tea powder using response surface methodology.

PubMed

Huang, Kuo-Jong; Wu, Jia-Jiuan; Chiu, Yung-Ho; Lai, Cheng-Yung; Chang, Chieh-Ming J

2007-10-31

This study examines cosolvent-modified supercritical carbon dioxide (SC-CO2) to remove caffeine from and to retain catechins in green tea powder. The response surface method was adopted to determine the optimal operation conditions in terms of the extraction efficiencies and concentration factors of caffeine and catechins during the extractions. When SC-CO2 was used at 333 K and 300 bar, 91.5% of the caffeine was removed and 80.8% of catechins were retained in the tea: 3600 g of carbon dioxide was used in the extraction of 4 g of tea soaked with 1 g of water. Under the same extraction conditions, 10 g of water was added to <800 g of carbon dioxide in an extraction that completely removed caffeine (that is, the caffeine extraction efficiency was 100%). The optimal result as predicted by three-factor response surface methodology and supported by experimental data was that in 1.5 h of extraction, 640 g of carbon dioxide at 323 K and 275 bar with the addition of 6 g of water extracted 71.9% of the caffeine while leaving 67.8% of the catechins in 8 g of tea. Experimental data indicated that supercritical carbon dioxide decaffeination increased the concentrations of caffeine in the SC-CO2 extracts at 353 K.

Caffeine use in a Super Rugby game and its relationship to post-game sleep.

PubMed

Dunican, Ian C; Higgins, Charles C; Jones, Maddison J; Clarke, Michael W; Murray, Kevin; Dawson, Brian; Caldwell, John A; Halson, Shona L; Eastwood, Peter R

2018-05-01

To examine the relationship between regular game-related caffeine consumption on sleep after an evening Super Rugby game. Twenty elite rugby union players wore a wrist-activity monitor to measure sleep for three days before, three days after and on the night of an evening Super Rugby game (19:00-21:00). Players ingested caffeine as they would normally (i.e. before and sometimes during a game) and saliva samples were collected before (17:00) and after (21:30) the game for caffeine concentration. Compared to the nights leading up to the game, on the night of the game, players went to bed 3 h later (23:08 ± 66 min vs 02:11 ± 114 min; p < .001) and had 1:30 hh:mm less sleep (5:54 ± 2:59 vs 8:02 ± 1:24 hh:mm; p < .05) and four players did not sleep after the game. Post-game caffeine saliva concentrations were greater than pre-game levels in 17 players (Pre-game 0.40 µg/mL vs Post-game 2.77 µg/mL; p < .001). The increase in caffeine saliva concentrations was moderately associated with an increase in sleep latency (p < .05), a decrease in sleep efficiency (p < .05), and a trend for a decrease in sleep duration (p = .06) on game night. Caffeine consumption before a Super Rugby game markedly increases post-game saliva caffeine levels. This may contribute to the observed 3.5 h delay in time at sleep onset and the 1.5 h reduction in sleep duration on the night of the game. This study highlights the need for a strategic approach to the use of caffeine within a Super Rugby team considering the potential effect on post-game sleep.

Effects of acute caffeine withdrawal on Short Category Test performance in sleep-deprived individuals.

PubMed

Killgore, William D S; Kahn-Greene, Ellen T; Killgore, Desiree B; Kamimori, Gary H; Balkin, Thomas J

2007-12-01

Caffeine is a popular stimulant often used to counter the effects of sleep loss and fatigue. Withdrawal from caffeine may produce mild declines in simple cognitive capacities such as attention and concentration, but it is unclear whether more complex cognitive functions, such as abstract reasoning or concept formation, may be similarly affected. To assess the effect of acute caffeine withdrawal on executive functioning during sleep deprivation, 26 healthy volunteers were administered in double-blind form either repeated doses of caffeine or placebo over two nights of continuous wakefulness. The 108-item Short Category Test was administered after 56 hr. of total sleep deprivation (9 hr. post-caffeine administration). The caffeine group scored significantly more poorly, making approximately 57% more errors on the test than the placebo group. These findings suggest that acute caffeine withdrawal during prolonged sleep deprivation has an adverse effect on abstract reasoning and concept formation.

A preliminary nationwide survey of the presence of emerging contaminants in drinking and source waters in Brazil.

PubMed

Machado, Kelly C; Grassi, Marco Tadeu; Vidal, Cristiane; Pescara, Igor C; Jardim, Wilson F; Fernandes, Andreia N; Sodré, Fernando F; Almeida, Fernanda V; Santana, Joyce S; Canela, Maria Cristina; Nunes, Camila R O; Bichinho, Kátia M; Severo, Flaviana J R

2016-12-01

This is the first nationwide survey of emerging contaminants in Brazilian waters. One hundred drinking water samples were investigated in 22 Brazilian state capitals. In addition, seven source water samples from two of the most populous regions of the country were evaluated. Samples were collected from June to September of 2011 and again during the same period in 2012. The study covered emerging contaminants of different classes, including hormones, plasticizers, herbicides, triclosan and caffeine. The analytical method for the determination of the compounds was based on solid-phase extraction followed by analysis via liquid chromatography electrospray triple-quadrupole mass spectrometry (LC-MS/MS). Caffeine, triclosan, atrazine, phenolphthalein and bisphenol A were found in at least one of the samples collected in the two sampling campaigns. Caffeine and atrazine were the most frequently detected substances in both drinking and source water. Caffeine concentrations in drinking water ranged from 1.8ngL -1 to values above 2.0μgL -1 while source-water concentrations varied from 40ngL -1 to about 19μgL -1 . For atrazine, concentrations were found in the range from 2.0 to 6.0ngL -1 in drinking water and at concentrations of up to 15ngL -1 in source water. The widespread presence of caffeine in samples of treated water is an indication of the presence of domestic sewage in the source water, considering that caffeine is a compound of anthropogenic origin. Copyright © 2016 Elsevier B.V. All rights reserved.

Caffeine inhibits STAT1 signaling and downregulates inflammatory pathways involved in autoimmunity.

PubMed

Iris, Merve; Tsou, Pei-Suen; Sawalha, Amr H

2018-04-18

Caffeine is a widely consumed pharmacologically active product. We focused on characterizing immunomodulatory effects of caffeine on peripheral blood mononuclear cells. Caffeine at high doses showed a robust downregulatory effect on cytokine activity and genes related to several autoimmune diseases including lupus and rheumatoid arthritis. Dose-dependent validation experiments showed downregulation at the mRNA levels of key inflammation-related genes including STAT1, TNF, IFNG, and PPARG. TNF and PPARG were suppressed even with the lowest caffeine dose tested, which corresponds to the serum concentration of caffeine after administration of one cup of coffee. Cytokine levels of IL-8, MIP-1β, IL-6, IFN-γ, GM-CSF, TNF, IL-2, IL-4, MCP-1, and IL-10 were decreased significantly with caffeine treatment. Upstream regulator analysis suggests that caffeine inhibits STAT1 signaling, which was confirmed by showing reduced phosphorylated STAT1 after caffeine treatment. Further studies exploring disease-modulating potential of caffeine in autoimmune diseases and further exploring the mechanisms involved are warranted. Copyright © 2018 Elsevier Inc. All rights reserved.

Influence of caffeine ingestion on perceived mood states, concentration, and arousal levels during a 75-min university lecture.

PubMed

Peeling, Peter; Dawson, Brian

2007-12-01

This investigation aimed to assess the effect of a caffeine supplement on perceived mood state, concentration, and arousal during a 75-min university lecture. Methods. This randomized, blind, cross-over design investigation ran over a course of 2 consecutive weeks. During week 1, 10 third-year Human Movement and Exercise Science students were assigned to either a caffeine- or placebo-supplemented group and were subsequently required to attend a 75-min exercise rehabilitation lecture. Seven days later, students were assigned to the opposite supplementation group before attending a second follow-on lecture, equal in duration to that of week 1. At the conclusion of each lecture, students were required to complete a mood perception questionnaire to assess the perceived level of mood state, concentration, and arousal during the lecture. The results showed that after caffeine consumption, students perceived themselves to be significantly more awake, clear minded, energetic, alert, and anxious (P < 0.05). Additionally, students also felt they were better able to concentrate and had a greater level of arousal than when the placebo was consumed (P < 0.05). In conclusion, the results of this investigation show that university students report enhanced perceptual feelings of behavior and mood state when a low dose of caffeine is consumed 60 min prior to a 75-min academic lecture.

Initial proteome analysis of caffeine-induced proteins in Aspergillus tamarii using two-dimensional fluorescence difference gel electrophoresis.

PubMed

Gutiérrez-Sánchez, Gerardo; Atwood, James; Kolli, V S Kumar; Roussos, Sévastianos; Augur, Christopher

2012-04-01

Caffeine is toxic to most microorganisms. However, some filamentous fungi, such as Aspergillus tamarii, are able to metabolize this alkaloid when fed caffeine as the sole nitrogen source. The aim of the present work was to identify intracellular A. tamarii proteins, regulated by caffeine, using fluorescence difference two-dimensional gel electrophoresis. Specific proteins from two culture media of A. tamarii grown either on ammonium sulfate or caffeine as the sole nitrogen source were analysed by mass spectrometry. Thirteen out of a total of 85 differentially expressed spots were identified after database search. Identified up-regulated proteins include phosphoglycerate kinase, malate dehydrogenase, dyp-type peroxidase family protein, heat shock protein, Cu, Zn superoxidase dismutase and xanthine dehydrogenase. Some of the proteins identified in this study are involved in the caffeine degradation pathway as well as in stress response, suggesting that stress proteins could be involved in caffeine metabolism in filamentous fungi.

Associations between smoking and caffeine consumption in two European cohorts

PubMed Central

Taylor, Amy E.; Ware, Jennifer J.; McMahon, George; Hottenga, Jouke‐Jan; Baselmans, Bart M. L.; Willemsen, Gonneke; Boomsma, Dorret I.; Munafò, Marcus R.; Vink, Jacqueline M.

2016-01-01

Abstract Aims To estimate associations between smoking initiation, smoking persistence and smoking heaviness and caffeine consumption in two population‐based samples from the Netherlands and the United Kingdom. Design Observational study employing data on self‐reported smoking behaviour and caffeine consumption. Setting Adults from the general population in the Netherlands and the United Kingdom. Participants Participants from the Netherlands Twin Register [NTR: n = 21 939, mean age 40.8, standard deviation (SD) = 16.9, 62.6% female] and the Avon Longitudinal Study of Parents and Children (ALSPAC: n = 9086, mean age 33.2, SD = 4.7, 100% female). Measurements Smoking initiation (ever versus never smoking), smoking persistence (current versus former smoking), smoking heaviness (number of cigarettes smoked) and caffeine consumption in mg per day through coffee, tea, cola and energy drinks. Findings After correction for age, gender (NTR), education and social class (ALSPAC), smoking initiation was associated with consuming on average 52.8 [95% confidence interval (CI) = 45.6–60.0; NTR] and 59.5 (95% CI = 51.8–67.2; ALSPAC) mg more caffeine per day. Smoking persistence was also associated with consuming more caffeine [+57.9 (95% CI = 45.2–70.5) and +83.2 (95% CI = 70.2–96.3) mg, respectively]. Each additional cigarette smoked per day was associated with 3.7 (95% CI = 1.9–5.5; NTR) and 8.4 (95% CI = 6.9–10.0; ALSPAC) mg higher daily caffeine consumption in current smokers. Smoking was associated positively with coffee consumption and less strongly with cola and energy drinks. For tea, associations were positive in ALSPAC and negative in NTR. Conclusions There appears to be a positive association between smoking and caffeine consumption in the Netherlands and the United Kingdom. PMID:26750569

Caffeine accelerates recovery from general anesthesia via multiple pathways.

PubMed

Fong, Robert; Khokhar, Suhail; Chowdhury, Atif N; Xie, Kelvin G; Wong, Josiah Hiu-Yuen; Fox, Aaron P; Xie, Zheng

2017-09-01

Various studies have explored different ways to speed emergence from anesthesia. Previously, we have shown that three drugs that elevate intracellular cAMP (forskolin, theophylline, and caffeine) accelerate emergence from anesthesia in rats. However, our earlier studies left two main questions unanswered. First, were cAMP-elevating drugs effective at all anesthetic concentrations? Second, given that caffeine was the most effective of the drugs tested, why was caffeine more effective than forskolin since both drugs elevate cAMP? In our current study, emergence time from anesthesia was measured in adult rats exposed to 3% isoflurane for 60 min. Caffeine dramatically accelerated emergence from anesthesia, even at the high level of anesthetic employed. Caffeine has multiple actions including blockade of adenosine receptors. We show that the selective A 2a adenosine receptor antagonist preladenant or the intracellular cAMP ([cAMP] i )-elevating drug forskolin, accelerated recovery from anesthesia. When preladenant and forskolin were tested together, the effect on anesthesia recovery time was additive indicating that these drugs operate via different pathways. Furthermore, the combination of preladenant and forskolin was about as effective as caffeine suggesting that both A 2A receptor blockade and [cAMP] i elevation play a role in caffeine's ability to accelerate emergence from anesthesia. Because anesthesia in rodents is thought to be similar to that in humans, these results suggest that caffeine might allow for rapid and uniform emergence from general anesthesia in humans at all anesthetic concentrations and that both the elevation of [cAMP] i and adenosine receptor blockade play a role in this response. NEW & NOTEWORTHY Currently, there is no method to accelerate emergence from anesthesia. Patients "wake" when they clear the anesthetic from their systems. Previously, we have shown that caffeine can accelerate emergence from anesthesia. In this study, we show that caffeine is effective even at high levels of anesthetic. We also show that caffeine operates by both elevating intracellular cAMP levels and by blocking adenosine receptors. This complicated pharmacology makes caffeine especially effective in accelerating emergence from anesthesia. Copyright © 2017 the American Physiological Society.

Caffeine in Boston Harbor past and present, assessing its utility as a tracer of wastewater contamination in an urban estuary

EPA Science Inventory

Sites throughout Boston Harbor were analyzed for caffeine to assess its utility as a tracer in identifying sources of sanitary wastewater. Caffeine ranged from 15 ng/L in the outer harbor to a high of 185 ng/L in the inner harbor. Inner harbor concentrations were a result of comb...

Caffeine content of decaffeinated coffee.

PubMed

McCusker, Rachel R; Fuehrlein, Brian; Goldberger, Bruce A; Gold, Mark S; Cone, Edward J

2006-10-01

Caffeine is the most widely consumed drug in the world with coffee representing a major source of intake. Despite widespread availability, various medical conditions necessitate caffeine-restricted diets. Patients on certain prescription medications are advised to discontinue caffeine intake. Such admonition has implications for certain psychiatric patients because of pharmacokinetic interactions between caffeine and certain anti-anxiety drugs. In an effort to abstain from caffeine, patients may substitute decaffeinated for caffeinated coffee. However, decaffeinated beverages are known to contain caffeine in varying amounts. The present study determined the caffeine content in a variety of decaffeinated coffee drinks. In phase 1 of the study, 10 decaffeinated samples were collected from different coffee establishments. In phase 2 of the study, Starbucks espresso decaffeinated (N=6) and Starbucks brewed decaffeinated coffee (N=6) samples were collected from the same outlet to evaluate variability of caffeine content of the same drink. The 10 decaffeinated coffee samples from different outlets contained caffeine in the range of 0-13.9 mg/16-oz serving. The caffeine content for the Starbucks espresso and the Starbucks brewed samples collected from the same outlet were 3.0-15.8 mg/shot and 12.0-13.4 mg/16-oz serving, respectively. Patients vulnerable to caffeine effects should be advised that caffeine may be present in coffees purported to be decaffeinated. Further research is warranted on the potential deleterious effects of consumption of "decaffeinated" coffee that contains caffeine on caffeine-restricted patients. Additionally, further exploration is merited for the possible physical dependence potential of low doses of caffeine such as those concentrations found in decaffeinated coffee.

Isolation and characterization of a thermally stable recombinant anti-caffeine heavy-chain antibody fragment.

PubMed

Ladenson, Ruth C; Crimmins, Dan L; Landt, Yvonne; Ladenson, Jack H

2006-07-01

We have isolated and characterized a caffeine-specific, heavy-chain-only antibody fragment (V(HH)) from llama that is capable of being utilized to analyze caffeine in hot and cold beverages. Camelid species (llama and camel) were selected for immunization because of their potential to make heat-stable, heavy-chain-only antibodies. Llamas and camels were immunized with caffeine covalently linked to keyhole limpet hemocyanin, and recombinant antibody techniques were used to create phage displayed libraries of variable region fragments of the heavy-chain antibodies. Caffeine-specific V(HH) fragments were selected by their ability to bind to caffeine/bovine serum albumin (BSA) and confirmed by a positive reaction in a caffeine enzyme-linked immunosorbent assay (caffeine ELISA). One of these V(HH) fragments (VSA2) was expressed as a soluble protein and shown to recover its reactivity after exposure to temperatures up to 90 degrees C. In addition, VSA2 was able to bind caffeine at 70 degrees C. A competition caffeine ELISA was developed for the measurement of caffeine in beverages, and concentrations of caffeine obtained for coffee, Coca-Cola Classic, and Diet Coke agreed well with high performance liquid chromatography (HPLC) determination and literature values. VSA2 showed minimal cross reactivity with structurally related methylxanthines.

Population pharmacokinetics of caffeine in healthy male adults using mixed-effects models.

PubMed

Seng, K-Y; Fun, C-Y; Law, Y-L; Lim, W-M; Fan, W; Lim, C-L

2009-02-01

Caffeine has been shown to maintain or improve the performance of individuals, but its pharmacokinetic profile for Asians has not been well characterized. In this study, a population pharmacokinetic model for describing the pharmacokinetics of caffeine in Singapore males was developed. The data were also analysed using non-compartmental models. Data gathered from 59 male volunteers, who each ingested a single caffeine capsule in two clinical trials (3 or 5 mg/kg), were analysed via non-linear mixed-effects modelling. The participants' covariates, including age, body weight, and regularity of caffeinated-beverage consumption or smoking, were analysed in a stepwise fashion to identify their potential influence on caffeine pharmacokinetics. The final pharmacostatistical model was then subjected to stochastic simulation to predict the plasma concentrations of caffeine after oral (204, 340 and 476 mg) dosing regimens (repeated dosing every 6, 8 or 12 h) over a hypothetical 3-day period. The data were best described by a one-compartmental model with first-order absorption and first-order elimination. Smoking status was an influential covariate for clearance: clearance (mL/min) = 110*SMOKE + 114, where SMOKE was 0 and 1 for the non-smoker and the smoker respectively. Interoccasion variability was smaller compared to interindividual variability in clearance, volume and absorption rate (27% vs. 33%, 10% vs. 15% and 23% vs. 51% respectively). The extrapolated elimination half-lives of caffeine in the non-smokers and the smokers were 4.3 +/- 1.5 and 3.0 +/- 0.7 h respectively. Dosing simulations indicated that dosing regimens of 340 mg (repeated every 8 h) and 476 mg (repeated every 6 h) should achieve population-averaged caffeine concentrations within the reported beneficial range (4.5-9 microg/mL) in the non-smokers and the smokers respectively over 72 h. The population pharmacokinetic model satisfactorily described the disposition and variability of caffeine in the data. Mixed-effects modelling showed that the dose of caffeine depended on cigarette smoking status.

Zolpidem 10 mg given at daytime is not antagonized by 300 mg caffeine in man.

PubMed

Mattila, M J; Nurminen, M L; Vainio, P; Vanakoski, J

1998-07-01

Caffeine counteracts various effects of traditional benzodiazepines (BZDs). As zolpidem, a short-acting hypnotic, is an atypical GABAA-BZD agonist, we investigated when caffeine would counteract the effects of zolpidem as well. In daytime study I, zolpidem 10 mg (capsule) and caffeine 150 or 300 mg (in decaffeinated coffee) were given, alone and in combinations, to parallel groups (n = 15-17) of healthy students in double-blind and placebo-controlled manner. Objective and subjective tests were done before and 45 min and 90 min after intake. Ranked delta values (changes from baseline) were analysed by one-way contrast ANOVA and Scheffe's tests. In daytime study II, four healthy subjects took zolpidem 10 mg alone, and together with blinded caffeine 250 mg or (at -45 min) erythromycin 750 mg. Objective and subjective effects were measured and plasma zolpidem concentrations assayed at baseline and 45 min and 90 min after zolpidem intake. In study I, practice effects after placebo (ad + 30%) were seen for letter cancellation and digit symbol substitution but not for flicker fusion tests. Zolpidem alone significantly impaired (P < 0.05 vs delta placebo) letter cancellation and digit symbol substitution at 45 min and 90 min, lowered the flicker fusion threshold at 45 min, and caused subjective drowsiness, mental slowness, clumsiness and feeling of poor performance. Caffeine alone showed a non-significant trend to improve objective performance. The combined effects of zolpidem and either dose of caffeine matched those measured after zolpidem alone. Zolpidem + caffeine 300 mg was not stronger than zolpidem + caffeine 150 mg in impairing immediate memory and causing subjective sedation. In study II, zolpidem caused objective and subjective sedation; neither caffeine nor erythromycin modulated the effects of zolpidem or plasma zolpidem concentrations. The sedative effects of 10 mg of zolpidem are not antagonized by 150-300 mg of caffeine in pharmacodynamic or pharmacokinetic terms.

Heterogeneity in phenotypes based on smoking status in the Great Lakes Smoker Sibling Registry.

PubMed

Pomerleau, Cynthia S; Pomerleau, Ovide F; Snedecor, Sandy M; Gaulrapp, Stefanie; Kardia, Sharon L R

2004-12-01

We investigated whether 52 same-sex sibling pairs discordant for ever-smoking differed on psychiatric cofactors, alcohol and caffeine use, and responses to initial exposure to smoking. Ever-smokers scored significantly higher on measures of novelty seeking, depression, and childhood ADHD, and on alcohol dependence, alcohol intake, and caffeine intake. They reported significantly more pleasurable experiences, dizziness, "buzz," and relaxation upon initial exposure to smoking and significantly fewer displeasurable sensations, nausea, and cough than did nicotine-exposed, never-smoking siblings. Ever-smokers had significantly fewer years of education than their never-smoking siblings, suggesting that the concentration of smokers in lower socioeconomic strata may be partly due to downward mobility among smokers, possibly because of the observed elevation in psychiatric cofactors, which may interfere with academic performance. These findings are consistent with differences previously identified in unrelated ever- and never-smokers. Because same-sex siblings typically share a large set of common environments during childhood, our findings could be due either to genetic differences among siblings and/or (excepting educational level and responses to early exposure) to differences in adult environments.

A Randomized, Two-Way Crossover Study to Evaluate the Pharmacokinetics of Caffeine Delivered Using Caffeinated Chewing Gum Versus a Marketed Caffeinated Beverage in Healthy Adult Volunteers.

PubMed

Sadek, Paul; Pan, Xiao; Shepherd, Phil; Malandain, Elise; Carney, John; Coleman, Hugh

2017-12-01

Background: This study was conducted to compare the pharmacokinetics of caffeine delivered using caffeinated chewing gum to that delivered using a marketed caffeinated beverage (instant coffee) in 16 healthy adult volunteers. Materials and Methods: This was a controlled open-label, randomized, two-period crossover study. Caffeinated chewing gum and a serving of instant coffee, each containing ∼50 mg caffeine, were administered with blood samples collected before and up to 24 hours after administration starts. Plasma caffeine levels were analyzed using validated liquid chromatography coupled with tandem mass spectrometry methodology. Results: There were no statistical differences between the two caffeine products in t max ( p  = 0.3308) and k a ( p  = 0.3894). Although formulated at ∼50 mg caffeine each, mean dose released from chewing gum was ∼18% less than beverage. Dose-normalized area under the concentration-time curve (AUC) 0-t , AUC 0-∞ , and C max was similar between products. Although the criteria were not set a priori and the study was not powered for concluding bioequivalence, the 90% confidence intervals fell within the bioequivalence limit of 80% to 125%. Conclusions: Existing scientific literature on caffeine, based mostly on data from caffeinated beverages, can be leveraged to support the safety of caffeine delivered by chewing gum and current maximum safe caffeine dose advice should be applicable irrespective of delivery method.

Caffeine Stimulation of Cortisol Secretion Across the Waking Hours in Relation to Caffeine Intake Levels

PubMed Central

Lovallo, William R.; Whitsett, Thomas L.; al'Absi, Mustafa; Sung, Bong Hee; Vincent, Andrea S.; Wilson, Michael F.

2008-01-01

Objective Caffeine increases cortisol secretion in people at rest or undergoing mental stress. It is not known whether tolerance develops in this response with daily intake of caffeine in the diet. We therefore tested the cortisol response to caffeine challenge after controlled levels of caffeine intake. Methods Men (N = 48) and women (N = 48) completed a double-blind, crossover trial conducted over 4 weeks. On each week, subjects abstained for 5 days from dietary caffeine and instead took capsules totaling 0 mg, 300 mg, and 600 mg/day in 3 divided doses. On day 6, they took capsules with either 0 mg or 250 mg at 9:00 AM, 1:00 PM, and 6:00 PM, and cortisol was sampled from saliva collected at 8 times from 7:30 AM to 7:00 PM. Results After 5 days of caffeine abstinence, caffeine challenge doses caused a robust increase in cortisol across the test day (p < .0001). In contrast, 5 days of caffeine intake at 300 mg/day and 600 mg/day abolished the cortisol response to the initial 9:00 AM caffeine dose, although cortisol levels were again elevated between 1:00 PM and 7:00 PM (p = .02 to .002) after the second caffeine dose taken at 1:00 PM. Cortisol levels declined to control levels during the evening sampling period. Conclusion Cortisol responses to caffeine are reduced, but not eliminated, in healthy young men and women who consume caffeine on a daily basis. PMID:16204431

The Physiological and Performance Effects of Caffeine Gum Consumed During A Simulated Half-Time By Professional Academy Rugby Union Players.

PubMed

M, Russell; N A, Reynolds; B T, Crewther; C J, Cook; L, Kilduff

2017-11-27

Despite the prevalence of caffeine as an ergogenic aid, few studies have examined the use of caffeinated gums, especially during half-time in team sports. The physiological (blood lactate, salivary hormone concentrations) and performance (repeated sprints, cognitive function) effects of consuming caffeine gum during a simulated half-time were examined. Professional academy rugby union players (n=14) completed this double-blind, randomized, counterbalanced study. Following pre-exercise measurements , players chewed a placebo (PL) gum for five min before a standardized warm-up and completing repeated sprint testing (RSSA1). Thereafter, during a 15 min simulated half-time period, players chewed either caffeine (CAF: 400 mg; 4.1 ± 0.5 mg·kg) or PL gum for five min before completing a second repeated sprint test (RSSA2). Blood lactate, salivary testosterone and cortisol concentrations, and indices of cognitive function (i.e., reaction time and Stroop test) were measured at baseline, pre-RSSA1, post-RSSA1, pre-RSSA2 and post-RSSA2. Sprint performance was not affected by CAF (P=0.995) despite slower sprint times following the first sprint of both RSSA tests (all P<0.002). Following half-time, salivary testosterone increased by 70% (+97±58 pg·mL) in CAF versus PLA (P<0.001) whereas salivary cortisol remained unchanged (P=0.307). Cognitive performance was unaffected by time and trial (all P>0.05). Although performance effects were absent, chewing caffeine gum increased the salivary testosterone concentrations of professional rugby union players over a simulated half-time. Practitioners may therefore choose to recommend caffeine gum between successive exercise bouts due to the increases in salivary testosterone observed; a variable associated with increased motivation and high-intensity exercise performance.

Spectrophotometric investigation of the hetero-association of Caffeine and thiazine dye in aqueous solution

NASA Astrophysics Data System (ADS)

Bolotin, P. A.; Baranovsky, S. F.; Evstigneev, M. P.

2006-06-01

The self-association of thiazine dye, Methylene Blue (MB), and its hetero-association with Caffeine (CAF), were studied in aqueous solution by means of spectrophotometry in the visible range of spectrum. Concentration and temperature dependences of molar absorption of the interacting molecules were used to analyse dynamic equilibrium in solution in terms of two-component model of molecular hetero-association. The magnitudes of equilibrium dimerization and hetero-association constants as well as thermodynamic parameters, enthalpy and entropy, were determined. The calculation of the fraction of different types of associates in the mixed solution, containing Methylene Blue and Caffeine, was done. It was concluded that the hetero-association of Methylene Blue and Caffeine molecules results in lower effective concentration of the dye in solution, which may account for the alteration of its biological activity.

Integrating nanohybrid membranes of reduced graphene oxide: chitosan: silica sol gel with fiber optic SPR for caffeine detection

NASA Astrophysics Data System (ADS)

Kant, Ravi; Tabassum, Rana; Gupta, Banshi D.

2017-05-01

Caffeine is the most popular psychoactive drug consumed in the world for improving alertness and enhancing wakefulness. However, caffeine consumption beyond limits can result in lot of physiological complications in human beings. In this work, we report a novel detection scheme for caffeine integrating nanohybrid membranes of reduced graphene oxide (rGO) in chitosan modified silica sol gel (rGO: chitosan: silica sol gel) with fiber optic surface plasmon resonance. The chemically synthesized nanohybrid membrane forming the sensing route has been dip coated over silver coated unclad central portion of an optical fiber. The sensor works on the mechanism of modification of dielectric function of sensing layer on exposure to analyte solution which is manifested in terms of red shift in resonance wavelength. The concentration of rGO in polymer network of chitosan and silica sol gel and dipping time of the silver coated probe in the solution of nanohybrid membrane have been optimized to extricate the supreme performance of the sensor. The optimized sensing probe possesses a reasonably good sensitivity and follows an exponentially declining trend within the entire investigating range of caffeine concentration. The sensor boasts of an unparalleled limit of detection value of 1.994 nM and works well in concentration range of 0-500 nM with a response time of 16 s. The impeccable sensor methodology adopted in this work combining fiber optic SPR with nanotechnology furnishes a novel perspective for caffeine determination in commercial foodstuffs and biological fluids.

Investigation of pharmaceutical drugs and caffeine-containing foods using Fourier and terahertz time-domain spectroscopy

NASA Astrophysics Data System (ADS)

KaraliÅ«nas, Mindaugas; Venckevičius, Rimvydas; Kašalynas, Irmantas; Puc, Uroš; Abina, Andreja; Jeglič, Anton; Zidanšek, Aleksander; Valušis, Gintaras

2015-08-01

Several pharmaceutical drugs, such as alprazolam, ibuprofen, acetaminophen, activated carbon and others, and caffeine-containing foods were tested using terahertz (THz) time domain spectroscopy in the range from 0.3 to 2 THz. The dry powder of pharmaceutical drugs was mixed with HDPE and pressed into the pellets using hydraulic press. The coffee grounds were also pressed into the pellets after ball-milling and mixing with HDPE. The caffeine containing liquid foods were dried out on the paper strips of various stacking. Experiments allow one to determine characteristic spectral signatures of the investigated substances within THz range caused by active pharmaceutical ingredients, like in the case of caffeine, as well as supporting pharmaceutical ingredients. Spectroscopic THz imaging approach is considered as a possible option to identify packaged pharmaceutical drugs. The caffeine spectral features in the tested caffeine containing foods are difficult to observed due to the low caffeine concentration and complex caffeine chemical surrounding.

Is caffeine a cognitive enhancer?

PubMed

Nehlig, Astrid

2010-01-01

The effects of caffeine on cognition were reviewed based on the large body of literature available on the topic. Caffeine does not usually affect performance in learning and memory tasks, although caffeine may occasionally have facilitatory or inhibitory effects on memory and learning. Caffeine facilitates learning in tasks in which information is presented passively; in tasks in which material is learned intentionally, caffeine has no effect. Caffeine facilitates performance in tasks involving working memory to a limited extent, but hinders performance in tasks that heavily depend on working memory, and caffeine appears to rather improve memory performance under suboptimal alertness conditions. Most studies, however, found improvements in reaction time. The ingestion of caffeine does not seem to affect long-term memory. At low doses, caffeine improves hedonic tone and reduces anxiety, while at high doses, there is an increase in tense arousal, including anxiety, nervousness, jitteriness. The larger improvement of performance in fatigued subjects confirms that caffeine is a mild stimulant. Caffeine has also been reported to prevent cognitive decline in healthy subjects but the results of the studies are heterogeneous, some finding no age-related effect while others reported effects only in one sex and mainly in the oldest population. In conclusion, it appears that caffeine cannot be considered a ;pure' cognitive enhancer. Its indirect action on arousal, mood and concentration contributes in large part to its cognitive enhancing properties.

Aminophylline and caffeine for reversal of adverse symptoms associated with regadenoson SPECT MPI.

PubMed

Doran, Jesse A; Sajjad, Waseem; Schneider, Marabel D; Gupta, Rohit; Mackin, Maria L; Schwartz, Ronald G

2017-06-01

Aminophylline shortages led us to compare intravenous (IV) aminophylline with IV and oral (PO) caffeine during routine pharmacologic stress testing with SPECT MPI. We measured presence, duration, and reversal of adverse symptoms and cardiac events following regadenoson administration in consecutive patients randomized to IV aminophylline (100 mg administered over 30-60 seconds), IV caffeine citrate (60 mg infused over 3-5 minutes), or PO caffeine as coffee or diet cola. Of 241 patients, 152 (63%) received regadenoson reversal intervention. Complete (CR), predominant (PRE), or partial (PR) reversal was observed in 99%. CR by IV aminophylline (87%), IV caffeine (87%), and PO caffeine (78%) were similar (P = NS). Time to CR (162 ± 12.6 seconds, mean ± SD) was similar in treatment arms. PO caffeine was inferior to IV aminophylline for CR + PRE. IV aminophylline and IV caffeine provide rapid, safe reversal of regadenoson-induced adverse effects during SPECT MPI. Oral caffeine appeared similarly effective for CR but not for the combined CR + PRE. Our results suggest PO caffeine may be an effective initial strategy for reversal of regadenoson, but IV aminophylline or IV caffeine should be available to optimize symptom reversal as needed.

Periodical reactivation under the effect of caffeine attenuates fear memory expression in rats.

PubMed

Pedraza, Lizeth K; Sierra, Rodrigo O; Lotz, Fernanda N; Alvares, Lucas de Oliveira

2018-05-08

In the last decade, several studies have shown that fear memories can be attenuated by interfering with reconsolidation. However, most of the pharmacological agents used in preclinical studies cannot be administered to humans. Caffeine is one of the world's most popular psychoactive drugs and its effects on cognitive and mood states are well documented. Nevertheless, the influence of caffeine administration on fear memory processing is not as clear. We employed contextual fear conditioning in rats and acute caffeine administration under a standard memory reconsolidation protocol or periodical memory reactivation. Additionally, potential rewarding/aversion and anxiety effects induced by caffeine were evaluated by conditioning place preference or open field, respectively. Caffeine administration was able to attenuate weak fear memories in a standard memory reconsolidation protocol; however, periodical memory reactivation under caffeine effect was necessary to attenuate strong and remote memories. Moreover, caffeine promoted conditioned place preference and anxiolytic-like behavior, suggesting that caffeine weakens the initial learning during reactivation through counterconditioning mechanisms. Thus, our study shows that rewarding and anxiolytic effects of caffeine during fear reactivation can change the emotional valence of fear memory. It brings a new promising pharmacological approach based on drugs widely used such as caffeine to treat fear-related disorders.

Synergistic cytotoxicity and mechanism of caffeine and lysozyme on hepatoma cell line HepG2

NASA Astrophysics Data System (ADS)

Yang, Hongchao; Li, Jingjuan; Cui, Lin; Ren, Yanqing; Niu, Liying; Wang, Xinguo; Huang, Yun; Cui, Lijian

2018-03-01

The influences of caffeine, lysozyme and the joint application of them on the hepatoma cell line HepG2 proliferation inhibition and cell apoptosis were observed by 3-(4, 5-dimethyl-2-thiazyl)-2, 5-diphenyl-2H-tetrazolium bromide assay and Hoechst 33342, which showed the proliferation inhibition rate of the joint application on HepG2 cells was 47.21%, significantly higher than caffeine or lysozyme, and the joint application promoted the apoptosis of HepG2 cells obviously. Van't Hoff classical thermodynamics formula, the Föster theory of non-radiation energy transfer and fluorescence phase diagram were used to manifest that the process of lysozyme binding to caffeine followed a two-state model, which was spontaneous at low temperature driven by enthalpy change, and the predominant intermolecular force was hydrogen bonding or Van der Waals force to stabilize caffeine-lysozyme complex with the distance 5.86 nm. The attenuated total reflection-Fourier transform infrared spectra indicated that caffeine decreased the relative contents of α-helix and β-turn, which inferred the structure of lysozyme tended to be "loose". Synchronous fluorescence spectra and ultraviolet spectra supported the above conclusion. The amino acid residues in the cleft of lysozyme were exposed and electropositivity was increased attributing to the loose structure, which were conducive to increasing caffeine concentration on the HepG2 cell surface by electrostatic interaction to show synergistic effect. The great quantities of microvilli on the liver cancer cell membrane surface, is beneficial for the lysozyme-caffeine compound to aggregate on cell surface to increase the concentration of caffeine to play stronger physiological role by electrostatic effect.

Comparisons of contact chemoreception and food acceptance by larvae of polyphagous Helicoverpa armigera and oligophagous Bombyx mori.

PubMed

Zhang, Hui-Jie; Faucher, Cécile P; Anderson, Alisha; Berna, Amalia Z; Trowell, Stephen; Chen, Quan-Mei; Xia, Qing-You; Chyb, Sylwester

2013-08-01

We compared food choice and the initial response to deterrent treated diet between fifth instars of Helicoverpa armigera, a polyphagous generalist pest, and Bombyx mori, an oligophagous specialist beneficial. Bombyx mori was more behaviorally sensitive to salicin than to caffeine. The relative sensitivities were reversed for H. armigera, which was tolerant to the highest levels of salicin found in natural sources but sensitive to caffeine. A single gustatory receptor neuron (GRN) in the medial styloconic sensillum of B. mori was highly sensitive to salicin and caffeine. The styloconic sensilla of H. armigera did not respond consistently to either of the bitter compounds. Phagostimulants also were tested. Myo-inositol and sucrose were detected specifically by two GRNs located in B. mori lateral styloconic sensillum, whereas, in H. armigera, sucrose was sensed by a GRN in the lateral sensillum, and myo-inositol by a GRN in the medial sensillum. Myo-inositol responsiveness in both species occurred at or below 10(-3) mM, which is far below the naturally occurring concentration of 1 mM in plants. Larval responses to specific plant secondary compounds appear to have complex determinants that may include host range, metabolic capacity, and gustatory repertoire.

Influence of Caffeine Ingestion on Perceived Mood States, Concentration, and Arousal Levels during a 75-Min University Lecture

ERIC Educational Resources Information Center

Peeling, Peter; Dawson, Brian

2007-01-01

This investigation aimed to assess the effect of a caffeine supplement on perceived mood state, concentration, and arousal during a 75-min university lecture. Methods. This randomized, blind, cross-over design investigation ran over a course of 2 consecutive weeks. During "week" 1, 10 third-year Human Movement and Exercise Science…

Relationships Between Caffeine Intake and Risk for Probable Dementia or Global Cognitive Impairment: The Women's Health Initiative Memory Study.

PubMed

Driscoll, Ira; Shumaker, Sally A; Snively, Beverly M; Margolis, Karen L; Manson, JoAnn E; Vitolins, Mara Z; Rossom, Rebecca C; Espeland, Mark A

2016-12-01

Nonhuman studies suggest a protective effect of caffeine on cognition. Although human literature remains less consistent, reviews suggest a possible favorable relationship between caffeine consumption and cognitive impairment or dementia. We investigated the relationship between caffeine intake and incidence of cognitive impairment or probable dementia in women aged 65 and older from the Women's Health Initiative Memory Study. All women with self-reported caffeine consumption at enrollment were included (N = 6,467). In 10 years or less of follow-up with annual assessments of cognitive function, 388 of these women received a diagnosis of probable dementia based on a 4-phase protocol that included central adjudication. We used proportional hazards regression to assess differences in the distributions of times until incidence of probable dementia or composite cognitive impairment among women grouped by baseline level of caffeine intake, adjusting for risk factors (hormone therapy, age, race, education, body mass index, sleep quality, depression, hypertension, prior cardiovascular disease, diabetes, smoking, and alcohol consumption). Women consuming above median levels (mean intake = 261mg) of caffeine intake for this group were less likely to develop incident dementia (hazard ratio = 0.74, 95% confidence interval [0.56, 0.99], p = .04) or any cognitive impairment (hazard ratio = 0.74, confidence interval [0.60, 0.91], p = .005) compared to those consuming below median amounts (mean intake = 64mg) of caffeine for this group. Our findings suggest lower odds of probable dementia or cognitive impairment in older women whose caffeine consumption was above median for this group and are consistent with the existing literature showing an inverse association between caffeine intake and age-related cognitive impairment. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Development of a biosensor for caffeine.

PubMed

Babu, V R Sarath; Patra, S; Karanth, N G; Kumar, M A; Thakur, M S

2007-01-23

We have utilized a microbe, which can degrade caffeine to develop an Amperometric biosensor for determination of caffeine in solutions. Whole cells of Pseudomonas alcaligenes MTCC 5264 having the capability to degrade caffeine were immobilized on a cellophane membrane with a molecular weight cut off (MWCO) of 3000-6000 by covalent crosslinking method using glutaraledhyde as the bifunctional crosslinking agent and gelatin as the protein based stabilizing agent (PBSA). The biosensor system was able to detect caffeine in solution over a concentration range of 0.1 to 1 mg mL(-1). With read-times as short as 3 min, this caffeine biosensor acts as a rapid analysis system for caffeine in solutions. Interestingly, successful isolation and immobilization of caffeine degrading bacteria for the analysis of caffeine described here was enabled by a novel selection strategy that incorporated isolation of caffeine degrading bacteria capable of utilizing caffeine as the sole source of carbon and nitrogen from soils and induction of caffeine degrading capacity in bacteria for the development of the biosensor. This biosensor is highly specific for caffeine and response to interfering compounds such as theophylline, theobromine, paraxanthine, other methyl xanthines and sugars was found to be negligible. Although a few biosensing methods for caffeine are reported, they have limitations in application for commercial samples. The development and application of new caffeine detection methods remains an active area of investigation, particularly in food and clinical chemistry. The optimum pH and temperature of measurement were 6.8 and 30+/-2 degrees C, respectively. Interference in analysis of caffeine due to different substrates was observed but was not considerable. Caffeine content of commercial samples of instant tea and coffee was analyzed by the biosensor and the results compared well with HPLC analysis.

Acute high-caffeine exposure increases autophagic flux and reduces protein synthesis in C2C12 skeletal myotubes.

PubMed

Hughes, M A; Downs, R M; Webb, G W; Crocker, C L; Kinsey, S T; Baumgarner, Bradley L

2017-04-01

Caffeine is a highly catabolic dietary stimulant. High caffeine concentrations (1-10 mM) have previously been shown to inhibit protein synthesis and increase protein degradation in various mammalian cell lines. The purpose of this study was to examine the effect of short-term caffeine exposure on cell signaling pathways that regulate protein metabolism in mammalian skeletal muscle cells. Fully differentiated C2C12 skeletal myotubes either received vehicle (DMSO) or 5 mM caffeine for 6 h. Our analysis revealed that caffeine promoted a 40% increase in autolysosome formation and a 25% increase in autophagic flux. In contrast, caffeine treatment did not significantly increase the expression of the skeletal muscle specific ubiquitin ligases MAFbx and MuRF1 or 20S proteasome activity. Caffeine treatment significantly reduced mTORC1 signaling, total protein synthesis and myotube diameter in a CaMKKβ/AMPK-dependent manner. Further, caffeine promoted a CaMKII-dependent increase in myostatin mRNA expression that did not significantly contribute to the caffeine-dependent reduction in protein synthesis. Our results indicate that short-term caffeine exposure significantly reduced skeletal myotube diameter by increasing autophagic flux and promoting a CaMKKβ/AMPK-dependent reduction in protein synthesis.

The buzz on caffeine in invertebrates: effects on behavior and molecular mechanisms.

PubMed

Mustard, Julie A

2014-04-01

A number of recent studies from as diverse fields as plant-pollinator interactions, analyses of caffeine as an environmental pollutant, and the ability of caffeine to provide protection against neurodegenerative diseases have generated interest in understanding the actions of caffeine in invertebrates. This review summarizes what is currently known about the effects of caffeine on behavior and its molecular mechanisms in invertebrates. Caffeine appears to have similar effects on locomotion and sleep in both invertebrates and mammals. Furthermore, as in mammals, caffeine appears to have complex effects on learning and memory. However, the underlying mechanisms for these effects may differ between invertebrates and vertebrates. While caffeine's ability to cause release of intracellular calcium stores via ryanodine receptors and its actions as a phosphodiesterase inhibitor have been clearly established in invertebrates, its ability to interact with invertebrate adenosine receptors remains an important open question. Initial studies in insects and mollusks suggest an interaction between caffeine and the dopamine signaling pathway; more work needs to be done to understand the mechanisms by which caffeine influences signaling via biogenic amines. As of yet, little is known about whether other actions of caffeine in vertebrates, such as its effects on GABAA and glycine receptors, are conserved. Furthermore, the pharmacokinetics of caffeine remains to be elucidated. Overall behavioral responses to caffeine appear to be conserved amongst organisms; however, we are just beginning to understand the mechanisms underlying its effects across animal phyla.

Measurement of caffeine and its three primary metabolites in human plasma by HPLC-ESI-MS/MS and clinical application.

PubMed

Chen, Feng; Hu, Zhe-Yi; Parker, Robert B; Laizure, S Casey

2017-06-01

Caffeine is a mild stimulant with significant potential for abuse, being consumed in larger doses with the widespread availability of energy drinks and by novel routes of administration such as inspired powder, oral sprays and electronic cigarettes. How these recent changes in caffeine consumption affecting caffeine disposition and abuse potential is of growing concern. In the study of caffeine disposition in humans, it is common to only measure the caffeine concentration; however, caffeine's three major metabolites (paraxanthine, theobromine and theophylline) retain central nervous system stimulant activity that may contribute to the overall pharmacological activity and toxicity. Therefore, it would be scientifically more rigorous to measure caffeine and its major metabolites in the evaluation of caffeine disposition in human subjects. Herein, we report a method for the simultaneous quantification of caffeine and its three major metabolites in human plasma by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry (HPLC-ESI-MS/MS). Human plasma samples were treated by simple protein precipitation and the analytes were separated using a 6 min gradient program. Precision and accuracy were well within in the 15% acceptance range. The simple sample preparation, short runtime, sensitivity and the inclusion of caffeine's major metabolites make this assay methodology optimal for the study of caffeine's pharmacokinetics and pharmacodynamics in human subjects. Copyright © 2016 John Wiley & Sons, Ltd.

An optimized and validated SPE-LC-MS/MS method for the determination of caffeine and paraxanthine in hair.

PubMed

De Kesel, Pieter M M; Lambert, Willy E; Stove, Christophe P

2015-11-01

Caffeine is the probe drug of choice to assess the phenotype of the drug metabolizing enzyme CYP1A2. Typically, molar concentration ratios of paraxanthine, caffeine's major metabolite, to its precursor are determined in plasma following administration of a caffeine test dose. The aim of this study was to develop and validate an LC-MS/MS method for the determination of caffeine and paraxanthine in hair. The different steps of a hair extraction procedure were thoroughly optimized. Following a three-step decontamination procedure, caffeine and paraxanthine were extracted from 20 mg of ground hair using a solution of protease type VIII in Tris buffer (pH 7.5). Resulting hair extracts were cleaned up on Strata-X™ SPE cartridges. All samples were analyzed on a Waters Acquity UPLC® system coupled to an AB SCIEX API 4000™ triple quadrupole mass spectrometer. The final method was fully validated based on international guidelines. Linear calibration lines for caffeine and paraxanthine ranged from 20 to 500 pg/mg. Precision (%RSD) and accuracy (%bias) were below 12% and 7%, respectively. The isotopically labeled internal standards compensated for the ion suppression observed for both compounds. Relative matrix effects were below 15%RSD. The recovery of the sample preparation procedure was high (>85%) and reproducible. Caffeine and paraxanthine were stable in hair for at least 644 days. The effect of the hair decontamination procedure was evaluated as well. Finally, the applicability of the developed procedure was demonstrated by determining caffeine and paraxanthine concentrations in hair samples of ten healthy volunteers. The optimized and validated method for determination of caffeine and paraxanthine in hair proved to be reliable and may serve to evaluate the potential of hair analysis for CYP1A2 phenotyping. Copyright © 2015 Elsevier B.V. All rights reserved.

Monitoring of caffeine consumption effect on skin blood properties by diffuse reflectance spectroscopy

NASA Astrophysics Data System (ADS)

Milanic, Matija; Marin, Ana; Stergar, Jost; Verdel, Nina; Majaron, Boris

2017-07-01

Caffeine is the most widely consumed psychoactive substance in the world. It affects many tissues and organs, in particular central nervous system, heart, and blood vessels. The effect of caffeine on vascular smooth muscle cells is an initial transient contraction followed by significant vasodilatation. In this study we investigate the use of diffuse reflectance spectroscopy (DRS) for monitoring of vascular changes in human skin induced by caffeine consumption. DRS spectra were recorded on volar sides of the forearms of ten healthy volunteers at time delays of 0, 30, 60, 120, and 180 minutes after consumption of caffeine, while one subject served as a negative control. Analytical diffusion approximation solutions for diffuse reflectance from three-layer structures were used to assess skin composition (e.g., dermal blood volume fraction and oxygen saturation) by fitting to experimental data. The results demonstrate that cutaneous vasodynamics induced by caffeine consumption can be monitored by DRS, while changes in the control subject not consuming caffeine were insignificant.

Coffee and caffeine consumption and the risk of hypertension in postmenopausal women.

PubMed

Rhee, Jinnie J; Qin, FeiFei; Hedlin, Haley K; Chang, Tara I; Bird, Chloe E; Zaslavsky, Oleg; Manson, JoAnn E; Stefanick, Marcia L; Winkelmayer, Wolfgang C

2016-01-01

The associations of coffee and caffeine intakes with the risk of incident hypertension remain controversial. We sought to assess longitudinal relations of caffeinated coffee, decaffeinated coffee, and total caffeine intakes with mean blood pressure and incident hypertension in postmenopausal women in the Women's Health Initiative Observational Study. In a large prospective study, type and amount of coffee and total caffeine intakes were assessed by using self-reported questionnaires. Hypertension status was ascertained by using measured blood pressure and self-reported drug-treated hypertension. The mean intakes of caffeinated coffee, decaffeinated coffee, and caffeine were 2-3 cups/d, 1 cup/d, and 196 mg/d, respectively. Using multivariable linear regression, we examined the associations of baseline intakes of caffeinated coffee, decaffeinated coffee, and caffeine with measured systolic and diastolic blood pressures at annual visit 3 in 29,985 postmenopausal women who were not hypertensive at baseline. We used Cox proportional hazards models to estimate HRs and their 95% CIs for time to incident hypertension. During 112,935 person-years of follow-up, 5566 cases of incident hypertension were reported. Neither caffeinated coffee nor caffeine intake was associated with mean systolic or diastolic blood pressure, but decaffeinated coffee intake was associated with a small but clinically irrelevant decrease in mean diastolic blood pressure. Decaffeinated coffee intake was not associated with mean systolic blood pressure. Intakes of caffeinated coffee, decaffeinated coffee, and caffeine were not associated with the risk of incident hypertension (P-trend > 0.05 for all). In summary, these findings suggest that caffeinated coffee, decaffeinated coffee, and caffeine are not risk factors for hypertension in postmenopausal women. © 2016 American Society for Nutrition.

Coffee and caffeine consumption and the risk of hypertension in postmenopausal women12

PubMed Central

Rhee, Jinnie J; Qin, FeiFei; Hedlin, Haley K; Chang, Tara I; Bird, Chloe E; Zaslavsky, Oleg; Manson, JoAnn E; Stefanick, Marcia L; Winkelmayer, Wolfgang C

2016-01-01

Background: The associations of coffee and caffeine intakes with the risk of incident hypertension remain controversial. Objective: We sought to assess longitudinal relations of caffeinated coffee, decaffeinated coffee, and total caffeine intakes with mean blood pressure and incident hypertension in postmenopausal women in the Women’s Health Initiative Observational Study. Design: In a large prospective study, type and amount of coffee and total caffeine intakes were assessed by using self-reported questionnaires. Hypertension status was ascertained by using measured blood pressure and self-reported drug-treated hypertension. The mean intakes of caffeinated coffee, decaffeinated coffee, and caffeine were 2–3 cups/d, 1 cup/d, and 196 mg/d, respectively. Using multivariable linear regression, we examined the associations of baseline intakes of caffeinated coffee, decaffeinated coffee, and caffeine with measured systolic and diastolic blood pressures at annual visit 3 in 29,985 postmenopausal women who were not hypertensive at baseline. We used Cox proportional hazards models to estimate HRs and their 95% CIs for time to incident hypertension. Results: During 112,935 person-years of follow-up, 5566 cases of incident hypertension were reported. Neither caffeinated coffee nor caffeine intake was associated with mean systolic or diastolic blood pressure, but decaffeinated coffee intake was associated with a small but clinically irrelevant decrease in mean diastolic blood pressure. Decaffeinated coffee intake was not associated with mean systolic blood pressure. Intakes of caffeinated coffee, decaffeinated coffee, and caffeine were not associated with the risk of incident hypertension (P-trend > 0.05 for all). Conclusion: In summary, these findings suggest that caffeinated coffee, decaffeinated coffee, and caffeine are not risk factors for hypertension in postmenopausal women. PMID:26657046

Liquid chromatographic determination of caffeine and adrenergic stimulants in food supplements sold in Brazilian e-commerce for weight loss and physical fitness.

PubMed

Viana, Carine; Zemolin, Gabriela M; Müller, Larissa S; Dal Molin, Thaís R; Seiffert, Helena; de Carvalho, Leandro M

2016-01-01

Methyl-xanthines and adrenergic stimulants, such as caffeine and synephrine, are commonly added to food supplements due to their stimulating and thermogenic effects. In addition, the abusive consumption of food supplements with ergogenic and aesthetic purposes has been observed worldwide. This work describes the study of caffeine, p-synephrine, hordenine, octopamine, tyramine, ephedrine and salicin as stimulants in dietary supplements marketed in Brazil for weight loss and physical fitness claims. A total of 94 different products were acquired from 30 Brazilian websites. Thus, the sampling of marketed supplements was performed in virtual commerce (e-commerce) with claims of weight loss, appetite reduction, fat burning and metabolism acceleration. The developed analytical method involved the separation of the stimulants by HPLC with diode array detection (HPLC-DAD) by using a gradient elution of flow rate (0.7-2.5 ml min(-1)) and mobile phase composition (0.1% H3PO4/methanol). The validated method was applied to the study of 46 dietary supplements. Caffeine, p-synephrine and ephedrine were found to be present as stimulants in 52% of the studied samples marketed as encapsulated or bulk forms. Caffeine was found to be present in concentrations that represent doses from 25.0 to 1476.7 mg day(-1). Synephrine was found in concentrations that represent doses from 59.1 to 127.0 mg day(-1). Ephedrine was found to be associated with caffeine in one formulation at a concentration representing a 26.1 mg day(-1) dosage.

Breast Milk and Hair Testing to Detect Illegal Drugs, Nicotine, and Caffeine in Donors to a Human Milk Bank.

PubMed

Escuder-Vieco, Diana; Garcia-Algar, Óscar; Joya, Xavier; Marchei, Emilia; Pichini, Simona; Pacifici, Roberta; Pallás-Alonso, Carmen Rosa

2016-08-01

The use of illegal drugs and tobacco is an exclusion criteria for accepting a nursing mother as a milk donor. The detection window for human milk testing is typically a few hours. Hair testing has been considered the gold standard to assess chronic exposure to these toxic substances. The aim of this study was to determine the levels of illegal drugs, nicotine, and caffeine in breast milk and hair samples from donors to assess whether these substances were being used during the donation period and the months leading up to it. Thirty-six samples of hair and breast milk were obtained from 36 donors. The tests performed identified nicotine, caffeine, morphine, cocaine, cannabis, amphetamines, codeine, methadone, and other substances derived therefrom. No illegal drugs were found in any of the samples analyzed. Nicotine and cotinine were found in 33.3% (12/36) of all hair samples. Among these 12 samples, 10 had cotinine concentrations consistent with cutoff values for unexposed nonsmokers, 1 had concentrations consistent with cutoff values for passive smokers, and 1 had concentrations consistent with cutoff values for active smokers. Caffeine was found in 77.7% of the hair samples and in 50% of the donor milk samples. The correlation for caffeine between donor milk and hair samples was r = 0.288, P = .0881. Donors do not use illegal drugs during either the donation period or the months leading up to it. They are occasionally exposed to tobacco smoke and almost all of them consume caffeine. © The Author(s) 2016.

Influence of caffeine on X-ray-induced killing and mutation in V79 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhattacharjee, S.B.; Bhattacharyya, N.; Chatterjee, S.

1987-02-01

Effects produced by caffeine on X-irradiated Chinese hamster V79 cells depended on the growth conditions of the cells. For exponentially growing cells, nontoxic concentrations of caffeine decreased the shoulder width from the survival curve, but the slope remained unchanged. The yield of mutants under the same conditions also remained unaffected. In case of density-inhibited cells, delaying trypsinization for 24 h after X irradiation increased the survival and decreased the yield of mutants. The presence of caffeine during this incubation period inhibited such recovery and significantly increased the yield of X-ray-induced mutants.

The buzz on caffeine in invertebrates: effects on behavior and molecular mechanisms

PubMed Central

Mustard, Julie A.

2014-01-01

A number of recent studies from as diverse fields as plant-pollinator interactions, analyses of caffeine as an environmental pollutant, and the ability of caffeine to provide protection against neurodegenerative diseases have generated interest in understanding the actions of caffeine in invertebrates. This review summarizes what is currently known about the effects of caffeine on behavior and its molecular mechanisms in invertebrates. Caffeine appears to have similar effects on locomotion and sleep in both invertebrates and mammals. Furthermore, as in mammals, caffeine appears to have complex effects on learning and memory. However, the underlying mechanisms for these effects may differ between invertebrates and vertebrates. While caffeine’s ability to cause release of intracellular calcium stores via ryanodine receptors and its actions as a phosphodiesterase inhibitor have been clearly established in invertebrates, its ability to interact with invertebrate adenosine receptors remains an important open question. Initial studies in insects and mollusks suggest an interaction between caffeine and the dopamine signaling pathway; more work needs to be done to understand the mechanisms by which caffeine influences signaling via biogenic amines. As of yet, little is known about whether other actions of caffeine in vertebrates, such as its effects on GABAA and glycine receptors, are conserved. Furthermore, the pharmacokinetics of caffeine remains to be elucidated. Overall behavioral responses to caffeine appear to be conserved amongst organisms; however, we are just beginning to understand the mechanisms underlying its effects across animal phyla. PMID:24162934

The influence of caffeine on sustained attention: an ERP study.

PubMed

Ruijter, J; Lorist, M M; Snel, J; De Ruiter, M B

2000-05-01

The present study investigated the effects of caffeine on sustained attention by measuring concentration and fatigue. Event-related potentials (ERPs) and behavioral measures were recorded from 12 participants who worked continuously for approximately 10 min in a self-paced reaction task under conditions of both caffeine (250 mg) and placebo. The ERP data revealed more positive frontal P2 and parietal P3 components in the caffeine condition. However, a combination of different indices of the behavioral data did not reveal any effects of caffeine intake. These results suggest that caffeine increases arousal, thereby reducing fatigue, as was observed in the ERP results. A probable explanation for the absence of any effects of caffeine in the behavioral data can be found in the demanding properties of the task that was used, thereby supporting evidence for more pronounced effects of caffeine in suboptimal conditions. In addition, these results appeal for an increase in the use of ERPs in drug research, in order to discover possible effects on the brain which do not necessarily result in behavioral changes.

Caffeine Suppresses the Activation of Hepatic Stellate Cells cAMP-Independently by Antagonizing Adenosine Receptors.

PubMed

Yamaguchi, Momoka; Saito, Shin-Ya; Nishiyama, Ryota; Nakamura, Misuzu; Todoroki, Kenichiro; Toyo'oka, Toshimasa; Ishikawa, Tomohisa

2017-01-01

During liver injury, hepatic stellate cells (HSCs) are activated by various cytokines and transdifferentiated into myofibroblast-like activated HSCs, which produce collagen, a major source of liver fibrosis. Therefore, the suppression of HSC activation is regarded as a therapeutic target for liver fibrosis. Several epidemiological reports have revealed that caffeine intake decreases the risk of liver disease. In this study, therefore, we investigated the effect of caffeine on the activation of primary HSCs isolated from mice. Caffeine suppressed the activation of HSC in a concentration-dependent manner. BAPTA-AM, an intracellular Ca 2+ chelator, had no effect on the caffeine-induced suppression of HSC activation. None of the isoform-selective inhibitors of phosphodiesterase1 to 5 affected changes in the morphology of HSC during activation, whereas CGS-15943, an adenosine receptor antagonist, inhibited them. Caffeine had no effect on intracellular cAMP level or on the phosphorylation of extracellular signal-regulated kinase (ERK)1/2. In contrast, caffeine significantly decreased the phosphorylation of Akt1. These results suggest that caffeine inhibits HSC activation by antagonizing adenosine receptors, leading to Akt1 signaling activation.

Caffeine and Sugars Interact in Aqueous Solutions: A Simulation and NMR Study

PubMed Central

Tavagnacco, Letizia; Engström, Olof; Schnupf, Udo; Saboungi, Marie-Louise; Himmel, Michael; Widmalm, Göran; Cesàro, Attilio; Brady, John W.

2012-01-01

Molecular dynamics simulations were carried out on several systems of caffeine interacting with simple sugars. These included a single caffeine molecule in a 3 molal solution of α-D-glucopyranose, at a caffeine concentration of 0.083 molal; a single caffeine in a 3 molal solution of β-D-glucopyranose, and a single caffeine molecule in a 1.08 molal solution of sucrose (table sugar). Parallel Nuclear Magnetic Resonance titration experiments were carried out on the same solutions under similar conditions. Consistent with previous thermodynamic experiments, the sugars were found to have an affinity for the caffeine molecules in both the simulations and experiments, and that the binding in these complexes occurs by face-to-face stacking of the hydrophobic triad of protons of the pyranose rings against the caffeine face, rather than by hydrogen bonding. For the disaccharide, the binding occurs via stacking of the glucose ring against the caffeine, with a lesser affinity for the fructose observed. These findings are consistent with the association being driven by hydrophobic hydration, and are similar to the previously observed binding of glucose rings to various other planar molecules, including indole, serotonin, and phenol. PMID:22897449

Caffeine and sugars interact in aqueous solutions: a simulation and NMR study.

PubMed

Tavagnacco, Letizia; Engström, Olof; Schnupf, Udo; Saboungi, Marie-Louise; Himmel, Michael; Widmalm, Göran; Cesàro, Attilio; Brady, John W

2012-09-27

Molecular dynamics simulations were carried out on several systems of caffeine interacting with simple sugars. These included a single caffeine molecule in a 3 m solution of α-D-glucopyranose, at a caffeine concentration of 0.083 m, a single caffeine in a 3 m solution of β-D-glucopyranose, and a single caffeine molecule in a 1.08 m solution of sucrose (table sugar). Parallel nuclear magnetic resonance titration experiments were carried out on the same solutions under similar conditions. Consistent with previous thermodynamic experiments, the sugars were found to have an affinity for the caffeine molecules in both the simulations and experiments, and the binding in these complexes occurs by face-to-face stacking of the hydrophobic triad of protons of the pyranose rings against the caffeine face, rather than by hydrogen bonding. For the disaccharide, the binding occurs via stacking of the glucose ring against the caffeine, with a lesser affinity for the fructose observed. These findings are consistent with the association being driven by hydrophobic hydration and are similar to the previously observed binding of glucose rings to various other planar molecules, including indole, serotonin, and phenol.

Caffeine levels in beverages from Argentina's market: application to caffeine dietary intake assessment.

PubMed

Olmos, V; Bardoni, N; Ridolfi, A S; Villaamil Lepori, E C

2009-03-01

The caffeine content of different beverages from Argentina's market was measured. Several brands of coffees, teas, mates, chocolate milks, soft and energy drinks were analysed by high-performance liquid chromatography (HPLC) with ultraviolet detection. The highest concentration level was found in short coffee (1.38 mg ml(-1)) and the highest amount per serving was found in instant coffee (95 mg per serving). A consumption study was also carried out among 471 people from 2 to 93 years of age to evaluate caffeine total dietary intake by age and to identify the sources of caffeine intake. The mean caffeine intake among adults was 288 mg day(-1) and mate was the main contributor to that intake. The mean caffeine intake among children of 10 years of age and under was 35 mg day(-1) and soft drinks were the major contributors to that intake. Children between 11 and 15 years old and teenagers (between 16 and 20 years) had caffeine mean intakes of 120 and 240 mg day(-1), respectively, and mate was the major contributor to those intakes. Drinking mate is a deep-rooted habit among Argentine people and it might be the reason for their elevated caffeine mean daily intake.

Enhancement of cytogenetic damage and of antineoplastic effect by caffeine in Ehrlich ascites tumor cells treated with cyclophosphamide in vivo.

PubMed

Mourelatos, D; Dozi-Vassiliades, J; Kotsis, A; Gourtsas, C

1988-03-01

Enhanced cytogenetic damage by cyclophosphamide (CP) was observed when Ehrlich ascites tumor cells were exposed in vivo to nontoxic concentrations of caffeine. One h before i.p. injection of 5-bromodeoxyuridine adsorbed to activated charcoal Ehrlich ascites tumor-bearing mice treated i.p. with CP appear to have a dose-dependent increase in sister chromatid exchange rates and cell division delays. Caffeine increased the survival time of the Ehrlich ascites tumor-bearing mice treated with CP and markedly reduced the ascitic volume. Therefore, the in vivo antitumor effect by CP in conjunction with caffeine appears to correlate well with the in vivo synergistic effect on cytogenetic damage caused by the combined CP plus caffeine treatment.

Nicotine and caffeine alter the effects of the LPS- primed mesenchymal stem cells on the co-cultured neutrophils.

PubMed

Abbasi, Ardeshir; Kukia, Nasim Rahmani; Froushani, Seyyed Meysam Abtahi; Hashemi, Seyed Mahmoud

2018-04-15

Mesenchymal stem cells (MSCs) express some of the nicotinic receptor subunits and adenosine receptors. The communication between tissue MSCs with neutrophils has been shown in previous studies. The aim of the present study is to determine the role of nicotine or caffeine on MSCs and its effects on neutrophils. After the isolation, MSCs were pulsed with LPS (10 ng/ml) for 1 h. Then, MSCs were incubated with different concentrations of caffeine (0.1, 0.5 and 1 mM) and or with different concentrations of nicotine (0.1, 0.5, and 1 μM) for 48 h. Afterwards, the medium was aspirated and the cells were used for co-culture experiment with neutrophil. The obtained data showed that LPS primed MSCs could decrease neutrophil vitality, whereas the treatment of MSCs with nicotine and/or especially a treatment with caffeine reverse this effect. Obtained data showed that when the LPS-primed MSCs were treated with nicotine or caffeine, the vitality of co-cultured neutrophils was significantly increased. The rate of the respiratory burst of neutrophils after co-culture by LPS-primed MSCs was decreased compared to the respiratory burst of neutrophil alone. Nicotine and/or caffeine treatment could reverse this reduction. Generally, these findings provide a new insight into understanding the anti-inflammatory and immunomodulatory effects of nicotine and caffeine. Copyright © 2018 Elsevier Inc. All rights reserved.

Caffeine strongly improves motility parameters of turkey spermatozoa with no effect on cell viability.

PubMed

Slanina, Tomáš; Miškeje, Michal; Tirpák, Filip; Błaszczyk, Martyna; Formicki, Grzegorz; Massányi, Peter

2018-03-01

The purpose of this study was to evaluate the impact of caffeine on turkey spermatozoa during in vitro incubation. Experimental samples were prepared by diluting the raw semen with nine different concentrations of caffeine - from 0.078125 mg/mL to 10 mg/mL. The individual motility parameters were evaluated by the Computer Assisted Semen Analyser (CASA) system, and the viability of spermatozoa was evaluated using eosin-nigrosin staining. Selected parameters were recorded at six time periods: 0, 1, 2, 3, 4 and 5 h at 5 °C and 41 °C. A significantly higher motility and progressive motility of spermatozoa (P < 0.01 and P < 0.001, respectively) was detected in the samples containing caffeine ranging from 0.15625 to 7.5 mg/mL as compared to the control sample at 5 °C. At an incubation temperature of 41 °C the positive effect of caffeine on motility parameters was observed only at the beginning of incubation (at times 0 and 1). The tested caffeine concentrations showed no significant effect on the viability of turkey spermatozoa at any time period of incubation. A higher percentage of dead spermatozoa was observed for incubation at 41 °C (from 5.96% to 11.1%) in comparison to 5 °C (from 1.62% to 5.79%). The results suggest that caffeine can be used as a suitable component of turkey semen extenders and has the potential to improve fertility.

Effect of caffeine on the ultraviolet light induction of SV40 virus from transformed hamster cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zamansky, G.B.; Kleinman, L.F.; Little, J.B.

1976-01-01

The effect of caffeine on the uv light induction of SV40 virus from two transformed hamster cell lines heterogeneous for the induction of infectious virus was studied. The amount of virus induced was significantly increased in both cell lines when exposure to uv light was followed by treatment with caffeine. Caffeine in the absence of uv irradiation did not stimulate virus induction, nor did it stimulate SV40 replication in a lytic infection. There was an apparent difference in the concentrations of caffeine which maximally stimulated SV40 virus induction in the two cell lines. This effect could not be explained bymore » differences in cell survival after exposure to uv light and caffeine. Since caffeine is known to cause the accumulation of gaps formed in DNA during postreplication repair of uv-irradiated rodent cells, our results support the hypothesis that the formation of gaps or breaks in DNA is an important early step in virus induction.« less

Caffeine: cognitive and physical performance enhancer or psychoactive drug?

PubMed

Cappelletti, Simone; Piacentino, Daria; Daria, Piacentino; Sani, Gabriele; Aromatario, Mariarosaria

2015-01-01

Caffeine use is increasing worldwide. The underlying motivations are mainly concentration and memory enhancement and physical performance improvement. Coffee and caffeine-containing products affect the cardiovascular system, with their positive inotropic and chronotropic effects, and the central nervous system, with their locomotor activity stimulation and anxiogenic-like effects. Thus, it is of interest to examine whether these effects could be detrimental for health. Furthermore, caffeine abuse and dependence are becoming more and more common and can lead to caffeine intoxication, which puts individuals at risk for premature and unnatural death. The present review summarizes the main findings concerning caffeine's mechanisms of action (focusing on adenosine antagonism, intracellular calcium mobilization, and phosphodiesterases inhibition), use, abuse, dependence, intoxication, and lethal effects. It also suggests that the concepts of toxic and lethal doses are relative, since doses below the toxic and/or lethal range may play a causal role in intoxication or death. This could be due to caffeine's interaction with other substances or to the individuals' preexisting metabolism alterations or diseases.

Consumption of an acute dose of caffeine reduces acquisition but not memory in the honey bee.

PubMed

Mustard, Julie A; Dews, Lauren; Brugato, Arlana; Dey, Kevin; Wright, Geraldine A

2012-06-15

Caffeine affects several molecules that are also involved in the processes underlying learning and memory such as cAMP and calcium. However, studies of caffeine's influence on learning and memory in mammals are often contradictory. Invertebrate model systems have provided valuable insight into the actions of many neuroactive compounds including ethanol and cocaine. We use the honey bee (Apis mellifera) to investigate how the ingestion of acute doses of caffeine before, during, and after conditioning influences performance in an appetitive olfactory learning and memory task. Consumption of caffeine doses of 0.01 M or greater during or prior to conditioning causes a significant reduction in response levels during acquisition. Although bees find the taste of caffeine to be aversive at high concentrations, the bitter taste does not explain the reduction in acquisition observed for bees fed caffeine before conditioning. While high doses of caffeine reduced performance during acquisition, the response levels of bees given caffeine were the same as those of the sucrose only control group in a recall test 24h after conditioning. In addition, caffeine administered after conditioning had no affect on recall. These results suggest that caffeine specifically affects performance during acquisition and not the processes involved in the formation of early long term memory. Copyright © 2012 Elsevier B.V. All rights reserved.

Caffeine Expectancy Questionnaire (CaffEQ): construction, psychometric properties, and associations with caffeine use, caffeine dependence, and other related variables.

PubMed

Huntley, Edward D; Juliano, Laura M

2012-09-01

Expectancies for drug effects predict drug initiation, use, cessation, and relapse, and may play a causal role in drug effects (i.e., placebo effects). Surprisingly little is known about expectancies for caffeine even though it is the most widely used psychoactive drug in the world. In a series of independent studies, the nature and scope of caffeine expectancies among caffeine consumers and nonconsumers were assessed, and a comprehensive and psychometrically sound Caffeine Expectancy Questionnaire (CaffEQ) was developed. After 2 preliminary studies, the CaffEQ was administered to 1,046 individuals from the general population along with other measures of interest (e.g., caffeine use history, anxiety). Exploratory factor analysis of the CaffEQ yielded a 7-factor solution. Subsequently, an independent sample of 665 individuals completed the CaffEQ and other measures, and a subset (n = 440) completed the CaffEQ again approximately 2 weeks later. Confirmatory factor analysis revealed good model fit, and test-retest reliability was very good. The frequency and quantity of caffeine use were associated with greater expectancies for withdrawal/dependence, energy/work enhancement, appetite suppression, social/mood enhancement, and physical performance enhancement and lower expectancies for anxiety/negative physical effects and sleep disturbance. Caffeine expectancies predicted various caffeine- associated features of substance dependence (e.g., use despite harm, withdrawal incidence and severity, perceived difficulty stopping use, tolerance). Expectancies for caffeine consumed via coffee were stronger than for caffeine consumed via soft drinks or tea. The CaffEQ should facilitate the advancement of our knowledge of caffeine and drug use in general. PsycINFO Database Record (c) 2012 APA, all rights reserved.

Alcohol and Caffeine: The Perfect Storm

PubMed Central

O'Brien, Mary Claire

2011-01-01

Although it is widely believed that caffeine antagonizes the intoxicating effects of alcohol, the molecular mechanisms underlying their interaction are incompletely understood. It is known that both caffeine and alcohol alter adenosine neurotransmission, but the relationship is complex, and may be dose dependent. In this article, we review the available literature on combining caffeine and alcohol. Ethical constraints prohibit laboratory studies that would mimic the high levels of alcohol intoxication achieved by many young people in real-world settings, with or without the addition of caffeine. We propose a possible neurochemical mechanism for the increase in alcohol consumption and alcohol-related consequences that have been observed in persons who simultaneously consume caffeine. Caffeine is a nonselective adenosine receptor antagonist. During acute alcohol intake, caffeine antagonizes the “unwanted” effects of alcohol by blocking the adenosine A1 receptors that mediate alcohol's somnogenic and ataxic effects. The A1 receptor–mediated “unwanted” anxiogenic effects of caffeine may be ameliorated by alcohol-induced increase in the extracellular concentration of adenosine. Moreover, by means of interactions between adenosine A2A and dopamine D2 receptors, caffeine-mediated blockade of adenosine A2A receptors can potentiate the effects of alcohol-induced dopamine release. Chronic alcohol intake decreases adenosine tone. Caffeine may provide a “treatment” for the withdrawal effects of alcohol by blocking the effects of upregulated A1 receptors. Finally, blockade of A2A receptors by caffeine may contribute to the reinforcing effects of alcohol. PMID:24761263

Does Caffeine Consumption Modify Cerebrospinal Fluid Amyloid-β Levels in Patients with Alzheimer's Disease?

PubMed

Travassos, Maria; Santana, Isabel; Baldeiras, Inês; Tsolaki, Magda; Gkatzima, Olymbia; Sermin, Genc; Yener, Görsev G; Simonsen, Anja; Hasselbalch, Steen G; Kapaki, Elisabeth; Mara, Bourbouli; Cunha, Rodrigo A; Agostinho, Paula; Blennow, Kaj; Zetterberg, Henrik; Mendes, Vera M; Manadas, Bruno; de Mendon, Alexandreça

2015-01-01

Caffeine may be protective against Alzheimer's disease (AD) by modulating amyloid-β (Aβ) metabolic pathways. The present work aimed to study a possible association of caffeine consumption with the cerebrospinal fluid (CSF) biomarkers, particularly Aβ. The study included 88 patients with AD or mild cognitive impairment. The consumption of caffeine and theobromine was evaluated using a validated food questionnaire. Quantification of caffeine and main active metabolites was performed with liquid chromatography coupled to tandem mass spectrometry. The levels of A(1-42), total tau, and phosphorylated tau in the CSF were determined using sandwich ELISA methods and other Aβ species, Aβ(X-38), Aβ(X-40), and Aβ(X-42), with the MSD Aβ Triplex assay. The concentration of caffeine was 0.79±1.15 μg/mL in the CSF and 1.20±1.88 μg/mL in the plasma. No correlation was found between caffeine consumption and Aβ42 in the CSF. However, a significant positive correlation was found between the concentrations of theobromine, both in the CSF and in the plasma, with Aβ42 in the CSF. Theobromine in the CSF was positively correlated with the levels of other xanthines in the CSF, but not in the plasma, suggesting that it may be formed by central metabolic pathways. In conclusion, caffeine consumption does not modify the levels of CSF biomarkers, and does not require to be controlled for when measuring CSF biomarkers in a clinical setting. Since theobromine is associated with a favorable Aβ profile in the CSF, the possibility that it might have a protective role in AD should be further investigated.

Does the presence of caffeine in the marine environment represent an environmental risk? A regional and global study.

PubMed

Dafouz, Raquel; Cáceres, Neus; Rodríguez-Gil, José Luis; Mastroianni, Nicola; López de Alda, Miren; Barceló, Damià; de Miguel, Ángel Gil; Valcárcel, Yolanda

2018-02-15

Caffeine is an emerging contaminant considered to be an indicator of human contamination that has been widely detected in various aquatic systems, especially in continental waters. Nevertheless, the extent of its possible environmental impact is yet to be determined. This study determined the presence of caffeine, and evaluated the environmental hazard posed by this substance, in the "Rías Gallegas", a series of costal inlets in north-west Spain which are of great ecological value and in which fishing and bivalve farming, are a significant source of income. Caffeine was found to be present at concentrations higher than the limit of quantification (LOQ=3.07ngL -1 ) in 15 of the 23 samples analysed, with the highest seawater concentration being 857ngL -1 (the highest measured in seawater in Spain). Six out of 22 seawater samples resulted in a hazard quotient (HQ) from chronic exposure higher than 1 with the highest being 17.14, indicating a high probability of adverse effects in the aquatic environment. Environmental Exposure Distributions (EEDs) generated from a literature review of caffeine levels reported previously in four out of the five continents, showed that 28% of all seawater samples, and 69% of all estuary water samples where caffeine has ever been measured resulted in HQ>1 for chronic exposure. Further studies into the potential adverse effects that may arise from exposure to caffeine in aquatic systems are still required. Indeed, the need to gain a more in-depth understanding of the long-term ecotoxicological effects of caffeine is essential to ensure the quality of our health and environment. Copyright © 2017 Elsevier B.V. All rights reserved.

Action of caffeine on x-irradiated HeLa cells. V. Identity of the sector of cells that expresses potentially lethal damage in G/sub 1/ and G/sub 2/

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beetham, K.L.; Tolmach, L.J.

1982-07-01

When HeLa S3 cells are irradiated in early G/sub 1/ with 4 Gy of 220-kV x rays and are then incubated in growth medium containing up to 5 mM caffeine, survival is reduced (as reported previously), reaching a concentration-dependent plateau. Cell killing presumably occurs as a result of the fixation of a portion of the potentially lethal damage the cells contain. These cells respond to continued treatment with caffeine at concentrations greater than 2 mM during S, but less so than during G/sub 1/. When they reach G/sub 2/ arrest, however, extensive cell killing again occurs (reported previously), presumably alsomore » the result of potentially lethal damage fixation. G/sub 1/-irradiated cultures that are treated with caffeine either continuously at a concentration in the range 1 to 5 mM, or at 10 mM for 8 hr and subsequently with the low concentration, achieve the same survival level in G/sub 2/, provided that the potentially lethal damage is not repaired during G/sub 1/ and S. Repair seems to be completely inhibited in the presence of 3 to 4 mM caffeine. The results indicate that fixation of potentially lethal damage occurs in the same sector of cells in G/sub 1/ and G/sub 2/, suggesting that the same cellular lesion gives rise to cell killing in the two phases.« less

Population pharmacokinetics of caffeine and its metabolites theobromine, paraxanthine and theophylline after inhalation in combination with diacetylmorphine.

PubMed

Zandvliet, Anthe S; Huitema, Alwin D R; de Jonge, Milly E; den Hoed, Rob; Sparidans, Rolf W; Hendriks, Vincent M; van den Brink, Wim; van Ree, Jan M; Beijnen, Jos H

2005-01-01

The stimulant effect of caffeine, as an additive in diacetylmorphine preparations for study purposes, may interfere with the pharmacodynamic effects of diacetylmorphine. In order to obtain insight into the pharmacology of caffeine after inhalation in heroin users, the pharmacokinetics of caffeine and its dimethylxanthine metabolites were studied. The objectives were to establish the population pharmacokinetics under these exceptional circumstances and to compare the results to published data regarding intravenous and oral administration in healthy volunteers. Diacetylmorphine preparations containing 100 mg of caffeine were used by 10 persons by inhalation. Plasma concentrations of caffeine, theobromine, paraxanthine and theophylline were measured by high performance liquid chromatography. Non-linear mixed effects modelling was used to estimate population pharmacokinetic parameters. The model was evaluated by the jack-knife procedure. Caffeine was rapidly and effectively absorbed after inhalation. Population pharmacokinetics of caffeine and its dimethylxanthine metabolites could adequately and simultaneously be described by a linear multi-compartment model. The volume of distribution for the central compartment was estimated to be 45.7 l and the apparent elimination rate constant of caffeine at 8 hr after inhalation was 0.150 hr(-1) for a typical individual. The bioavailability was approximately 60%. The presented model adequately describes the population pharmacokinetics of caffeine and its dimethylxanthine metabolites after inhalation of the caffeine sublimate of a 100 mg tablet. Validation proved the stability of the model. Pharmacokinetics of caffeine after inhalation and intravenous administration are to a large extent similar. The bioavailability of inhaled caffeine is approximately 60% in experienced smokers.

Load dependence of left ventricular contraction and relaxation. Effects of caffeine.

PubMed

Leite-Moreira, A F; Correia-Pinto, J; Gillebert, T C

1999-08-01

Load dependence of left ventricular (LV) contraction and relaxation was investigated at baseline and after alteration of intracellular calcium handling by caffeine. Afterload was increased by aortic clamp occlusions (n = 281) in anesthetized open-chest dogs (n = 7). Control and first heartbeat after the intervention were considered for analysis. Caffeine (50 mg/kg, iv) had no inotropic effect. The systolic LV pressure (LVP), developed in response to aortic occlusion, decreased as ejection proceeded and this pressure generating capacity was not affected by caffeine. Late-systolic aortic occlusions induced premature onset and accelerated rate of initial LVP fall at baseline and similarly after caffeine. Graded diastolic aortic occlusions induced systolic LVP elevations of various magnitudes. Smaller LVP elevations prolonged ejection and accelerated LVP fall, while larger elevations had opposite effects. The transition from acceleration to deceleration was observed at 83.1 +/- 1.1% of peak isovolumetric LVP at baseline and at lower loads, at 77.6 +/- 1.2%, after caffeine (p < 0.01). Isovolumetric heartbeats prolonged the time constant tau by 238 +/- 70% at baseline and only by 155 +/- 44% after caffeine (p < 0.01). The relaxation-systolic pressure relation, which describes afterload dependence of relaxation, was also modified by caffeine. Caffeine affected LV relaxation without altering contractility. As a consequence contraction-relaxation coupling was modified by caffeine. These results might help to understand load dependence of relaxation in conditions where intracellular calcium handling is altered.

Effects of caffeine on the inflammatory response induced by a 15-km run competition.

PubMed

Tauler, Pedro; Martínez, Sonia; Moreno, Carlos; Monjo, Marta; Martínez, Pau; Aguiló, Antoni

2013-07-01

The objective of this study is as follows: 1) to determine the effects of caffeine supplementation on the inflammatory response (IL-6 and IL-10 levels and leukocyte numbers) induced by a 15-km run competition and 2) to examine the effect of caffeine supplementation on the energetic metabolites as well as on the exercise-induced oxidative stress. A double-blinded study of supplementation with caffeine was performed. Athletes participating in the study (n = 33) completed a 15-km run competition. Before competition, athletes took 6 mg · kg(-1) body weight of caffeine (caffeine group, n = 17) or a placebo (placebo group, n = 16). Blood samples were taken before and after competition (immediately and after 2-h recovery). Leukocyte numbers were determined in blood. Concentrations of oxidative stress markers, antioxidants, interleukins (IL-6 and IL-10), caffeine, adrenaline, and energetic metabolites were measured in plasma or serum. Caffeine supplementation induced higher increases in circulating total leukocytes and neutrophils, with significant differences between groups after recovery. Adrenaline, glucose, and lactate levels increased after exercise, with higher increases in the caffeine group. Exercise induced significant increases in IL-6 and IL-10 plasma levels, with higher increases in the caffeine group. Caffeine supplementation induced higher increases in oxidative stress markers after the competition. Caffeine supplementation induced higher levels of IL-6 and IL-10 in response to exercise, enhancing the anti-inflammatory response. The caffeine-induced increase in adrenaline could be responsible for the higher increase in IL-6 levels, as well as for the increased lactate levels. Furthermore, caffeine seems to enhance oxidative stress induced by exercise.

Adolescent caffeine consumption increases adulthood anxiety-related behavior and modifies neuroendocrine signaling

PubMed Central

O’Neill, Casey E.; Newsom, Ryan J.; Stafford, Jacob; Scott, Talia; Archuleta, Solana; Levis, Sophia C.; Spencer, Robert L.; Campeau, Serge; Bachtell, Ryan K.

2016-01-01

Caffeine is a commonly used psychoactive substance and consumption by children and adolescents continues to rise. Here, we examine the lasting effects of adolescent caffeine consumption on anxiety-related behaviors and several neuroendocrine measures in adulthood. Adolescent male Sprague-Dawley rats consumed caffeine (0.3 g/L) for 28 consecutive days from postnatal day 28 (P28) to P55. Age-matched control rats consumed water. Behavioral testing for anxiety-related behavior began in adulthood (P62) 7 days after removal of caffeine. Adolescent caffeine consumption enhanced anxiety-related behavior in an open field, social interaction test, and elevated plus maze. Similar caffeine consumption in adult rats did not alter anxiety-related behavior after caffeine removal. Characterization of neuroendocrine measures was next assessed to determine whether the changes in anxiety were associated with modifications in the HPA axis. Blood plasma levels of corticosterone (CORT) were assessed throughout the caffeine consumption procedure in adolescent rats. Adolescent caffeine consumption elevated plasma CORT 24 h after initiation of caffeine consumption that normalized over the course of the 28-day consumption procedure. CORT levels were also elevated 24 h after caffeine removal and remained elevated for 7 days. Despite elevated basal CORT in adult rats that consumed caffeine during adolescence, the adrenocorticotropic hormone (ACTH) and CORT response to placement on an elevated pedestal (a mild stressor) was significantly blunted. Lastly, we assessed changes in basal and stress-induced c-fos and corticotropin-releasing factor (Crf) mRNA expression in brain tissue collected at 7 days withdrawal from adolescent caffeine. Adolescent caffeine consumption increased basal c-fos mRNA in the paraventricular nucleus of the hypothalamus. Adolescent caffeine consumption had no other effects on the basal or stress-induced c-fos mRNA changes. Caffeine consumption during adolescence increased basal Crf mRNA in the central nucleus of the amygdala, but no additional effects of stress or caffeine consumption were observed in other brain regions. Together these findings suggest that adolescent caffeine consumption may increase vulnerability to psychiatric disorders including anxiety-related disorders, and this vulnerability may result from dysregulation of the neuroendocrine stress response system. PMID:26874560

Caffeine, cognitive failures and health in a non-working community sample.

PubMed

Smith, Andrew P

2009-01-01

Most studies of the effects of caffeine on performance have been conducted in the laboratory and further information is required on the real-life effects of caffeine consumption on cognition. In addition, possible effects of caffeine consumption on a range of health outcomes should also be assessed in these studies to enable cost-benefit analyses to be conducted. Secondary analyses of a large epidemiological database (N = 3223 non-working participants, 57% female, with a mean age of 49.6 years, range 17-92 years) were conducted to examine associations between caffeine consumption (mean caffeine consumption was 140 mg/day, range 0-1800 mg) and cognitive failures (errors of memory, attention and action) in a non-working sample. Associations between caffeine consumption and physical and mental health problems were also examined. The study involved secondary analyses of a database formed by combining the Bristol Stress and Health at Work and Cardiff Health and Safety at Work studies. Associations between caffeine consumption and frequency of cognitive failures and health outcomes were examined in a sample of non-workers. After controlling for possible confounding factors significant associations between caffeine consumption and fewer cognitive failures were observed. Initial analyses suggested that many health variables were associated with regular level of caffeine consumption. However, most of the significant effects of caffeine disappeared when demographic and lifestyle factors were controlled for. Consumption of caffeine was, however, associated with a reduced risk of depression. These effects were also observed in separate analyses examining the source of the caffeine (coffee and tea). Overall, the results show that caffeine consumption may benefit cognitive functioning in a non-working population. This confirms earlier findings from working samples. This beneficial effect of caffeine was not associated with negative health consequences. Indeed, consumption of caffeine was found to be associated with a reduced risk of depression.

Caffeine increases the motivation to obtain non-drug reinforcers in rats

PubMed Central

Sheppard, A. Brianna; Gross, Skyler C.; Pavelka, Sarah A.; Hall, Melanie J.; Palmatier, Matthew I.

2012-01-01

BACKGROUND Caffeine is widely considered to be a reinforcer in humans, but this effect is difficult to measure in non-human animals. We hypothesized that caffeine may have dual reinforcing effects comparable to nicotine - limited primary reinforcing effects, but potent reinforcement enhancing effects. The present studies tested this hypothesis by investigating the effect of caffeine on responding for non-drug rewards. METHODS In two experiments, rats were shaped to respond on a progressive ratio (PR) schedule for sucrose solution (20% w/v; Experiment 1) or a fixed ratio 2 (FR2) schedule for a moderately reinforcing visual stimulus (VS; Experiment 2). Pretreatment with various doses of caffeine (0–50 mg/kg, intraperitoneal injection) were administered prior to tests over successive week days (M-F). In Experiment 1, acute administration of low-moderate caffeine doses (6.25–25 mg/kg) increased responding for sucrose under the PR schedule. This effect of caffeine declined over the initial 15 test days. In Experiment 2, only acute pretreatment with 12.5 mg/kg caffeine increased responding for the visual stimulus and complete tolerance to this effect of caffeine was observed over the 15 days of testing. In follow up tests we found that abstinence periods of 4 and 8 days resulted in incomplete recovery of the enhancing effects of caffeine. CONCLUSION The findings suggest that caffeine enhances the reinforcing effects of non-drug stimuli, but that the pharmacological profile of these effects may differ from other psychomotor stimulants. PMID:22336397

Chloride currents activated by caffeine in rat intestinal smooth muscle cells.

PubMed Central

Ohta, T; Ito, S; Nakazato, Y

1993-01-01

1. Current responses to caffeine in single smooth muscle cells isolated from rat intestine were studied with the whole-cell patch clamp technique. Intracellular calcium concentration, [Ca2+]i, was simultaneously monitored with fura-2 (0.1 mM) introduced into the cell through a patch pipette. 2. With a potassium-containing pipette solution, caffeine (10 mM) produced an outward current at a holding potential of 0 mV and an inward current at -60 mV, both of which were accompanied by parallel increases in [Ca2+]i. The outward current response disappeared after the removal of K+ from pipette solutions, indicating that caffeine activates a Ca(2+)-activated K+ conductance. 3. When NaCl was present in both pipette and external solutions as the major constituent, caffeine evoked an inward current at -60 mV simultaneously with a rise in [Ca2+]i. The reversal potential (Er) of this current was about 0 mV. 4. Substitution of Tris+ or choline+ for external Na+ did not alter the Er. When external Cl- was replaced by thiocyanate-, iodide- or glutamate-, the Er changed to respectively -55, -38 and +35 mV. 5. The current response to caffeine decreased with increasing concentration of EGTA in the pipette solution. The caffeine-induced current and the intracellular Ca2+ transient was still observed for a few minutes after exposure of the cells to Ca(2+)-free external solution containing 2 mM EGTA. Caffeine failed to produce an inward current and Ca2+ transient after treatment with extracellular ryanodine. 6. It is concluded that caffeine caused an increase in membrane Cl- conductance and in K+ conductance resulting from a rise in [Ca2+]i derived from ryanodine-sensitive intracellular Ca2+ stores in isolated smooth muscle cells of the rat intestine. PMID:8229831

Protonation of caffeine: A theoretical and experimental study

NASA Astrophysics Data System (ADS)

Bahrami, Hamed; Tabrizchi, Mahmoud; Farrokhpour, Hossein

2013-03-01

Protonation of caffeine was examined by ion mobility spectrometry equipped with two ionization sources, corona discharge (CD) and UV photoionization. Three peaks were observed in ion mobility spectrum by simultaneously running the two ionization sources. Experimental and theoretical evidence was collected to link the observed peaks to caffeine related ionic species. One peak was attributed to the M+ ion while the other two were assigned to different protonated isomers of caffeine. In the case of CD ionization source, it was observed that different sites of caffeine compete for protonation and their relative intensities, depends on the sample concentration as well as the nature of the reactant ions. The new concept of "internal proton affinity" (IPA) was defined to express the tendency of holding the added proton for each atom in a molecule.

A novel strategy for selection of allosteric ribozymes yields RiboReporter™ sensors for caffeine and aspartame

PubMed Central

Ferguson, Alicia; Boomer, Ryan M.; Kurz, Markus; Keene, Sara C.; Diener, John L.; Keefe, Anthony D.; Wilson, Charles; Cload, Sharon T.

2004-01-01

We have utilized in vitro selection technology to develop allosteric ribozyme sensors that are specific for the small molecule analytes caffeine or aspartame. Caffeine- or aspartame-responsive ribozymes were converted into fluorescence-based RiboReporter™ sensor systems that were able to detect caffeine or aspartame in solution over a concentration range from 0.5 to 5 mM. With read-times as short as 5 min, these caffeine- or aspartame-dependent ribozymes function as highly specific and facile molecular sensors. Interestingly, successful isolation of allosteric ribozymes for the analytes described here was enabled by a novel selection strategy that incorporated elements of both modular design and activity-based selection methods typically used for generation of catalytic nucleic acids. PMID:15026535

Aflatoxin in detannin coffee and tea and its destruction.

PubMed

Hasan, H A H

2002-05-01

The aflatoxins produced byAspergillus parasiticus var. globosus IMI 12090 in detannin-caffeinated coffee and black tea were five times more concentrated than in regular coffee and tea. The activity of caffeine and tannin on the fungus growth and aflatoxin production in liquid broth was tested at three levels: viz. 0.1, 0.3, and 0.6%. Tannin and caffeine induced 95% inhibition in aflatoxins at 0.3% and 0.6%, respectively. The antiaflatoxigenic properties of regular coffee and tea appear to be due to tannin, followed by caffeine. The roasting of contaminated coffee beans at 200 degrees C for 20 min is effective in the destruction of aflatoxins.

Effects of Morning Caffeine’ Ingestion on Mood States, Simple Reaction Time, and Short-Term Maximal Performance on Elite Judoists

PubMed Central

Souissi, Makram; Abedelmalek, Salma; Chtourou, Hamdi; Atheymen, Rim; Hakim, Ahmed; Sahnoun, Zouhair

2012-01-01

Purpose The purpose of the present study was to evaluate the ergogenic effect of caffeine ingestion on mood state, simple reaction time, and muscle power during the Wingate test recorded in the morning on elite Judoists. Methods Twelve elite judoists (age: 21.08 ± 1.16 years, body mass: 83.75 ± 20.2 kg, height: 1.76 ±6.57 m) participated in this study. Mood states, simple reaction time, and muscle power during the Wingate test were measured during two test sessions at 07:00 h and after placebo or caffeine ingestion (i.e. 5 mg/kg). Plasma concentrations of caffeine were measured before (T0) and 1-h after caffeine’ ingestion (T1) and after the Wingate test (T3). Results Our results revealed an increase of the anxiety and the vigor (P<0.01), a reduction of the simple reaction time (P<0.001) and an improvement of the peak and mean powers during the Wingate test. However, the fatigue index during this test was unaffected by the caffeine ingestion. In addition, plasma concentration of caffeine was significantly higher at T1 in comparison with T0. Conclusions In conclusion, the results of this study suggest that morning caffeine ingestion has ergogenic properties with the potential to benefit performance, increase anxiety and vigor, and decrease the simple reaction time. PMID:23012635

Induction of cytogenetic damage in human lymphocytes in vitro and of antineoplastic effects in Ehrlich ascites tumor cells in vivo treated by methotrexate, hyperthermia and/or caffeine.

PubMed

Maskaleris, T; Lialiaris, T; Triantaphyllidis, C

1998-12-03

The synergistic effect of methotrexate (at concentrations between 3. 1 and 100 nM) and its combinations with caffeine (618 microM) and/or hyperthermia (42 degreesC for 2 h) on the frequency of sister chromatid exchanges (SCEs), the proliferating rate index and the mitotic index in cultured human lymphocytes, was examined. Also, the in vivo antineoplastic effects of methotrexate (at a concentration of 0.45 microg/g body weight) and its combination with caffeine (120 microg/g body weight), both on the survival time and the increase of the weight of tumor of BALB/c mice inoculated with Ehrlich ascites tumor cells was examined in the present study. The results indicated that: (a) the triple combination of methotrexate, caffeine and hyperthermia synergistically increased the levels of SCEs and exerted cytostatic and cytotoxic action and (b) the combination of methotrexate and caffeine significantly increased the survival span of the mice inoculated with Ehrlich ascites tumor cells and reduced the increase of the weight of their tumors at rates higher than in the case of methotrexate by itself. It is suggested that the above triple combination (methotrexate plus caffeine plus hyperthermia) could achieve increased effectiveness of methotrexate, better therapy results, and could be successfully applied in the treatment of various types of cancer. Copyright 1998 Elsevier Science B.V.

Caffeine induces sustained apoptosis of human gastric cancer cells by activating the caspase-9/caspase-3 signalling pathway

PubMed Central

Liu, Hanyang; Zhou, Yan; Tang, Liming

2017-01-01

Caffeine is one of the most widely consumed substances found in beverages, and has demonstrated anticancer effects in several types of cancer. The present study aimed to examine the anticancer effects of caffeine on gastric cancer (GC) cells (MGC-803 and SGC-7901) in vitro, and to determine whether the apoptosis-related caspase-9/−3 pathway is associated with these effects. The sustained antiproliferative effects of caffeine on gastric cancer were also investigated. GC cell viability and proliferation were evaluated using cell counting and colony forming assays, following treatment with various concentrations of caffeine. Flow cytometry was performed to assess cell cycle dynamics and apoptosis. Western blot analysis was conducted to detect the activity of the caspase-9/−3 pathway. The results indicated that caffeine treatment significantly suppressed GC cell growth and viability and induced apoptosis by activating the caspase-9/−3 pathway. Furthermore, the anticancer effects of caffeine appeared to be sustained, as the caspase-9/−3 pathway remained active following caffeine withdrawal. In conclusion, caffeine may function as a sustained anticancer agent by activating the caspase-9/−3 pathway, which indicates that it may be useful as a therapeutic candidate in gastric cancer. PMID:28677810

Effects of Cola-Flavored Beverages and Caffeine on Streptococcus mutans Biofilm Formation and Metabolic Activity.

PubMed

Dotsey, Roger P; Moser, Elizabeth A S; Eckert, George J; Gregory, Richard L

To examine the effects of cola-flavored beverages and caffeine on growth and metabolism of Streptococcus mutans biofilm. This study was designed to determine if carbonated beverages or caffeine can increase S. mutans growth and biofilm formation and metabolic activity in vitro, potentially leading to increased S. mutans-associated cariogenicity in children that consume them. Six different cola-flavored products, plus pure caffeine, and pure high fructose corn syrup (HFCS), at different concentrations similar to those in the beverages were tested. A 16-hour culture of S. mutans was treated with different dilutions in bacteriological media. To test for the effect on biofilm formation, the biofilm was stained with crystal violet. The absorbance was determined to evaluate biofilm growth. Biofilm metabolic activity was measured based on biofilm having the ability to reduce XTT to a water-soluble orange compound. The inclusion of HFCS in the beverages, as well as pure HFCS, significantly enhanced bacterial biofilm formation and metabolic activity. Pure caffeine and the presence of caffeine in beverages did not significantly increase biofilm formation, but pure caffeine significantly increased metabolism, and Diet Coke had significantly greater metabolic activity than Caffeine-Free Diet Coke. HFCS increases both the biofilm formation and metabolism of S. mutans, and caffeine in some cases increases metabolism of S. mutans.

Improved 2000-meter rowing performance in competitive oarswomen after caffeine ingestion.

PubMed

Anderson, M E; Bruce, C R; Fraser, S F; Stepto, N K; Klein, R; Hopkins, W G; Hawley, J A

2000-12-01

Eight competitive oarswomen (age, 22 +/- 3 years; mass, 64.4 +/- 3.8 kg) performed three simulated 2,000-m time trials on a rowing ergometer. The trials, which were preceded by a 24-hour dietary and training control and 72 hours of caffeine abstinence, were conducted 1 hour after ingesting caffeine (6 or 9 mg á kg-1 body mass) or placebo. Plasma free fatty acid concentrations before exercise were higher with caffeine than placebo (0.67 +/- 0.34 vs. 0.72 +/- 0.36 vs. 0.30 +/- 0.10 mM for 6 and 9 mg á kg-1 caffeine and placebo, respectively; p <.05). Performance time improved 0.7% (95% confidence interval [CI] 0 to 1.5%) with 6 mg á kg-1 caffeine and 1. 3% (95% CI 0.5 to 2.0%) with 9 mg á kg-1 caffeine. The first 500 m of the 2,000 m was faster with the higher caffeine dose compared with placebo or the lower dose (1.53 +/- 0.52 vs.1.55 +/- 0.62 and 1. 56 +/- 0.43 min; p =.02). We concluded that caffeine produces a worthwhile enhancement of performance in a controlled laboratory setting, primarily by improving the first 500 m of a 2,000-m row.

Theacrine (1,3,7,9-tetramethyluric acid) synthesis in leaves of a Chinese tea, kucha (Camellia assamica var. kucha).

PubMed

Zheng, Xin-Qiang; Ye, Chuang-Xing; Kato, Misako; Crozier, Alan; Ashihara, Hiroshi

2002-05-01

Theacrine (1,3,7,9-tetramethyluric acid) and caffeine were the major purine alkaloids in the leaves of an unusual Chinese tea known as kucha (Camellia assamica var. kucha). Endogenous levels of theacrine and caffeine in expanding buds and young leaves were ca. 2.8 and 0.6-2.7% of the dry wt, respectively, but the concentrations were lower in the mature leaves. Radioactivity from S-adenosyl-L-[methyl-14C]methionine was incorporated into theacrine as well as theobromine and caffeine by leaf disks of kucha, indicating that S-adenosyl-L-methionine acts as the methyl donor not only for caffeine biosynthesis but also for theacrine production. [8-14C]Caffeine was converted to theacrine by kucha leaves with highest incorporation occurring in expanding buds. When [8-14C]adenosine, the most effective purine precursor for caffeine biosynthesis in tea (Camellia sinensis), was incubated with young kucha leaves for 24 h, up to 1% of total radioactivity was recovered in theacrine. However, pulse-chase experiments with [8-14C]adenosine demonstrated much more extensive incorporation of label into caffeine than theacrine, possibly because of dilution of [14C]caffeine produced by the large endogenous caffeine pool. These results indicate that in kucha leaves theacrine is synthesized from caffeine in what is probably a three-step pathway with 1,3,7-methyluric acid acting an intermediate. This is a first demonstration that theacrine is synthesized from adenosine via caffeine.

Multidrug resistance transporters Snq2p and Pdr5p mediate caffeine efflux in Saccharomyces cerevisiae.

PubMed

Tsujimoto, Yoshiyuki; Shimizu, Yoshihiro; Otake, Kazuya; Nakamura, Tatsuya; Okada, Ryutaro; Miyazaki, Toshitaka; Watanabe, Kunihiko

2015-01-01

SNQ2 was identified as a caffeine-resistance gene by screening a genomic library of Saccharomyces cerevisiae in a multicopy vector YEp24. SNQ2 encodes an ATP-binding cassette transporter and is highly homologous to PDR5. Multicopy of PDR5 also conferred resistance to caffeine, while its resistance was smaller than that of SNQ2. Residual caffeine contents were analyzed after transiently exposing cells to caffeine. The ratios of caffeine contents were 21.3 ± 8.8% (YEp24-SNQ2) and 81.9 ± 8.7% (YEp24-PDR5) relative to control (YEp24, 100%). In addition, multicopies of SNQ2 or PDR5 conferred resistance to rhodamine 6G (R6G), which was widely used as a substrate for transport assay. R6G was exported by both transporters, and their efflux activities were inhibited by caffeine with half-maximal inhibitory concentrations of 5.3 ± 1.9 (YEp24-SNQ2) and 17.2 ± 9.6 mM (YEp24-PDR5). These results demonstrate that Snq2p is a more functional transporter of caffeine than Pdr5p in yeast cells.

Effects of caffeine on radiation-induced phenomena associated with cell- cycle traverse of mammalian cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walters, R.A.; Gurley, L.R.; Tobby, R.A.

1974-02-01

Caffeine induced a state of G/sub 1/ arrest when added to an exponentially growing culture of Chinese hamster cells (line CHO). In addition to its effect on cell-cycle traverse, caffeine ameliorated a number of the responses of cells to ionizing radiation. The duration of the division delay period following x-irradiation of caffeine-treated cells was reduced, and the magnitude of reduction was dependent on caffeine concentration. Cells irradiated during the DNA synthetic phase in the presence of caffeine were delayed less in their exit from S, measured autoradiographically, and the radiation-induced reduction of radioactive thymidine incorporation into DNA was lessened. Cellsmore » synchronized by isoleucine deprivation, while being generally less sensitive to the effects of ionizing radiation than mitotically synchronized cells, were equally responsive to the effects of caffeine. The x-rayinduced reduction of phosphorylation of lysine-rich histone F1 was less in caffeine-treated cells than in untreated cells. Finally, survival after irradiation was only slightly reduced in caffeinetreated cells. A possible role of cyclic AMP in cell-cycle traverse of irradiated cells is discussed. (auth)« less

The Determination of Caffeine in Coffee: Sense or Nonsense?

ERIC Educational Resources Information Center

Beckers, Jozef L.

2004-01-01

The presence of caffeine in coffee is determined by the use of separation devices and UV-vis spectrophotometry. The results indicate that the use of various analytical tools helps to perceive the higher concentration values obtained through UV-vis spectrophotometry than with separation methods.

Improvements in Concentration, Working Memory, and Sustained Attention Following Consumption of a Natural Citicoline-Caffeine Beverage

PubMed Central

Bruce, Steven E.; Werner, Kimberly B.; Preston, Brittany F.; Baker, Laurie M.

2015-01-01

The present study examined the neurocognitive and electrophysiological effects of a citicoline-caffeine-based beverage in 60 healthy adult participants enrolled in a randomized, double-blind, placebo-controlled trial. Measures of electrical brain activity using electroencephalogram (EEG) and neuropsychological measures examining attention, concentration, and reaction time were administered. Compared to placebo, participants receiving the citicoline-caffeine beverage exhibited significantly faster maze learning times and reaction times on a continuous performance test, fewer errors in a Go No-Go task, and better accuracy on a measure of information processing speed. EEG results examining P450 event related potentials (ERP) revealed that participants receiving the citicoline-caffeine beverage exhibited higher P450 amplitudes than controls, suggesting an increase in sustained attention. Overall, these findings suggest that the beverage significantly improved sustained attention, cognitive effort, and reaction times in healthy adults. Evidence of improved P450 amplitude indicates a general improvement in the ability to accommodate new and relevant information within working memory and overall enhanced brain activation. PMID:25046515

Energy drink consumption and impact on caffeine risk.

PubMed

Thomson, Barbara M; Campbell, Donald M; Cressey, Peter; Egan, Ursula; Horn, Beverley

2014-01-01

The impact of caffeine from energy drinks occurs against a background exposure from naturally occurring caffeine (coffee, tea, cocoa and foods containing these ingredients) and caffeinated beverages (kola-type soft drinks). Background caffeine exposure, excluding energy drinks, was assessed for six New Zealand population groups aged 15 years and over (n = 4503) by combining concentration data for 53 caffeine-containing foods with consumption information from the 2008/09 New Zealand Adult Nutrition Survey (ANS). Caffeine exposure for those who consumed energy drinks (n = 138) was similarly assessed, with inclusion of energy drinks. Forty-seven energy drink products were identified on the New Zealand market in 2010. Product volumes ranged from 30 to 600 ml per unit, resulting in exposures of 10-300 mg caffeine per retail unit consumed. A small percentage, 3.1%, of New Zealanders reported consuming energy drinks, with most energy drink consumers (110/138) drinking one serving per 24 h. The maximum number of energy drinks consumed per 24 h was 14 (total caffeine of 390 mg). A high degree of brand loyalty was evident. Since only a minor proportion of New Zealanders reported consuming energy drinks, a greater number of New Zealanders exceeded a potentially adverse effect level (AEL) of 3 mg kg(-1) bw day(-1) for caffeine from caffeine-containing foods than from energy drinks. Energy drink consumption is not a risk at a population level because of the low prevalence of consumption. At an individual level, however, teenagers, adults (20-64 years) and females (16-44 years) were more likely to exceed the AEL by consuming energy drinks in combination with caffeine-containing foods.

Intake of caffeine from all sources and reasons for use by college students.

PubMed

Mahoney, Caroline R; Giles, Grace E; Marriott, Bernadette P; Judelson, Daniel A; Glickman, Ellen L; Geiselman, Paula J; Lieberman, Harris R

2018-04-10

Caffeine intake in a convenience sample of U.S. college students (N = 1248) was surveyed at five geographically-dispersed United States (U.S.) universities. Intake from coffee, tea, soft drinks, energy drinks, gums, and medications was assessed. Associations between caffeine intake and demographic variables including sex, age, race/ethnicity, family income, general health, exercise, weight variables and tobacco use were examined. Reasons for use of caffeine-containing products were assessed. Caffeine, in any form, was consumed by 92% of students in the past year. Mean daily caffeine consumption for all students, including non-consumers, was 159 mg/d with a mean intake of 173 mg/d among caffeine users. Coffee was the main source of caffeine intake in male (120 mg/d) and female (111 mg/d) consumers. Male and female students consumed 53 vs. 30 mg/d of caffeine in energy drinks, respectively, and 28% consumed energy drinks with alcohol on at least one occasion. Students provided multiple reasons for caffeine use including: to feel awake (79%); enjoy the taste (68%); the social aspects of consumption (39%); improve concentration (31%); increase physical energy (27%); improve mood (18%); and alleviate stress (9%). As in the general U.S. population, coffee is the primary source of caffeine intake among the college students surveyed. Energy drinks provide less than half of total daily caffeine intake but more than among the general population. Students, especially women, consume somewhat more caffeine than the general population of individuals aged 19-30 y but less than individuals aged 31-50 y. Published by Elsevier Ltd.

Caffeine expectancy: instrument development in the Rasch measurement framework.

PubMed

Heinz, Adrienne J; Kassel, Jon D; Smith, Everett V

2009-09-01

Although caffeine is the most widely consumed psychoactive drug in the world, the mechanisms associated with consumption are not well understood. Nonetheless, outcome expectancies for caffeine use are thought to underlie caffeine's reinforcing properties. To date, however, there is no available, sufficient measure by which to assess caffeine expectancy. Therefore, the current study sought to develop such a measure employing Rasch measurement models. Unlike traditional measurement development techniques, Rasch analyses afford dynamic and interactive control of the analysis process and generate helpful information to guide instrument construction. A 5-stage developmental process is described, ultimately yielding a 37-item Caffeine Expectancy Questionnaire (CEQ) comprised of 4 factors representing "withdrawal symptoms," "positive effects," "acute negative effects," and "mood effects." Initial evaluation of the CEQ yielded sufficient evidence for various aspects of validity. Although additional research with more heterogeneous samples is required to further assess the measure's reliability and validity, the CEQ demonstrates potential with regard to its utility in experimental laboratory research and clinical application. 2009 APA, all rights reserved.

The potentiation by caffeine of X-ray damage to cultured human skin fibroblasts from normal subjects and ataxia-telangiectasia patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Furcinitti, P.S.

1983-07-01

Caffeine was found to potentiate X-ray-induced killing of human diploid fibroblasts from a normal subject and an ataxia-telangiectasia (AT) patient when it was present at 2 mM concentration for 30 to 66 hr postirradiation. The dose-modifying factor for caffeine-treated normal cells had an average value of 1.26 +/- 0.13 which did not vary significantly with treatment time or X-ray dose. The dose-modifying factor for caffeine-treated AT cells was 1.12 +/- 0.12 at 30 hr, rose to 1.66 +/- 0.17 at 41 hr, and decreased to 1.31 +/- 0.13 at 66 hr. Thus no clear difference was observed between these twomore » cell strains' susceptibility to postirradiation caffeine treatment.« less

Potentiation by caffeine of x-ray damage to cultured human skin fibroblasts from normal subjects and ataxia-telangiectasia patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Furcinitti, P.S.

1983-07-01

Caffeine was found to potentiate x-ray-induced killing of human diploid fibroblasts from a normal subject and an ataxia-telangiectasia (AT) patient when it was present at 2 mM concentration for 30 to 66 h postirradiation. The dose-modifying factor for caffeine-treated normal cells had an average value of 1.26 +- 0.13 which did not vary significantly with treatment time or x-ray dose. The dose-modifying factor for caffeine-treated AT cells was 1.12 +- 0.12 at 30 h, rose to 1.66 +- 0.17 at 41 h, and decreased to 1.31 +- 0.13 at 66 h. Thus no clear difference was observed between these twomore » cell strains' susceptibility to postirradiation caffeine treatment.« less

Caffeine and suicide: a systematic review.

PubMed

Silva, Adriana Cardoso; de Oliveira Ribeiro, Natalia Pinho; de Mello Schier, Alexandre Rafael; Pereira, Valeska Martinho; Vilarim, Marina Machado; Pessoa, Tamires Marinho; Arias-Carrión, Oscar; Machado, Sergio; Nardi, Antonio Egidio

2014-01-01

Suicide is considered a deliberate act initiated and concluded by a person with full knowledge or expectation of a fatal result, and one of the main symptoms of depression. An individual's conscious and excessive ingestion of a damaging substance is also considered to be an attempted suicide. Despite limited knowledge of caffeine abuse, deaths from overdose of caffeine have been reported in the literature. Thus, this study aims to review the existing literature on caffeine consumption and suicide attempts and deaths, investigating the relation between caffeine consumption and suicide attempts and deaths. We found 24 studies that discuss the relationship between caffeine and suicide. The findings revealed that, despite being an addictive substance and potentially fatal in higher doses, caffeine was still a rare factor in a number of studies concerning its relation with suicide attempts and death. The majority of the research found in this study was of the case study type. Furthermore, the majority of studies focus on the assistance offered to the victim and the procedures undertaken to control the bodily damage created. The existing studies indicate the substance may act as either a direct or an indirect agent in suicide. Therefore, a better understanding of how caffeine may be linked to suicide is crucial for its prevention.

Caffeine consumption and self-assessed stress, anxiety, and depression in secondary school children.

PubMed

Richards, Gareth; Smith, Andrew

2015-12-01

Previous research suggests that effects of caffeine on behaviour are positive unless one is investigating sensitive groups or ingestion of large amounts. Children are a potentially sensitive subgroup, and especially so considering the high levels of caffeine currently found in energy drinks. The present study used data from the Cornish Academies Project to investigate associations between caffeine (both its total consumption, and that derived separately from energy drinks, cola, tea, and coffee) and single-item measures of stress, anxiety, and depression, in a large cohort of secondary school children from the South West of England. After adjusting for additional dietary, demographic, and lifestyle covariates, positive associations between total weekly caffeine intake and anxiety and depression remained significant, and the effects differed between males and females. Initially, effects were also observed in relation to caffeine consumed specifically from coffee. However, coffee was found to be the major contributor to high overall caffeine intake, providing explanation as to why effects relating to this source were also apparent. Findings from the current study increase our knowledge regarding associations between caffeine intake and stress, anxiety, and depression in secondary school children, though the cross-sectional nature of the research made it impossible to infer causality. © The Author(s) 2015.

Caffeine consumption and self-assessed stress, anxiety, and depression in secondary school children

PubMed Central

Richards, Gareth; Smith, Andrew

2015-01-01

Previous research suggests that effects of caffeine on behaviour are positive unless one is investigating sensitive groups or ingestion of large amounts. Children are a potentially sensitive subgroup, and especially so considering the high levels of caffeine currently found in energy drinks. The present study used data from the Cornish Academies Project to investigate associations between caffeine (both its total consumption, and that derived separately from energy drinks, cola, tea, and coffee) and single-item measures of stress, anxiety, and depression, in a large cohort of secondary school children from the South West of England. After adjusting for additional dietary, demographic, and lifestyle covariates, positive associations between total weekly caffeine intake and anxiety and depression remained significant, and the effects differed between males and females. Initially, effects were also observed in relation to caffeine consumed specifically from coffee. However, coffee was found to be the major contributor to high overall caffeine intake, providing explanation as to why effects relating to this source were also apparent. Findings from the current study increase our knowledge regarding associations between caffeine intake and stress, anxiety, and depression in secondary school children, though the cross-sectional nature of the research made it impossible to infer causality. PMID:26508718

Reconnaissance of Pharmaceutical Chemicals in Urban Streams of the Tualatin River Basin, Oregon, 2002

USGS Publications Warehouse

Rounds, Stewart A.; Doyle, Micelis C.; Edwards, Patrick M.; Furlong, Edward T.

2009-01-01

A reconnaissance of pharmaceutical chemicals in urban streams of the Tualatin River basin was conducted in July 2002 in an effort to better understand the occurrence and distribution of such compounds, and to determine whether they might be useful indicators of human-related stream contamination. Of the 21 pharmaceutical chemicals and metabolites tested, only 6 (acetaminophen, caffeine, carbamazepine, codeine, cotinine, and sulfamethoxazole) were detected in filtered stream samples from 10 sites. The concentrations of most of the detected compounds were relatively low (less than 0.05 microgram per liter). The most frequently detected compounds were cotinine (a nicotine metabolite, 8 of 10 samples) and caffeine (a stimulant, 7 of 10 samples). More compounds were detected in urban stream samples than in samples from forested or agricultural drainages. Filtered water samples also were collected from four locations within an advanced wastewater treatment facility to quantify the relative amounts of these chemicals in a municipal waste stream and to determine the degree to which those chemicals are removed by treatment processes. Fifteen pharmaceutical chemicals or metabolites were detected in wastewater treatment facility influent, with concentrations far exceeding those measured in streams. Only five of those compounds, however, were detected in the treated effluent (carbamazepine, cotinine, ibuprofen, metformin, and sulfamethoxazole) and most of those were at concentrations less than 0.2 microgram per liter. The target pharmaceutical chemicals and metabolites showed limited potential for use as tracers of specific types of human-related contamination in Tualatin River basin streams because of widespread sources (caffeine, for example) or extremely low concentrations. Caffeine and cotinine are likely to be good indicators of sources that can occur in urban areas, such as sewage spills or leaks or the widespread use and careless disposal of tobacco products and caffeine-containing beverages. Neither compound, however, is likely to be a good tracer for a specific source unless that source is large. The presence of 1,7-dimethylxanthine (a caffeine metabolite) concurrently with caffeine might indicate the presence of untreated wastewater; in contrast, the absence of the metabolite might help rule out that source. Acetaminophen might make a good tracer for untreated wastewater because of its common usage, high concentration in raw wastewater, and effective removal via treatment. Carbamazepine and sulfamethoxazole have the potential to be good indicators of treated wastewater because of their incomplete removal in treatment facilities. Some of these pharmaceutical chemicals, either singly or in combination, might prove useful as tracers of contamination after further study.

Electrochemical Determination of Caffeine Content in Ethiopian Coffee Samples Using Lignin Modified Glassy Carbon Electrode.

PubMed

Amare, Meareg; Aklog, Senait

2017-01-01

Lignin film was deposited at the surface of glassy carbon electrode potentiostatically. In contrast to the unmodified glassy carbon electrode, an oxidative peak with an improved current and overpotential for caffeine at modified electrode showed catalytic activity of the modifier towards oxidation of caffeine. Linear dependence of peak current on caffeine concentration in the range 6 × 10 -6 to 100 × 10 -6  mol L -1 with determination coefficient and method detection limit (LoD = 3 s/slope) of 0.99925 and 8.37 × 10 -7  mol L -1 , respectively, supplemented by recovery results of 93.79-102.17% validated the developed method. An attempt was made to determine the caffeine content of aqueous coffee extracts of Ethiopian coffees grown in four coffee cultivating localities (Wonbera, Wolega, Finoteselam, and Zegie) and hence to evaluate the correlation between users preference and caffeine content. In agreement with reported works, caffeine contents (w/w%) of 0.164 in Wonbera coffee; 0.134 in Wolega coffee; 0.097 in Finoteselam coffee; and 0.089 in Zegie coffee were detected confirming the applicability of the developed method for determination of caffeine in a complex matrix environment. The result indicated that users' highest preference for Wonbera and least preference for Zegie cultivated coffees are in agreement with the caffeine content.

The influence of caffeine ingestion on strength and power performance in female team-sport players.

PubMed

Ali, Ajmol; O'Donnell, Jemma; Foskett, Andrew; Rutherfurd-Markwick, Kay

2016-01-01

The aim of this study was to examine the influence of caffeine supplementation on knee flexor and knee extensor strength before, during and after intermittent running exercise in female team-sport players taking oral contraceptive steroids (OCS). Ten healthy females (24 ± 4 years; 59.7 ± 3.5 kg; undertaking 2-6 training sessions per week) taking low-dose monophasic oral contraceptives of the same hormonal composition took part in a randomised, double-blind, placebo-controlled crossover-design trial. Sixty minutes following the ingestion of a capsule containing 6 mg∙kg -1 body mass anhydrous caffeine or artificial sweetener (placebo), participants completed a 90-min intermittent treadmill-running protocol. Isometric strength performance and eccentric and concentric strength and power of the knee flexors and knee extensors (using isokinetic dynamometer), as well as countermovement jump (CMJ), was measured before, during and after the exercise protocol, as well as ~12 h post-exercise. Blood samples were taken before, during and post-exercise to measure glucose, insulin and free fatty acids (FFA). Caffeine supplementation significantly increased eccentric strength of the knee flexors ( P  < 0.05) and eccentric power of both the knee flexors ( P  < 0.05) and extensors ( P  < 0.05). However, there was no effect on isometric or concentric parameters, or CMJ performance. FFA was elevated with caffeine supplementation over time ( P  < 0.05) while levels of glucose and insulin were not affected by caffeine intake. Caffeine supplementation increased eccentric strength and power in female team-sport players taking OCS both during an intermittent running protocol and the following morning.

Characteristics of caffeine intoxication-related death in Tokyo, Japan, between 2008 and 2013.

PubMed

Suzuki, Hideto; Tanifuji, Takanobu; Abe, Nobuyuki; Maeda, Masako; Kato, Yukihisa; Shibata, Mikiyoshi; Fukunaga, Tatsushige

2014-10-01

Caffeine is widely available in beverages and over-the-counter products; however, in large doses, it can lead to lethal arrhythmia. This study aims to clarify the characteristics of caffeine intoxication-related deaths in Tokyo, Japan. Among the 4754 forensic autopsy cases between 2008 and 2013 in which a toxicological investigation was performed, cases in which the blood concentration of caffeine exceeded toxic levels (15 μg/ml) were selected (N = 22). We examined subjects' ages, medical histories, direct/underlying causes of death, and manner of death. We also assessed concurrent drug substance detection and identified the origin of the caffeine. More than 60% of the subjects were between the ages of 20 and 49 years (n = 14, 63.6%). Sixteen cases (72.7%) showed a history of psychiatric diseases such as depression and sleep disorders. The underlying cause of death for all cases except two was caffeine intoxication, and manner of death was classified as undetermined (n = 11), accidental (n = 7), suicide (n = 2), or others (n = 2). Toxicological analysis revealed the presence of ingredients common to analgesics/cold remedies in 12 cases (54.5%). The origin of the caffeine was identified in 11 cases (50.0%); the proportion of identification was significantly lower among the cases in which analgesic/cold remedy ingredients were not detected (20.0%). Caffeine intoxication-related deaths mainly occurred in young and middle-aged persons with common psychiatric diseases. Psychiatrists should take note of caffeine dependence while diagnosing common psychiatric symptoms. In half of the cases, the origin of the caffeine was unidentified; nevertheless, dietary sources or over-the-counter drugs containing caffeine were suspected. As it becomes easier to obtain caffeinated products, continuous monitoring of the number of deaths from caffeine intoxication, in addition to detailed investigations of the caffeine's origin, will be necessary.

Stability of ochratoxin A (OTA) during processing and decaffeination in commercial roasted coffee beans.

PubMed

Nehad, E A; Farag, M M; Kawther, M S; Abdel-Samed, A K M; Naguib, K

2005-08-01

The fate of ochratoxin A (OTA) during the processing of artificially contaminated green coffee beans, the effect of decaffeination on the production of OTA in green and roasted coffee beans, and the effect of caffeine on the growth and OTA production by Aspergillus ochraceus were studied. The data indicated that the roasting, milling and decoction (brewing and Turkish coffee making) processes caused different percentage reductions in OTA. Decaffeinated samples showed a significantly higher concentration of OTA production than the caffeinated ones. A significantly higher percentage of OTA was reduced when the decaffeination process was performed before roasting treatment. Caffeine at 1.0 and 2.0% concentrations completely prevented OTA production and completely inhibited A. ochraceus growth in YES medium after 3-21 days.

The quantal nature of calcium release to caffeine in single smooth muscle cells results from activation of the sarcoplasmic reticulum Ca(2+)-ATPase.

PubMed

Steenbergen, J M; Fay, F S

1996-01-26

Calcium release from intracellular stores occurs in a graded manner in response to increasing concentrations of either inositol 1,4,5-trisphosphate or caffeine. To investigate the mechanism responsible for this quantal release phenomenon, [Ca2+] changes inside intracellular stores in isolated single smooth muscle cells were monitored with mag-fura 2. Following permeabilization with saponin or alpha-toxin the dye, loaded via its acetoxymethyl ester, was predominantly trapped in the sarcoplasmic reticulum (SR). Low caffeine concentrations in the absence of ATP induced only partial Ca2+ release; however, after inhibiting the calcium pump with thapsigargin the same stimulus released twice as much Ca2+. When the SR Ca(2+)-ATPase was rendered non-functional by depleting its "ATP pool," submaximal caffeine doses almost fully emptied the stores of Ca2+. We conclude that quantal release of Ca2+ in response to caffeine in these smooth muscle cells is largely due to the activity of the SR Ca(2+)-ATPase, which appears to return a portion of the released Ca2+ back to the SR, even in the absence of ATP. Apparently the SR Ca(2+)-ATPase is fueled by ATP, which is either compartmentalized or bound to the SR.

Effects of theobromine and caffeine on mood and vigilance.

PubMed

Judelson, Daniel A; Preston, Amy G; Miller, Debra L; Muñoz, Colleen X; Kellogg, Mark D; Lieberman, Harris R

2013-08-01

Like caffeine, theobromine crosses the blood-brain barrier and binds to adenosine receptors, suggesting it might share caffeine's beneficial effects on mood and vigilance. Therefore, the purpose of this study was to assess the effect of theobromine doses commonly found in foods on mood and vigilance parameters sensitive to caffeine. Caffeine was tested as a positive control. Twenty-four men (age, 23 [3] years) completed 6 double-blind trials during which they consumed experimental beverages, assessed their mood using standardized self-report questionnaires, and completed a 2-hour visual vigilance task. Three experimental doses (100, 200, and 400 mg theobromine) were delivered in a cocoa-based beverage; 3 matched control treatments (0 mg theobromine, 400 mg theobromine, and 100 mg caffeine) were delivered in a non-cocoa beverage. Mean salivary concentrations of theobromine exhibited significant dose-dependent differences (400 mg trials > 200 mg trial > 100 mg trial > 0 mg trials; P < 0.005). At every dose tested, theobromine failed to consistently affect mood state or vigilance (P > 0.05), but 100-mg caffeine significantly decreased lethargy/fatigue and increased vigor (P = 0.006 and 0.011, respectively). These findings indicate theobromine does not influence mood and vigilance when administered in nutritionally relevant doses, despite sharing many of caffeine's structural characteristics.

Caffeine Reduces Reaction Time and Improves Performance in Simulated-Contest of Taekwondo

PubMed Central

Santos, Victor G. F.; Santos, Vander R. F.; Felippe, Leandro J. C.; Almeida, Jose W.; Bertuzzi, Rômulo; Kiss, Maria A. P. D. M.; Lima-Silva, Adriano E.

2014-01-01

The aim of this study was to investigate the effects of caffeine on reaction time during a specific taekwondo task and athletic performance during a simulated taekwondo contest. Ten taekwondo athletes ingested either 5 mg·kg−1 body mass caffeine or placebo and performed two combats (spaced apart by 20 min). The reaction-time test (five kicks “Bandal Tchagui”) was performed immediately prior to the first combat and immediately after the first and second combats. Caffeine improved reaction time (from 0.42 ± 0.05 to 0.37 ± 0.07 s) only prior to the first combat (P = 0.004). During the first combat, break times during the first two rounds were shorter in caffeine ingestion, followed by higher plasma lactate concentrations compared with placebo (P = 0.029 and 0.014, respectively). During the second combat, skipping-time was reduced, and relative attack times and attack/skipping ratio was increased following ingestion of caffeine during the first two rounds (all P < 0.05). Caffeine resulted in no change in combat intensity parameters between the first and second combat (all P > 0.05), but combat intensity was decreased following placebo (all P < 0.05). In conclusion, caffeine reduced reaction time in non-fatigued conditions and delayed fatigue during successive taekwondo combats. PMID:24518826

Effects of coffee/caffeine on brain health and disease: What should I tell my patients?

PubMed

Nehlig, Astrid

2016-04-01

Over the last decade, Food Regulation Authorities have concluded that coffee/caffeine consumption is not harmful if consumed at levels of 200 mg in one sitting (around 2½ cups of coffee) or 400 mg daily (around 5 cups of coffee). In addition, caffeine has many positive actions on the brain. It can increase alertness and well-being, help concentration, improve mood and limit depression. Caffeine may disturb sleep, but only in sensitive individuals. It may raise anxiety in a small subset of particularly sensitive people. Caffeine does not seem to lead to dependence, although a minority of people experience withdrawal symptoms. Caffeine can potentiate the effect of regular analgesic drugs in headache and migraine. Lifelong coffee/caffeine consumption has been associated with prevention of cognitive decline, and reduced risk of developing stroke, Parkinson's disease and Alzheimer's disease. Its consumption does not seem to influence seizure occurrence. Thus, daily coffee and caffeine intake can be part of a healthy balanced diet; its consumption does not need to be stopped in elderly people. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The Effects of Caffeine Supplementation on Physiological Responses to Submaximal Exercise in Endurance-Trained Men.

PubMed

Glaister, Mark; Williams, Benjamin Henley; Muniz-Pumares, Daniel; Balsalobre-Fernández, Carlos; Foley, Paul

2016-01-01

The aim of this study was to evaluate the effects of caffeine on physiological responses to submaximal exercise, with a focus on blood lactate concentration ([BLa]). Using a randomised, single-blind, crossover design; 16 endurance-trained, male cyclists (age: 38 ± 8 years; height: 1.80 ± 0.05 m; body mass: 76.6 ± 7.8 kg; [Formula: see text]: 4.3 ± 0.6 L∙min-1) completed four trials on an electromagnetically-braked cycle ergometer. Each trial consisted of a six-stage incremental test (3 minute stages) followed by 30 minutes of passive recovery. One hour before trials 2-4, participants ingested a capsule containing 5 mg∙kg-1 of either caffeine or placebo (maltodextrin). Trials 2 and 3 were designed to evaluate the effects of caffeine on various physiological responses during exercise and recovery. In contrast, Trial 4 was designed to evaluate the effects of caffeine on [BLa] during passive recovery from an end-exercise concentration of 4 mmol∙L-1. Relative to placebo, caffeine increased [BLa] during exercise, independent of exercise intensity (mean difference: 0.33 ± 0.41 mmol∙L-1; 95% likely range: 0.11 to 0.55 mmol∙L-1), but did not affect the time-course of [BLa] during recovery (p = 0.604). Caffeine reduced ratings of perceived exertion (mean difference: 0.5 ± 0.7; 95% likely range: 0.1 to 0.9) and heart rate (mean difference: 3.6 ± 4.2 b∙min-1; 95% likely range: 1.3 to 5.8 b∙min-1) during exercise, with the effect on the latter dissipating as exercise intensity increased. Supplement × exercise intensity interactions were observed for respiratory exchange ratio (p = 0.004) and minute ventilation (p = 0.034). The results of the present study illustrate the clear, though often subtle, effects of caffeine on physiological responses to submaximal exercise. Researchers should be aware of these responses, particularly when evaluating the physiological effects of various experimental interventions.

Caffeine-containing energy drink improves sprint performance during an international rugby sevens competition.

PubMed

Del Coso, Juan; Portillo, Javier; Muñoz, Gloria; Abián-Vicén, Javier; Gonzalez-Millán, Cristina; Muñoz-Guerra, Jesús

2013-06-01

The aim of this study was to determine the effects of a caffeine-containing energy drink on physical performance during a rugby sevens competition. A second purpose was to investigate the post-competition urinary caffeine concentration derived from the energy drink intake. On two non-consecutive days of a friendly tournament, 16 women from the Spanish National rugby sevens Team (mean age and body mass = 23 ± 2 years and 66 ± 7 kg) ingested 3 mg of caffeine per kg of body mass in the form of an energy drink (Fure(®), ProEnergetics) or the same drink without caffeine (placebo). After 60 min for caffeine absorption, participants performed a 15-s maximal jump test, a 6 × 30 m sprint test, and then played three rugby sevens games against another national team. Individual running pace and instantaneous speed during the games were assessed using global positioning satellite (GPS) devices. Urine samples were obtained pre and post-competition. In comparison to the placebo, the ingestion of the energy drink increased muscle power output during the jump series (23.5 ± 10.1 vs. 25.6 ± 11.8 kW, P = 0.05), running pace during the games (87.5 ± 8.3 vs. 95.4 ± 12.7 m/min, P < 0.05), and pace at sprint velocity (4.6 ± 3.3 vs. 6.1 ± 3.4 m/min, P < 0.05). However, the energy drink did not affect maximal running speed during the repeated sprint test (25.0 ± 1.5 vs. 25.0 ± 1.7 km/h). The ingestion of the energy drink resulted in a higher post-competition urine caffeine concentration than the placebo (3.3 ± 0.7 vs. 0.2 ± 0.1 μg/mL; P < 0.05). In summary, 3 mg/kg of caffeine in the form of a commercially available energy drink considerably enhanced physical performance during a women's rugby sevens competition.

Adolescent intake of caffeinated energy drinks does not affect adult alcohol consumption in C57BL/6 and BALB/c mice.

PubMed

Robins, Meridith T; DeFriel, Julia N; van Rijn, Richard M

2016-08-01

The rise in marketing and mass consumption of energy drink products by adolescents poses a largely unknown risk on adolescent development and drug reward. Yet, with increasing reports of acute health issues present in young adults who ingest large quantities of energy drinks alone or in combination with alcohol, the need to elucidate these potential risks is pressing. Energy drinks contain high levels of caffeine and sucrose; therefore, exposure to energy drinks may lead to changes in drug-related behaviors since caffeine and sucrose consumption activates similar brain pathways engaged by substances of abuse. With a recent study observing that adolescent caffeine consumption increased cocaine sensitivity, we sought to investigate how prolonged energy drink exposure in adolescence alters alcohol use and preference in adulthood. To do so, we utilized three different energy drink exposure paradigms and two strains of male mice (C57BL/6 and BALB/c) to monitor the effect of caffeine exposure via energy drinks in adolescence on adult alcohol intake. These paradigms included two models of volitional consumption of energy drinks or energy drink-like substances and one model of forced consumption of sucrose solutions with different caffeine concentrations. Following adolescent exposure to these solutions, alcohol intake was monitored in a limited-access, two-bottle choice between water and increasing concentrations of alcohol during adulthood. In none of the three models or two strains of mice did we observe that adolescent 'energy drink' consumption or exposure was correlated with changes in adult alcohol intake or preference. While our current preclinical results suggest that exposure to large amounts of caffeine does not alter future alcohol intake, differences in caffeine metabolism between mice and humans need to be considered before translating these results to humans. Copyright © 2016 Elsevier Inc. All rights reserved.

Polymer modified glassy carbon electrode for the electrochemical determination of caffeine in coffee.

PubMed

Amare, Meareg; Admassie, Shimelis

2012-05-15

4-Amino-3-hydroxynaphthalene sulfonic acid (AHNSA) was electropolymerized on a glassy carbon electrode. The deposited film showed electrocatalytic activity towards the oxidation of caffeine. The polymer-modified electrode showed high sensitivity, selectivity and stability in the determination of caffeine in coffee. The peak current increased linearly with the concentration of caffeine in the range of 6 × 10(-8) to 4 × 10(-5) mol L(-1), with a detection limit of 1.37 × 10(-7) mol L(-1) (LoD = 3δ/slope). Analysis of caffeine in coffee was affected neither by sample matrices nor by structurally similar compounds. Recoveries ranging between 93.75 ± 2.32 and 100.75 ± 3.32 were achieved from coffee extracts indicating the applicability of the developed method for real sample analyses. Copyright © 2012 Elsevier B.V. All rights reserved.

Serum caffeine and paraxanthine concentrations and menstrual cycle function: correlations with beverage intakes and associations with race, reproductive hormones, and anovulation in the BioCycle Study.

PubMed

Schliep, Karen C; Schisterman, Enrique F; Wactawski-Wende, Jean; Perkins, Neil J; Radin, Rose G; Zarek, Shvetha M; Mitchell, Emily M; Sjaarda, Lindsey A; Mumford, Sunni L

2016-07-01

Clinicians often recommend limiting caffeine intake while attempting to conceive; however, few studies have evaluated the associations between caffeine exposure and menstrual cycle function, and we are aware of no previous studies assessing biological dose via well-timed serum measurements. We assessed the relation between caffeine and its metabolites and reproductive hormones in a healthy premenopausal cohort and evaluated potential effect modification by race. Participants (n = 259) were followed for ≤2 menstrual cycles and provided fasting blood specimens ≤8 times/cycle. Linear mixed models were used to estimate associations between serum caffeine biomarkers and geometric mean reproductive hormones, whereas Poisson regression was used to assess risk of sporadic anovulation. The highest compared with the lowest serum caffeine tertile was associated with lower total testosterone [27.9 ng/dL (95% CI: 26.7, 29.0 ng/dL) compared with 29.1 ng/dL (95% CI: 27.9, 30.3 ng/dL), respectively] and free testosterone [0.178 ng/mL (95% CI: 0.171, 0.185 ng/dL) compared with 0.186 ng/mL (95% CI: 0.179, 0.194 ng/dL), respectively] after adjustment for age, race, percentage of body fat, daily vigorous exercise, perceived stress, depression, dietary factors, and alcohol intake. The highest tertiles compared with the lowest tertiles of caffeine and paraxanthine were also associated with reduced risk of anovulation [adjusted RRs (aRRs): 0.39 (95% CI: 0.18, 0.87) and 0.40 (95% CI: 0.18, 0.87), respectively]. Additional adjustment for self-reported coffee intake did not alter the reproductive hormone findings and only slightly attenuated the results for serum caffeine and paraxanthine and anovulation. Although reductions in the concentrations of total testosterone and free testosterone and decreased risk of anovulation were greatest in Asian women, there was no indication of effect modification by race. Caffeine intake, irrespective of the beverage source, may be associated with reduced testosterone and improved menstrual cycle function in healthy premenopausal women. © 2016 American Society for Nutrition.

Serum caffeine and paraxanthine concentrations and menstrual cycle function: correlations with beverage intakes and associations with race, reproductive hormones, and anovulation in the BioCycle Study12

PubMed Central

Schisterman, Enrique F; Wactawski-Wende, Jean; Perkins, Neil J; Radin, Rose G; Zarek, Shvetha M; Mitchell, Emily M; Sjaarda, Lindsey A; Mumford, Sunni L

2016-01-01

Background: Clinicians often recommend limiting caffeine intake while attempting to conceive; however, few studies have evaluated the associations between caffeine exposure and menstrual cycle function, and we are aware of no previous studies assessing biological dose via well-timed serum measurements. Objectives: We assessed the relation between caffeine and its metabolites and reproductive hormones in a healthy premenopausal cohort and evaluated potential effect modification by race. Design: Participants (n = 259) were followed for ≤2 menstrual cycles and provided fasting blood specimens ≤8 times/cycle. Linear mixed models were used to estimate associations between serum caffeine biomarkers and geometric mean reproductive hormones, whereas Poisson regression was used to assess risk of sporadic anovulation. Results: The highest compared with the lowest serum caffeine tertile was associated with lower total testosterone [27.9 ng/dL (95% CI: 26.7, 29.0 ng/dL) compared with 29.1 ng/dL (95% CI: 27.9, 30.3 ng/dL), respectively] and free testosterone [0.178 ng/mL (95% CI: 0.171, 0.185 ng/dL) compared with 0.186 ng/mL (95% CI: 0.179, 0.194 ng/dL), respectively] after adjustment for age, race, percentage of body fat, daily vigorous exercise, perceived stress, depression, dietary factors, and alcohol intake. The highest tertiles compared with the lowest tertiles of caffeine and paraxanthine were also associated with reduced risk of anovulation [adjusted RRs (aRRs): 0.39 (95% CI: 0.18, 0.87) and 0.40 (95% CI: 0.18, 0.87), respectively]. Additional adjustment for self-reported coffee intake did not alter the reproductive hormone findings and only slightly attenuated the results for serum caffeine and paraxanthine and anovulation. Although reductions in the concentrations of total testosterone and free testosterone and decreased risk of anovulation were greatest in Asian women, there was no indication of effect modification by race. Conclusion: Caffeine intake, irrespective of the beverage source, may be associated with reduced testosterone and improved menstrual cycle function in healthy premenopausal women. PMID:27225433

Early Caffeine and Weaning from Mechanical Ventilation in Preterm Infants: A Randomized, Placebo-Controlled Trial.

PubMed

Amaro, Cynthia M; Bello, Jose A; Jain, Deepak; Ramnath, Alexandra; D'Ugard, Carmen; Vanbuskirk, Silvia; Bancalari, Eduardo; Claure, Nelson

2018-05-01

To evaluate in a randomized, double-blind, placebo-controlled trial the effect of early caffeine on the age of first successful extubation in preterm infants. Preterm infants born at 23-30 weeks of gestation requiring mechanical ventilation in the first 5 postnatal days were randomized to receive a 20 mg/kg loading dose followed by 5 mg/kg/day of caffeine or placebo until considered ready for extubation. The placebo group received a blinded loading dose of caffeine before extubation. Infants were randomized to receive caffeine (n = 41) or placebo (n = 42). Age at first successful extubation did not differ between early caffeine (median, 24 days; IQR, 10-41 days) and control groups (median, 20 days; IQR, 9-43 days; P = .7). An interim analysis at 75% enrollment showed a trend toward higher mortality in 1 of the groups and the data safety and monitoring board recommended stopping the trial. Unblinded analysis revealed mortality did not differ significantly between the early caffeine (9 [22%]) and control groups (5 [12%]; P = .22). Early initiation of caffeine in this group of premature infants did not reduce the age of first successful extubation. A nonsignificant trend toward higher mortality in the early caffeine group led to a cautious decision to stop the trial. These findings suggest caution with early use of caffeine in mechanically ventilated preterm infants until more efficacy and safety data become available. ClinicalTrials.gov: NCT01751724. Copyright © 2018 Elsevier Inc. All rights reserved.

Coffee Ingestion Suppresses Hyperglycemia in Streptozotocin-Induced Diabetic Mice.

PubMed

Kobayashi, Misato; Kurata, Takao; Hamana, Yoshiki; Hiramitsu, Masanori; Inoue, Takashi; Murai, Atsushi; Horio, Fumihiko

2017-01-01

Coffee consumption reduces the risk of type 2 diabetes in humans, but the mechanism remains unclear. In this study, we investigated the effect of coffee on pancreatic β-cells in the induction of diabetes by streptozotocin (STZ) treatment in mice. We examined the effect of coffee, caffeine, or decaffeinated coffee ingestion on STZ-induced hyperglycemia. After STZ injection in Exp. 1 and 2, serum glucose concentration and water intake in coffee ingestion (Coffee group) tended to be lowered or was significantly lowered compared to those in water ingestion (Water group) instead of coffee. In Exp. 1, the values for water intake and serum glucose concentration in caffeine ingestion (Caffeine group) were similar to those in the Water group. In Exp. 2, serum glucose concentrations in the decaffeinated coffee ingestion (Decaf group) tended to be lower than those in the Water group. Pancreatic insulin contents tended to be higher in the Coffee and Decaf groups than in the Water group (Exp. 1 and 2). In Exp. 3, subsequently, we showed that coffee ingestion also suppressed the deterioration of hyperglycemia in diabetic mice which had been already injected with STZ. This study showed that coffee ingestion prevented the development of STZ-induced diabetes and suppressed hyperglycemia in STZ-diabetic mice. Caffeine or decaffeinated coffee ingestion did not significantly suppress STZ-induced hyperglycemia. These results suggest that the combination of caffeine and other components of decaffeinated coffee are needed for the preventive effect on pancreatic β-cell destruction. Coffee ingestion may contribute to the maintenance of pancreatic insulin contents.

Effects of caffeine on performance and mood: withdrawal reversal is the most plausible explanation.

PubMed

James, Jack E; Rogers, Peter J

2005-10-01

Although it is widely believed that caffeine can enhance human performance and mood, the validity of this belief has been questioned, giving rise to debate. The central question is whether superior performance and mood after caffeine represent net benefits, or whether differences between caffeine and control conditions are due to reversal of adverse withdrawal effects. To provide a focussed review of relevant experimental studies with the aim of clarifying current understanding regarding the effects of caffeine on human performance and mood. To avoid the shortcomings of standard placebo-controlled studies, which are ambiguous due to failure to control for the confounding influence of withdrawal reversal, three main experimental approaches have been employed: studies that compare consumers and low/non-consumers, pre-treatment and ad lib consumption studies, and long-term withdrawal studies. Of the three approaches, only long-term withdrawal studies are capable of unambiguously revealing the net effects of caffeine. Overall, there is little evidence of caffeine having beneficial effects on performance or mood under conditions of long-term caffeine use vs abstinence. Although modest acute effects may occur following initial use, tolerance to these effects appears to develop in the context of habitual use of the drug. Appropriately controlled studies show that the effects of caffeine on performance and mood, widely perceived to be net beneficial psychostimulant effects, are almost wholly attributable to reversal of adverse withdrawal effects associated with short periods of abstinence from the drug.

Methylated liquor treatment process in caffeine production

NASA Astrophysics Data System (ADS)

Zhou, Junbo; Yang, Mingyang; Huang, Wenjia; Cui, Shenglu; Gao, Liping

2018-02-01

The caffeine production process produces a large amount of sodium methyl sulphate in the methylated mother liquor. In order to recycle this part of ingredient, we use the mother liquid of Shijiazhuang Xin Nuowei Pharmaceutical Co., Ltd. as the object of study, the use of “nanofiltration (NF) - Dish Type Reverse Osmosis (DTRO) “combination of membrane technology for desalination and concentration. The experimental results show that the concentration of sodium sulfate in the nanofiltration solution is 0.37 g • L -1, the rejection rate is 98%, and the concentration of sodium methyl sulfate in DTRO concentrated solution is 453.80 g • L -1, which meets the requirements of the enterprise.

Action of caffeine on x-irradiated HeLa cells. III. enhancement of x-ray-induced killing during G/sub 2/ arrest

DOE Office of Scientific and Technical Information (OSTI.GOV)

Busse, P.M.; Bose, S.K.; Jones, R.W.

1978-11-01

The ability of caffeine to enhance the expression of potentially lethal x-ray damage in HeLa S3 cells was examined as a function of the age of the cells in the generation cycle. Synchronous populations were irradiated at different times after mitotic collection and treated for various intervals with 1 mM caffeiene, which causes negligible killing of unirradiated cells. The response was thereby determined as a function of cell age at both the time of irradiation and the time of exposure to caffeine. The amount of cell killing depends strongly on when in the cycle caffeine is present and only weaklymore » on when the cells are irradiated. If cells are irradiated in early G/sub 1/, caffeine treatment enhances killing for 2 to 3 hr. No additional enhancement is observed until 16 to 17 hr postcollection, corresponding to G/sub 2/; here they enter a second period of much greater sensitivity. Similarly, fluorodeoxyuridine resynchronized cells irradiated during S and treated with caffeine suffer no enhanced killing until they pass into this sensitive phase in G/sub 2/, approximately 7 hr after release from the fluorodeoxyuridine block. The sensitive period appears to coincide with G/sub 2/ arrest. The rate and extent of killing during this period are dependent upon the x-ray dose and the caffeine concentration. In the absence of caffeine, cells irradiated in G/sub 1/ lose sensitivity to caffeine in about 9 hr; they do so faster in G/sub 2/. It is concluded that the potentially lethal x-ray damage expressed on treatment with caffeine is retained for many hours in the presence of caffeine and is maximally manifested by G/sub 2/-arrested cells.« less

Improvements on neuromuscular performance with caffeine ingestion depend on the time-of-day.

PubMed

Mora-Rodríguez, Ricardo; Pallarés, Jesús G; López-Gullón, José María; López-Samanes, Álvaro; Fernández-Elías, Valentín E; Ortega, Juan F

2015-05-01

To determine whether the ergogenic effects of caffeine ingestion on neuromuscular performance are similar when ingestion takes place in the morning and in the afternoon. Double blind, cross-over, randomized, placebo controlled design. Thirteen resistance-trained males carried out bench press and full squat exercises against four incremental loads (25%, 50%, 75% and 90% 1RM), at maximal velocity. Trials took place 60 min after ingesting either 6 mg kg(-1) of caffeine or placebo. Two trials took place in the morning (AMPLAC and AMCAFF) and two in the afternoon (PMPLAC and PMCAFF), all separated by 36-48 h. Tympanic temperature, plasma caffeine concentration and side-effects were measured. Plasma caffeine increased similarly during AMCAFF and PMCAFF. Tympanic temperature was lower in the mornings without caffeine effects (36.7±0.4 vs. 37.0±0.5°C for AM vs. PM; p<0.05). AMCAFF increased propulsive velocity above AMPLAC to levels similar to those found in the PM trials for the 25%, 50%, 75% 1RM loads in the SQ exercise (5.4-8.1%; p<0.05). However, in the PM trials, caffeine ingestion did not improve propulsive velocity at any load during BP or SQ. The negative side effects of caffeine were more prevalent in the afternoon trials (13 vs. 26%). The ingestion of a moderate dose of caffeine counteracts the muscle contraction velocity declines observed in the morning against a wide range of loads. Caffeine effects are more evident in the lower body musculature. Evening caffeine ingestion not only has little effect on neuromuscular performance, but increases the rate of negative side-effects reported. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Influence of menthol on caffeine disposition and pharmacodynamics in healthy female volunteers.

PubMed

Gelal, Ayse; Guven, Hulya; Balkan, Dilara; Artok, Levent; Benowitz, Neal L

2003-09-01

The present study was undertaken to determine whether a single oral dose of menthol affects the metabolism of caffeine, a cytochrome P(450) 1A2 (CYP1A2) substrate, and pharmacological responses to caffeine in people. Eleven healthy female subjects participated in a randomized, double-blind, two-way crossover study, comparing the kinetics and effects of a single oral dose of caffeine (200 mg) in coffee taken together with a single oral dose of menthol (100 mg) or placebo capsules. Serum caffeine concentrations and cardiovascular and subjective parameters were measured throughout the study. Co-administration of menthol resulted in an increase of caffeine t(max) values from 43.6+/-20.6 min (mean+/-SD) to 76.4+/-28.0 min ( P<0.05). The C(max) values of caffeine were lower in the menthol phase than in the placebo phase, but this effect was not statistically significant ( P=0.06). (AUC)(0-24), (AUC)(0- infinity ), terminal half-life and oral clearance were not affected by menthol. Only nine subjects' cardiovascular data were included in the analysis because of technical problems during the measurements. After caffeine, heart rate decreased in both treatment phases. The maximum decrease in heart rate was less in the menthol phase (-8.9+/-3.9 beats/min) than in the placebo phase (-13.1+/-2.1 beats/min) ( P=0.024). There were no statistically significant differences in systolic and diastolic blood pressures between the two treatments. We conclude that a single oral dose of pure menthol (100 mg) delays caffeine absorption and blunts the heart-rate slowing effect of caffeine, but does not affect caffeine metabolism. The possibility that menthol slows the absorption of other drugs should be considered.

A risk-benefit assessment of paracetamol (acetaminophen) combined with caffeine.

PubMed

Palmer, Hazel; Graham, Garry; Williams, Kenneth; Day, Richard

2010-06-01

To determine the risk: benefit of paracetamol combined with caffeine in the short-term management of acute pain conditions. Database searches were conducted to identify double-blind trials comparing paracetamol/caffeine with paracetamol alone (benefit analysis) and any data pertaining to hepatotoxicity of paracetamol when combined with caffeine (risk analysis). Paracetamol/caffeine (1,000 mg/130 mg) vs paracetamol (1,000 mg) alone. Assessment of benefit has been derived by meta-analysis. Information on the pain condition and number of patients studied, dosing regimen, study design and analgesic outcome measures (total pain relief scores) was extracted and dichotomous outcomes were obtained by calculating the number of patients in each treatment group who achieved at least 50% of the maximum total pain relief score. Assessment of risk has been made by appraisal of the literature. Eight studies from four papers provided sufficient quantitative data for satisfactory meta-analysis. The relative benefit (of achieving at least 50% pain relief) of paracetamol/caffeine vs paracetamol alone was 1.12 (95% Confidence Interval 1.05-1.19) across a number of acute pain states (dysmenorrhoea, headache, post-partum pain, and dental pain). Review of the effects of the combination of paracetamol and caffeine on the liver revealed no compelling data to suggest a clinically meaningful increase in hepatotoxicity with use of paracetamol/caffeine combinations. Paracetamol/caffeine (1,000 mg/130 mg) is effective and safe for use in acute management of pain. The hepatotoxicity of overdoses of paracetamol results from its oxidative metabolism, caffeine does not produce any increase in oxidative metabolism of therapeutic concentrations of paracetamol.

Effects of caffeine on endurance capacity and psychological state in young females and males exercising in the heat.

PubMed

Suvi, Silva; Timpmann, Saima; Tamm, Maria; Aedma, Martin; Kreegipuu, Kairi; Ööpik, Vahur

2017-01-01

Acute caffeine ingestion is considered effective in improving endurance capacity and psychological state. However, current knowledge is based on the findings of studies that have been conducted on male subjects mainly in temperate environmental conditions, but some physiological and psychological effects of caffeine differ between the sexes. The purpose of this study was to compare the physical performance and psychological effects of caffeine in young women and men exercising in the heat. Thirteen male and 10 female students completed 2 constant-load walks (60% of thermoneutral peak oxygen consumption on a treadmill until volitional exhaustion) in a hot-dry environment (air temperature, 42 °C; relative humidity, 20%) after caffeine (6 mg·kg -1 ) and placebo (wheat flour) ingestion in a double-blind, randomly assigned, crossover manner. Caffeine, compared with placebo, induced greater increases (p < 0.05) in heart rate (HR) and blood lactate concentrations in both males and females but had no impact on rectal or skin temperatures or on walking time to exhaustion in subjects of either gender. Caffeine decreased (p < 0.05) ratings of perceived exertion and fatigue in males, but not in females. In females, but not in males, a stronger belief that they had been administered caffeine was associated with a shorter time to exhaustion. In conclusion, acute caffeine ingestion increases HR and blood lactate levels during exercise in the heat, but it has no impact on thermoregulation or endurance capacity in either gender. Under exercise-heat stress, caffeine reduces ratings of perceived exertion and fatigue in males but not in females.

Foetal response to maternal coffee intake: role of habitual versus non-habitual caffeine consumption.

PubMed

Mulder, E J H; Tegaldo, L; Bruschettini, P; Visser, G H A

2010-11-01

Little is known about the effect on the human foetus of long-term and acute exposure to caffeine. We studied the organisation of foetal sleep-wake states in 13 healthy near-term foetuses over a wide range of maternal plasma caffeine concentrations (0-13 μg/mL) reflecting normal lifestyle conditions (day 0) and again following intake of two cups of regular coffee (~300 mg of caffeine) intermitted by 50 h of abstinence (day 2; acute effects). On either day, 2 h simultaneous recordings were made of foetal heart rate, general-, eye-, and breathing-movements. The recordings were analysed for the presence of each of four foetal behavioural states: quiet- and active-sleep, quiet- and active-wakefulness. There was a linear relationship between maternal caffeine content and the incidence of foetal general movements during active sleep on day 0 (R = 0.74; P < 0.02). After coffee loading on day 2, foetuses of non- or low-caffeine consumers showed increases in active wakefulness (P < 0.001), general movements (P < 0.05) and heart rate variation (P < 0.01) but lower basal heart rate (P < 0.01) compared with their day 0 values. The changes in foetal heart rate (variation) and behaviour occurred between 90 and 180 min post-consumption. In contrast, foetuses of habitual caffeine consumers remained unaffected suggestive of foetal tolerance to caffeine. The results indicate differential performance between foetuses regularly exposed to caffeine and those caffeine-naive, both under normal maternal lifestyle conditions and in response to maternal coffee ingestion.

Effect of caffeine on superior mesenteric artery blood flow velocities in preterm neonates.

PubMed

Abdel Wahed, Mohamed A; Issa, Hanan M; Khafagy, Soha M; Abdel Raouf, Shaimaa M

2017-09-22

To investigate the effect of caffeine infusion on superior mesenteric artery (SMA) blood flow velocities (BFV) in preterm infants. Prospective observational study on 38 preterm neonates 28-33 +6 weeks gestation, who developed apnea on their first day of life, and caffeine citrate infusion was initiated at a loading dose of 20 mg/kg, followed by a maintenance dose of 5-10 mg/kg/day. Duplex ultrasound measurements of SMA BFV were recorded: peak systolic velocity (PSV), end diastolic velocity (EDV) and resistive index (RI), at 15 min before, 1-, 2- and 6-h after caffeine loading dose, and 2 h after two maintenance doses. There was a significant reduction in PSV 1-h (p = .008), a significant decrease in EDV 1- and 2-h (p = .000 and p = .005, respectively) and a significant increase in RI 1- and 2-h (p = .003 and p = .005, respectively) following caffeine loading dose, as compared to values before caffeine infusion. No significant effect of caffeine maintenance doses on SMA BFV was observed (p > .05). Blood flow in SMA is significantly reduced after caffeine citrate infusion at a loading dose of 20 mg/kg. This effect continues for at least 2 h. Meanwhile, SMA BFV seems not affected by maintenance doses.

The influence of recrystallized caffeine on water-swellable polymethacrylate mucoadhesive buccal films.

PubMed

Morales, Javier O; Su, Rong; McConville, Jason T

2013-06-01

The aim of this work was to investigate the influence of particles on the properties of polymethacrylate films intended for buccal delivery. A solvent casting method was used with Eudragit RS and RL (ERS and ERL, respectively) as film-forming rate-controlling polymers, with caffeine as a water-soluble model drug. The physicochemical properties of the model films for a series of formulations with increasing concentrations of caffeine were determined in terms of morphology, mechanical and mucoadhesive properties, drug content uniformity, and drug release and associated kinetics. Typically regarded as non-mucoadhesive polymers, ERS and mainly ERL, were found to be good mucoadhesives, with ERL01 exhibiting a work of mucoadhesion (WoA) of 118.9 μJ, which was about five to six times higher than that observed for commonly used mucoadhesives such as Carbopol(®) 974P (C974P, 23.9 μJ) and polycarbophil (PCP, 17.4 μJ). The mucoadhesive force for ERL01 was found to be significantly lower yet comparable to C974P and PCP films (211.1 vs. 329.7 and 301.1 mN, respectively). Inspection of cross-sections of the films indicated that increasing the concentration of caffeine was correlated with the appearance of recrystallized agglomerates. In conclusion, caffeine agglomerates had detrimental effects in terms of mucoadhesion, mechanical properties, uniformity, and drug release at large particle sizes. ERL series of films exhibited very rapid release of caffeine while ERS series showed controlled release. Analysis of release profiles revealed that kinetics changed from a diffusion controlled to a first-order release mechanism.

Caffeine inhibits gene conversion by displacing Rad51 from ssDNA

PubMed Central

Tsabar, Michael; Mason, Jennifer M.; Chan, Yuen-Ling; Bishop, Douglas K.; Haber, James E.

2015-01-01

Efficient repair of chromosomal double-strand breaks (DSBs) by homologous recombination relies on the formation of a Rad51 recombinase filament that forms on single-stranded DNA (ssDNA) created at DSB ends. This filament facilitates the search for a homologous donor sequence and promotes strand invasion. Recently caffeine treatment has been shown to prevent gene targeting in mammalian cells by increasing non-productive Rad51 interactions between the DSB and random regions of the genome. Here we show that caffeine treatment prevents gene conversion in yeast, independently of its inhibition of the Mec1ATR/Tel1ATM-dependent DNA damage response or caffeine's inhibition of 5′ to 3′ resection of DSB ends. Caffeine treatment results in a dosage-dependent eviction of Rad51 from ssDNA. Gene conversion is impaired even at low concentrations of caffeine, where there is no discernible dismantling of the Rad51 filament. Loss of the Rad51 filament integrity is independent of Srs2's Rad51 filament dismantling activity or Rad51's ATPase activity and does not depend on non-specific Rad51 binding to undamaged double-stranded DNA. Caffeine treatment had similar effects on irradiated HeLa cells, promoting loss of previously assembled Rad51 foci. We conclude that caffeine treatment can disrupt gene conversion by disrupting Rad51 filaments. PMID:26019181

Reversible neuronal and muscular toxicity of caffeine in developing vertebrates.

PubMed

Rodriguez, Rufino S; Haugen, Rebecca; Rueber, Alexandra; Huang, Cheng-Chen

2014-06-01

This study utilizes zebrafish embryos to understand the cellular and molecular mechanisms of caffeine toxicity in developing vertebrate embryos. By using a high concentration of caffeine, we observed almost all the phenotypes that have been described in humans and/or in other animal models, including neural tube closure defect, jittery, touch insensitivity, and growth retardation as well as a drastic coiled body phenotype. Zebrafish embryos exposed to 5mM caffeine exhibited high frequent movement, 10 moves/min comparing with around 3 moves/min in control embryos, within half an hour post exposure (HPE). They later showed twitching, uncoordinated movement, and eventually severe body curvature by 6HPE. Exposure at later stages resulted in the same phenotypes but more posteriorly. Surprisingly, when caffeine was removed before 6HPE, the embryos were capable of recovering but still exhibited mild curvature and shorter bodies. Longer exposure caused irreversible body curvature and lethality. These results suggest that caffeine likely targets the neuro-muscular physiology in developing embryos. Immunohistochemistry revealed that the motorneurons in treated embryos developed shorter axons, abnormal branching, and excessive synaptic vesicles. Developing skeletal muscles also appeared smaller and lacked the well-defined boundaries seen in control embryos. Finally, caffeine increases the expression of genes involved in synaptic vesicle migration. In summary, our results provide molecular understanding of caffeine toxicity on developing vertebrate embryos. Published by Elsevier Inc.

Gender differences in the effects of cathinone and the interaction with caffeine on temperature and locomotor activity in the rat.

PubMed

Alsufyani, Hadeel A; Docherty, James R

2017-08-15

We have investigated gender differences in the effects of cathinone and the interaction with caffeine on temperature and movement activity in Wistar rats. Telemetry probes were implanted in rats under isoflurane anaesthesia, and 7 days later, temperature and activity were recorded in conscious unrestrained animals. Caffeine (10mg/lkg) or vehicle, and 30min later, cathinone (5mg/kg) or vehicle, were injected subcutaneously. Cathinone produced significant and marked increases in activity, and the response to cathinone was significantly greater in female animals. The combination of caffeine and cathinone causes a short lived potentiation followed by a prolonged inhibition of the activity response to cathinone. Cathinone alone had minor effects on temperature. However, the combination of caffeine and cathinone produced a significant acute rise in temperature only in male rats in the 90min after cathinone injection. Hence, cathinone caused greater increases in activity in female than in male rats. Secondly, caffeine produced an initial potentiation followed by a prolonged inhibition of the activity response to cathinone. Thirdly, cathinone in combination with caffeine significantly raised temperature acutely in male but not female rats. These differences highlight the need to carry out gender studies of the actions of stimulants. Copyright © 2017 Elsevier B.V. All rights reserved.

Simultaneous Determination of Caffeine and Vitamin B6 in Energy Drinks by High-Performance Liquid Chromatography (HPLC)

ERIC Educational Resources Information Center

Leacock, Rachel E.; Stankus, John J.; Davis, Julian M.

2011-01-01

A high-performance liquid chromatography experiment to determine the concentration of caffeine and vitamin B6 in sports energy drinks has been developed. This laboratory activity, which is appropriate for an upper-level instrumental analysis course, illustrates the standard addition method and simultaneous determination of two species. (Contains 1…

Caffeine-Induced Ca2+ Oscillations in Type I Horizontal Cells of the Carp Retina and the Contribution of the Store-Operated Ca2+ Entry Pathway

PubMed Central

Lv, Ting; Gong, Hai-Qing; Liang, Pei-Ji

2014-01-01

The mechanisms of release, depletion, and refilling of endoplasmic reticulum (ER) Ca2+ were investigated in type I horizontal cells of the carp retina using a fluo-3-based Ca2+ imaging technique. Exogenous application of caffeine, a ryanodine receptor agonist, induced oscillatory intracellular free Ca2+ concentration ([Ca2+]i) responses in a duration- and concentration-dependent manner. In Ca2+-free Ringer’s solution, [Ca2+]i transients could also be induced by a brief caffeine application, whereas subsequent caffeine application induced no [Ca2+]i increase, which implied that extracellular Ca2+ was required for ER refilling, confirming the necessity of a Ca2+ influx pathway for ER refilling. Depletion of ER Ca2+ by thapsigargin triggered a Ca2+ influx which could be blocked by the store-operated channel inhibitor 2-APB, which proved the existence of the store-operated Ca2+ entry pathway. Taken together, these results suggested that after being depleted by caffeine, the ER was replenished by Ca2+ influx via store-operated channels. These results reveal the fine modulation of ER Ca2+ signaling, and the activation of the store-operated Ca2+ entry pathway guarantees the replenishment of the ER so that the cell can be ready for response to the subsequent stimulus. PMID:24918937

Effects of paraxanthine and caffeine on sleep, locomotor activity, and body temperature in orexin/ataxin-3 transgenic narcoleptic mice.

PubMed

Okuro, Masashi; Fujiki, Nobuhiro; Kotorii, Nozomu; Ishimaru, Yuji; Sokoloff, Pierre; Nishino, Seiji

2010-07-01

Caffeine, an adenosine A1 and A2a receptor antagonist, is a widely consumed stimulant and also used for the treatment of hypersomnia; however, the wake-promoting potency of caffeine is often not strong enough, and high doses may induce side effects. Caffeine is metabolized to paraxanthine, theobromine, and theophylline. Paraxanthine is a central nervous stimulant and exhibits higher potency at A1 and A2 receptors, but has lower toxicity and lesser anxiogenic effects than caffeine. We evaluated the wake-promoting efficacy of paraxanthine, caffeine, and a reference wake-promoting compound, modafinil, in a mice model of narcolepsy, a prototypical disease model of hypersomnia. Orexin/ataxin-3 transgenic (TG) and wild-type (WT) mice were subjected to oral administration (at ZT 2 and ZT14) of 3 doses of paraxanthine, caffeine, modafinil, or vehicle. Paraxanthine, caffeine, and modafinil significantly promoted wakefulness in both WT and narcoleptic TG mice and proportionally reduced NREM and REM sleep in both genotypes. The wake-promoting potency of 100 mg/kg p.o. of paraxanthine during the light period administration roughly corresponds to that of 200 mg/kg p.o. of modafinil. The wake-promoting potency of paraxanthine is greater and longer lasting than that of the equimolar concentration of caffeine, when the drugs were administered during the light period. The wake-promotion by paraxanthine, caffeine, and modafinil are associated with an increase in locomotor activity and body temperature. However, the higher doses of caffeine and modafinil, but not paraxanthine, induced hypothermia and reduced locomotor activity, thereby confirming the lower toxicity of paraxanthine. Behavioral evaluations of anxiety levels in WT mice revealed that paraxanthine induced less anxiety than caffeine did. Because it is also reported to provide neuroprotection, paraxanthine may be a better wake-promoting agent for hypersomnia associated with neurodegenerative diseases.

Prenatal caffeine exposure induced a lower level of fetal blood leptin mainly via placental mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Yi-meng; Luo, Han-wen; Kou, Hao

It's known that blood leptin level is reduced in intrauterine growth retardation (IUGR) fetus, and placental leptin is the major source of fetal blood leptin. This study aimed to investigate the decreased fetal blood leptin level by prenatal caffeine exposure (PCE) and its underlying placental mechanisms. Pregnant Wistar rats were intragastrically administered caffeine (30–120 mg/kg day) from gestational day 9 to 20. The level of fetal serum leptin and the expression of placental leptin-related genes were analyzed. Furthermore, we investigated the molecular mechanism of the reduced placental leptin's expression by treatment with caffeine (0.8–20 μM) in the BeWo cells. Inmore » vivo, PCE significantly decreased fetal serum leptin level in caffeine dose-dependent manner. Meanwhile, placental mRNA expression of adenosine A2a receptor (Adora2a), cAMP-response element binding protein (CREB), a short-type leptin receptor (Ob-Ra) and leptin was reduced in the PCE groups. In vitro, caffeine significantly decreased the mRNA expression of leptin, CREB and ADORA2A in concentration and time-dependent manners. The addition of ADORA2A agonist or adenylyl cyclase (AC) agonist reversed the inhibition of leptin expression induced by caffeine. PCE induced a lower level of fetal blood leptin, which the primary mechanism is that caffeine inhibited antagonized Adora2a and AC activities to decreased cAMP synthesis, thus inhibited the expression of the transcription factor CREB and target gene leptin in the placenta. Meantime, the reduced transportation of maternal leptin by placental Ob-Ra also contributed to the reduced fetal blood leptin. Together, PCE decreased fetal blood leptin mainly via reducing the expression and transportation of leptin in the placenta. - Highlights: • Caffeine reduced fetal blood leptin level. • Caffeine inhibited placental leptin production and transport. • Caffeine down-regulated placental leptin expression via antagonizing ADORA2. • Caffeine inhibited placental leptin transport via decreased OB-Ra expression.« less

A Prospective Randomized, Double-Blind, Two-Period Crossover Pharmacokinetic Trial Comparing Green Coffee Bean Extract-A Botanically Sourced Caffeine-With a Synthetic USP Control.

PubMed

Morton, Kayce; Knight, Katelin; Kalman, Douglas; Hewlings, Susan

2018-04-16

Coffee is a primary dietary source of the chlorogenic acids (CGAs) of phenolic compounds. Coffee contains caffeine and other phytonutrients, including CGAs. Caffeine on its own has been well characterized and descried pharmacokinetically in the literature, less so for CGAs. The purpose of this double-blind crossover study was to determine the comparative pharmacokinetics of CGAs with caffeine (natural extract) with synthetic caffeine (US Pharmacopeia [USP] standard). Sixteen healthy male subjects were randomly assigned to take 1 dose of product 1, 60 mg of botanically sourced caffeine from 480 mg of green coffee bean extract, or product 2, 60 mg of synthetic USP caffeine, with 5 days between. Blood analysis was done to determine the levels of CGA compounds, more specifically 3-, 4-, and 5-caffeoylquinic acid (CQA), and serum caffeine. The natural caffeine extract exhibited mean peak concentrations (C max ) of 3-CQA (11.4 ng/mL), 4-CQA (6.84 ng/mL), and 5-CQA (7.20 ng/mL). The mean systemic 4-hour exposure (AUC 0-4 h ) was 3-CQA (27.3 ng·h/mL), 4-CQA (16.1 ng·h/mL), and 5-CQA (15.7 ng·h/mL). The median t max was 3-CQA (1.00 hour), 4-CQA (1.00 hour), and 5-CQA (1.50 hours). The t max of caffeine was 0.75 hours (natural extract) and 0.63 hours (synthetic caffeine). C max and AUC 0-4 h of serum caffeine were statistically equivalent between products. The geometric least-squares mean ratios (GMRs) of C max and AUC 0-4 h of caffeine were 97.77% (natural extract) and 98.33% (synthetic caffeine). It would appear that CGA compounds from the natural caffeine extract are bioavailable, and 3-CGA may be the compound most absorbed. In addition, caffeine sourced from natural extract versus synthetic were statistically similar for pharmacokinetic parameters. There were no adverse events or safety concerns. © 2018 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

Caffeine in floral nectar enhances a pollinator's memory of reward.

PubMed

Wright, G A; Baker, D D; Palmer, M J; Stabler, D; Mustard, J A; Power, E F; Borland, A M; Stevenson, P C

2013-03-08

Plant defense compounds occur in floral nectar, but their ecological role is not well understood. We provide evidence that plant compounds pharmacologically alter pollinator behavior by enhancing their memory of reward. Honeybees rewarded with caffeine, which occurs naturally in nectar of Coffea and Citrus species, were three times as likely to remember a learned floral scent as were honeybees rewarded with sucrose alone. Caffeine potentiated responses of mushroom body neurons involved in olfactory learning and memory by acting as an adenosine receptor antagonist. Caffeine concentrations in nectar did not exceed the bees' bitter taste threshold, implying that pollinators impose selection for nectar that is pharmacologically active but not repellent. By using a drug to enhance memories of reward, plants secure pollinator fidelity and improve reproductive success.

Caffeine in floral nectar enhances a pollinator’s memory of reward

PubMed Central

Wright, G. A.; Baker, D. D.; Palmer, M. J.; Stabler, D.; Mustard, J. A.; Power, E. F.; Borland, A. M.; Stevenson, P. C.

2015-01-01

Plant defence compounds occur in floral nectar, but their ecological role is not well-understood. We provide the first evidence that plant compounds pharmacologically alter pollinator behaviour by enhancing their memory of reward. Honeybees rewarded with caffeine, which occurs naturally in nectar of Coffea and Citrus species, were three times more likely to remember a learned floral scent than those rewarded with sucrose alone. Caffeine potentiated responses of mushroom body neurons involved in olfactory learning and memory by acting as an adenosine receptor antagonist. Caffeine concentrations in nectar never exceeded the bees’ bitter taste threshold, implying that pollinators impose selection for nectar that is pharmacologically active but not repellent. By using a drug to enhance memories of reward, plants secure pollinator fidelity and improve reproductive success. PMID:23471406

Caffeine-based food supplements and beverages: Trends of consumption for performance purposes and safety concerns.

PubMed

Bessada, Sílvia M F; Alves, Rita C; Oliveira, M Beatriz P P

2018-07-01

Nowadays, daily food supplementation regarding the improvement of physical and mental performance is a growing trend in sport practitioners, young students and active people. Food supplements are foodstuffs, labeled under food law and not obliged to safety assessments before their commercialization. Several products are commercialized claiming ergogenic effects as marketing strategies. Caffeine is often one of their main ingredients, as it increases both physical performance and concentration. This manuscript presents a general overview of the current caffeine-based food supplements and energy drinks available in the Portuguese market, as well as the consuming trends regarding their ergogenic effects, performance purposes, and active ingredients. Product claims, recommended daily intakes, caffeine pharmacology, and safety concerns aspects are also discussed aspects. Copyright © 2018 Elsevier Ltd. All rights reserved.

Acute Caffeinated Coffee Consumption Does not Improve Time Trial Performance in an 800-m Run: A Randomized, Double-Blind, Crossover, Placebo-Controlled Study.

PubMed

Marques, Alexandre C; Jesus, Alison A; Giglio, Bruna M; Marini, Ana C; Lobo, Patrícia C B; Mota, João F; Pimentel, Gustavo D

2018-05-23

Studies evaluating caffeinated coffee (CAF) can reveal ergogenic effects; however, studies on the effects of caffeinated coffee on running are scarce and controversial. To investigate the effects of CAF consumption compared to decaffeinated coffee (DEC) consumption on time trial performances in an 800-m run in overnight-fasting runners. A randomly counterbalanced, double-blind, crossover, placebo-controlled study was conducted with 12 healthy adult males with experience in amateur endurance running. Participants conducted two trials on two different occasions, one day with either CAF or DEC, with a one-week washout. After arriving at the data collection site, participants consumed the soluble CAF (5.5 mg/kg of caffeine) or DEC and after 60 min the run was started. Before and after the 800-m race, blood pressure and lactate and glucose concentrations were measured. At the end of the run, the ratings of perceived exertion (RPE) scale was applied. The runners were light consumers of habitual caffeine, with an average ingestion of 91.3 mg (range 6⁻420 mg/day). Time trial performances did not change between trials (DEF: 2.38 + 0.10 vs. CAF: 2.39 + 0.09 min, p = 0.336), nor did the RPE (DEC: 16.5 + 2.68 vs. CAF: 17.0 + 2.66, p = 0.326). No difference between the trials was observed for glucose and lactate concentrations, or for systolic and diastolic blood pressure levels. CAF consumption failed to enhance the time trial performance of an 800-m run in overnight-fasting runners, when compared with DEC ingestion. In addition, no change was found in RPE, blood pressure levels, or blood glucose and lactate concentrations between the two trials.

Coffee-Antihypertensive Drug Interaction: A Hemodynamic and Pharmacokinetic Study With Felodipine.

PubMed

Bailey, David G; Dresser, George K; Urquhart, Brad L; Freeman, David J; Arnold, John Malcolm

2016-12-01

A period of abstinence from coffee to permit caffeine elimination appears to enable increased blood pressure on subsequent exposure. We hypothesized that this would offset the antihypertensive effect of the dihydropyridine calcium channel blocker felodipine. A randomized, single-dose, crossover study assessed hemodynamic and pharmacokinetic effects following 2 days without coffee and caffeine-containing foods. Consistently brewed black coffee (2×300ml), felodipine maximum recommended dose (10mg), and coffee plus felodipine were tested in middle-aged normotensive subjects. Pretreatment plasma caffeine concentrations were unquantifiable. After coffee, blood pressure changes (mm Hg) averaged over study hours 1-4 were increased for brachial systolic (7.6, P < 0.001) and diastolic (4.9, P < 0.001) and aortic systolic (7.4, P < 0.001), pulse (3.0, P < 0.05) and augmentation (1.4, P < 0.05) relative to baseline. After coffee plus felodipine, they were higher for brachial systolic (4.0, P < 0.05) and diastolic (3.9, P < 0.001) and aortic systolic (4.6, P < 0.05) compared to felodipine alone. The pressor effects of coffee and its modulation by felodipine were variable among individuals. Coffee containing caffeine (127mg) caused maximum pressor effect. Caffeine and felodipine pharmacokinetics were similar for coffee and felodipine given alone or in combination indicating an interaction having a pharmacodynamic basis. Plasma felodipine concentration-diastolic blood pressure reduction relationship shifted with coffee such that doubling the felodipine concentration would eliminate the pressor effect. However, this may increase the risk of adverse drug events particularly during the timeframe without coffee. Intermittent coffee ingestion might complicate hypertension diagnosis and management for many individuals. © American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Effect of post-exercise caffeine and green coffee bean extract consumption on blood glucose and insulin concentrations.

PubMed

Beam, Jason R; Gibson, Ann L; Kerksick, Chad M; Conn, Carole A; White, Ailish C; Mermier, Christine M

2015-02-01

The aim of this study was to investigate the effects of ingesting caffeine and green coffee bean extract on blood glucose and insulin concentrations during a post-exercise oral glucose tolerance test. Ten male cyclists (age: 26 ± 5 y; height: 179.9 ± 5.4 cm; weight: 77.6 ± 13.3 kg; body mass index: 24 ± 4.3 kg/m(2); VO2 peak: 55.9 ± 8.4 mL·kg·min(-1)) participated in this study. In a randomized order, each participant completed three 30-min bouts of cycling at 60% of peak power output. Immediately after exercise, each participant consumed 75 g of dextrose with either 5 mg/kg body weight of caffeine, 10 mg/kg of green coffee bean extract (5 mg/kg chlorogenic acid), or placebo. Venous blood samples were collected immediately before and after exercise during completion of the oral glucose tolerance test. No significant time × treatment effects for blood glucose and insulin were found. Two-h glucose and insulin area under the curve values, respectively, for the caffeine (658 ± 74 mmol/L and 30,005 ± 13,304 pmol/L), green coffee bean extract (637 ± 100 mmol/L and 31,965 ± 23,586 pmol/L), and placebo (661 ± 77 mmol/L and 27,020 ± 12,339 pmol/L) trials were not significantly different (P > 0.05). Caffeine and green coffee bean extract did not significantly alter postexercise blood glucose and insulin concentrations when compared with a placebo. More human research is needed to determine the impact of these combined nutritional treatments and exercise on changes in blood glucose and insulin. Copyright © 2015 Elsevier Inc. All rights reserved.

Stacking and Branching in Self-Aggregation of Caffeine in Aqueous Solution: From the Supramolecular to Atomic Scale Clustering.

PubMed

Tavagnacco, Letizia; Gerelli, Yuri; Cesàro, Attilio; Brady, John W

2016-09-22

The dynamical and structural properties of caffeine solutions at the solubility limit have been investigated as a function of temperature by means of MD simulations, static and dynamic light scattering, and small angle neutron scattering experiments. A clear picture unambiguously supported by both experiment and simulation emerges: caffeine self-aggregation promotes the formation of two distinct types of clusters: linear aggregates of stacked molecules, formed by 2-14 caffeine molecules depending on the thermodynamic conditions and disordered branched aggregates with a size in the range 1000-3000 Å. While the first type of association is well-known to occur under room temperature conditions for both caffeine and other purine systems, such as nucleotides, the presence of the supramolecular aggregates has not been reported previously. MD simulations indicate that branched structures are formed by caffeine molecules in a T-shaped arrangement. An increase of the solubility limit (higher temperature but also higher concentration) broadens the distribution of cluster sizes, promoting the formation of stacked aggregates composed by a larger number of caffeine molecules. Surprisingly, the effect on the branched aggregates is rather limited. Their internal structure and size do not change considerably in the range of solubility limits investigated.

Supraadditive formation of micronuclei in preimplantation mouse embryos in vitro after combined treatment with X-rays and caffeine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mueller, W.U.S.; Streffer, C.; Wurm, R.

1985-01-01

The influence of caffeine (0.1 or 2 mM), X-rays (0.24 Gy or 0.94 Gy, or of a combination of both on the formation of micronuclei in early stages of preimplantation mouse embryos in vitro was studied. X-rays as well as caffeine induced micronuclei. The dose-effect curve after irradiation was linear for the dose range measured. Caffeine did not induce micronuclei if the concentration was 1 mM or less; between 1 mM and 7 mM, however, there was a linear increase in the number of micronuclei. A considerable enhancement of the number of radiation-induced micronuclei was observed when irradiation of themore » embryos was followed by a treatment with caffeine. Not only was the sum of the single effects exceeded by the combination effects, but the combination results even lay in the range of supraadditivity of the envelope of additivity.« less

Caffeine: Cognitive and Physical Performance Enhancer or Psychoactive Drug?

PubMed Central

Cappelletti, Simone; Daria, Piacentino; Sani, Gabriele; Aromatario, Mariarosaria

2015-01-01

Caffeine use is increasing worldwide. The underlying motivations are mainly concentration and memory enhancement and physical performance improvement. Coffee and caffeine-containing products affect the cardiovascular system, with their positive inotropic and chronotropic effects, and the central nervous system, with their locomotor activity stimulation and anxiogenic-like effects. Thus, it is of interest to examine whether these effects could be detrimental for health. Furthermore, caffeine abuse and dependence are becoming more and more common and can lead to caffeine intoxication, which puts individuals at risk for premature and unnatural death. The present review summarizes the main findings concerning caffeine’s mechanisms of action (focusing on adenosine antagonism, intracellular calcium mobilization, and phosphodiesterases inhibition), use, abuse, dependence, intoxication, and lethal effects. It also suggests that the concepts of toxic and lethal doses are relative, since doses below the toxic and/or lethal range may play a causal role in intoxication or death. This could be due to caffeine’s interaction with other substances or to the individuals' preexisting metabolism alterations or diseases. PMID:26074744

Coffee consumption is associated with higher plasma adiponectin concentrations in women with or without type 2 diabetes: a prospective cohort study

PubMed Central

Williams, Catherine J.; Fargnoli, Jessica L.; Hwang, Janice J.; van Dam, Rob M.; Blackburn, George L.; Hu, Frank B.; Mantzoros, Christos S.

2009-01-01

To test whether the beneficial effects of coffee consumption in metabolism might be explained by changes in circulating levels of adiponectin, we evaluated self-reported habitual coffee and tea consumption and caffeine intake as predictors of plasma adiponectin concentrations among 982 diabetic and 1058 non-diabetic women without cardiovascular disease from the Nurses' Health Study. Women with and without diabetes who drank ≥4 cups of coffee per day had significantly higher adiponectin concentrations than those who didn't drink coffee regularly (7.7 vs. 6.1 μg/ml, respectively, in diabetic women, P=0.004; 15.0 vs. 13.2 μg/ml in nondiabetic women, P=0.04). Similar associations were observed for caffeine intake. We confirm previously reported inverse associations of coffee consumption with inflammatory markers, C-reactive protein and tumor necrosis factor-α receptor II. Adjustment for adiponectin did not weaken these associations, nor did adjustment for inflammatory markers attenuate the association between coffee consumption and adiponectin. High consumption of caffeine-containing coffee is associated with higher adiponectin and lower inflammatory marker concentrations. PMID:18070989

Caffeinated forage tricks honeybees into increasing foraging and recruitment behaviors.

PubMed

Couvillon, Margaret J; Al Toufailia, Hasan; Butterfield, Thomas M; Schrell, Felix; Ratnieks, Francis L W; Schürch, Roger

2015-11-02

In pollination, plants provide food reward to pollinators who in turn enhance plant reproduction by transferring pollen, making the relationship largely cooperative; however, because the interests of plants and pollinators do not always align, there exists the potential for conflict, where it may benefit both to cheat the other [1, 2]. Plants may even resort to chemistry: caffeine, a naturally occurring, bitter-tasting, pharmacologically active secondary compound whose main purpose is to detract herbivores, is also found in lower concentrations in the nectar of some plants, even though nectar, unlike leaves, is made to be consumed by pollinators. [corrected]. A recent laboratory study showed that caffeine may lead to efficient and effective foraging by aiding honeybee memory of a learned olfactory association [4], suggesting that caffeine may enhance bee reward perception. However, without field data, the wider ecological significance of caffeinated nectar remains difficult to interpret. Here we demonstrate in the field that caffeine generates significant individual- and colony-level effects in free-flying worker honeybees. Compared to a control, a sucrose solution with field-realistic doses of caffeine caused honeybees to significantly increase their foraging frequency, waggle dancing probability and frequency, and persistency and specificity to the forage location, resulting in a quadrupling of colony-level recruitment. An agent-based model also demonstrates how caffeine-enhanced foraging may reduce honey storage. Overall, caffeine causes bees to overestimate forage quality, tempting the colony into sub-optimal foraging strategies, which makes the relationship between pollinator and plant less mutualistic and more exploitative. VIDEO ABSTRACT. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of Caffeine Supplementation on Plasma and Blood Mononuclear Cell Interleukin-10 Levels After Exercise.

PubMed

Tauler, Pedro; Martinez, Sonia; Martinez, Pau; Lozano, Leticia; Moreno, Carlos; Aguiló, Antoni

2016-02-01

This study compared the response of interleukin (IL)-10, and also of IL-6 and IL-12 p40, to exercise and caffeine supplementation between plasma and blood mononuclear cells (BMNCs). Participants in the study (n = 28) were randomly allocated in a double-blind fashion to either caffeine (n = 14) or placebo (n = 14) treatments. One hour before completing a 15-km run competition, athletes took 6 mg/kg body mass of caffeine or a placebo. Plasma and BMNCs were purified from blood samples taken before and after competition. Concentrations of interleukins (IL-10, IL-6, and IL-12 p40), cyclic adenosine monophosphate (cAMP), caffeine, adrenaline, and cortisol were measured in plasma. IL-10, IL-6, and IL-12 p40 and cAMP levels were also determined in BMNCs. Exercise induced significant increases in IL-6 and IL-10 plasma levels, with higher increases in the caffeine-supplemented group. After 2-hr recovery, these levels returned to almost preexercise values. However, no effect of caffeine on BMNC cytokines was observed. IL-10, IL-6, and IL-12 p40 levels in BMNCs increased mainly at 2 hr postexercise. cAMP levels increased postexercise in plasma and after recovery in BMNCs, but no effects of caffeine were observed. In conclusion, caffeine did not modify cytokine levels in BMNCs in response to exercise. However, higher increases of IL-10 were observed in plasma after exercise in the supplemented participants, which could suppose an enhancement of the anti-inflammatory properties of exercise.

Effects of a Caffeine-Containing Energy Drink on Simulated Soccer Performance

PubMed Central

Del Coso, Juan; Muñoz-Fernández, Víctor E.; Muñoz, Gloria; Fernández-Elías, Valentín E.; Ortega, Juan F.; Hamouti, Nassim; Barbero, José C.; Muñoz-Guerra, Jesús

2012-01-01

Background To investigate the effects of a caffeine-containing energy drink on soccer performance during a simulated game. A second purpose was to assess the post-exercise urine caffeine concentration derived from the energy drink intake. Methodology/Principal Findings Nineteen semiprofessional soccer players ingested 630±52 mL of a commercially available energy drink (sugar-free Red Bull®) to provide 3 mg of caffeine per kg of body mass, or a decaffeinated control drink (0 mg/kg). After sixty minutes they performed a 15-s maximal jump test, a repeated sprint test (7×30 m; 30 s of active recovery) and played a simulated soccer game. Individual running distance and speed during the game were measured using global positioning satellite (GPS) devices. In comparison to the control drink, the ingestion of the energy drink increased mean jump height in the jump test (34.7±4.7 v 35.8±5.5 cm; P<0.05), mean running speed during the sprint test (25.6±2.1 v 26.3±1.8 km · h−1; P<0.05) and total distance covered at a speed higher than 13 km · h−1 during the game (1205±289 v 1436±326 m; P<0.05). In addition, the energy drink increased the number of sprints during the whole game (30±10 v 24±8; P<0.05). Post-exercise urine caffeine concentration was higher after the energy drink than after the control drink (4.1±1.0 v 0.1±0.1 µg · mL−1; P<0.05). Conclusions/significance A caffeine-containing energy drink in a dose equivalent to 3 mg/kg increased the ability to repeatedly sprint and the distance covered at high intensity during a simulated soccer game. In addition, the caffeinated energy drink increased jump height which may represent a meaningful improvement for headers or when players are competing for a ball. PMID:22348079

Effects of a caffeine-containing energy drink on simulated soccer performance.

PubMed

Del Coso, Juan; Muñoz-Fernández, Víctor E; Muñoz, Gloria; Fernández-Elías, Valentín E; Ortega, Juan F; Hamouti, Nassim; Barbero, José C; Muñoz-Guerra, Jesús

2012-01-01

To investigate the effects of a caffeine-containing energy drink on soccer performance during a simulated game. A second purpose was to assess the post-exercise urine caffeine concentration derived from the energy drink intake. Nineteen semiprofessional soccer players ingested 630 ± 52 mL of a commercially available energy drink (sugar-free Red Bull®) to provide 3 mg of caffeine per kg of body mass, or a decaffeinated control drink (0 mg/kg). After sixty minutes they performed a 15-s maximal jump test, a repeated sprint test (7 × 30 m; 30 s of active recovery) and played a simulated soccer game. Individual running distance and speed during the game were measured using global positioning satellite (GPS) devices. In comparison to the control drink, the ingestion of the energy drink increased mean jump height in the jump test (34.7 ± 4.7 v 35.8 ± 5.5 cm; P<0.05), mean running speed during the sprint test (25.6 ± 2.1 v 26.3 ± 1.8 km · h(-1); P<0.05) and total distance covered at a speed higher than 13 km · h(-1) during the game (1205 ± 289 v 1436 ± 326 m; P<0.05). In addition, the energy drink increased the number of sprints during the whole game (30 ± 10 v 24 ± 8; P<0.05). Post-exercise urine caffeine concentration was higher after the energy drink than after the control drink (4.1 ± 1.0 v 0.1 ± 0.1 µg · mL(-1); P<0.05). A caffeine-containing energy drink in a dose equivalent to 3 mg/kg increased the ability to repeatedly sprint and the distance covered at high intensity during a simulated soccer game. In addition, the caffeinated energy drink increased jump height which may represent a meaningful improvement for headers or when players are competing for a ball.

Molecular imprinting of caffeine on cellulose/silica composite and its characterization

NASA Astrophysics Data System (ADS)

Gill, Rajinder Singh

This dissertation presents a study to prepare molecularly imprinted inorganic/organic hybrid composite which not only confirm the higher binding capabilities for the target molecule (template) but also discriminate its structural analogs. Molecularly imprinted Cellulose/Silica composite (MIP) was prepared by using caffeine as the template. Silica derived from TEOS by using sol-gel techniques was deposited on cheap, abundant organic matrix such as cellulose, which can provide a filtering medium while coffee brewing. Removal of the template from the precursor was verified by Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS). Remarkably reduced intensity of -NH2 scissor like mode of caffeine and the presence of traces of "N" by elemental analysis, confirmed the complete removal of caffeine on washing with ethanol. Cellulose to TEOS mass ratio of 2:1 was found to be close to optimal during our analysis. Energy dispersive spectroscopy results leads to an important fact that the deposition of silica was stable even at 373 K. Focus was on the adsorption affinities of caffeine by MIP and was tested by performing relative adsorption of caffeine by MIP and blank (standard) using demountable path length cell in IR. It was observed that MIP showed almost 3-folds higher adsorption capabilities as compared to blank. The initial rate of adsorption of caffeine by MIP is much higher than blank which is one of the desirable feature according the its intended use. The higher adsorption of caffeine by MIP not only depends on the amount of silica deposited but also the available binding sites present on its surface. Selectivity of MIP was also verified by the competitive adsorption of caffeine and its structure analogs such as theophylline. Clearly, MIP showed greater and more rapid binding capabilities for caffeine than theophylline. At short contact times, the binding capability for caffeine is almost 1.8 times greater than the binding capabilities for theophylline.

Determination of trigonelline, nicotinic acid, and caffeine in Yunnan Arabica coffee by microwave-assisted extraction and HPLC with two columns in series.

PubMed

Liu, Hongcheng; Shao, Jinliang; Li, Qiwan; Li, Yangang; Yan, Hong Mei; He, Lizhong

2012-01-01

A simple, rapid method was developed for simultaneous extraction of trigonelline, nicotinic acid, and caffeine from coffee, and separation by two chromatographic columns in series. The trigonelline, nicotinic acid, and caffeine were extracted with microwave-assisted extraction (MAE). The optimal conditions selected were 3 min, 200 psi, and 120 degrees C. The chromatographic separation was performed with two columns in series, polyaromatic hydrocarbon C18 (250 x 4.6 mm id, 5 microm particle size) and Bondapak NH2 (300 x 3.9 mm id, 5 microm particle size). Isocratic elution was with 0.02 M phosphoric acid-methanol (70 + 30, v/v) mobile phase at a flow rate of 0.8 mL/min. Good recoveries and RSD values were found for all analytes in the matrix. The LOD of the three compounds was 0.02 mg/L, and the LOQ was 0.005% in the matrix. The concentrations of trigonelline, nicotinic acid, and caffeine in instant coffee, roasted coffee, and raw coffee (Yunnan Arabica coffee) were assessed by MAE and hot water extraction; the correlation coefficients between concentrations of the three compounds obtained were close to 1.

Combined effects of caffeine and zinc in the maternal diet on fetal brains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakamoto, T.; Gottschalk, S.B.; Yazdani, M.

1991-03-15

The authors have reported that caffeine (C) intake during the lactational period by dams decreases the Zn content of the brain in their offspring. The objective of the present study is to determine how C plus Zn supplementation to the maternal diet during gestation affects the fetal brains. Timed-pregnant rats at day 3 of gestation were randomly divided into 4 groups (G). G1 was fed a 20% protein diet as a control, G2 was fed a diet supplemented with Zn, G3 was fed a diet with C and G4 was fed a diet with C and Zn. At day 22more » of gestation, fetuses were taken out surgically. Fetal brains were removed. Their weights, DNA, Zn, protein, cholesterol, caffeine concentration, and alkaline phosphatase activity were determined. Body and brain weights and cholesterol contents in G4 were greater than in G1, whereas Zn concentration and alkaline phosphatase activity were less. Zn concentration and Zn/DNA in G2 were greater than in G1. Cholesterol content in G4 was higher than in G3. Although mean caffeine concentration in brain and plasma in G4 was greater than in G3, there was no statistical significance between the G due to the wide fluctuation among the pups. It is concluded that supplementation of C and Zn in the maternal diet during gestation could influence fetal brain composition differently than C supplementation alone. Supplementation of Zn alone showed minor effects.« less

Effects of Paraxanthine and Caffeine on Sleep, Locomotor Activity, and Body Temperature in Orexin/Ataxin-3 Transgenic Narcoleptic Mice

PubMed Central

Okuro, Masashi; Fujiki, Nobuhiro; Kotorii, Nozomu; Ishimaru, Yuji; Sokoloff, Pierre; Nishino, Seiji

2010-01-01

Study Objective: Caffeine, an adenosine A1 and A2a receptor antagonist, is a widely consumed stimulant and also used for the treatment of hypersomnia; however, the wake-promoting potency of caffeine is often not strong enough, and high doses may induce side effects. Caffeine is metabolized to paraxanthine, theobromine, and theophylline. Paraxanthine is a central nervous stimulant and exhibits higher potency at A1 and A2 receptors, but has lower toxicity and lesser anxiogenic effects than caffeine. Design: We evaluated the wake-promoting efficacy of paraxanthine, caffeine, and a reference wake-promoting compound, modafinil, in a mice model of narcolepsy, a prototypical disease model of hypersomnia. Orexin/ataxin-3 transgenic (TG) and wild-type (WT) mice were subjected to oral administration (at ZT 2 and ZT14) of 3 doses of paraxanthine, caffeine, modafinil, or vehicle. Results: Paraxanthine, caffeine, and modafinil significantly promoted wakefulness in both WT and narcoleptic TG mice and proportionally reduced NREM and REM sleep in both genotypes. The wake-promoting potency of 100 mg/kg p.o. of paraxanthine during the light period administration roughly corresponds to that of 200 mg/kg p.o. of modafinil. The wake-promoting potency of paraxanthine is greater and longer lasting than that of the equimolar concentration of caffeine, when the drugs were administered during the light period. The wake-promotion by paraxanthine, caffeine, and modafinil are associated with an increase in locomotor activity and body temperature. However, the higher doses of caffeine and modafinil, but not paraxanthine, induced hypothermia and reduced locomotor activity, thereby confirming the lower toxicity of paraxanthine. Behavioral evaluations of anxiety levels in WT mice revealed that paraxanthine induced less anxiety than caffeine did. Conclusions: Because it is also reported to provide neuroprotection, paraxanthine may be a better wake-promoting agent for hypersomnia associated with neurodegenerative diseases. Citation: Okuro M; Fujiki N; Kotorii N; Ishimaru Y; Sokoloff P; Nishino S. Effects of paraxanthine and caffeine on sleep, locomotor activity, and body temperature in orexin/ataxin-3 transgenic narcoleptic mice. SLEEP 2010;33(7):930-942. PMID:20614853

Diphlorethohydroxycarmalol of Ishige okamurae and Caffeine Modified the Expression of Extracellular Fibrillars during Adipogenesis of Mouse Subcutaneous Adipose Derived Stem Cell

PubMed Central

Jeon, Younmi; Song, Siyoung; Kim, Hagju; Cheon, Yong-Pil

2013-01-01

Although, one of the etiologies of localized lipodystrophy of the subcutaneous connective tissue (cellulite) is the histological alternation of adipose tissue, the characteristics of expression of the components of extracellular matrix (ECM) components during adipogenesis are not uncovered. In this study, the effects of caffeine and Ishige okamurae originated diphlorethohydroxycarmalol (DPHC) on the expression of extracellualr fibers was analyzed with quantitative RT-PCR during differentiation induction of mouse subcutaneous adipose derived stem cells (msADSC) into adipocyte. The expression levels of Col1a, Col3a1, and Col61a were decreased by the adipogenci induction in a time-dependent manners. However, Col2a mRNA and Col4a1 mRNA expressions were oposit to them. Caffeine and DPHC stimulated the changes of the expression of these collagens. Eln mRNA expression was increased by induction. DPHC stimulated the expression of it. Mfap5 mRNA expression was deceased in both adipogenic cell and matured adipocytes. Caffeine suppressed the expression of Mfap5 but the effect of DPHC was different by the concentration. The expression of bioglycan, decorin, and lumican were also modified by caffeine and DPHC in a concentration-dependent manner. Based on this study, we revealed firstly the effects of caffeine and DPHC on the expression of collagens, elastin, and glycoproteins during adipogenesis of msADSCs. Those results suggest that DPHC may have antiadipogenic effect and has more positive effets on normal adipose tissue generation and work as suppressor the abnormality of ECM structure. Such results indicate that DPHC can be applied in keeping the stability of the ECM of adipogenic tissues. PMID:25949143

Effects of Caffeine on Countermovement-Jump Performance Variables in Elite Male Volleyball Players.

PubMed

Zbinden-Foncea, Hermann; Rada, Isabel; Gomez, Jesus; Kokaly, Marco; Stellingwerff, Trent; Deldicque, Louise; Peñailillo, Luis

2018-02-01

To examine the effects of a moderate dose of caffeine in elite male volleyball players on countermovement-jump (CMJ) performance, as well as temporal concentric- and eccentric-phase effects. Ten elite male volleyball players took part in 2 experimental days via a randomized crossover trial 1 wk apart in which they ingested either 5 mg/kg of caffeine or a placebo in double-blind fashion. Heart rate and blood pressure were measured at rest and 60 min postingestion. Afterward, subjects also performed 3 CMJ trials 60 min postingestion, of which the average was used for further analysis. They filled out a questionnaire on possible side effects 24 h posttrial. Caffeine intake, compared with placebo, increased CMJ peak concentric force (6.5% ± 6.4%; P = .01), peak power (16.2% ± 8.3%; P < .01), flight time (5.3% ± 3.4%; P < .01), velocity at peak power (10.6% ± 8.0%; P < .01), peak displacement (10.8% ± 6.5%; P < .01), peak velocity (12.6% ± 7.4%; P < .01), peak acceleration (13.5% ± 8.5%; P < .01), and the force developed at peak power (6.0% ± 4.0%; P < .01) and reduced the time between peak power and peak force (16.7% ± 21.6%, P = .04). Caffeine increased diastolic blood pressure by 13.0% ± 8.9% (P < .05), whereas no adverse side effects were found. The ingestion of 5 mg/kg of anhydrous caffeine improves overall CMJ performance without inducing side effects.

Synthesis and Characterization of a New Bivalent Ligand Combining Caffeine and Docosahexaenoic Acid.

PubMed

Fernández-Dueñas, Víctor; Azuaje, Jhonny; Morató, Xavier; Cordobilla, Begoña; Domingo, Joan Carles; Sotelo, Eddy; Ciruela, Francisco

2017-02-27

Caffeine is a promising drug for the management of neurodegenerative diseases such as Parkinson's disease (PD), demonstrating neuroprotective properties that have been attributed to its interaction with the basal ganglia adenosine A2A receptor (A2AR). However, the doses needed to exert these neuroprotective effects may be too high. Thus, it is important to design novel approaches that selectively deliver this natural compound to the desired target. Docosahexaenoic acid (DHA) is the major omega-3 fatty acid in the brain and can act as a specific carrier of caffeine. Furthermore, DHA displays properties that may lead to its use as a neuroprotective agent. In the present study, we constructed a novel bivalent ligand covalently linking caffeine and DHA and assessed its pharmacological activity and safety profile in a simple cellular model. Interestingly, the new bivalent ligand presented higher potency as an A2AR inverse agonist than caffeine alone. We also determined the range of concentrations inducing toxicity both in a heterologous system and in primary striatal cultures. The novel strategy presented here of attaching DHA to caffeine may enable increased effects of the drug at desired sites, which could be of interest for the treatment of PD.

Effects of oral administration of energy drinks on blood chemistry, tissue histology and brain acetylcholine in rabbits.

PubMed

Ebuehi, O A T; Ajayl, O E; Onyeulor, A L; Awelimobor, D

2011-01-01

Energy drinks are canned or bottled carbonated beverages that contain large amounts of caffeine and sugar with additional ingredients, such as B-Vitamins, amino acids and herbal stimulants. Previous reports have shown that consumption of large amounts of these energy drinks may result in adverse health consequences. The present study is to ascertain if oral administration of energy drinks, such as "power horse" and "red bull", may affect blood chemistry, tissue histology and acetyl choline levels in rabbits. Five ml of power horse and red bull energy drinks, caffeine and saline (control) were orally administered daily for 36 days to rabbits. Body weight, feed and water intake were measured every other day. The blood samples were taken by cardiac puncture for blood chemistry measurement and their liver, heart and brain tissues were used for histological assay. The plasma, liver, brain and heart acetylcholine levels were also determined. There were no significant differences in the body weight, feed intake and organ weights of rabbits administered energy drinks or caffeine as compared to the control. The blood chemistry results showed that the activities of the aspartate and alanine amino transferase, concentrations of plasma creatinine, uric acid and albumin were increased in the control as compared to the red bull and caffeine administered rabbits. The concentrations of total protein, total cholesterol, triglyceride, high density lipoprotein (HDL) and low density lipoprotein (LDL) and glucose concentrations were increased in power horse and red bull administered rabbits as compared to caffeine administered rabbits and control rabbits. The concentrations of plasma and brain acetylcholine of rabbits administered power horse and red bull were significantly higher than in the control, while it was lower in liver and heart acetyl choline levels. The histopathological findings of the brain and liver show that there were no obvious histopathological abnormalities in the brain, liver and heart of rabbits administered power horse or red bull and caffeine as compared to the control rabbits. Data of the present study indicate that oral administration of the energy drinks, specifically power horse and red bull, affected blood chemistry, liver enzymes activities, but do not significantly affect the histopathology of the brain, heart and liver of the rabbits. This findings suggest that energy drinks may alter cholinergic neurotransmission and neural functions mediated by acetylcholine.

Caffeine protects against experimental acute pancreatitis by inhibition of inositol 1,4,5-trisphosphate receptor-mediated Ca2+ release

PubMed Central

Huang, Wei; Cane, Matthew C; Mukherjee, Rajarshi; Szatmary, Peter; Zhang, Xiaoying; Elliott, Victoria; Ouyang, Yulin; Chvanov, Michael; Latawiec, Diane; Wen, Li; Booth, David M; Haynes, Andrea C; Petersen, Ole H; Tepikin, Alexei V; Criddle, David N

2017-01-01

Objective Caffeine reduces toxic Ca2+ signals in pancreatic acinar cells via inhibition of inositol 1,4,5-trisphosphate receptor (IP3R)-mediated signalling, but effects of other xanthines have not been evaluated, nor effects of xanthines on experimental acute pancreatitis (AP). We have determined effects of caffeine and its xanthine metabolites on pancreatic acinar IP3R-mediated Ca2+ signalling and experimental AP. Design Isolated pancreatic acinar cells were exposed to secretagogues, uncaged IP3 or toxins that induce AP and effects of xanthines, non-xanthine phosphodiesterase (PDE) inhibitors and cyclic adenosine monophosphate and cyclic guanosine monophosphate (cAMP/cGMP) determined. The intracellular cytosolic calcium concentration ([Ca2+]C), mitochondrial depolarisation and necrosis were assessed by confocal microscopy. Effects of xanthines were evaluated in caerulein-induced AP (CER-AP), taurolithocholic acid 3-sulfate-induced AP (TLCS-AP) or palmitoleic acid plus ethanol-induced AP (fatty acid ethyl ester AP (FAEE-AP)). Serum xanthines were measured by liquid chromatography-mass spectrometry. Results Caffeine, dimethylxanthines and non-xanthine PDE inhibitors blocked IP3-mediated Ca2+ oscillations, while monomethylxanthines had little effect. Caffeine and dimethylxanthines inhibited uncaged IP3-induced Ca2+ rises, toxin-induced Ca2+ release, mitochondrial depolarisation and necrotic cell death pathway activation; cAMP/cGMP did not inhibit toxin-induced Ca2+ rises. Caffeine significantly ameliorated CER-AP with most effect at 25 mg/kg (seven injections hourly); paraxanthine or theophylline did not. Caffeine at 25 mg/kg significantly ameliorated TLCS-AP and FAEE-AP. Mean total serum levels of dimethylxanthines and trimethylxanthines peaked at >2 mM with 25 mg/kg caffeine but at <100 µM with 25 mg/kg paraxanthine or theophylline. Conclusions Caffeine and its dimethylxanthine metabolites reduced pathological IP3R-mediated pancreatic acinar Ca2+ signals but only caffeine ameliorated experimental AP. Caffeine is a suitable starting point for medicinal chemistry. PMID:26642860

Nonfatal and fatal intoxications with pure caffeine - report of three different cases.

PubMed

Magdalan, Jan; Zawadzki, Marcin; Skowronek, Rafał; Czuba, Magdalena; Porębska, Barbara; Sozański, Tomasz; Szpot, Paweł

2017-09-01

Caffeine is not usually perceived as a drug by most people because it is found in many foods and drinks, including caffeinated energy drinks, as well as in over the counter analgesics and cold preparations. Recently in Poland it has become increasingly common to take pure caffeine, bought through online stores, as a psychoanaleptic. This creates a much higher risk of severe and even fatal poisoning in comparison with the risk associated with the abuse of food products and non-prescription medicines containing low doses of caffeine. This paper presents three different cases of poisoning that occurred when pure caffeine was taken as psychostimulant; in cases 1 and 2 poisoning was the result of a single overdose, while in the case 3 poisoning resulted from a cumulative overdose. In the case 1 there was a severe intoxication (persistent vomiting, hypotension, tremor), and the concentration of caffeine in the blood was found to be 80.16 μg/mL. The patient was treated using hemodialysis, which caused a rapid decrease in blood levels of caffeine and relief of the clinical symptoms of poisoning. Cases 2 and 3 were fatal poisonings, and recorded levels of caffeine in post mortem blood samples were 140.64 μg/mL and 613.0 μg/mL. In case 2 the patient died 10 min after admission to hospital as a result of sudden cardiac arrest, which was preceded by an attack of convulsions, and in case 3 death occurred in home and was also sudden in nature. Taking pure caffeine as a stimulant is associated with a high risk of overdose and the development of serious and even fatal poisoning, and those using pure caffeine are generally completely unaware of these risks. In such cases, death is usually sudden due to functional mechanisms.

Coffee and caffeine intake and male infertility: a systematic review.

PubMed

Ricci, Elena; Viganò, Paola; Cipriani, Sonia; Somigliana, Edgardo; Chiaffarino, Francesca; Bulfoni, Alessandro; Parazzini, Fabio

2017-06-24

Semen quality, a predictor of male fertility, has been suggested declining worldwide. Among other life style factors, male coffee/caffeine consumption was hypothesized to influence semen parameters, but also sperm DNA integrity. To summarize available evidence, we performed a systematic review of observational studies on the relation between coffee/caffeine intake and parameters of male fertility including sperm ploidy, sperm DNA integrity, semen quality and time to pregnancy. A systematic literature search was performed up to November 2016 (MEDLINE and EMBASE). We included all observational papers that reported the relation between male coffee/caffeine intake and reproductive outcomes: 1. semen parameters, 2. sperm DNA characteristics, 3. fecundability. All pertinent reports were retrieved and the relative reference lists were systematically searched in order to identify any potential additional studies that could be included. We retrieved 28 papers reporting observational information on coffee/caffeine intake and reproductive outcomes. Overall, they included 19,967 men. 1. Semen parameters did not seem affected by caffeine intake, at least caffeine from coffee, tea and cocoa drinks, in most studies. Conversely, other contributions suggested a negative effect of cola-containing beverages and caffeine-containing soft drinks on semen volume, count and concentration. 2. As regards sperm DNA defects, caffeine intake seemed associated with aneuploidy and DNA breaks, but not with other markers of DNA damage. 3. Finally, male coffee drinking was associated to prolonged time to pregnancy in some, but not all, studies. The literature suggests that caffeine intake, possibly through sperm DNA damage, may negatively affect male reproductive function. Evidence from epidemiological studies on semen parameters and fertility is however inconsistent and inconclusive. Well-designed studies with predefined criteria for semen analysis, subject selection, and life style habits definition, are essential to reach a consistent evidence on the effect of caffeine on semen parameters and male fertility.

[Comutagenic action of sodium selenite and caffeine on S. typhimurium TA 1535 with its subsequent treatment by N-nitrosomethylurea].

PubMed

Balanski, R M

1988-01-01

The comutagenic activity of sodium selenite and caffeine was studied by the Ames test. Reproduction of S. typhimurium TA1535 for 4 h at 37 degrees C in the nutrient broth with sodium selenide (5 micrograms/ml) significantly increased sensitivity of bacterial cells to the mutagenic action of 2-3 mM N-nitrosomethylurea (NMU). When using threshold concentrations of NMU the potentiation of mutagenesis reached 625.2%. The addition of 0.19 mg/ml of caffeine to the nutrient medium also led (though the action was less pronounced) to an increase in sensitivity of bacterial cells to the NMU mutagenic action. Reproduction of S. typhimurium TA1535 in the medium containing sodium selenide and caffeine did not cause an increase in the frequency of spontaneous his+-revertant mutations.

Smoking and caffeine consumption: a genetic analysis of their association.

PubMed

Treur, Jorien L; Taylor, Amy E; Ware, Jennifer J; Nivard, Michel G; Neale, Michael C; McMahon, George; Hottenga, Jouke-Jan; Baselmans, Bart M L; Boomsma, Dorret I; Munafò, Marcus R; Vink, Jacqueline M

2017-07-01

Smoking and caffeine consumption show a strong positive correlation, but the mechanism underlying this association is unclear. Explanations include shared genetic/environmental factors or causal effects. This study employed three methods to investigate the association between smoking and caffeine. First, bivariate genetic models were applied to data of 10 368 twins from the Netherlands Twin Register in order to estimate genetic and environmental correlations between smoking and caffeine use. Second, from the summary statistics of meta-analyses of genome-wide association studies on smoking and caffeine, the genetic correlation was calculated by LD-score regression. Third, causal effects were tested using Mendelian randomization analysis in 6605 Netherlands Twin Register participants and 5714 women from the Avon Longitudinal Study of Parents and Children. Through twin modelling, a genetic correlation of r0.47 and an environmental correlation of r0.30 were estimated between current smoking (yes/no) and coffee use (high/low). Between current smoking and total caffeine use, this was r0.44 and r0.00, respectively. LD-score regression also indicated sizeable genetic correlations between smoking and coffee use (r0.44 between smoking heaviness and cups of coffee per day, r0.28 between smoking initiation and coffee use and r0.25 between smoking persistence and coffee use). Consistent with the relatively high genetic correlations and lower environmental correlations, Mendelian randomization provided no evidence for causal effects of smoking on caffeine or vice versa. Genetic factors thus explain most of the association between smoking and caffeine consumption. These findings suggest that quitting smoking may be more difficult for heavy caffeine consumers, given their genetic susceptibility. © 2016 The Authors.Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

Two Distinct Pathways for Metabolism of Theophylline and Caffeine Are Coexpressed in Pseudomonas putida CBB5▿ †

PubMed Central

Yu, Chi Li; Louie, Tai Man; Summers, Ryan; Kale, Yogesh; Gopishetty, Sridhar; Subramanian, Mani

2009-01-01

Pseudomonas putida CBB5 was isolated from soil by enrichment on caffeine. This strain used not only caffeine, theobromine, paraxanthine, and 7-methylxanthine as sole carbon and nitrogen sources but also theophylline and 3-methylxanthine. Analyses of metabolites in spent media and resting cell suspensions confirmed that CBB5 initially N demethylated theophylline via a hitherto unreported pathway to 1- and 3-methylxanthines. NAD(P)H-dependent conversion of theophylline to 1- and 3-methylxanthines was also detected in the crude cell extracts of theophylline-grown CBB5. 1-Methylxanthine and 3-methylxanthine were subsequently N demethylated to xanthine. CBB5 also oxidized theophylline and 1- and 3-methylxanthines to 1,3-dimethyluric acid and 1- and 3-methyluric acids, respectively. However, these methyluric acids were not metabolized further. A broad-substrate-range xanthine-oxidizing enzyme was responsible for the formation of these methyluric acids. In contrast, CBB5 metabolized caffeine to theobromine (major metabolite) and paraxanthine (minor metabolite). These dimethylxanthines were further N demethylated to xanthine via 7-methylxanthine. Theobromine-, paraxanthine-, and 7-methylxanthine-grown cells also metabolized all of the methylxanthines mentioned above via the same pathway. Thus, the theophylline and caffeine N-demethylation pathways converged at xanthine via different methylxanthine intermediates. Xanthine was eventually oxidized to uric acid. Enzymes involved in theophylline and caffeine degradation were coexpressed when CBB5 was grown on theophylline or on caffeine or its metabolites. However, 3-methylxanthine-grown CBB5 cells did not metabolize caffeine, whereas theophylline was metabolized at much reduced levels to only methyluric acids. To our knowledge, this is the first report of theophylline N demethylation and coexpression of distinct pathways for caffeine and theophylline degradation in bacteria. PMID:19447909

Smoking and caffeine consumption: a genetic analysis of their association

PubMed Central

Taylor, Amy E.; Ware, Jennifer J.; Nivard, Michel G.; Neale, Michael C.; McMahon, George; Hottenga, Jouke‐Jan; Baselmans, Bart M. L.; Boomsma, Dorret I.; Munafò, Marcus R.; Vink, Jacqueline M.

2016-01-01

Abstract Smoking and caffeine consumption show a strong positive correlation, but the mechanism underlying this association is unclear. Explanations include shared genetic/environmental factors or causal effects. This study employed three methods to investigate the association between smoking and caffeine. First, bivariate genetic models were applied to data of 10 368 twins from the Netherlands Twin Register in order to estimate genetic and environmental correlations between smoking and caffeine use. Second, from the summary statistics of meta‐analyses of genome‐wide association studies on smoking and caffeine, the genetic correlation was calculated by LD‐score regression. Third, causal effects were tested using Mendelian randomization analysis in 6605 Netherlands Twin Register participants and 5714 women from the Avon Longitudinal Study of Parents and Children. Through twin modelling, a genetic correlation of r0.47 and an environmental correlation of r0.30 were estimated between current smoking (yes/no) and coffee use (high/low). Between current smoking and total caffeine use, this was r0.44 and r0.00, respectively. LD‐score regression also indicated sizeable genetic correlations between smoking and coffee use (r0.44 between smoking heaviness and cups of coffee per day, r0.28 between smoking initiation and coffee use and r0.25 between smoking persistence and coffee use). Consistent with the relatively high genetic correlations and lower environmental correlations, Mendelian randomization provided no evidence for causal effects of smoking on caffeine or vice versa. Genetic factors thus explain most of the association between smoking and caffeine consumption. These findings suggest that quitting smoking may be more difficult for heavy caffeine consumers, given their genetic susceptibility. PMID:27027469

Effect of hydrophobicity of pharmaceuticals and personal care products for adsorption on activated carbon: Adsorption isotherms, kinetics and mechanism.

PubMed

Kaur, Harkirat; Bansiwal, Amit; Hippargi, Girivyankatesh; Pophali, Girish R

2017-09-11

Adsorption of three pharmaceuticals and personal care products (PPCPs), namely caffeine, ibuprofen and triclosan on commercial powdered activated carbon was examined in aqueous medium. The contaminants were chosen based on their diverse log K ow (octanol-water partition coefficient) viz. - 0.07 for caffeine, 3.97 for ibuprofen and 4.76 for triclosan to examine the role of hydrophobicity on adsorption process. The adsorbent characterisation was achieved using BET surface area, SEM, pore size distribution studies and FTIR. Influence of mass of PAC, contact time, solution pH and initial concentration on adsorption capacity of PAC was studied. Adsorption isotherms and kinetics were applied to establish the mechanism of adsorption. The kinetics followed pseudo-second order with physisorption occurring through particle diffusion. The Freundlich model fitted best among the isotherm models. The adsorption capacity increased in the order CFN < IBU < TCS which correlates with increasing hydrophobicity (log K ow ), molecular weight and decreasing water solubility, respectively. We conclude that micro-pollutant hydrophobicity contributes towards adsorption on activated carbon.

A Biomathematical Model of the Restoring Effects of Caffeine on Cognitive Performance During Sleep Deprivation

DTIC Science & Technology

2013-01-01

following inhibitory Emax model to formulate the PD effect: gPD tð Þ ¼ 1 gPK ðtÞ gPK50 þgPK ðtÞ , ð3Þ where gPK (t) denotes the concentration of caffeine...the maximal effect is observed when gPK is infinitely large, i.e., when gPD approaches zero. Also, the baseline effect, i.e., the effect in the absence... gPK (t) at discrete- time index t, with t¼1, 2, y, for an orally administered caffeine dose given at time index t0 can be expressed by the following

Chronic ingestion of a low dose of caffeine induces tolerance to the performance benefits of caffeine.

PubMed

Beaumont, Ross; Cordery, Philip; Funnell, Mark; Mears, Stephen; James, Lewis; Watson, Phillip

2017-10-01

This study examined effects of 4 weeks of caffeine supplementation on endurance performance. Eighteen low-habitual caffeine consumers (<75 mg · day -1 ) were randomly assigned to ingest caffeine (1.5-3.0 mg · kg -1 day -1 ; titrated) or placebo for 28 days. Groups were matched for age, body mass, V̇O 2peak and W max (P > 0.05). Before supplementation, all participants completed one V̇O 2peak test, one practice trial and 2 experimental trials (acute 3 mg · kg -1 caffeine [precaf] and placebo [testpla]). During the supplementation period a second V̇O 2peak test was completed on day 21 before a final, acute 3 mg · kg -1 caffeine trial (postcaf) on day 29. Trials consisted of 60 min cycle exercise at 60% V̇O 2peak followed by a 30 min performance task. All participants produced more external work during the precaf trial than testpla, with increases in the caffeine (383.3 ± 75 kJ vs. 344.9 ± 80.3 kJ; Cohen's d effect size [ES] = 0.49; P = 0.001) and placebo (354.5 ± 55.2 kJ vs. 333.1 ± 56.4 kJ; ES = 0.38; P = 0.004) supplementation group, respectively. This performance benefit was no longer apparent after 4 weeks of caffeine supplementation (precaf: 383.3 ± 75.0 kJ vs. postcaf: 358.0 ± 89.8 kJ; ES = 0.31; P = 0.025), but was retained in the placebo group (precaf: 354.5 ± 55.2 kJ vs. postcaf: 351.8 ± 49.4 kJ; ES = 0.05; P > 0.05). Circulating caffeine, hormonal concentrations and substrate oxidation did not differ between groups (all P > 0.05). Chronic ingestion of a low dose of caffeine develops tolerance in low-caffeine consumers. Therefore, individuals with low-habitual intakes should refrain from chronic caffeine supplementation to maximise performance benefits from acute caffeine ingestion.

Making the Most of the "Daphnia" Heart Rate Lab: Optimizing the Use of Ethanol, Nicotine & Caffeine

ERIC Educational Resources Information Center

Corotto, Frank; Ceballos, Darrel; Lee, Adam; Vinson, Lindsey

2010-01-01

Students commonly test the effects of chemical agents on the heart rate of the crustacean "Daphnia" magna, but the procedure has never been optimized. We determined the effects of three concentrations of ethanol, nicotine, and caffeine and of a control solution on heart rate in "Daphnia." Ethanol at 5% and 10% (v/v) reduced mean heart rate to…

Jet Lag in Military Operations: Field Trial of L-Tryptophan in Reducing Sleep-Loss Effects

DTIC Science & Technology

1986-03-21

in decreased fatigue and desire to sleep. improved information processing and concentration, faster temperature rhythm adaptation, greater encoding...tea, soda containing caffeine, chocolate milk, chocolate candy, etc.). Beverages without caffeine could be ingested, Including decaffeinated coffee...subjects wore devices for ambulatory monitoring of physiological processes . We used the Medilog 9-channel recorder available from Oxford Hedilog, Inc

The perinatal effects of maternal caffeine intake on fetal and neonatal brain levels of testosterone, estradiol, and dihydrotestosterone in rats.

PubMed

Karaismailoglu, S; Tuncer, M; Bayrak, S; Erdogan, G; Ergun, E L; Erdem, A

2017-08-01

Testosterone, estradiol, and dihydrotestosterone are the main sex steroid hormones responsible for the organization and sexual differentiation of brain structures during early development. The hypothalamo-pituitary-adrenocortical axis, adrenal cells, and gonads play a key role in the production of sex steroids and express adenosine receptors. Caffeine is a non-selective adenosine antagonist; therefore, it can modulate metabolic pathways in these tissues. Besides, the proportion of pregnant women that consume caffeine is ∼60%. That is why the relationship between maternal caffeine consumption and fetal development is important. Therefore, we aimed to investigate this modulatory effect of maternal caffeine consumption on sex steroids in the fetal and neonatal brain tissues. Pregnant rats were treated with a low (0.3 g/L) or high (0.8 g/L) dose of caffeine in their drinking water during pregnancy and lactation. The testosterone, estradiol, and dihydrotestosterone levels in the frontal cortex and hypothalamus were measured using radioimmunoassay at embryonic day 19 (E19), birth (PN0), and postnatal day 4 (PN4). The administration of low-dose caffeine increased the body weight in PN4 male and female rats and anogenital index in PN4 males. The administration of high-dose caffeine decreased the adrenal weight in E19 male rats and increased testosterone levels in the frontal cortex of E19 female rats and the hypothalamus of PN0 male rats. Maternal caffeine intake during pregnancy affects sex steroid levels in the frontal cortex and hypothalamus of the offspring. This concentration changes of the sex steroids in the brain may influence behavioral and neuroendocrine functions at some point in adult life.

Caffeine and length dependence of staircase potentiation in skeletal muscle.

PubMed

Rassier, D E; Tubman, L A; MacIntosh, B R

1998-01-01

Skeletal muscle sensitivity to Ca2+ is greater at long lengths, and this results in an optimal length for twitch contractions that is longer than optimal length for tetanic contractions. Caffeine abolishes this length dependence of Ca2+ sensitivity. Muscle length (ML) also affects the degree of staircase potentiation. Since staircase potentiation is apparently caused by an increased Ca2+ sensitivity of the myofilaments, we tested the hypothesis that caffeine depresses the length dependence of staircase potentiation. In situ isometric twitch contractions of rat gastrocnemius muscle before and after 10 s of 10-Hz stimulation were analyzed at seven different lengths to evaluate the length dependence of staircase potentiation. In the absence of caffeine, length dependence of Ca2+ sensitivity was observed, and the degree of potentiation after 10-Hz stimulation showed a linear decrease with increased length (DT = 1.47 - 0.05 ML, r2 = 0.95, where DT is developed tension). Length dependence of Ca2+ sensitivity was decreased by caffeine when caffeine was administered in amounts estimated to result in 0.5 and 0.75 mM concentrations. Furthermore, the negative slope of the relationship between staircase potentiation and muscle length was diminished at the lower caffeine dose, and the slope was not different from zero after the higher dose (DT = 1.53 - 0.009 ML, r2 = 0.43). Our study shows that length dependence of Ca2+ sensitivity in intact skeletal muscle is diminished by caffeine. Caffeine also suppressed the length dependence of staircase potentiation, suggesting that the mechanism of this length dependence may be closely related to the mechanism for length dependence of Ca2+ sensitivity.

Effects of caffeine on behavioral and inflammatory changes elicited by copper in zebrafish larvae: Role of adenosine receptors.

PubMed

Cruz, Fernanda Fernandes; Leite, Carlos Eduardo; Kist, Luiza Wilges; de Oliveira, Giovanna Medeiros; Bogo, Maurício Reis; Bonan, Carla Denise; Campos, Maria Martha; Morrone, Fernanda Bueno

2017-04-01

This study investigated the effects of caffeine in the behavioral and inflammatory alterations caused by copper in zebrafish larvae, attempting to correlate these changes with the modulation of adenosine receptors. To perform a survival curve, 7dpf larvae were exposed to 10μM CuSO 4 , combined to different concentrations of caffeine (100μM, 500μM and 1mM) for up to 24h. The treatment with copper showed lower survival rates only when combined with 500μM and 1mM of caffeine. We selected 4 and 24h as treatment time-points. The behavior evaluation was done by analyzing the traveled distance, the number of entries in the center, and the length of permanence in the center and the periphery of the well. The exposure to 10μM CuSO 4 plus 500μM caffeine at 4 and 24h changed the behavioral parameters. To study the inflammatory effects of caffeine, we assessed the PGE 2 levels by using UHPLC-MS/MS, and TNF, COX-2, IL-6 and IL-10 gene expression by RT-qPCR. The expression of adenosine receptors was also evaluated with RT-qPCR. When combined to copper, caffeine altered inflammatory markers depending on the time of exposure. Adenosine receptors expression was significantly increased, especially after 4h exposure to copper and caffeine together or separately. Our results demonstrated that caffeine enhances the inflammation induced by copper by decreasing animal survival, altering inflammatory markers and promoting behavioral changes in zebrafish larvae. We also conclude that alterations in adenosine receptors are related to those effects. Copyright © 2017 Elsevier Inc. All rights reserved.

[Influence of personality traits on reaction performance in volunteers after a single administration of placebo, crotylbarbital and caffeine].

PubMed

Meyer, F P; Walther, T; Walther, H

1983-01-01

We examined the influence of single applications of placebo, caffeine (7 mg/kg), and crotylbarbital (2 mg/kg) on reaction and attention performance in 15 volunteers. A newly developed reaction-time apparatus permits the reaction time to be split for differentiation between initiation time and movement time. Moreover, simple and complex attention performance can be quantified. The volunteers were selected as to the dimensions of "introversion/extraversion" and "emotional lability/stability" by means of the Freiburg Personality Inventory. Labile volunteers responded to placebo faster than stables. Caffeine improved mainly the performance of introverted subjects. Crotylbarbital was without influence on the reaction time at the threshold dose applied.

D-ribose--an additive with caffeine.

PubMed

Herrick, Jim; Shecterle, L M; St Cyr, J A

2009-05-01

Caffeine acts as a stimulant, in which approximately 90% of people in the United States consume daily. Besides its beneficial effects, many individuals have experienced unpleasant reactions following the consumption of caffeine: such as insomnia, an increase in heart rate, feelings of nervousness, headaches, occasional lightheadedness, a state of "jitters," and a potential "crash" state following its metabolism. Researchers have proposed mechanisms responsible for caffeine's interactions, which include its blocking capacity of adenosine receptors, its role with the pituitary gland, increasing levels of dopamine, and its role with the intracellular release of calcium from the sarcoplasmic reticulum, which is dependent on intracellular adenosine triphosphate levels. Specific substrates have been investigated to lessen the undesirable effects of caffeine and still preserve its stimulatory benefits. The results of these investigations have produced no positive consensus. However, D-ribose, an important pentose carbohydrate in the energy molecule of adenosine triphosphate, as well as our genetic code and other cellular processes, could offer such a solution to this problem. D-ribose could potentially aid in maintaining or potentially lowering extra-cellular adenosine concentrations, aid in the flux of intracellular calcium, aid in intracellular energy production, and potentially lessen the perceived "crash" state felt by many. Every cell requires adequate levels of energy to maintain its integrity and function. Caffeine has the potential to task this energy equilibrium. D-ribose with caffeine may be the substrate to aid in the potential intracellular energy demand, aid in lessening the perceived unpleasant side effects of caffeine, and still preserving the desired benefits of this stimulant consumed by all of us daily.

Caffeine increases sugar-sweetened beverage consumption in a free-living population: a randomised controlled trial.

PubMed

Keast, Russell S J; Swinburn, Boyd A; Sayompark, Dhoungsiri; Whitelock, Susie; Riddell, Lynn J

2015-01-28

Excessive sugar-sweetened beverage (SSB) consumption has been associated with overweight and obesity. Caffeine is a common additive to SSB, and through dependence effects, it has the potential to promote the consumption of caffeine-containing foods. The objective of the present study was to assess the influence that caffeine has on the consumption of SSB. Participants (n 99) were blindly assigned to either a caffeinated SSB (C-SSB) or a non-caffeinated SSB (NC-SSB) group. Following randomisation, all participants completed a 9 d flavour-conditioning paradigm. They then completed a 28 d ad libitum intake intervention where they consumed as much or as little of C-SSB or NC-SSB as desired. The amount consumed (ml) was recorded daily, 4 d diet diaries were collected and liking of SSB was assessed at the start and end of the intervention. Participants (n 50) consuming the C-SSB had a daily SSB intake of 419 (sd 298) ml (785 (sd 559) kJ/d) over the 28 d intervention, significantly more than participants (n 49) consuming the NC-SSB (273 (sd 278) ml/d, 512 (sd 521) kJ/d) (P=0.05). However, participants who consumed the C-SSB liked the SSB more than those who consumed the NC-SSB (6.3 v. 6.0 on a nine-point hedonic scale, P= 0.022). The addition of low concentrations of caffeine to the SSB significantly increases the consumption of the SSB. Regulating caffeine as a food additive may be an effective strategy to decrease the consumption of nutrient-poor high-energy foods and beverages.

Enhancement of High-Intensity Actions and Physical Performance During a Simulated Brazilian Jiu-Jitsu Competition With a Moderate Dose of Caffeine.

PubMed

Diaz-Lara, Francisco Javier; Del Coso, Juan; Portillo, Javier; Areces, Francisco; García, Jose Manuel; Abián-Vicén, Javier

2016-10-01

Although caffeine is one of the most commonly used substances in combat sports, information about its ergogenic effects on these disciplines is very limited. To determine the effectiveness of ingesting a moderate dose of caffeine to enhance overall performance during a simulated Brazilian jiu-jitsu (BJJ) competition. Fourteen elite BJJ athletes participated in a double-blind, placebo-controlled experimental design. In a random order, the athletes ingested either 3 mg/kg body mass of caffeine or a placebo (cellulose, 0 mg/kg) and performed 2 simulated BJJ combats (with 20 min rest between them), following official BJJ rules. Specific physical tests such as maximal handgrip dynamometry, maximal height during a countermovement jump, permanence during a maximal static-lift test, peak power in a bench-press exercise, and blood lactate concentration were measured at 3 specific times: before the first combat and immediately after the first and second combats. The combats were video-recorded to analyze fight actions. After the caffeine ingestion, participants spent more time in offensive actions in both combats and revealed higher blood lactate values (P < .05). Performance in all physical tests carried out before the first combat was enhanced with caffeine (P < .05), and some improvements remained after the first combat (eg, maximal static-lift test and bench-press exercise; P < .05). After the second combat, the values in all physical tests were similar between caffeine and placebo. Caffeine might be an effective ergogenic aid for improving intensity and physical performance during successive elite BJJ combats.

Choline- versus imidazole-based ionic liquids as functional ingredients in topical delivery systems: cytotoxicity, solubility, and skin permeation studies.

PubMed

Santos de Almeida, Tânia; Júlio, Ana; Saraiva, Nuno; Fernandes, Ana Sofia; Araújo, Maria Eduarda M; Baby, André Rolim; Rosado, Catarina; Mota, Joana Portugal

2017-11-01

Poor drug solubility represents a problem for the development of topical formulations. Since ionic liquids (ILs) can be placed in either lipophilic or hydrophilic solutions, they may be advantageous vehicles in such delivery systems. Nonetheless, it is vital to determine their usefulness when used at concentrations were cell viability is maintained, which was considered herein. Five different ILs were prepared-three imidazole-based ILs: [C2mim][Br], [C4mim][Br], and [C6mim][Br]; and two choline-based ILs: [Cho][Phe] and [Cho][Glu]. Their cytotoxicity in human keratinocytes (HaCat cells), their influence in drug solubility and in percutaneous permeation, using pig skin membranes, was evaluated. Caffeine and salicylic acid were used as model actives. Choline-based ILs proved to be more suitable as functional ingredients, since they showed higher impact on drug solubility and a lower cytotoxicity. The major solubility enhancement was observed for caffeine and further solubility studies were carried out with this active in several concentrations of the choline-based ILs (0.1; 0.2; 0.5; 1.0; 3.0 and 5.0%, w/w) at 25 °C and 32 °C. Solubility was greatly influenced by concentrations up to 0.5%. The choline-based ILs showed no significant impact on the skin permeation, for both actives. The size of the imidazole-based ILs alkyl chain enhances the caffeine solubility and permeation, but also the ILs cytotoxicity. Stable O/W emulsions and gels were prepared containing the less toxic choline-based ILs and caffeine. Our results indicate that the choline-based ILs were effective functional ingredients, since, when used at nontoxic concentrations, they allowed a higher drug loading, while maintaining the stability of the formulations.

Determination of catechins and caffeine in camillia sinensis raw materials, extracts, and dietary supplements by HPLC-uv: single-laboratory validation.

PubMed

Roman, Mark C

2013-01-01

A rapid method has been developed to quantify seven catechins and caffeine in green tea (Camillia sinensis) raw material and powdered extract, and dietary supplements containing green tea extract. The method utilizes RP HPLC with a phenyl-based stationary phase and gradient elution. Detection is by UV absorbance. The total run time, including column re-equilibration, is 13 min. Single-laboratory validation (SLV) has been performed on the method to determine the repeatability, accuracy, selectivity, LOD, LOQ, ruggedness, and linearity for (+)-catechin, (-)-epicatechin, (-)-epicatechin gallate, (-)-epigallocatechin, (-)-gallocatechin gallate, (-)-epigallocatechin gallate, and (+)-gallocatechin, as well as caffeine. Repeatability precision and recovery results met AOAC guidelines for SLV studies for all catechins and caffeine down to a level of approximately 20 mg/g. Finished products containing high concentrations of minerals require the use of EDTA to prevent decomposition of the catechins.

Caffeine modifies blood glucose availability during prolonged low-intensity exercise in individuals with type-2 diabetes

PubMed Central

da Silva, Luiz Augusto; de Freitas, Leandro; Medeiros, Thiago Emannuel; Osiecki, Raul; Garcia Michel, Renan; Snak, André Luiz

2014-01-01

Objective: The study investigated the effect of supplementation with maltodextrin (CHO) alone or associated to caffeine during exercise in T2DM subjects. Methods: Pilot study, using eight subjects with T2DM, aged 55±10 years, received CHO (1 g/kg) or caffeine (1.5 mg/kg) alone or associated before exercise protocol. The exercise was executed at 40% heart rate (HR) reserve for 40 min, with 10-min recovery. Blood pressure (BP) and perceived exertion scale (Borg) were checked every 2 min. Blood glucose (BG) was checked every 10 min. For statistical analysis, ANOVA test was used and the value was considered statistically significant at p <0.05. Results: The results showed that BP and HR did not change significantly among all treatments. Caffeine promoted a significant reduction in BG of 75 mg/dL (65%, p <0.05) during 40 min of exercise protocol compared to all groups. Conclusion: Supplementation with 1.5 mg/kg of caffeine reduces BG concentration during prolonged exercise in T2DM patients. PMID:25100892

Rapid tea catechins and caffeine determination by HPLC using microwave-assisted extraction and silica monolithic column.

PubMed

Rahim, A A; Nofrizal, S; Saad, Bahruddin

2014-03-15

A rapid reversed-phase high performance liquid chromatographic method using a monolithic column for the determination of eight catechin monomers and caffeine was developed. Using a mobile phase of water:acetonitrile:methanol (83:6:11) at a flow rate of 1.4 mL min(-1), the catechins and caffeine were isocratically separated in about 7 min. The limits of detection and quantification were in the range of 0.11-0.29 and 0.33-0.87 mg L(-1), respectively. Satisfactory recoveries were obtained (94.2-105.2 ± 1.8%) for all samples when spiked at three concentrations (5, 40 and 70 mg L(-1)). In combination with microwave-assisted extraction (MAE), the method was applied to the determination of the catechins and caffeine in eleven tea samples (6 green, 3 black and 2 oolong teas). Relatively high levels of caffeine were found in black tea, but higher levels of the catechins, especially epigallocatechin gallate (EGCG) were found in green teas. Copyright © 2013 Elsevier Ltd. All rights reserved.

Quantitative determination of caffeine and alcohol in energy drinks and the potential to produce positive transdermal alcohol concentrations in human subjects.

PubMed

Ayala, Jessica; Simons, Kelsie; Kerrigan, Sarah

2009-01-01

The purpose of this study was to determine whether non-alcoholic energy drinks could result in positive "alcohol alerts" based on transdermal alcohol concentration (TAC) using a commercially available electrochemical monitoring device. Eleven energy drinks were quantitatively assayed for both ethanol and caffeine. Ethanol concentrations for all of the non-alcoholic energy drinks ranged in concentration from 0.03 to 0.230% (w/v) and caffeine content per 8-oz serving ranged from 65 to 126 mg. A total of 15 human subjects participated in the study. Subjects consumed between 6 and 8 energy drinks over an 8-h period. The SCRAM II monitoring device was used to determine TACs every 30 min before, during, and after the study. None of the subjects produced TAC readings that resulted in positive "alcohol alerts". TAC measurements for all subjects before, during and after the energy drink study period (16 h total) were <0.02% (w/v). Subjects in the study consumed a quantity of non-alcoholic energy drink that greatly exceeds what would be considered typical. Based on these results, it appears that energy drink consumption is an unlikely explanation for elevated TACs that might be identified as potential drinking episodes or "alcohol alerts" using this device.

Reconnaissance of selected PPCP compounds in Costa Rican surface waters.

PubMed

Spongberg, Alison L; Witter, Jason D; Acuña, Jenaro; Vargas, José; Murillo, Manuel; Umaña, Gerardo; Gómez, Eddy; Perez, Greivin

2011-12-15

Eighty-six water samples were collected in early 2009 from Costa Rican surface water and coastal locations for the analysis of 34 pharmaceutical and personal care product compounds (PPCPs). Sampling sites included areas receiving treated and untreated wastewaters, and urban and rural runoff. PPCPs were analyzed using a combination of solid phase extraction and liquid chromatography tandem mass spectrometry. The five most frequently detected compounds were doxycycline (77%), sulfadimethoxine (43%), salicylic acid (41%), triclosan (34%) and caffeine (29%). Caffeine had the maximum concentration of 1.1 mg L(-1), possibly due to coffee bean production facilities upstream. Other compounds found in high concentrations include: doxycycline (74 μg L(-1)), ibuprofen (37 μg L(-1)), gemfibrozil (17 μg L(-1)), acetominophen (13 μg L(-1)) and ketoprofen (10 μg L(-1)). The wastewater effluent collected from an oxidation pond had similar detection and concentrations of compounds compared to other studies reported in the literature. Waters receiving runoff from a nearby hospital showed higher concentrations than other areas for many PPCPs. Both caffeine and carbamazepine were found in low frequency compared to other studies, likely due to enhanced degradation and low usage, respectively. Overall concentrations of PPCPs in surface waters of Costa Rica are inline with currently reported occurrence data from around the world, with the exception of doxycycline. Published by Elsevier Ltd.

Individual differences in the energizing effects of caffeine on effort-based decision-making tests in rats.

PubMed

SanMiguel, Noemí; Pardo, Marta; Carratalá-Ros, Carla; López-Cruz, Laura; Salamone, John D; Correa, Mercè

2018-06-01

Motivated behavior is characterized by activation and high work output. Nucleus accumbens (Nacb) modulates behavioral activation and effort-based decision-making. Caffeine is widely consumed because of its energizing properties. This methylxanthine is a non-selective adenosine A 1 /A 2A receptor antagonist. Adenosine receptors are highly concentrated in Nacb. Adenosine agonists injected into Nacb, shift preference towards low effort alternatives. The present studies characterized effort-related effects of caffeine in a concurrent progressive ratio (PROG)/free reinforcer choice procedure that requires high levels of work output, and generates great variability among different animals. Male Sprague-Dawley rats received an acute dose of caffeine (2.5-20.0 mg/kg, IP) and 30 min later were tested in operant boxes. One group was food-restricted and had to lever pressed for high carbohydrate pellets, another group was non-food-restricted and lever pressed for a high sucrose solution. Caffeine (2.5 and 5.0 mg/kg) increased lever pressing in food-restricted animals that were already high responders. However, in non-restricted animals, caffeine (5.0 and 10.0 mg/kg) increased work output only among low responders. In fact, caffeine (10.0 and 20.0 mg/kg) in non-restricted animals, reduced lever pressing among high responders in the PROG task, and also in a different group of animals lever pressing in an easy task (fixed ratio 7 schedule) that uniformly generates high levels of responding. Caffeine did not modify sucrose preference or consumption under free access conditions. Thus, when animals do not have a homeostatic need, caffeine can help those not very intrinsically motivated to work harder for a more palatable reward. However, caffeine can disrupt performance of animals intrinsically motivated to work hard for a better reward. Copyright © 2018 Elsevier Inc. All rights reserved.

Polyphenol-Retaining Decaffeinated Cocoa Powder Obtained by Supercritical Carbon Dioxide Extraction and Its Antioxidant Activity

PubMed Central

Kobori, Kinji; Maruta, Yuto; Mineo, Shigeru; Shigematsu, Toru; Hirayama, Masao

2013-01-01

Cocoa beans contain many functional ingredients such as theobromine and polyphenols, but also contain a relatively high amount of caffeine, which can negatively impact human health. It is therefore desirable to reduce caffeine levels in cocoa powder used to make chocolate or cocoa beverages while retaining functional ingredients. We have established conditions for supercritical carbon dioxide (SCCO2) extraction that remove 80.1% of the caffeine from cocoa powder while retaining theobromine (94.1%) and polyphenols (84.7%). The antioxidant activity of the decaffeinated cocoa powder (DCP) made with this optimized SCCO2 extraction method was 85.3% that of non-processed cocoa powder. The total procyanidin and total polyphenol concentrations of the DCPs resulting from various SCCO2 extractions showed a significant positive correlation with oxygen radical absorbance capacity (ORAC). The correlation coefficient between total polyphenols and ORAC was higher than that between total procyanidins and ORAC; thus, the concentration of total polyphenols might be a greater factor in the antioxidant activity of DCP. These results indicate that we could remove large quantities of caffeine from conventional high-cocoa products while retaining the functional benefits of high polyphenol content. This SCCO2 extraction method is expected to be applicable high-cocoa products, such as dark chocolate. PMID:28239130

Polyphenol-Retaining Decaffeinated Cocoa Powder Obtained by Supercritical Carbon Dioxide Extraction and Its Antioxidant Activity.

PubMed

Kobori, Kinji; Maruta, Yuto; Mineo, Shigeru; Shigematsu, Toru; Hirayama, Masao

2013-10-14

Cocoa beans contain many functional ingredients such as theobromine and polyphenols, but also contain a relatively high amount of caffeine, which can negatively impact human health. It is therefore desirable to reduce caffeine levels in cocoa powder used to make chocolate or cocoa beverages while retaining functional ingredients. We have established conditions for supercritical carbon dioxide (SCCO₂) extraction that remove 80.1% of the caffeine from cocoa powder while retaining theobromine (94.1%) and polyphenols (84.7%). The antioxidant activity of the decaffeinated cocoa powder (DCP) made with this optimized SCCO₂ extraction method was 85.3% that of non-processed cocoa powder. The total procyanidin and total polyphenol concentrations of the DCPs resulting from various SCCO₂ extractions showed a significant positive correlation with oxygen radical absorbance capacity (ORAC). The correlation coefficient between total polyphenols and ORAC was higher than that between total procyanidins and ORAC; thus, the concentration of total polyphenols might be a greater factor in the antioxidant activity of DCP. These results indicate that we could remove large quantities of caffeine from conventional high-cocoa products while retaining the functional benefits of high polyphenol content. This SCCO₂ extraction method is expected to be applicable high-cocoa products, such as dark chocolate.

Metabolic Relations between Methylxanthines and Methyluric Acids in Coffea L. 1

PubMed Central

Petermann, Joseph B.; Baumann, Thomas W.

1983-01-01

Metabolism of purine alkaloids in the leaves of Coffea dewevrei De Wild et Durand var excelsa Chev, Coffea liberica Bull ex Hiern and Coffea abeokutae Cramer was studied by analyzing leaf discs collected during vegetative development and by feeding the following radioactive tracers: [14C]theobromine, [14C]caffeine, and [14C]theacrine (1,3,7,9-tetramethyluric acid). Their principal metabolites were quantitatively and qualitatively determined. All three species convert the precursors to the same radioactive products, and proceed through the same four maturity stages characterized by the alkaloid accumulation pattern and by a particular transformation potency: (stage 1) young plant accumulating caffeine, transforms theobromine to caffeine; (stage 2) caffeine is gradually replaced by theacrine, theobromine and caffeine are converted to theacrine; (stage 3) theacrine disappears whereas liberine (O(2), 1,9-thrimethyluric acid) accumulates, theacrine is metabolized to liberine; (stage 4) branched-out plant containing liberine but no theacrine, caffeine is converted rapidly to liberine via theacrine. Methylliberine (O(2),1,7,9-tetramethyluric acid), presumably the direct precursor of liberine, is occasionally found in low concentrations at stage 3 and 4. The collective term `liberio-excelsoid' introduced by geneticists for the numerous races or species of Pachycoffea is in accordance with the phytochemical equality found in this work. PMID:16663351

Fluoride content in caffeinated, decaffeinated and herbal teas.

PubMed

Chan, J T; Koh, S H

1996-01-01

The fluoride contents of infusions prepared from 44 different brands and types of teas were measured. Fluoride concentrations ranged from 0.34 to 3.71 ppm (mean = 1.50 ppm) in caffeinated tea infusions, 0.02-0.14 ppm (mean = 0.05 ppm) in herbal tea infusions, and 1.01-5.20 ppm (mean = 3.19) in decaffeinated tea infusions. This is the first report of the fluoride content of decaffeinated teas. The mean fluoride content of decaffeinated tea infusions is significantly (p < 0.01) higher than the corresponding caffeinated tea. The use of mineral water containing a naturally high fluoride level during the process of decaffeination is the most likely explanation of the above observation.

Bioavailability of paracetamol with/without caffeine in Egyptian patients with hepatitis C virus.

PubMed

El-Lakkany, Naglaa M; Hendawy, Ahmed S; Seif El-Din, Sayed H; Ashour, Ahmed A; Atta, Raafat; Abdel-Aziz, Abdel-Aziz H; Mansour, Ahmed M; Botros, Sanaa S

2016-05-01

This study investigates the involvement of liver dysfunction in the modulation of paracetamol pharmacokinetic profile in genotype-4 HCV patients treated with either paracetamol alone (Para) or in combination with caffeine (Para-Caf). Twenty healthy volunteers and 20 Child-Pugh B HCV patients, each divided into two equal subgroups, were examined, whose liver/kidney functions were correlated with their main clinical manifestation. After an overnight fasting, healthy and hepatic subjects received either a single dose of Para (1000 mg paracetamol) or Para-Caf (1000 mg paracetamol/130 mg caffeine). Two milliliters of saliva samples were collected prior to and at different time-intervals after drug administration and analyzed using HPLC. There was a noticeable increase in the mean concentration time profile of salivary paracetamol concentrations in hepatic patients, with concomitant decrease in paracetamol clearance (CLT), along with induction in the primary pharmacokinetic (PK) parameters, C max, AUC(0-8 h) and AUC(0-∞) (by about 95, 82, and 64 %, respectively, after treatment with Para, and 98, 96, and 101 %, respectively, after treatment with Para-Caf), when compared with the corresponding parameters in healthy subjects. Additionally, the healthy subjects treated with Para-Caf exhibited bioinequivalent increase in C max, K a, and t 1/2 with decrease in T max when compared with the healthy individuals treated with Para alone. A similar pattern was recorded in hepatic patients after addition of caffeine to paracetamol, with even augmented significant increase in K a and t 1/2 (by 100 and 32 %, respectively). Liver dysfunction modified the PK of paracetamol expressed as earlier effective paracetamol concentration, with obvious decrease in its clearance. Caffeine induced faster absorption (evidenced by shorter T max and higher K a) and prolonged t 1/2 of paracetamol, the effects that were more profound in hepatic patients. Further studies are needed to evaluate the influence of liver damage on paracetamol pharmacokinetics whenever repeated dosing is applied, to avoid possible drug accumulation.

Synthesis and characterization of a thermo-sensitive poly( N-methyl acryloylglycine methyl ester) used as a drug release carrier

NASA Astrophysics Data System (ADS)

Deng, Kui-Lin; Zhong, Hai-Bin; Jiao, Yi-Suo; Fan, Ting; Qiao, Xiao; Zhang, Peng-Fei; Ren, Xiao-Bo

2010-06-01

In this article, poly( N-methyl acryloylglycine methyl ester) (PNMAME) was prepared as a novel thermosensitive material with a lower critical solution temperature (LCST) at around 49.5°C. The chemical structures of the monomer NMAME and PNMAME were characterized by 1H NMR and IR measurements. The LCST was investigated systematically as a function of PNMAME concentration, inorganic salt solution and pH value. The results indicated that LCST of PNMAME was obviously dependent on PNMAME concentration and pH. The LCST was increased with a decrease in pH value and PNMAME concentration. To obtain a thermo-sensitive hydrogel with the phase transition temperature close to human body temperature, the copolymerization was conducted between NMAME and N-acryloylglycine ethyl ester (NAGEE). The release behavior of caffeine was evaluated at different temperatures and contents of cross-linkers ( N, N-methylenebis(acrylamide) (NMBA)). The increase of cross-linker content led to a decrease in the release rate of caffeine due to higher crossing density in the hydrogel network. In addition, a faster release of caffeine from the hydrogel with 3% NMBA at 37°C was found in contrast to that at 18°C.

Peri-operative oral caffeine does not prevent postoperative atrial fibrillation after heart valve surgery with cardiopulmonary bypass: A randomised controlled clinical trial.

PubMed

Lagier, David; Nee, Laetitia; Guieu, Régis; Kerbaul, François; Fenouillet, Emmanuel; Roux, Nicolas; Giorgi, Roch; Theron, Alexis; Grisoli, Dominique; Gariboldi, Vlad; Collart, Frederic; Bruder, Nicolas; Velly, Lionel; Guidon, Catherine

2018-04-26

Raised plasma levels of endogenous adenosine after cardiac surgery using cardiopulmonary bypass (CPB) have been related to the incidence of postoperative atrial fibrillation (POAF). We wished to assess if caffeine, an adenosine receptor antagonist could have a beneficial effect on the incidence of POAF. A randomised controlled study. Single University Hospital. One hundred and ten patients scheduled for heart valve surgery with CPB. We randomly assigned patients to receive peri-operative oral caffeine (400 mg every 8 h for 2 days) or placebo. Adenosine plasma concentrations and caffeine pharmacokinetic profile were evaluated in a subgroup of 50 patients. The primary endpoint was the rate of atrial fibrillation during postoperative hospital stay. The current study was stopped for futility by the data monitoring board after an interim analysis. The incidence of atrial fibrillation was similar in the caffeine and in the placebo group during hospital stay (33 vs. 29%, P = 0.67) and the first 3 postoperative days (18 vs. 15%; P = 0.60). Basal and postoperative adenosine plasma levels were significantly associated with the primary outcome. Adenosine plasma levels were similar in the two treatment groups. Caffeine administration was associated with a higher incidence of postoperative nausea and vomiting (27 vs. 7%, P = 0.005). Oral caffeine does not prevent POAF after heart valve surgery with CPB but increased the incidence of postoperative nausea and vomiting. ClinicalTrials.gov, no.: NCT01999829.

The effect of caffeine on orthodontic tooth movement in rats

PubMed Central

Shirazi, Mohsen; Vaziri, Hamed; Salari, Behzad; Motahhari, Pouria; Etemad-Moghadam, Shahroo; Dehpour, Ahmad Reza

2017-01-01

Objective(s): to determine the effect of different doses of caffeine on orthodontic tooth movement (OTM) in rats. Materials and Methods: Forty male 250-300 g Sprague-Dawley rats were randomly divided into four groups of ten animals each and received 0 (control), 1 g/l, 2 g/l and 3 g/l caffeine in tap water for 3 days. Orthodontic appliances were ligated between the maxillary first molars and incisors on the 4th day of the study period. All rats were sacrificed after 2 weeks of treatment after which OTM was measured. Hematoxylin/eosin-stained sections of the molars were prepared and the mesial roots were examined for resorption-lacunae depth and osteoclast number. ANOVA was used for statistical analysis (P<0.05). Results: A significant decrease in OTM was observed only in the 2 g/l (P=0.043) and 3 g/l (P<0.01) caffeine-receiving rats compared to the control animals. Osteoclast counts and resorption-lacunae depths demonstrated significant differences between each of the caffeine groups and control rats (P<0.05). None of the variables showed significant differences between the caffeine groups (P>0.05). Conclusion: According to our findings, one of the effects of caffeine consumption during orthodontic treatment in rats was decreased root resorption. Additionally, concentrations of 2 g/l and 3 g/l inhibited OTM which seems to be due to its influence on osteoclast numbers. PMID:28392897

Combined long-term caffeine intake and exercise inhibits the development of diabetic nephropathy in OLETF rats.

PubMed

Suzuki, Masato; Shindo, Daisuke; Suzuki, Ryuichiro; Shirataki, Yoshiaki; Waki, Hidefumi

2017-05-01

This study was performed to examine the effects of long-term caffeine-intake, with and without exercise, on the progression of diabetic nephropathy (DN) in an obese diabetic rat model. Thirty-two male Otsuka Long-Evans Tokushima fatty (OLETF) rats were assigned to sedentary (OLETF-Sed), exercise (OLETF-Ex), caffeine-intake (OLETF-Caf), and combined (OLETF-Caf + Ex) groups. Caffeine-intake groups were fed rat chow containing caffeine (90.7 ± 4.7 mg/kg/day). The OLETF-Ex and OLETF-Caf + Ex groups were able to run voluntarily at any time using a rotatory wheel. Body weight (BW) and blood pressure (BP) were measured weekly from 24 to 29 wk of age. Pre- and posttreatment serum glucose, insulin, and creatinine concentrations were measured, and a 24 h urine sample was collected for measurement of creatinine clearance (Ccr) and albumin excretion (UE Alb ). After treatment, the kidneys were removed for morphological analysis. The OLETF-Caf and OLETF-Caf + Ex groups exhibited no BP increase during the study. Both the caffeine-intake groups exhibited a significant increase in urine volume (UV), electrolyte excretion, and Ccr, and decreased UE Alb , following treatment. Furthermore, no structural damage was observed in the kidneys of rats from either caffeine-intake group, whereas the OLETF-Sed and OLETF-Ex groups exhibited DN progression. This study demonstrates that caffeine-intake alone and/or combined with exercise significantly decreases BW and improves glucose intolerance, without the progression of DN. Further research should be performed to examine whether the quantities of caffeine contained in a normal human daily intake also have a protective effect against kidney damage. NEW & NOTEWORTHY The present study showed that caffeine administration alone and/or combined with exercise results in an improvement of diabetic nephropathy (DN), including an increase in creatinine clearance and urinary Na excretion, a decrease in urinary protein excretion, and in renal morphological findings. To our knowledge, there are no other studies showing that caffeine administration inhibits DN progression. Copyright © 2017 the American Physiological Society.

Caffeine Improves Triathlon Performance: A Field Study in Males and Females.

PubMed

Potgieter, Sunita; Wright, Hattie H; Smith, Carine

2018-06-01

The ergogenic effect of caffeine on endurance exercise is commonly accepted. We aimed to elucidate realistically the effect of caffeine on triathlon event performance using a field study design, while allowing investigation into potential mechanisms at play. A double-blind, randomized, crossover field trial was conducted. Twenty-six triathletes (14 males and 12 females; mean ±SD: age = 37.8 ± 10.6 years, habitual caffeine intake = 413 ± 505 mg/day, percentage body fat = 14.5 ± 7.2%, and training/week = 12.8 ± 4.5 hr) participated in this study. Microencapsulated caffeine (6 mg/kg body weight) was supplemented 60 min pretrial. Performance data included time to completion, rating of perceived exertion, and profile of mood states. Blood samples taken before, during, and postrace were analyzed for cortisol, testosterone, and full blood count. Capillary blood lactate concentrations were assessed prerace, during transitions, and 3, 6, 9, 12, and 15 min after triathlons. Caffeine supplementation resulted in a 3.7% reduction in swim time (33.5 ± 7.0 vs. 34.8 ± 8.1 min, p < .05) and a 1.3% reduction in time to completion (149.6 ± 19.8 vs. 151.5 ± 18.6 min, p < .05) for the whole group. Gender differences and individual responses are also presented. Caffeine did not alter the rating of perceived exertion significantly, but better performance after caffeine supplementation suggests a central effect resulting in greater overall exercise intensity at the same rating of perceived exertion. Caffeine supplementation was associated with higher postexercise cortisol levels (665 ± 200 vs. 543 ± 169 nmol/L, p < .0001) and facilitated greater peak blood lactate accumulation (analysis of variance main effect, p < .05). We recommend that triathlon athletes with relatively low habitual caffeine intake may ingest 6 mg/kg body weight caffeine, 45-60 min before the start of Olympic-distance triathlon to improve their performance.

Plasma electrolytes in relation to altitude tolerance in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Purshottam, T.

1979-04-01

Plasma concentrations of Na(+), K(+) and Cl(-) ions did not change significantly whereas that of (HCO3)- dropped to one-third of its initial value in rats during their 15 min of gasping at a simulated altitude of 10,000 m at 33 C, which was their survival threshold. Administration of methamphetamine (2 mg/kg), imipramine (2 mg/kg) and adrenaline (7 mg/kg) i.p. were ineffective in prolonging the survival time of rats, whereas acetazolamide (40 mg/kg), furosemide (2 mg/kg) and caffeine citrate (10 mg/kg) significantly increased their survival under hypoxia, (p less than 0.001, 0.01, and 0.05, respectively).

Role of Cytochrome P450 3A4 and 1A2 Phenotyping in Patients with Advanced Non-small-Cell Lung Cancer Receiving Erlotinib Treatment.

PubMed

Parra-Guillen, Zinnia P; Berger, Peter B; Haschke, Manuel; Donzelli, Massimiliano; Winogradova, Daria; Pfister, Bogumila; Früh, Martin; Gillessen, Silke; Krähenbühl, Stephan; Kloft, Charlotte; Joerger, Markus

2017-10-01

Erlotinib is metabolized by cytochrome p450 (CYP) 3A and CYP1A. This study assessed CYP3A4 (midazolam) and CYP1A2 (caffeine) phenotyping in plasma and dried blood spots (DBS) for predicting the pharmacokinetics and toxicity of erlotinib in 36 patients with advanced NSCLC. On day 1, erlotinib 150 mg OD was initiated, and the two oral probe drugs midazolam (2 mg) and caffeine (100 mg) were added on day 1. Plasma and DBS were collected for erlotinib, OSI-420 and probe drugs for up to 6 hr on day 1 and 2-weekly up to week 10. Probe drugs, erlotinib and OSI-420 were analysed using LC-MS-MS, and PK data were processed using population modelling. A high correlation was found between plasma and DBS concentrations for erlotinib (R 2  = 0.960, p < 0.0001), OSI-420 (R 2  = 0.971, p < 0.0001), midazolam (R 2  = 0.995, p < 0.0001) and caffeine (R 2  = 0.968, p < 0.0001). Apparent oral caffeine clearance was significantly correlated with erlotinib clearance (R 2  = 0.33, p = 0.048), while midazolam clearance was not (R 2  = -0.09, p = 0.596). Erlotinib clearance was lower in patients experiencing grade 2 or 3 rash as compared to patients experiencing grade 0 or 1 rash (3.15 versus 3.93 L/hr, p = 0.086 for Student's t-test). The results suggest that probe drug phenotyping is unlikely to substitute therapeutic drug monitoring of erlotinib in patients with advanced NSCLC, but erlotinib PK sampling from DBS may replace more invasive venous sampling and facilitate TDM in patients with cancer. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Effect of caffeine, caffeic acid and their various combinations on enzymes of cholinergic, monoaminergic and purinergic systems critical to neurodegeneration in rat brain-In vitro.

PubMed

Akomolafe, S F; Akinyemi, A J; Ogunsuyi, O B; Oyeleye, S I; Oboh, G; Adeoyo, O O; Allismith, Y R

2017-09-01

Caffeine and caffeic acid are two bioactive compounds that are present in plant foods and are major constituent of coffee, cocoa, tea, cola drinks and chocolate. Although not structurally related, caffeine and caffeic acid has been reported to elicit neuroprotective properties. However, their different proportional distribution in food sources and possible effect of such interactions are not often taken into consideration. Therefore, in this study, we investigated the effect of caffeine, caffeic acid and their various combinations on activities of some enzymes [acetylcholinesterase (AChE), monoamine oxidase (MAO) ecto-nucleoside triphosphate diphosphohydrolase (E-NTPase), ecto-5 1 -nucleotidase (E-NTDase) and Na + /K + ATPase relevant to neurodegeneration in vitro in rat brain. The stock concentration of caffeine and caffiec acid and their various proportional combinations were prepared and their interactions with the activities of these enzymes were assessed (in vitro) in different brain structures. The Fe 2+ and Cu 2+ chelating abilities of the samples were also investigated. The results revealed that caffeine, caffeic acid and their various combinations exhibited inhibitory effect on activities of AChE, MAO, E-NTPase and E-NTDase, but stimulatory effect on Na + /K + ATPase activity. The combinations also exhibited Fe 2+ and Cu 2+ chelating abilities. Considering the various combinations, a higher caffeine to caffeic acid ratio produced significantly highest enzyme modulatory effects; these were significantly lower to the effect of caffeine alone but significantly higher than the effect of caffeic acid alone. These findings may provide new insight into the effect of proportional combination of these bioactive compounds as obtained in many foods especially with respect to their neuroprotective effects. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of long term caffeine treatment on A1 and A2 adenosine receptor binding and on mRNA levels in rat brain.

PubMed

Johansson, B; Ahlberg, S; van der Ploeg, I; Brené, S; Lindefors, N; Persson, H; Fredholm, B B

1993-04-01

The effect of long-term oral treatment with caffeine on A1 and A2 receptors in the rat brain was studied. Caffeine was added to the drinking water and the animals were sacrificed after a 12 day treatment period. The plasma caffeine concentration was close to 100 microM. A1 receptors were studied using quantitative autoradiography with [3H]cyclohexyladenosine (CHA). Caffeine treatment increased the number of A1 receptors in the CA3 subfield of the hippocampus from 337 to 393 fmol/mg with no change in KD (0.692 vs. 0.675 nM). A1 mRNA was measured using Northern blots and quantitative in situ hybridization. There was no increase in A1 mRNA. A2a receptors, located in dopamine rich regions of the rat brain, were studied with quantitative autoradiography using [3H]CGS 21680 as the ligand, and the A2a mRNA was determined using quantitative in situ hybridization. Caffeine treatment produced no significant change in either receptor number or mRNA, even though the apparent Bmax tended to increase from 322 +/- 8 to 352 +/- 8 fmol/mg. The results show that treatment with caffeine in a dose that causes tolerance to several effects of caffeine and increases some effects of adenosine analogues increases the number of A1 receptors without any change in A1 mRNA, suggesting that the adaptive changes are at a post-translational level. There were no significant changes in A2 receptors indicating that the two types are regulated differently and/or that the amount of endogenous agonist is sufficient to regulate A1, but not A2 receptors.

Feeling smart: Effects of caffeine and glucose on cognition, mood and self-judgment.

PubMed

Ullrich, Susann; de Vries, Yfke C; Kühn, Simone; Repantis, Dimitris; Dresler, Martin; Ohla, Kathrin

2015-11-01

During education and early career, young adults often face examinations and assessment centers. Coffee and energy drinks are convenient and commonly used to enhance or maintain performance in these situations. Whether these macronutrients improve performance in a demanding and drawn-out multi-task situation is not clear. Using double-blind, placebo-controlled studies, we set out to examine the effects of caffeine and glucose in an assessment center-like situation, under natural consumption conditions, in a group of young adults who were heterogeneous with respect to consumption patterns. We measured multi-task performance including logical thinking, processing speed, numeric and verbal memory, attention and the ability to concentrate, and mood over a two-hour period. Caffeine and glucose were administered in common beverages with appropriate placebo controls allowing the assessment of psychological effects of expectancy. Importantly, and in contrast to most previous studies, participants retained their habitual caffeine and sugar intake (studies 1 and 2) as this represents common behavior. Based on the bulk of literature, we hypothesized that (i) caffeine enhances attentional performance and mood, while performance in more complex tasks will remain unchanged, and that (ii) glucose enhances performance on memory tasks accompanied with negative mood. Our results provide evidence that neither caffeine nor glucose significantly influence cognitive performance when compared with placebo, water, or no treatment controls in a multi-task setting. Yet, caffeine and, by trend, placebo improve dispositions such that participants perceive preserved mental energy throughout the test procedure. These subjective effects were stronger after 24 h caffeine abstinence (study 3). Future studies will have to address whether these mood changes actually result in increased motivation during a challenging task.

Validation of a screening questionnaire for a human milk bank to determine the presence of illegal drugs, nicotine, and caffeine.

PubMed

Escuder-Vieco, Diana; Garcia-Algar, Óscar; Pichini, Simona; Pacifici, Roberta; García-Lara, Nadia Raquel; Pallás-Alonso, Carmen Rosa

2014-04-01

To validate the health and lifestyle questionnaire answered by donors to a human milk bank with respect to the presence of illegal drugs, nicotine, and caffeine levels in donor milk. A total of 400 human milk samples from 63 donors were analyzed by liquid chromatography tandem mass spectrometry for the presence of 14 illegal drugs, nicotine, and caffeine. Demographics and clinical and lifestyle data (illegal drugs, tobacco, and caffeinated beverage use) were collected from the required screening questionnaire of a human milk bank. The relationship between the 2 evaluation techniques was determined. Illegal drugs were not found in donor milk. Nicotine (46.1 ng/mL) and cotinine (138.6 ng/mL) were quantified in one milk sample from a donor who did not report tobacco use in the questionnaire (1.6% false negative). Caffeine was detected in 45.3% (181/400) of the total milk samples, with a mean concentration of 496 ± 778 ng/mL. The sensitivity and specificity of the questionnaire to detect caffeine in donor milk was 46% and 77%, respectively. The lifestyle questionnaire is reliable for the assessment of illicit drug use by donors to a human milk bank, but there are certain limitations regarding the identification of second-hand smoke exposure and the disclosure of consumption of caffeinated beverages. Data such as smoking habits of partners, type and volume of beverage or food containing caffeine, method of preparation, and time of day of consumption should be collected by the questionnaire. Copyright © 2014 Mosby, Inc. All rights reserved.

Randomized Controlled Trial of High-Volume Energy Drink Versus Caffeine Consumption on ECG and Hemodynamic Parameters.

PubMed

Fletcher, Emily A; Lacey, Carolyn S; Aaron, Melenie; Kolasa, Mark; Occiano, Andrew; Shah, Sachin A

2017-04-26

Caffeine in doses <400 mg is typically not considered arrhythmogenic, but little is known about the additional ingredients in energy drinks. We evaluated the ECG and blood pressure (BP) effects of high-volume energy drink consumption compared with caffeine alone. This was a randomized, double-blind, controlled, crossover study in 18 young, healthy volunteers. Participants consumed either 946 mL (32 ounces) of energy drink or caffeinated control drink, both of which contained 320 mg of caffeine, separated by a 6-day washout period. ECG, peripheral BP, and central BP measurements were obtained at baseline and 1, 2, 4, 6, and 24 hours post study drink consumption. The time-matched, baseline-adjusted changes were compared. The change in corrected QT interval from baseline in the energy drink arm was significantly higher than the caffeine arm at 2 hours (0.44±18.4 ms versus -10.4±14.8 ms, respectively; P =0.02). The QTc changes were not different at other time points. While both the energy drink and caffeine arms raised systolic BP in a similar fashion initially, the systolic BP was significantly higher at 6 hours when compared with the caffeine arm (4.72±4.67 mm Hg versus 0.83±6.09 mm Hg, respectively; P =0.01). Heart rate, diastolic BP, central systolic BP, and central diastolic BP showed no evidence of a difference between groups at any time point. Post energy drink, augmentation index was lower at 6 hours. The corrected QT interval and systolic BP were significantly higher post high-volume energy drink consumption when compared with caffeine alone. Larger clinical trials validating these findings and evaluation of noncaffeine ingredients within energy drinks are warranted. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02023723. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Retention of sequential drug discriminations under fixed-interval schedules for long time periods without training.

PubMed

Li, Mi; McMillan, Donald E

2003-08-22

The experiments showed that sequential drug discriminations can be learned and retained under a fixed-interval (FI) schedule for more than 18 months without additional training under a complex three-choice procedure. Pigeons were trained to discriminate among 5 mg/kg pentobarbital, 2 mg/kg D-amphetamine, and saline. After responding stabilized, dose-response curves were determined for other drugs. Subsequently, pentobarbital was replaced with 5 mg/kg morphine as a training drug, and D-amphetamine was replaced with 30 mg/kg caffeine. After the pigeons learned these new discriminations, dose-response curves were redetermined. Initially, chlordiazepoxide substituted for pentobarbital, cocaine substituted for D-amphetamine, and nicotine partially substituted for D-amphetamine. Morphine, Delta9-tetrahydrocannabinol, and caffeine did not substitute for either drug. After retraining with morphine and caffeine, responding occurred on the pentobarbital/morphine key after pentobarbital, chlordiazepoxide and morphine and on the D-amphetamine/caffeine key after D-amphetamine, cocaine and caffeine. After nicotine and Delta9-tetrahyrdocannabinol, responding occurred on the saline key. These data show that drug discriminations learned under fixed-interval schedules are retained for long time periods, even when discrimination training with other drugs occurs during the retention period.

Nanofiltration for concentration of roasted coffee extract: From bench to pilot

NASA Astrophysics Data System (ADS)

Dat, Lai Quoc; Quyen, Nguyen Thi Ngoc

2017-09-01

This paper focused on the application of nanofiltration (NF) for concentration of the roasted coffee extract in instant coffee processing. Three kinds of NF membranes were screened for separation capacity of total dry solid (TDS), polyphenols (PPs) and caffeine in roasted coffee extract and NF99 membrane showed the good performance for the NF of the extract. The crossflow NF with NF99 membrane at pilot scale was investigated for technical assessment of concentration of roasted coffee extract. Maximum theoretical concentration was estimated as 6.06. Recovery yields of TDS, PPs and caffeine were higher than 70% at 4.4 of concentration factor. The content of TDS in accumulative permeate was lower than 2.0 g/L. The fouling of NF was also solved by the suitable cleaning procedure with recovery index being 97.7%. Results of research indicate that it is feasible to apply NF for concentration of the roasted coffee extract in instant coffee production.

[Severe caffeine poisoning with rhabdomyolysis].

PubMed

Wolter, J; Grün, D; Otto, S

2018-04-01

We report the case of a young man who took a large amount of caffeine powder dissolved in water in a suicide attempt. He was found comatose. The initial diagnosis was difficult. In hospital he suffered from rhabdomyolysis with renal failure and sepsis rapidly developed. After renal replacement treatment with hemodialysis, long-term artificial ventilation with tracheotomy and a 3‑week stay in the intensive care unit, the patient could be discharged to a rehabilitation center.

Alcohol, cannabis, nicotine, and caffeine use and symptom distress in schizophrenia.

PubMed

Hamera, E; Schneider, J K; Deviney, S

1995-09-01

The high prevalence of substance use, e.g., alcohol and illegal and nonprescribed drugs, in schizophrenia is widely recognized. One explanation for this high prevalence is that substance use may be a self-initiated method for managing symptoms. To test whether the intake of four substances--alcohol, cannabis, nicotine, and caffeine--would increase with increases in symptom distress, daily self-reports of symptom distress and substance intake over 12 weeks were analyzed with pooled time series analyses. Compliance with neuroleptic medication was added to the analyses to control for any changes in prescribed medication compliance while using nonprescribed drugs or alcohol. Of the four substances studied, only nicotine was significantly related to symptom distress. Higher distress with prodromal symptoms was related to decreases in nicotine use. Analysis of caffeine did not meet the criteria for significance but does provide direction for further research. Higher distress, with neurotic symptoms, was related to increases in caffeine use. Further research is needed to clarify the relationship between nicotine and symptoms.

Association of riboflavin, caffeine, and sodium salicylate in aqueous solution

NASA Astrophysics Data System (ADS)

Baranovskii, S. F.; Bolotin, P. A.

2007-03-01

We have used UV and visible spectrophotometry to study self-association of aromatic riboflavin molecules (RFN, vitamin B2, 7,8-dimethyl-10-N-(1'-D-ribityl)isoalloxazine) in aqueous solution (pH 6.86) at T = 298 K, using a dimer model. We have determined the equilibrium dimerization constant for riboflavin, KdB = 125 ± 40 M-1. We have studied heteroassociation in the system of molecules of 7,8-dimethyl-10-ribitylisoalloxazine with 1,3,7-trimethylxanthine (caffeine) and sodium salicylate (NAS) in aqueous solution (pH 6.86; T = 298 K). We have determined the heteroassociation constants for RFN-NAS and RFN-caffeine molecules in the absence and in the presence of urea in solutions using a modified Benesi-Hildebrand equation: 25 ± 4, 17 ± 3, and 74 ± 11, 53 ± 7 M-1 respectively. We have determined the dimerization constants for NAS (2.7 ± 0.5 M-1) and caffeine (17.0 ± 1.5 M-1). We conclude that heteroassociation of the aromatic molecules leads to a lower effective riboflavin concentration in solution, and the presence of urea in mixed solutions leads to an decrease in the complexation constants for the RFN-NAS and RFN-caffeine systems.

[Determination of catechins and caffeine in tea and tea beverages by high-performance liquid chromatography].

PubMed

Ling, Yun; Zhao, Yun-feng; Li, Zhi-jun; Zhang, Gong; Wu, Yongning

2005-03-01

A high-performance liquid chromatography method was developed for the determination of total tea catechin and caffeine. The catechins needed to be determined are: (-)-catechin, (-)-epigallocatechin, (-)-epigallocatechin gallate, (-)-epicatechin, (-)-epicatechin gallate, (-)-gallocatechin, (-)-gallocatechin gallate, (-)-catechin gallate and caffeine. The catechins in the tea was extracted with water:ethanol (3:7) by sonication for 20 min. After the extraction solution was centrifuged, it was analyzed by HPLC. The column used was a CAPCELL PAK C18 MG (4.6mm I.D. x 150mm) and gradient elution at constant column temperature with 30 degrees C under UV detector with 210nm. Mobile phase A was 0.1% H3PO4 in water, mobile phase B was 0.1% H3PO4 in methanol with the flow rate 1ml/min. The results showed that the concentration of the catechins and caffeine and their peak areas achieved good linear relation, r > 0.999. The recoveries were between 61.7%-117.3%. RSD was below 10%. With this method, some tea samples were determined, the results were favorable. The method can be applied for determination of catechin and caffeine in tea and tea beverages.

Stimulation and inhibition of bacterial growth by caffeine dependent on chloramphenicol and a phenolic uncoupler--a ternary toxicity study using microfluid segment technique.

PubMed

Cao, Jialan; Kürsten, Dana; Schneider, Steffen; Köhler, J Michael

2012-10-01

A droplet-based microfluidic technique for the fast generation of three dimensional concentration spaces within nanoliter segments was introduced. The technique was applied for the evaluation of the effect of two selected antibiotic substances on the toxicity and activation of bacterial growth by caffeine. Therefore a three-dimensional concentration space was completely addressed by generating large sequences with about 1150 well separated microdroplets containing 216 different combinations of concentrations. To evaluate the toxicity of the ternary mixtures a time-resolved miniaturized optical double endpoint detection unit using a microflow-through fluorimeter and a two channel microflow-through photometer was used for the simultaneous analysis of changes on the endogenous cellular fluorescence signal and on the cell density of E. coli cultivated inside 500 nL microfluid segments. Both endpoints supplied similar results for the dose related cellular response. Strong non-linear combination effects, concentration dependent stimulation and the formation of activity summits on bolographic maps were determined. The results reflect a complex response of growing bacterial cultures in dependence on the combined effectors. A strong caffeine induced enhancement of bacterial growth was found at sublethal chloramphenicol and sublethal 2,4-dinitrophenol concentrations. The reliability of the method was proved by a high redundancy of fluidic experiments. The results indicate the importance of multi-parameter investigations for toxicological studies and prove the potential of the microsegmented flow technique for such requirements.

Caffeine May Reduce Perceived Sweet Taste in Humans, Supporting Evidence That Adenosine Receptors Modulate Taste.

PubMed

Choo, Ezen; Picket, Benjamin; Dando, Robin

2017-09-01

Multiple recent reports have detailed the presence of adenosine receptors in sweet sensitive taste cells of mice. These receptors are activated by endogenous adenosine in the plasma to enhance sweet signals within the taste bud, before reporting to the primary afferent. As we commonly consume caffeine, a powerful antagonist for such receptors, in our daily lives, an intriguing question we sought to answer was whether the caffeine we habitually consume in coffee can inhibit the perception of sweet taste in humans. 107 panelists were randomly assigned to 2 groups, sampling decaffeinated coffee supplemented with either 200 mg of caffeine, about the level found in a strong cup of coffee, or an equally bitter concentration of quinine. Participants subsequently performed sensory testing, with the session repeated in the alternative condition in a second session on a separate day. Panelists rated both the sweetened coffee itself and subsequent sucrose solutions as less sweet in the caffeine condition, despite the treatment having no effect on bitter, sour, salty, or umami perception. Panelists were also unable to discern whether they had consumed the caffeinated or noncaffeinated coffee, with ratings of alertness increased equally, but no significant improvement in reaction times, highlighting coffee's powerful placebo effect. This work validates earlier observations in rodents in a human population. © 2017 Institute of Food Technologists®.

Caffeine accelerates recovery from general anesthesia

PubMed Central

Wang, Qiang; Fong, Robert; Mason, Peggy; Fox, Aaron P.

2013-01-01

General anesthetics inhibit neurotransmitter release from both neurons and secretory cells. If inhibition of neurotransmitter release is part of an anesthetic mechanism of action, then drugs that facilitate neurotransmitter release may aid in reversing general anesthesia. Drugs that elevate intracellular cAMP levels are known to facilitate neurotransmitter release. Three cAMP elevating drugs (forskolin, theophylline, and caffeine) were tested; all three drugs reversed the inhibition of neurotransmitter release produced by isoflurane in PC12 cells in vitro. The drugs were tested in isoflurane-anesthetized rats. Animals were injected with either saline or saline containing drug. All three drugs dramatically accelerated recovery from isoflurane anesthesia, but caffeine was most effective. None of the drugs, at the concentrations tested, had significant effects on breathing rates, O2 saturation, heart rate, or blood pressure in anesthetized animals. Caffeine alone was tested on propofol-anesthetized rats where it dramatically accelerated recovery from anesthesia. The ability of caffeine to accelerate recovery from anesthesia for different chemical classes of anesthetics, isoflurane and propofol, opens the possibility that it will do so for all commonly used general anesthetics, although additional studies will be required to determine whether this is in fact the case. Because anesthesia in rodents is thought to be similar to that in humans, these results suggest that caffeine might allow for rapid and uniform emergence from general anesthesia in human patients. PMID:24375022

Inducing somatic meiosis-like reduction at high frequency by caffeine in root-tip cells of Vicia faba.

PubMed

Chen, Y; Zhang, L; Zhou, Y; Geng, Y; Chen, Z

2000-07-20

Germinated seeds of Vicia faba were treated in caffeine solutions of different concentration for different durations to establish the inducing system of somatic meiosis-like reduction. The highest frequency of somatic meiosis-like reduction could reach up to 54.0% by treating the root tips in 70 mmol/l caffeine solution for 2 h and restoring for 24 h. Two types of somatic meiosis-like reduction were observed. One was reductional grouping, in which the chromosomes in a cell usually separated into two groups, and the role of spindle fibers did not show. The other type was somatic meiosis, which was analogous to meiosis presenting in gametogenesis, and chromosome pairing and chiasmata were visualized.

Congenital myopathy results from misregulation of a muscle Ca2+ channel by mutant Stac3

PubMed Central

Linsley, Jeremy W.; Hsu, I-Uen; Groom, Linda; Yarotskyy, Viktor; Lavorato, Manuela; Horstick, Eric J.; Linsley, Drew; Wang, Wenjia; Franzini-Armstrong, Clara; Dirksen, Robert T.; Kuwada, John Y.

2017-01-01

Skeletal muscle contractions are initiated by an increase in Ca2+ released during excitation–contraction (EC) coupling, and defects in EC coupling are associated with human myopathies. EC coupling requires communication between voltage-sensing dihydropyridine receptors (DHPRs) in transverse tubule membrane and Ca2+ release channel ryanodine receptor 1 (RyR1) in the sarcoplasmic reticulum (SR). Stac3 protein (SH3 and cysteine-rich domain 3) is an essential component of the EC coupling apparatus and a mutation in human STAC3 causes the debilitating Native American myopathy (NAM), but the nature of how Stac3 acts on the DHPR and/or RyR1 is unknown. Using electron microscopy, electrophysiology, and dynamic imaging of zebrafish muscle fibers, we find significantly reduced DHPR levels, functionality, and stability in stac3 mutants. Furthermore, stac3NAM myofibers exhibited increased caffeine-induced Ca2+ release across a wide range of concentrations in the absence of altered caffeine sensitivity as well as increased Ca2+ in internal stores, which is consistent with increased SR luminal Ca2+. These findings define critical roles for Stac3 in EC coupling and human disease. PMID:28003463

Effectiveness of Psycho-Physiological Portable Devices to Analyse Effect of Ergogenic Aids in Military Population.

PubMed

Diaz-Manzano, Montaña; Robles-Pérez, José Juan; Herrera-Mendoza, Ketty; Herrera-Tapias, Beliña; Fernández-Lucas, Jesús; Aznar-Lain, Susana; Clemente-Suárez, Vicente Javier

2018-03-24

Caffeine is one of the ergogenic substances most used by warfighters in current operation areas, but the effect on the organic response and operational performed is already poor knowledge. This research aimed to study the acute effect of 400 mg of caffeine monohydrate on the psycho-physiological response and rifle marksmanship of warfighters during a close quarter combat simulation. We analysed parameter of heart rate, blood lactate, cortical arousal, state anxiety and marksmanship of 20 Spanish Army veteran warfighters before and after a close quarter combat simulation in a double-blind procedure, also a correlation analysis was conducted between all the study variables. Marksmanship of warfighters did not improve with the caffeine ingestion, but it produced an increase in blood lactate concentration (caffeine: 1.9 ± 0.5 vs. 9.2 ± 1.1 mmol.l -1 ; placebo: 1.8 ± 0.7 vs. 6.9 ± 2.2 mmol.l -1 ), cortical arousal (% of change: caffeine: 2.51; placebo: -1.96) and heart rate (caffeine: 80.0 ± 7.2 vs. 172.9 ± 28.2 bpm; placebo: 79.3 ± 6.4 vs. 154.0 ± 26.8 bpm). In addition, higher heart rate values correlated negatively with marksmanship in close quarter combat. We concluded that caffeine intake did not improve the warfighters rifle marksmanship in close quarter combat possibly due to the increase in the physiological response.

Single and combined effects of beetroot juice and caffeine supplementation on cycling time trial performance.

PubMed

Lane, Stephen C; Hawley, John A; Desbrow, Ben; Jones, Andrew M; Blackwell, James R; Ross, Megan L; Zemski, Adam J; Burke, Louise M

2014-09-01

Both caffeine and beetroot juice have ergogenic effects on endurance cycling performance. We investigated whether there is an additive effect of these supplements on the performance of a cycling time trial (TT) simulating the 2012 London Olympic Games course. Twelve male and 12 female competitive cyclists each completed 4 experimental trials in a double-blind Latin square design. Trials were undertaken with a caffeinated gum (CAFF) (3 mg·kg(-1) body mass (BM), 40 min prior to the TT), concentrated beetroot juice supplementation (BJ) (8.4 mmol of nitrate (NO3(-)), 2 h prior to the TT), caffeine plus beetroot juice (CAFF+BJ), or a control (CONT). Subjects completed the TT (females: 29.35 km; males: 43.83 km) on a laboratory cycle ergometer under conditions of best practice nutrition: following a carbohydrate-rich pre-event meal, with the ingestion of a carbohydrate-electrolyte drink and regular oral carbohydrate contact during the TT. Compared with CONT, power output was significantly enhanced after CAFF+BJ and CAFF (3.0% and 3.9%, respectively, p < 0.01). There was no effect of BJ supplementation when used alone (-0.4%, p = 0.6 compared with CONT) or when combined with caffeine (-0.9%, p = 0.4 compared with CAFF). We conclude that caffeine (3 mg·kg(-1) BM) administered in the form of a caffeinated gum increased cycling TT performance lasting ∼50-60 min by ∼3%-4% in both males and females. Beetroot juice supplementation was not ergogenic under the conditions of this study.

Using Caffeine as a Water Quality Indicator in the Ambient Monitoring Program for Third Fork Creek Watershed, Durham, North Carolina

PubMed Central

Spence, Porché L

2015-01-01

Caffeine has been suggested as a chemical indicator for domestic wastewater in freshwater systems, although it is not included in water quality monitoring programs. The Third Fork Creek watershed in Durham, NC, is highly urbanized, with a history of receiving untreated wastewater from leaking and overflowing sanitary sewers. The poor water quality originating in the Third Fork Creek watershed threatens its intended uses and jeopardizes drinking water, aquatic life, and recreational activities provided by Jordan Lake. Organic waste contaminants have been detected in both Third Fork Creek watershed and Jordan Lake; however, the sampling periods were temporary, resulting in a few samples collected during nonstorm periods. It is recommended that (1) the concentration of caffeine and other organic waste contaminants are determined during storm and nonstorm periods and (2) caffeine is monitored regularly with traditional water quality indicators to evaluate the health of Third Fork Creek watershed. PMID:26157335

Caffeine and rolipram affect Smad signalling and TGF-β1 stimulated CTGF and transgelin expression in lung epithelial cells.

PubMed

Fehrholz, Markus; Speer, Christian P; Kunzmann, Steffen

2014-01-01

Caffeine administration is an important part of the therapeutic treatment of bronchopulmonary dysplasia (BPD) in preterm infants. However, caffeine mediated effects on airway remodelling are still undefined. The TGF-β/Smad signalling pathway is one of the key pathways involved in airway remodelling. Connective tissue growth factor (CTGF), a downstream mediator of TGF-β, and transgelin, a binding and stabilising protein of the cytoskeleton, are both regulated by TGF-β1 and play an important role in airway remodelling. Both have also been implicated in the pathogenesis of BPD. The aim of the present study was to clarify whether caffeine, an unspecific phosphodiesterase (PDE) inhibitor, and rolipram, a prototypical PDE-4 selective inhibitor, were both able to affect TGF-β1-induced Smad signalling and CTGF/transgelin expression in lung epithelial cells. Furthermore, the effect of transgelin knock-down on Smad signalling was studied. The pharmacological effect of caffeine and rolipram on Smad signalling was investigated by means of a luciferase assay via transfection of a TGF-β1-inducible reporter plasmid in A549 cells. The regulation of CTGF and transgelin expression by caffeine and rolipram were studied by promoter analysis, real-time PCR and Western blot. Endogenous transgelin expression was down-regulated by lentiviral transduction mediating transgelin-specific shRNA expression. The addition of caffeine and rolipram inhibited TGF-β1 induced reporter gene activity in a concentration-related manner. They also antagonized the TGF-β1 induced up-regulation of CTGF and transgelin on the promoter-, the mRNA-, and the protein-level. Functional analysis showed that transgelin silencing reduced TGF-β1 induced Smad-signalling and CTGF induction in lung epithelial cells. The present study highlights possible new molecular mechanisms of caffeine and rolipram including an inhibition of Smad signalling and of TGF-β1 regulated genes involved in airway remodelling. An understanding of these mechanisms might help to explain the protective effects of caffeine in prevention of BPD and suggests rolipram to be a potent replacement for caffeine.

Chemoprevention of dibenzo[a,l]pyrene transplacental carcinogenesis in mice born to mothers administered green tea: primary role of caffeine

PubMed Central

Castro, David J.; Yu, Zhen; Löhr, Christiane V.; Pereira, Clifford B.; Giovanini, Jack N.; Fischer, Kay A.; Orner, Gayle A.; Dashwood, Roderick H.; Williams, David E.

2008-01-01

Our laboratory recently developed a mouse model of transplacental induction of lymphoma, lung and liver cancer by the polycyclic aromatic hydrocarbon, dibenzo[a,l]pyrene (DBP). Pregnant B6129SF1 females, bred to 129S1/SvIm males, were treated on day 17 of gestation with an oral dose of 15 mg/kg DBP. Beginning on day 0 of gestation, dams were given (ad lib) buffered water, 0.5% green tea, 0.5% decaffeinated green tea, caffeine or epigallocatechin-3-gallate (EGCG) (both at equivalent concentrations found in tea). The concentration of the teas (and corresponding caffeine and EGCG) was increased to 1.0% upon entering the second trimester, 1.5% at onset of the third trimester and continued at 1.5% until pups were weaned at 21 days of age. Offspring were raised with normal drinking water and AIN93G diet. Beginning at 2 months of age, offspring experienced significant mortalities due to an aggressive T-cell lymphoma as seen in our previous studies. Ingestion of caffeinated, but not decaffeinated, green tea provided modest but significant protection (P = 0.03) against mortality. Caffeine provided a more robust (P = 0.006) protection, but EGCG was without effect. Offspring also developed DBP-dependent lung adenomas. All treatments significantly reduced lung tumor multiplicity relative to controls (P < 0.02). EGCG was most effective at decreasing tumor burden (P = 0.005) by on average over 40% compared with controls. Induction of Cytochrome P450 (Cyp)1b1 in maternal liver may reduce bioavailability of DBP to the fetus as a mechanism of chemoprevention. This is the first demonstration that maternal ingestion of green tea, during pregnancy and nursing, provides protection against transplacental carcinogenesis. PMID:18635525

Distributions of pharmaceuticals in an urban estuary during both dry- and wet-weather conditions

USGS Publications Warehouse

Benotti, M.J.; Brownawell, Bruce J.

2007-01-01

Pharmaceuticals and selected major human metabolites are ubiquitous in Jamaica Bay, a wastewater-impacted estuary at concentrations in the low ng/L to low ??g/L range. Concentrations throughout the bay are often consistent with conservative behavior during dry-weather conditions, as evidenced by nearly linear concentration-salinity relationships. Deviation from conservative behavior is noted for some pharmaceuticals and attributed to microbial degradation. Caffeine, cotinine, nicotine, and paraxanthine were detected with the greatest analytical signal, although evidence is presented for in situ removal, especially for nicotine and caffeine. There is little evidence for significant removal of carbamazepine and sulfamethoxazole, suggesting they are more conservative and useful wastewater tracers. Immediately following heavy precipitation, which induced a combined sewer overflow (CSO) event, the concentrations of all compounds but acetaminophen and nicotine decreased or disappeared. This observation is consistent with a simple model illustrating the effect of precipitation has on pharmaceutical concentration in the wastewater stream, given the balance between dilution from rain and the bypass of treatment. ?? 2007 American Chemical Society.

Influence of the urine flow rate on some caffeine metabolite ratios used to assess CYP1A2 activity.

PubMed

Sinués, Blanca; Fanlo, Ana; Bernal, María Luisa; Mayayo, Esteban; Soriano, María Antonia; Martínez-Ballarin, Enrique

2002-12-01

Five established metabolite ratios (MRs) to measure P450 CYP1A2 activity--MR1 (17X + 17U)/137X, MR2 (AFMU + 1X + 1U)/17U, MR3 (17X/137X), MR4 (AFMU + 1X + 1U + 17X + 17U)/137X, and MR5 (AFMU + 1X + 1U)/17X--were calculated in urine 4-5 hours after caffeine intake. First, to assess the potential of omeprazole to induce CYP1A2 activity, a caffeine test was performed in 27 subjects on two occasions: before and after 14 days on omeprazole (20 mg/day). Samples of urine were analyzed by high-performance liquid chromatography (HPLC) to quantify caffeine and metabolites used to calculate the different caffeine MRs. MR1, MR3, and MR4 were enhanced after treatment; the percentage of change was inversely associated with that of the urine flow, with r values of -0.48, -0.49, and -0.47, respectively. However, MR2 or MR5 were not modified. To determine the reason for these contradictory results, the authors analyzed data of metabolites, ratios, and their components (numerators and denominators) from 152 subjects (who underwent one caffeine test) and their relationship with the urinary flow. Caffeine concentration in urine was the only compound nondependent on the urine flow. Consistently, ratios containing caffeine (MR1, MR3, and MR4) were highly influenced by the rate of urine excretion, since the flow dependence of their numerators is not canceled out by that of caffeine in their denominators. The dependency of the caffeine excretion on renal factors may explain the opposite results found with the different ratios in the aforementioned prospective study of drug interaction, the absence of closer correlations of the five MRs to each other, the discrepancies about the type of frequency distribution of the different MRs (either normal or multimodal), and the higher sensitivity of MR2 to detect gender differences in CYP1A2 activity found in this study. In summary, the data clearly emphasize the need for a strict control of the liquid intake to avoid high urine flows when MRs containing caffeine are used to assess CYP1A2 activity, especially in studies of drug interactions.

Stability of catechins in green tea nutraceutical products: application of solid phase extraction-thin layer chromatography densitometry.

PubMed

Abd-Elsalam, Heba-Alla H; Al-Ghobashy, Medhat A; Zaazaa, Hala E; Ibrahim, Mohamed A

2014-08-01

Epigallocatechin gallate (EGCG) is a powerful antioxidant and commonly used nutraceutical. Accelerated stability of EGCG in tablet formulations was investigated. LLE and SPE were employed for sample clean-up and enrichment of EGCG over caffeine. Samples were analysed after spiking with fixed concentration of gallic acid (GA), in order to verify reproducibility of analysis. A TLC-densitometric assay was developed and validated for determination of % loss EGCG. EGCG, GA and caffeine were resolved with Rf values 0.54, 0.69 and 0.80, respectively. LC-MS/MS was used to verify identity and purity of the EGCG band. Determination was carried out over a concentration range of 0.50-5.00μg/band and 0.20-2.40μg/band for GA and caffeine, respectively. Results showed significant reduction in EGCG content after one, three and six months: 24.00%, 28.00% and 52.00% respectively. Results continue to demonstrate that stability of nutraceutical products should be investigated in-depth using industry-oriented protocols before granting marketing authorisation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of the endcapping of reversed-phase high-performance liquid chromatography adsorbents on the adsorption isotherm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gritti, Fabrice; Guiochon, Georges A

2005-09-01

The retention mechanisms of n-propylbenzoate, 4-t ert-butylphenol, and caffeine on the endcapped Symmetry-C{sub 18} and the non-endcapped Resolve-C{sub 18} are compared. The adsorption isotherms were measured by frontal analysis (FA), using as the mobile phase mixtures of methanol or acetonitrile and water of various compositions. The isotherm data were modeled and the adsorption energy distributions calculated. The surface heterogeneity increases faster with decreasing methanol concentration on the non-endcapped than on the endcapped adsorbent. For instance, for methanol concentrations exceeding 30% (v/v), the adsorption of caffeine is accounted for by assuming three and two different types of adsorption sites on Resolve-C{submore » 18} and Symmetry-C{sub 18}, respectively. This is explained by the effect of the mobile phase composition on the structure of the C{sub 18}-bonded layer. The bare surface of bonded silica appears more accessible to solute molecules at high water contents in the mobile phase. On the other hand, replacing methanol by a stronger organic modifier like acetonitrile dampens the differences between non-endcapped and endcapped stationary phase and decreases the degree of surface heterogeneity of the adsorbent. For instance, at acetonitrile concentrations exceeding 20%, the surface appears nearly homogeneous for the adsorption of caffeine.« less

Conformation of ryanodine receptor-2 gates store-operated calcium entry in rat pulmonary arterial myocytes

PubMed Central

Lin, Amanda H.Y.; Sun, Hui; Paudel, Omkar; Lin, Mo-Jun; Sham, James S.K.

2016-01-01

Aims Store-operated Ca2+ entry (SOCE) contributes to a multitude of physiological and pathophysiological functions in pulmonary vasculatures. SOCE attributable to inositol 1,4,5-trisphosphate receptor (InsP3R)-gated Ca2+ store has been studied extensively, but the role of ryanodine receptor (RyR)-gated store in SOCE remains unclear. The present study aims to delineate the relationship between RyR-gated Ca2+ stores and SOCE, and characterize the properties of RyR-gated Ca2+ entry in pulmonary artery smooth muscle cells (PASMCs). Methods and results PASMCs were isolated from intralobar pulmonary arteries of male Wister rats. Application of the RyR1/2 agonist 4-chloro-m-cresol (4-CmC) activated robust Ca2+ entry in PASMCs. It was blocked by Gd3+ and the RyR2 modulator K201 but was unaffected by the RyR1/3 antagonist dantrolene and the InsP3R inhibitor xestospongin C, suggesting RyR2 is mainly involved in the process. siRNA knockdown of STIM1, TRPC1, and Orai1, or interruption of STIM1 translocation with ML-9 significantly attenuated the 4-CmC-induced SOCE, similar to SOCE induced by thapsigargin. However, depletion of RyR-gated store with caffeine failed to activate Ca2+ entry. Inclusion of ryanodine, which itself did not cause Ca2+ entry, uncovered caffeine-induced SOCE in a concentration-dependent manner, suggesting binding of ryanodine to RyR is permissive for the process. This Ca2+ entry had the same molecular and pharmacological properties of 4-CmC-induced SOCE, and it persisted once activated even after caffeine washout. Measurement of Ca2+ in sarcoplasmic reticulum (SR) showed that 4-CmC and caffeine application with or without ryanodine reduced SR Ca2+ to similar extent, suggesting store-depletion was not the cause of the discrepancy. Moreover, caffeine/ryanodine and 4-CmC failed to initiate SOCE in cells transfected with the ryanodine-binding deficient mutant RyR2-I4827T. Conclusions RyR2-gated Ca2+ store contributes to SOCE in PASMCs; however, store-depletion alone is insufficient but requires a specific RyR conformation modifiable by ryanodine binding to activate Ca2+ entry. PMID:27013634

Biphasic decay of the Ca transient results from increased sarcoplasmic reticulum Ca leak

PubMed Central

Sankaranarayanan, Rajiv; Li, Yatong; Greensmith, David J.; Eisner, David A.

2016-01-01

Key points Ca leak from the sarcoplasmic reticulum through the ryanodine receptor (RyR) reduces the amplitude of the Ca transient and slows its rate of decay.In the presence of β‐adrenergic stimulation, RyR‐mediated Ca leak produces a biphasic decay of the Ca transient with a fast early phase and a slow late phase.Two forms of Ca leak have been studied, Ca‐sensitising (induced by caffeine) and non‐sensitising (induced by ryanodine) and both induce biphasic decay of the Ca transient.Only Ca‐sensitising leak can be reversed by traditional RyR inhibitors such as tetracaine.Ca leak can also induce Ca waves. At low levels of leak, waves occur. As leak is increased, first biphasic decay and then slowed monophasic decay is seen. The level of leak has major effects on the shape of the Ca transient. Abstract In heart failure, a reduction in Ca transient amplitude and contractile dysfunction can by caused by Ca leak through the sarcoplasmic reticulum (SR) Ca channel (ryanodine receptor, RyR) and/or decreased activity of the SR Ca ATPase (SERCA). We have characterised the effects of two forms of Ca leak (Ca‐sensitising and non‐sensitising) on calcium cycling and compared with those of SERCA inhibition. We measured [Ca2+]i with fluo‐3 in voltage‐clamped rat ventricular myocytes. Increasing SR leak with either caffeine (to sensitise the RyR to Ca activation) or ryanodine (non‐sensitising) had similar effects to SERCA inhibition: decreased systolic [Ca2+]i, increased diastolic [Ca2+]i and slowed decay. However, in the presence of isoproterenol, leak produced a biphasic decay of the Ca transient in the majority of cells while SERCA inhibition produced monophasic decay. Tetracaine reversed the effects of caffeine but not of ryanodine. When caffeine (1 mmol l−1) was added to a cell which displayed Ca waves, the wave frequency initially increased before waves disappeared and biphasic decay developed. Eventually (at higher caffeine concentrations), the biphasic decay was replaced by slow decay. We conclude that, in the presence of adrenergic stimulation, Ca leak can produce biphasic decay; the slow phase results from the leak opposing Ca uptake by SERCA. The degree of leak determines whether decay of Ca waves, biphasic or monophasic, occurs. PMID:26537441

Extraction of methylxanthines from guaraná seeds, maté leaves, and cocoa beans using supercritical carbon dioxide and ethanol.

PubMed

Saldaña, Marleny D A; Zetzl, Carsten; Mohamed, Rahoma S; Brunner, G

2002-08-14

New experimental data on the extraction of caffeine from guaraná seeds and maté tea leaves, and theobromine from cocoa beans, with supercritical CO2 were obtained using a high-pressure extraction apparatus. The effect of the addition of ethanol to carbon dioxide on the extraction efficiency was also investigated. Caffeine extraction yields of 98% of the initial caffeine content in both wet ground guaraná seeds and maté tea leaves were obtained. Extractions of caffeine from guaraná seeds and maté tea leaves also exhibited a retrograde behavior for the two temperatures considered in this work. In the removal of theobromine from cocoa beans, a much smaller extraction yield was obtained with longer extraction periods and consequently larger solvent requirements. The results of this study confirm the higher selectivity of CO2 for caffeine in comparison with that for theobromine, and also the influence of other components in each particular natural product on the extraction of methylxanthines. The effect of the addition of ethanol to carbon dioxide on the extraction of methylxanthines was significant, particularly in the extraction of theobromine from cocoa beans. In general, the use of ethanol results in lower solvent and energy requirements and thereby improved extraction efficiency.

Design and evaluation of a restraint-free small animal inhalation dosing chamber.

PubMed

McConville, Jason T; Williams, Robert O; Carvalho, Thiago C; Iberg, Aimee N; Johnston, Keith P; Talbert, Robert L; Burgess, David; Peters, Jay I

2005-01-01

The aim of research was to design a small, restraint free, low stress animal dosing chamber for inhalation studies, and to investigate distribution of a model drug within the chamber. A small animal dosing chamber was designed that consisted of a polymethylmethacrylate (PMMA) airtight box (40.6 x 11.4 x 21.6 cm) with a hinged top, having a nominal wall thickness of 1.25 cm. The chamber was designed to hold up to 14 mice, each having a floor area of approximately 63 cm2, in accordance with Institutional Animal Care and Use Committee (IACUC) guidelines. A "rodent proof" distribution fan was attached to the center of the hinged closure lid. The chamber was divided into 1 inch2 zones (120 in total) to enable a profile of drug distribution within the chamber to be obtained. Small holes were drilled into the side of the chamber and sealed using Parafilm to allow access to the sampling zones. Syringes (5 mL) with appropriate length polytetrafluoroethylene (PTFE) tubing were inserted into the holes to reach the sampling zones (eight on either side of the chamber giving a total of 16 zones). An aqueous caffeine solution (2% w/v) in glycerol (25% w/v) was prepared and nebulized into the chamber using an Aeroneb Pro nebulizer. Caffeine containing droplets were circulated into the chamber at a flow rate of 1.5 L/min(-1), and the air was recirculated in a closed system for a total of 20 minutes to ensure a high concentration of caffeine droplets throughout. Following nebulization, air samples (5 mL) were withdrawn from the 16 sampling zones of the sealed chamber. The process was repeated in quadruplet until a total of 64 sampling zones had been sampled. The entire experiment was also repeated with the absence of the "rodent-proof" distribution fan. Drug concentrations were calculated from a calibration curve of caffeine using UV absorbance at 272 nm. An average mass of caffeine (Standard Deviation; S.D.) of 5.0 (4.2) mg was detected throughout the chamber when the distribution fan was fitted, and caffeine 12.6 (9.7) mg was detected without the fan. This indicated that presence of the fan caused impingement of the drug on both the chamber walls and fan components; effectively removing nebulized drug from circulation within the chamber. The distribution of drug was plotted using a 3D graph; this revealed a lower concentration at the periphery and a higher concentration in the center of the chamber both with and without the distribution fan in place. In conclusion, a humane, nonrestraint rodent dosing chamber was designed for the efficient delivery of nebulized drugs for up to 14 mice simultaneously. The highest levels of the model drug caffeine were detectable throughout the small animal dosing chamber without the distribution fan. A circulation flow rate of 1.5 L/min(-1) was found to be adequate to distribute drug in the chamber. Surprisingly, the results demonstrate that avoiding the use of a distribution fan altogether maximizes the drug concentration within the chamber by reducing impingement of the nebulized drug. The small animal, restraint-free dosing chamber represents an advancement in reproducible dosing via the pulmonary route in the small animal model. The dosing chamber may be adapted to present the lung with an almost unlimited array of compounds, encompassing drugs, toxic compounds, and even pathogens, while still maintaining a relatively stress-free microenvironment for the test subject and furthermore, total safety for the operator.

Effect of a moderate caffeine dose on endurance cycle performance and thermoregulation during prolonged exercise in the heat.

PubMed

Beaumont, Ross E; James, Lewis J

2017-11-01

This study investigated the influence of a moderate caffeine dose on endurance cycle performance and thermoregulation during prolonged exercise in high ambient temperature. Double-blind cross-over study. Eight healthy, recreationally active males (mean±SD; age: 22±1 years; body mass: 71.1±8.5kg; VO 2peak : 55.9±5.8mLkg -1 min -1 ; W max : 318±37W) completed one VO 2peak test, one familiarisation trial and two experimental trials. After an overnight fast, participants ingested a placebo or a 6mgkg -1 caffeine dose 60min before exercise. The exercise protocol consisted of 60min of cycle exercise at 55% W max , followed by a 30min performance task (total kJ produced) in 30°C and 50% RH. Performance was enhanced (Cohen's d effect size=0.22) in the caffeine trial (363.8±47.6kJ) compared with placebo (353.0±49.0kJ; p=0.004). Caffeine did not influence core (p=0.188) or skin temperature (p=0.577) during exercise. Circulating prolactin (p=0.572), cortisol (p=0.842) and the estimated rates of fat (p=0.722) and carbohydrate oxidation (p=0.454) were also similar between trial conditions. Caffeine attenuated perceived exertion during the initial 60min of exercise (p=0.033), with no difference in thermal stress across trials (p=0.911). Supplementation with 6mgkg -1 caffeine improved endurance cycle performance in a warm environment, without differentially influencing thermoregulation during prolonged exercise at a fixed work-rate versus placebo. Therefore, moderate caffeine doses which typically enhance performance in temperate environmental conditions also appear to benefit endurance performance in the heat. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Time for tea: mood, blood pressure and cognitive performance effects of caffeine and theanine administered alone and together.

PubMed

Rogers, Peter J; Smith, Jessica E; Heatherley, Susan V; Pleydell-Pearce, C W

2008-01-01

Although both contain behaviourally significant concentrations of caffeine, tea is commonly perceived to be a less stimulating drink than coffee. At least part of the explanation for this may be that theanine, which is present in tea but not coffee, has relaxing effects. There is also some evidence that theanine affects cognitive performance, and it has been found to reduce blood pressure in hypertensive rats. To study the subjective, behavioural and blood pressure effects of theanine and caffeine administered alone and together, in doses relevant to the daily tea consumption of regular tea drinkers. In a randomised, double-blind, placebo-controlled study, healthy adult participants (n = 48) received either 250-mg caffeine, 200-mg theanine, both or neither of these. They completed ratings of mood, including anxiety, and alertness, and had their blood pressure measured before and starting 40 min after drug administration. Anxiety was also assessed using a visual probe task. Caffeine increased self-rated alertness and jitteriness and blood pressure. Theanine antagonised the effect of caffeine on blood pressure but did not significantly affect jitteriness, alertness or other aspects of mood. Theanine also slowed overall reaction time on the visual probe task. Theanine is a physiologically and behaviourally active compound and, while it is unclear how its effects might explain perceived differences between tea and coffee, evidence suggests that it may be useful for reducing raised blood pressure.

Effects of acute caffeine supplementation on reducing exercise-associated hypoglycaemia in individuals with Type 1 diabetes mellitus.

PubMed

Zaharieva, D P; Miadovnik, L A; Rowan, C P; Gumieniak, R J; Jamnik, V K; Riddell, M C

2016-04-01

To determine the effects of acute caffeine ingestion on glycaemia during moderate to vigorous intensity aerobic exercise and in recovery in individuals with Type 1 diabetes. A total of 13 patients with Type 1 diabetes [eight women, five men: mean ± sd age 25.9 ± 8.8 years, BMI 71.9 ± 11.0 kg, maximal oxygen consumption 46.6 ± 12.7 ml/kg/min, body fat 19.9 ± 7.2%, duration of diabetes 14.4 ± 10.1 years and HbA1c 55 ± 8 mmol/mol (7.4 ± 0.8%)] were recruited. Participants ingested capsules that contained gelatin or pure caffeine (6.0 mg/kg body mass) and performed afternoon exercise for 45 min at 60% maximal oxygen consumption on two separate visits with only circulating basal insulin levels. The main finding was that a single caffeine dose attenuates the drop in glycaemia by 1.8 ± 2.8 mmol/l compared with placebo intake during exercise (P=0.056). Continuous glucose monitoring data, however, showed that caffeine was associated with elevated glycaemia at bedtime after exercise, compared with placebo, but lower glucose concentrations in the early morning the next day. Caffeine intake should be considered as another strategy that may modestly attenuate hypoglycaemia in individuals with Type 1 diabetes during exercise, but should be taken with precautionary measures as it may increase the risk of late-onset hypoglycaemia. © 2015 Diabetes UK.

Effect of caffeine on vestibular evoked myogenic potential: a systematic review with meta-analysis.

PubMed

Souza, Maria Eduarda Di Cavalcanti Alves de; Costa, Klinger Vagner Teixeira da; Menezes, Pedro de Lemos

2017-12-24

Caffeine can be considered the most consumed drug by adults worldwide, and can be found in several foods, such as chocolate, coffee, tea, soda and others. Overall, caffeine in moderate doses, results in increased physical and intellectual productivity, increases the capacity of concentration and reduces the time of reaction to sensory stimuli. On the other hand, high doses can cause noticeable signs of mental confusion and error induction in intellectual tasks, anxiety, restlessness, muscle tremors, tachycardia, labyrinthine changes, and tinnitus. Considering that the vestibular evoked myogenic potential is a clinical test that evaluates the muscular response of high intensity auditory stimulation, the present systematic review aimed to analyze the effects of caffeine on vestibular evoked myogenic potential. This study consisted of the search of the following databases: MEDLINE, CENTRAL, ScienceDirect, Scopus, Web of Science, LILACS, SciELO and ClinicalTrials.gov. Additionally, the gray literature was also searched. The search strategy included terms related to intervention (caffeine or coffee consumption) and the primary outcome (vestibular evoked myogenic potential). Based on the 253 potentially relevant articles identified through the database search, only two full-text publications were retrieved for further evaluation, which were maintained for qualitative analysis. Analyzing the articles found, caffeine has no effect on vestibular evoked myogenic potential in normal individuals. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Does caffeine influence the anticholinesterase and antioxidant properties of donepezil? Evidence from in vitro and in vivo studies.

PubMed

Oboh, Ganiyu; Ogunsuyi, Opeyemi Babatunde; Olonisola, Oluwaseyi Emmanuel

2017-04-01

Caffeine is adjudged world's most consumed pharmacologically active food component. With reports of the potential cognitive enhancing properties of caffeine, we sought to investigate if caffeine can influence the anticholinesterase and antioxidant properties of donepezil-a selective acetylcholinesterase (AChE) inhibitor used in the management of Alzheimer's disease (AD). In vitro, we investigated the effect of donepezil (DON), caffeine (CAF) and their various combinations on the activity of AChE in rat brain homogenate, as well as determined their antioxidant properties. In vivo, two rat groups were administered single oral dose of DON (5 mg/kg) and CAF (5 mg/kg) separately, while three groups, each received 5 mg/kg DON plus either 5, 50 or 100 mg/kg CAF for three hours, after which the rats were sacrificed and brain isolated. Results show that CAF concentration dependently and synergistically increased the anticholinesterase properties of DON in vitro. Also, CAF produced a significant influence on investigated in vitro antioxidant properties of DON. Furthermore, rats administered 5 mg/kg CAF and DON produced no significant difference in AChE activity compared to rats administered DON alone. However, co-administration of either 50 or 100 mg/kg CAF with DON lead to higher AChE activity compared to both control and DON groups. In addition, DON, CAF and their various combinations augmented brain antioxidant status in treated rats. We conclude that while low caffeine consumption may improve the antioxidant properties of donepezil without having a significant influence on its anticholinesterase effect, moderate-high caffeine consumption could also improve the antioxidant properties of donepezil but reduce its anticholinesterase effect; nevertheless, a comprehensive clinical trial is essential to fully explore these possibilities in human AD condition.

Wastewater analysis to monitor use of caffeine and nicotine and evaluation of their metabolites as biomarkers for population size assessment.

PubMed

Senta, Ivan; Gracia-Lor, Emma; Borsotti, Andrea; Zuccato, Ettore; Castiglioni, Sara

2015-05-01

The use of caffeine, nicotine and some major metabolites was investigated by wastewater analysis in 13 sewage treatment plants (STPs) across Italy, and their suitability was tested as qualitative and quantitative biomarkers for assessing population size and dynamics. A specific analytical method based on mass spectrometry was developed and validated in raw urban wastewater, and included two caffeine metabolites, 1-methylxanthine and 7-methylxanthine, never reported in wastewater before. All these compounds were found widely at the μg/L level. Mass loads, calculated by multiplying concentrations by the wastewater daily flow rate and normalized to the population served by each plant, were used to compare the profiles from different cities. Some regional differences were observed in the mass loads, especially for nicotine metabolites, which were significantly higher in the south than in the center and north of Italy, reflecting smoking prevalences from population surveys. There were no significant weekly trends, although the mean mass loads of caffeine and its metabolites were slightly lower during the weekend. Most caffeine and nicotine metabolites fulfilled the requirements for an ideal biomarker for the assessment of population size, i.e. being easily detectable in wastewater, stable in sewage and during sampling, and reflecting human metabolism. Nicotine metabolites were tested as quantitative biomarkers to estimate population size and the results agreed well with census data. Caffeine and its metabolites were confirmed as good qualitative biomarkers, but additional information is needed on the caffeine metabolism in relation to the multiple sources of its main metabolites. This exploratory study opens the way to the routine use of nicotine metabolites for estimating population size and dynamics. Copyright © 2015 Elsevier Ltd. All rights reserved.

Alcohol, caffeine, and nicotine consumption in adolescents: hair analysis versus self-report.

PubMed

Bertol, Elisabetta; Vaiano, Fabio; Boscolo-Berto, Rafael; Fioravanti, Alessia; Palumbo, Diego; Catalani, Valeria; Mari, Francesco; Patussi, Valentino; Serpelloni, Giovanni

2017-05-01

Clinical reliability of self-reported data for alcohol, caffeine, and nicotine consumptions is lacking, particularly in adolescents. To compare a self-report questionnaire and hair analysis to assess the reliability and effectiveness of the self-report. A cross-sectional study on 14-15-year-old Italian students (n = 874, 38% males, 62% females) was performed comparing self-reported data to hair analysis. The latter quantified hair concentrations of caffeine, nicotine, cotinine, ethyl glucuronide (EtG), and fatty acid ethyl esters (FAEEs) using mass spectrometry. Concordance between self-report and hair testing ranged from good to poor across substances and levels of use: poor for heavy alcohol intake (EtG: k = 0.36, 20 positive cases by hair analysis, false negative by self-report, 2.3% of total sample; FAEE k = 0.31, 25 positive cases, 2.9% of total sample); fair to poor for active smokers (k = 0.40, 125 positive cases, 14.3% of total sample); and moderate for caffeine (k = 0.57, 56 positive cases, 6.4% of total sample). Epidemiological studies on alcohol, caffeine, and nicotine consumption in adolescents may benefit from the inclusion of toxicological analysis on hair samples to overcome the under-reporting phenomenon of questionnaires and detect more cases of problematic substance use.

Determination of L-ephedrine, pseudoephedrine, and caffeine in rat plasma by liquid chromatography-tandem mass spectrometry.

PubMed

Cooper, Stephen D; Fletcher, Brenda L; Silinski, Melanie A Rehder; Brown, Sherri S; Lodge, Jon W; Fernando, Reshan A; Collins, Bradley J

2011-07-01

A rapid and simple liquid chromatography tandem mass spectrometry method was developed and validated for the simultaneous determination of L-ephedrine, pseudoephedrine, and caffeine in male Fisher-344 rat plasma at nanogram-per-milliliter concentrations for use in support of toxicology studies. Only 25 μL of plasma is required, and extraction is performed using a simple, single-step protein precipitation. The method was validated over a range of 2.09 to 5460 ng/mL for L-ephedrine, 2.09 to 5050 ng/mL for pseudoephedrine and 2.03 to 5340 ng/mL for caffeine. A binary gradient elution at 0.3 mL/min was used with a Waters XBridge Phenyl (2.1 × 150 mm, 3.5 μm) column and a Waters XBridge Phenyl 2.1- × 10-mm guard column at ambient temperature. The mobile phase consisted of 10 mM ammonium acetate in water (pH 5.0) and methanol. Caffeine trimethyl-(13)C(3) was used as the internal standard. The method was evaluated for linearity, recovery, precision, accuracy, and stability, and it was successfully applied in toxicokinetic studies of ephedrine, administered alone, in combination with caffeine, and in the herbal source Ma Huang.

Expression for caffeine biosynthesis and related enzymes in Camellia sinensis.

PubMed

Kato, Misako; Kitao, Naoko; Ishida, Mariko; Morimoto, Hanayo; Irino, Fumi; Mizuno, Kouichi

2010-01-01

Caffeine (1,3,7-trimethylxanthine) is a purine alkaloid that is present in high concentrations in the tea plant Camellia sinensis. Caffeine synthase (CS, EC 2.1.1.160) catalyzes the S-adenosyl-L-methionine-dependent N-3- and N-1-methylation of the purine base to form caffeine, the last step in the purine alkaloid biosynthetic pathway. We studied the expression profile of the tea caffeine synthase (TCS) gene in developing leaves and flowers by means of northern blot analysis, and compared it with those of phenylalanine ammonia lyase (PAL, EC 4.3.1.5), chalcone synthase (CHS, EC 2.3.1.74), and S-adenosyl-L-methionine synthase (SAMS, EC 2.5.1.6). The amount of TCS transcripts was highest in young leaves and declined markedly during leaf development, whereas it remained constant throughout the development of the flower. Environmental stresses other than heavy metal stress and plant hormone treatments had no effect on the expression of TCS genes, unlike the other three genes. Drought stress suppressed TCS gene expression in leaves, and the expression pattern mirrored that of the dehydrin gene. The amounts of TCS transcripts increased slightly on supply of a nitrogen source. We discuss the regulation of TCS gene expression.

Acute consumption of a caffeinated energy drink enhances aspects of performance in sprint swimmers.

PubMed

Lara, Beatriz; Ruiz-Vicente, Diana; Areces, Francisco; Abián-Vicén, Javier; Salinero, Juan José; Gonzalez-Millán, Cristina; Gallo-Salazar, César; Del Coso, Juan

2015-09-28

This study investigated the effect of a caffeinated energy drink on various aspects of performance in sprint swimmers. In a randomised and counterbalanced order, fourteen male sprint swimmers performed two acute experimental trials after the ingestion of a caffeinated energy drink (3 mg/kg) or after the ingestion of the same energy drink without caffeine (0 mg/kg; placebo). After 60 min of ingestion of the beverages, the swimmers performed a countermovement jump, a maximal handgrip test, a 50 m simulated competition and a 45 s swim at maximal intensity in a swim ergometer. A blood sample was withdrawn 1 min after the completion of the ergometer test. In comparison with the placebo drink, the intake of the caffeinated energy drink increased the height in the countermovement jump (49.4 (SD 5.3) v. 50.9 (SD 5.2) cm, respectively; P<0.05) and maximal force during the handgrip test with the right hand (481 (SD 49) v. 498 (SD 43) N; P<0.05). Furthermore, the caffeinated energy drink reduced the time needed to complete the 50 m simulated swimming competition (27.8 (SD 3.4) v. 27.5 (SD 3.2) s; P<0.05), and it increased peak power (273 (SD 55) v. 303 (SD 49) W; P <0.05) and blood lactate concentration (11.0 (SD 2.0) v. 11.7 (SD 2.1) mM; P<0.05) during the ergometer test. The caffeinated energy drink did not modify the prevalence of insomnia (7 v. 7%), muscle pain (36 v. 36%) or headache (0 v. 7%) during the hours following its ingestion (P>0.05). A caffeinated energy drink increased some aspects of swimming performance in competitive sprinters, whereas the side effects derived from the intake of this beverage were marginal at this dosage.

Chronic coffee and caffeine ingestion effects on the cognitive function and antioxidant system of rat brains.

PubMed

Abreu, Renata Viana; Silva-Oliveira, Eliane Moretto; Moraes, Márcio Flávio Dutra; Pereira, Grace Schenatto; Moraes-Santos, Tasso

2011-10-01

Coffee is a popular beverage consumed worldwide and its effect on health protection has been well studied throughout literature. This study investigates the effect of chronic coffee and caffeine ingestion on cognitive behavior and the antioxidant system of rat brains. The paradigms of open field and object recognition were used to assess locomotor and exploratory activities, as well as learning and memory. The antioxidant system was evaluated by determining the activities of glutathione reductase (GR), glutathione peroxidase (GPx) and superoxide dismutase (SOD), as well as the lipid peroxidation and reduced glutathione content. Five groups of male rats were fed for approximately 80 days with different diets: control diet (CD), fed a control diet; 3% coffee diet (3%Co) and 6% coffee diet (6%Co), both fed a diet containing brewed coffee; 0.04% caffeine diet (0.04%Ca) and 0.08% caffeine diet (0.08%Ca), both fed a control diet supplemented with caffeine. The estimated caffeine intake was approximately 20 and 40 mg/kg per day, for the 3%Co-0.04%Ca and 6%Co-0.08%Ca treatments, respectively. At 90 days of life, the animals were subjected to the behavioral tasks and then sacrificed. The results indicated that the intake of coffee, similar to caffeine, improved long-term memory when tested with object recognition; however, this was not accompanied by an increase in locomotor and exploratory activities. In addition, chronic coffee and caffeine ingestion reduced the lipid peroxidation of brain membranes and increased the concentration of reduced-glutathione. The activities of the GR and SOD were similarly increased, but no change in GPx activity could be observed. Thus, besides improving cognitive function, our data show that chronic coffee consumption modulates the endogenous antioxidant system in the brain. Therefore, chronic coffee ingestion, through the protection of the antioxidant system, may play an important role in preventing age-associated decline in the cognitive function. Copyright © 2011 Elsevier Inc. All rights reserved.

Drug Interactions with Clinafloxacin

PubMed Central

Randinitis, Edward J.; Alvey, Christine W.; Koup, Jeffery R.; Rausch, George; Abel, Robert; Bron, Nicola J.; Hounslow, Neil J.; Vassos, Artemios B.; Sedman, Allen J.

2001-01-01

Many fluoroquinolone antibiotics are inhibitors of cytochrome P450 enzyme systems and may produce potentially important drug interactions when administered with other drugs. Studies were conducted to determine the effect of clinafloxacin on the pharmacokinetics of theophylline, caffeine, warfarin, and phenytoin, as well as the effect of phenytoin on the pharmacokinetics of clinafloxacin. Concomitant administration of 200 or 400 mg of clinafloxacin reduces mean theophylline clearance by approximately 50 and 70%, respectively, and reduces mean caffeine clearance by 84%. (R)-Warfarin concentrations in plasma during clinafloxacin administration are 32% higher and (S)-warfarin concentrations do not change during clinafloxacin treatment. An observed late pharmacodynamic effect was most likely due to gut flora changes. Phenytoin has no effect on clinafloxacin pharmacokinetics, while phenytoin clearance is 15% lower during clinafloxacin administration. PMID:11502527

A dark brown roast coffee blend is less effective at stimulating gastric acid secretion in healthy volunteers compared to a medium roast market blend.

PubMed

Rubach, Malte; Lang, Roman; Bytof, Gerhard; Stiebitz, Herbert; Lantz, Ingo; Hofmann, Thomas; Somoza, Veronika

2014-06-01

Coffee consumption sometimes is associated with symptoms of stomach discomfort. This work aimed to elucidate whether two coffee beverages, containing similar amounts of caffeine, but differing in their concentrations of (β) N-alkanoyl-5-hydroxytryptamides (C5HTs), chlorogenic acids (CGAs), trigonelline, and N-methylpyridinium (N-MP) have different effects on gastric acid secretion in healthy volunteers. The intragastric pH after administration of bicarbonate with/without 200 mL of a coffee beverage prepared from a market blend or dark roast blend was analyzed in nine healthy volunteers. Coffee beverages were analyzed for their contents of C5HT, N-MP, trigonelline, CGAs, and caffeine using HPLC-DAD and HPLC-MS/MS. Chemical analysis revealed higher concentrations of N-MP for the dark brown blend (87 mg/L) compared to the market blend coffee (29 mg/L), whereas concentrations of C5HT (0.012 versus 0.343 mg/L), CGAs (323 versus 1126 mg/L), and trigonelline (119 versus 343 mg/L) were lower, and caffeine concentrations were similar (607 versus 674 mg/mL). Gastric acid secretion was less effectively stimulated after administration of the dark roast blend coffee compared to the market blend. Future studies are warranted to verify whether a high ratio of N-MP to C5HT and CGAs is beneficial for reducing coffee-associated gastric acid secretion. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hydrothermal-precipitation preparation of CdS@(Er3+:Y3Al5O12/ZrO2) coated composite and sonocatalytic degradation of caffeine.

PubMed

Huang, Yingying; Wang, Guowei; Zhang, Hongbo; Li, Guanshu; Fang, Dawei; Wang, Jun; Song, Youtao

2017-07-01

Here, we reported a novel method to dispose caffeine by means of ultrasound irradiation combinated with CdS@(Er 3+ :Y 3 Al 5 O 12 /ZrO 2 ) coated composite as sonocatalyst. The CdS@(Er 3+ :Y 3 Al 5 O 12 /ZrO 2 ) was synthesized via hydrothermal-precipitation method and then characterized by X-ray diffractometer (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray analysis (EDX) and UV-vis diffuse reflectance spectra (DRS). After that, the sonocatalytic degradation of caffeine in aqueous solution was conducted adopting CdS@(Er 3+ :Y 3 Al 5 O 12 /ZrO 2 ) and CdS@ZrO 2 coated composites as sonocatalysts. In addition, some influencing factors such as CdS and ZrO 2 molar proportion, caffeine concentration, ultrasonic irradiation time, sonocatalyst dosage and addition of several inorganic oxidants on sonocatalytic degradation of caffeine were investigated by using UV-vis spectra and gas chromatograph. The experimental results showed that the presence of Er 3+ :Y 3 Al 5 O 12 could effectively improve the sonocatalytic degradation activity of CdS@ZrO 2 . To a certain extent some inorganic oxidants can also enhance sonocatalytic degradation of caffeine in the presence of CdS@(Er 3+ :Y 3 Al 5 O 12 /ZrO 2 ). The best sonocatalytic degradation ratio (94.00%) of caffeine could be obtained when the conditions of 5.00mg/L caffeine, 1.00g/L prepared CdS@(Er 3+ :Y 3 Al 5 O 12 /ZrO 2 ), 10.00mmol/LK 2 S 2 O 8 , 180min ultrasonic irradiation (40kHz frequency and 50W output power), 100mL total volume and 25-28°C temperature were adopted. It seems that the method of sonocatalytic degradation caused by CdS@(Er 3+ :Y 3 Al 5 O 12 /ZrO 2 ) displayspotentialadvantages in disposing caffeine. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of a stiffness-angle law for simplifying the measurement of human hair stiffness.

PubMed

Jung, I K; Park, S C; Lee, Y R; Bin, S A; Hong, Y D; Eun, D; Lee, J H; Roh, Y S; Kim, B M

2018-04-01

This research examines the benefits of caffeine absorption on hair stiffness. To test hair stiffness, we have developed an evaluation method that is not only accurate, but also inexpensive. Our evaluation method for measuring hair stiffness culminated in a model, called the Stiffness-Angle Law, which describes the elastic properties of hair and can be widely applied to the development of hair care products. Small molecules (≤500 g mol -1 ) such as caffeine can be absorbed into hair. A common shampoo containing 4% caffeine was formulated and applied to hair 10 times, after which the hair stiffness was measured. The caffeine absorption of the treated hair was observed using Fourier-transform infrared spectroscopy (FTIR) with a focal plane array (FPA) detector. Our evaluation method for measuring hair stiffness consists of a regular camera and a support for single strands of hair. After attaching the hair to the support, the bending angle of the hair was observed with a camera and measured. Then, the hair strand was weighed. The stiffness of the hair was calculated based on our proposed Stiffness-Angle Law using three variables: angle, weight of hair and the distance the hair was pulled across the support. The caffeine absorption was confirmed by FTIR analysis. The concentration of amide bond in the hair certainly increased due to caffeine absorption. After caffeine was absorbed into the hair, the bending angle and weight of the hair changed. Applying these measured changes to the Stiffness-Angle Law, it was confirmed that the hair stiffness increased by 13.2% due to caffeine absorption. The theoretical results using the Stiffness-Angle Law agree with the visual examinations of hair exposed to caffeine and also the known results of hair stiffness from a previous report. Our evaluation method combined with our proposed Stiffness-Angle Law effectively provides an accurate and inexpensive evaluation technique for measuring bending stiffness of human hair. © 2018 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Low dose caffeine as a salivary tracer for the determination of gastric water emptying in fed and fasted state: A MRI validation study.

PubMed

Sager, Maximilian; Jedamzik, Philipp; Merdivan, Simon; Grimm, Michael; Schneider, Felix; Kromrey, Marie-Luise; Hasan, Mahmoud; Oswald, Stefan; Kühn, Jens; Koziolek, Mirko; Weitschies, Werner

2018-06-01

Improving our knowledge about human gastrointestinal physiology and its impact on oral drug delivery is crucial for the development of new therapies and effective drug delivery systems. The aim of this study was to develop an in vivo tool to determine gastric emptying of water by administration of a caffeine as a tracer substance followed by subsequent saliva caffeine analysis. For this purpose, 35 mg of caffeine were given to six healthy volunteers after a 10 h overnight together with 240 mL of tap water either on a fasted stomach or 30 min after the high-caloric, high-fat breakfast recommended for bioavailability/bioequivalence (BA/BE) studies. Caffeine was administered in form of an ice capsule in order to omit the contamination of the oral cavity with caffeine. Parallel to saliva sampling, magnetic resonance imaging (MRI) was applied in order to validate this novel approach. After administration of the ice capsule, MRI measurements were performed every 2 min for the first 20 min followed by further measurements after 25, 30, 35, 40, 50 and 60 min. Saliva samples were collected always 1 min after the MRI measurement in supine position in the MRI scanner and continued for further 240 min. The caffeine concentration in saliva was quantified after liquid-liquid extraction by a validated HPLC/MS-MS method. The obtained MRI data revealed a fast emptying of the co-administered water within 10 to 50 min in the fasted state and likewise in the fed state. Salivary caffeine kinetics showed a C max from 150 to 400 ng/mL with a t max from 20 to 90 min. MRI data were normalized by setting the maximum emptied volume to 100% and the salivary caffeine kinetics were normalized by setting C max to 100%. In order to compare the results obtained by the MRI and the saliva method, the normalized data for each volunteer was correlated based on a linear regression. In the fasted state the mean slope for six comparisons was 0.9114 ± 0.1500 and the mean correlation coefficient was 0.912 ± 0.055. In the fed state, a mean slope of 0.8326 ± 0.1630 and a mean correlation coefficient of 0.887 ± 0.047 were obtained. Based on these results, we could show that salivary caffeine concentrations are suitable to describe the emptying of water as a non-caloric liquid from the fasted and the fed stomach. The presented technique provides a straight-forward, inexpensive and noninvasive method to assess gastric emptying of hydrophilic liquids, which can be broadly used in oral biopharmaceutics. Possible applications are the characterization of real-life conditions, specific populations (e.g. elderly people) and the better understanding of the contribution of gastric emptying to pharmacokinetic profiles of orally administered drugs. Copyright © 2018 Elsevier B.V. All rights reserved.

Antimetastatic Efficacy of the Combination of Caffeine and Valproic Acid on an Orthotopic Human Osteosarcoma Cell Line Model in Nude Mice.

PubMed

Igarashi, Kentaro; Kawaguchi, Kei; Kiyuna, Tasuku; Murakami, Takashi; Yamamoto, Norio; Hayashi, Katsuhiro; Kimura, Hiroaki; Miwa, Shinji; Tsuchiya, Hiroyuki; Hoffman, Robert M

2017-03-01

We have previously reported that caffeine can enhance chemotherapy efficacy of bone and soft tissue sarcoma via cell-cycle perturbation. Valproic acid has histone deacetylase (HDAC) inhibitory activity. We have also reported the anti-tumor efficacy of combination treatment with caffeine and valproic acid against osteosarcoma primary tumors in a cell-line orthotopic mouse model. In this study, we performed combination treatment of caffeine and valproic acid on osteosarcoma cell lines in vitro and in spontaneous and experimental lung metastasis mouse models of osteosarcoma. Survival of 143B-RFP human osteosarcoma cells after exposure to caffeine and valproic acid for 72 hours was determined using the WST-8 assay. IC 50 values and combination indices were calculated. Mouse models of primary osteosarcoma and spontaneous lung metastasis were obtained by orthotopic intra-tibial injection of 143B-RFP cells. Valproic acid, caffeine, and combination of both drugs were administered from day 7, five times a week, for four weeks. Six weeks after orthotopic injection, lung samples were excised and observed with a fluorescence imaging system. A mouse model of experimental lung metastasis was obtained by tail vein injection of 143B-RFP cells. The mice were treated with these agents from day 0, five times a week for four weeks. Both caffeine and valproic acid caused concentration-dependent cell kill in vitro. Synergistic efficacy of the combination treatment was observed. In the spontaneous lung-metastasis model, the number of lung metastasis was 9.0±2.6 in the untreated group (G1); 10.8±2.9 in the caffeine group (G2); 10.0±3.1 in the valproic-acid group (G3); and 3.0±1.1 in the combination group (G4); (p=6.78E-5 control vs. combination; p=0.006 valproic acid vs. combination; p=0.003 caffeine vs. combination). In the experimental lung-metastasis model, the combination group significantly reduced lung metastases and improved overall survival (p=0.0005). Efficacy of the combination of caffeine and valproic acid was observed in vitro and in spontaneous and experimental lung-metastasis mouse models of osteosarcoma. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Short-term Effects of High-Dose Caffeine on Cardiac Arrhythmias in Patients With Heart Failure: A Randomized Clinical Trial.

PubMed

Zuchinali, Priccila; Souza, Gabriela C; Pimentel, Maurício; Chemello, Diego; Zimerman, André; Giaretta, Vanessa; Salamoni, Joyce; Fracasso, Bianca; Zimerman, Leandro I; Rohde, Luis E

2016-12-01

The presumed proarrhythmic action of caffeine is controversial. Few studies have assessed the effect of high doses of caffeine in patients with heart failure due to left ventricular systolic dysfunction at high risk for ventricular arrhythmias. To compare the effect of high-dose caffeine or placebo on the frequency of supraventricular and ventricular arrhythmias, both at rest and during a symptom-limited exercise test. Double-blinded randomized clinical trial with a crossover design conducted at the heart failure and cardiac transplant clinic of a tertiary-care university hospital. The trial included patients with chronic heart failure with moderate-to-severe systolic dysfunction (left ventricular ejection fraction <45%) and New York Heart Association functional class I to III between March 5, 2013, and October 2, 2015. Caffeine (100 mg) or lactose capsules, in addition to 5 doses of 100 mL decaffeinated coffee at 1-hour intervals, for a total of 500 mg of caffeine or placebo during a 5-hour protocol. After a 1-week washout period, the protocol was repeated. Number and percentage of ventricular and supraventricular premature beats assessed by continuous electrocardiographic monitoring. We enrolled 51 patients (37 [74%] male; mean [SD] age, 60.6 [10.9] years) with predominantly moderate-to-severe left ventricular systolic dysfunction (mean [SD] left ventricular ejection fraction, 29% [7%]); 31 [61%] had an implantable cardioverter-defibrillator device. No significant differences between the caffeine and placebo groups were observed in the number of ventricular (185 vs 239 beats, respectively; P = .47) and supraventricular premature beats (6 vs 6 beats, respectively; P = .44), as well as in couplets, bigeminal cycles, or nonsustained tachycardia during continuous electrocardiographic monitoring. Exercise test-derived variables, such as ventricular and supraventricular premature beats, duration of exercise, estimated peak oxygen consumption, and heart rate, were not influenced by caffeine ingestion. We observed no increases in ventricular premature beats (91 vs 223 vs 207 beats, respectively) in patients with higher levels of plasma caffeine concentration compared with lower plasma levels (P = .91) or with the placebo group (P = .74). Acute ingestion of high doses of caffeine did not induce arrhythmias in patients with systolic heart failure and at high risk for ventricular arrhythmias. clinicaltrials.gov Identifier: NCT02045992.

Determination of volatile organic compounds, catechins, caffeine and theanine in Jukro tea at three growth stages by chromatographic and spectrometric methods.

PubMed

Jeon, Dong Bok; Hong, Young Shin; Lee, Ga Hyun; Park, Yu Min; Lee, Cheong Mi; Nho, Eun Yeong; Choi, Ji Yeon; Jamila, Nargis; Khan, Naeem; Kim, Kyong Su

2017-03-15

Tea contains characteristic volatile organic compounds, polyphenols, caffeine and catechins, and is therefore among the most widely consumed beverages all over the world. In this study, fresh Jukro tea leaves collected from Damyang-gun (Jeollanam-do) at 40, 60 and 90day growth stages, were semi-fermented. The volatile organic compounds (VOCs) were extracted by simultaneous distillation-solvent extraction (SDE) and analyzed by gas chromatography/mass spectrometry (GC/MS). Catechins, caffeine and theanine were analyzed by high performance liquid chromatography (HPLC). A total of 159 VOCs were identified in the analyzed Jukro tea leaves. Comparatively, the increase in the concentrations of VOCs was high in 60day leaves. The content of catechins increased along the three growth stages, whereas caffeine, compared to 90day leaves, was higher for 40 and 60day leaves. Based on the results, the 60day leaves were found to be the most suitable and useful for making semi-fermented Jukro tea. Copyright © 2016 Elsevier Ltd. All rights reserved.

Multitracer test for the determination of transport and in-situ degradation of organic micro-contaminants in karst aquifers on the example of caffeine

NASA Astrophysics Data System (ADS)

Hillebrand, O.; Nödler, K.; Licha, T.; Geyer, T.

2012-04-01

The application of organic micro-contaminants as indicators for contamination sources in aquifers and surface-water bodies has been increasingly discussed in the literature over the last years. One of the proposed substances was caffeine. It served as indicator for wastewater-leakage to various systems. As well, wastewater volumes could be estimated from caffeine concentrations. Although caffeine is known to be degradable, the degradation rates are normally only determined from mass balances or laboratory experiments. Degradation rates obtained from mass balances are relatively uncertain, as the input-function is difficult to be assessed. Laboratory experiments are hardly capable to consider the full complexity of natural systems and can rarely be transferred to those. To solve this problem, in-situ degradation rates of reactive indicators have to be determined. Especially multitracer tests can be used to access compound-specific transport parameters and degradation rates, relative to conservative tracers. A multitracer test with caffeine and uranine has been performed in a karst system (catchment of the Gallusquelle spring, SW Germany). From the breakthrough curves of the tracers, the transport behavior and the in-situ degradation rate of caffeine could be deduced. The tracers were injected into a sinkhole with a linear distance of 3000 m to the spring. The mean residence time of the tracers was found to be 84 h at a flow velocity of 35 m/h. Throughout the whole experiment, the spring discharge was constant at 187 L/s. Uranine served as conservative reference-tracer for the calibration of a one-dimensional transport model with respect to solute-unspecific parameters. Relative to that, the tracer breakthrough curve of caffeine was interpreted. As solute-specific parameters the retardation coefficient as well as degradation rate of caffeine in the investigated karst aquifer could be determined. The results indicate, that caffeine is slightly retarded in the investigated aquifer (R= 1.031-1.046) and is readily degradable (half-life t1/2= 90-105 h; temperature of the spring water T= 8-9 °C). The degradation rate is surprisingly high. In general, no significant degradation is believed to occur, during the rapid transport in karst systems. The high degradation rates of caffeine illustrate the potential to use this substance as reactive tracer to indicate biological activity within the aquifer. Due to the good degradability of caffeine it does not pose a threat as long-time contamination and can therefore safely be used as reactive tracer in aquifer systems.

Alkaloid decomposition by DC pin-hole discharge in water solution

NASA Astrophysics Data System (ADS)

Klimova, Edita J.; Krcma, Frantisek; Jonisova, Lenka

2016-08-01

DC diaphragm discharge generated in a batch reactor was used to decompose two selected model alkaloids, caffeine and quinine in concentrations ranging from 10 to 50 ppm or 5 to 15 ppm, respectively. UV-vis spectrometry was utilized in evaluation of H2O2 production during the process as well as degradation of caffeine. Fluorescence spectrometry was used for quantification of quinine. High rates of decomposition were reached in both cases in the anode part of the reactor. On the other hand, up to four times lower decomposition was observed in the cathode part. Total removal efficiency gained up to 300 mg/kWh for caffeine and 210 mg/kWh for quinine. Contribution to the topical issue "6th Central European Symposium on Plasma Chemistry (CESPC-6)", edited by Nicolas Gherardi, Ester Marotta and Cristina Paradisi

1H NMR analysis of complexation of hydrotropic agents nicotinamide and caffeine with aromatic biologically active molecules in aqueous solution

NASA Astrophysics Data System (ADS)

Lantushenko, Anastasia O.; Mukhina, Yulia V.; Veselkov, Kyrill A.; Davies, David B.; Veselkov, Alexei N.

2004-07-01

NMR spectroscopy has been used to elucidate the molecular mechanism of solubilization action of hydrotropic agents nicotinamide (NA) and caffeine (CAF). Hetero-association of NA with riboflavine-mononucleotide (FMN) and CAF with low soluble in aqueous solution synthetic analogue of antibiotic actinomycin D, actinocyl-bis-(3-dimethylaminopropyl) amine (Actill), has been investigated by 500 MHz 1H NMR spectroscopy. Concentration and temperature dependences of proton chemical shifts have been analysed in terms of a statistical-thermodynamic model of indefinite self- and heteroassociation of aromatic molecules. The obtained results enable to conclude that NA-FMN and CAF-Actill intermolecular complexes are mainly stabilized by the stacking interactions of the aromatic chromophores. Hetero-association of the investigated molecules plays an important role in solubilization of aromatic drugs by hydrotropic agents nicotinamide and caffeine.

Hydrogel-Forming Microneedle Arrays Allow Detection of Drugs and Glucose In Vivo: Potential for Use in Diagnosis and Therapeutic Drug Monitoring

PubMed Central

Caffarel-Salvador, Ester; Brady, Aaron J.; Eltayib, Eyman; Meng, Teng; Alonso-Vicente, Ana; Gonzalez-Vazquez, Patricia; Torrisi, Barbara M.; Vicente-Perez, Eva Maria; Mooney, Karen; Jones, David S.; Bell, Steven E. J.; McCoy, Colin P.; McCarthy, Helen O.; McElnay, James C.; Donnelly, Ryan F.

2015-01-01

We describe, for the first time the use of hydrogel-forming microneedle (MN) arrays for minimally-invasive extraction and quantification of drug substances and glucose from skin in vitro and in vivo. MN prepared from aqueous blends of hydrolysed poly(methyl-vinylether-co-maleic anhydride) (11.1% w/w) and poly(ethyleneglycol) 10,000 daltons (5.6% w/w) and crosslinked by esterification swelled upon skin insertion by uptake of fluid. Post-removal, theophylline and caffeine were extracted from MN and determined using HPLC, with glucose quantified using a proprietary kit. In vitro studies using excised neonatal porcine skin bathed on the underside by physiologically-relevant analyte concentrations showed rapid (5 min) analyte uptake. For example, mean concentrations of 0.16 μg/mL and 0.85 μg/mL, respectively, were detected for the lowest (5 μg/mL) and highest (35 μg/mL) Franz cell concentrations of theophylline after 5 min insertion. A mean concentration of 0.10 μg/mL was obtained by extraction of MN inserted for 5 min into skin bathed with 5 μg/mL caffeine, while the mean concentration obtained by extraction of MN inserted into skin bathed with 15 μg/mL caffeine was 0.33 μg/mL. The mean detected glucose concentration after 5 min insertion into skin bathed with 4 mmol/L was 19.46 nmol/L. The highest theophylline concentration detected following extraction from a hydrogel-forming MN inserted for 1 h into the skin of a rat dosed orally with 10 mg/kg was of 0.363 μg/mL, whilst a maximum concentration of 0.063 μg/mL was detected following extraction from a MN inserted for 1 h into the skin of a rat dosed with 5 mg/kg theophylline. In human volunteers, the highest mean concentration of caffeine detected using MN was 91.31 μg/mL over the period from 1 to 2 h post-consumption of 100 mg Proplus® tablets. The highest mean blood glucose level was 7.89 nmol/L detected 1 h following ingestion of 75 g of glucose, while the highest mean glucose concentration extracted from MN was 4.29 nmol/L, detected after 3 hours skin insertion in human volunteers. Whilst not directly correlated, concentrations extracted from MN were clearly indicative of trends in blood in both rats and human volunteers. This work strongly illustrates the potential of hydrogel-forming MN in minimally-invasive patient monitoring and diagnosis. Further studies are now ongoing to reduce clinical insertion times and develop mathematical algorithms enabling determination of blood levels directly from MN measurements. PMID:26717198

Effects of caffeinated and decaffeinated coffee on biological risk factors for type 2 diabetes: a randomized controlled trial.

PubMed

Wedick, Nicole M; Brennan, Aoife M; Sun, Qi; Hu, Frank B; Mantzoros, Christos S; van Dam, Rob M

2011-09-13

Coffee consumption has been associated with a lower risk of type 2 diabetes in prospective cohort studies, but the underlying mechanisms remain unclear. The aim of this study was to evaluate the effects of regular and decaffeinated coffee on biological risk factors for type 2 diabetes. Randomized parallel-arm intervention conducted in 45 healthy overweight volunteers who were nonsmokers and regular coffee consumers. Participants were assigned to consumption of 5 cups (177 mL each) per day of instant caffeinated coffee, decaffeinated coffee, or no coffee (i.e., water) for 8 weeks. Average age was 40 years and body mass index was 29.5 kg/m2. Compared with consuming no coffee, consumption of caffeinated coffee increased adiponectin (difference in change from baseline 1.4 μg/mL; 95% CI: 0.2, 2.7) and interleukin-6 (difference: 60%; 95% CI: 8, 138) concentrations and consumption of decaffeinated coffee decreased fetuin-A concentrations (difference: -20%; 95% CI: -35, -1). For measures of glucose tolerance, insulin sensitivity, and insulin secretion, no significant differences were found between treatment groups. Although no changes in glycemia and/or insulin sensitivity were observed after 8 weeks of coffee consumption, improvements in adipocyte and liver function as indicated by changes in adiponectin and fetuin-A concentrations may contribute to beneficial metabolic effects of long-term coffee consumption. clinicaltrials.gov NCT00305097.

Control of separation and quantitative analysis by GC-FTIR

NASA Astrophysics Data System (ADS)

Semmoud, A.; Huvenne, Jean P.; Legrand, P.

1992-03-01

Software for 3-D representations of the 'Absorbance-Wavenumber-Retention time' is used to control the quality of the GC separation. Spectral information given by the FTIR detection allows the user to be sure that a chromatographic peak is 'pure.' The analysis of peppermint essential oil is presented as an example. This assurance is absolutely required for quantitative applications. In these conditions, we have worked out a quantitative analysis of caffeine. Correlation coefficients between integrated absorbance measurements and concentration of caffeine are discussed at two steps of the data treatment.

Improved Exercise Tolerance with Caffeine Is Associated with Modulation of both Peripheral and Central Neural Processes in Human Participants.

PubMed

Bowtell, Joanna L; Mohr, Magni; Fulford, Jonathan; Jackman, Sarah R; Ermidis, Georgios; Krustrup, Peter; Mileva, Katya N

2018-01-01

Caffeine has been shown to enhance exercise performance and capacity. The mechanisms remain unclear but are suggested to relate to adenosine receptor antagonism, resulting in increased central motor drive, reduced perception of effort, and altered peripheral processes such as enhanced calcium handling and extracellular potassium regulation. Our aims were to investigate how caffeine (i) affects knee extensor PCr kinetics and pH during repeated sets of single-leg knee extensor exercise to task failure and (ii) modulates the interplay between central and peripheral neural processes. We hypothesized that the caffeine-induced extension of exercise capacity during repeated sets of exercise would occur despite greater disturbance of the muscle milieu due to enhanced peripheral and corticospinal excitatory output, central motor drive, and muscle contractility. Nine healthy active young men performed five sets of intense single-leg knee extensor exercise to task failure on four separate occasions: for two visits (6 mg·kg -1 caffeine vs placebo), quadriceps 31 P-magnetic resonance spectroscopy scans were performed to quantify phosphocreatine kinetics and pH, and for the remaining two visits (6 mg·kg -1 caffeine vs placebo), femoral nerve electrical and transcranial magnetic stimulation of the quadriceps cortical motor area were applied pre- and post exercise. The total exercise time was 17.9 ± 6.0% longer in the caffeine (1,225 ± 86 s) than in the placebo trial (1,049 ± 73 s, p  = 0.016), and muscle phosphocreatine concentration and pH ( p < 0.05) were significantly lower in the latter sets of exercise after caffeine ingestion. Voluntary activation (VA) (peripheral, p  = 0.007; but not supraspinal, p  = 0.074), motor-evoked potential (MEP) amplitude ( p  = 0.007), and contractility (contraction time, p  = 0.009; and relaxation rate, p  = 0.003) were significantly higher after caffeine consumption, but at task failure MEP amplitude and VA were not different from placebo. Caffeine prevented the reduction in M-wave amplitude that occurred at task failure ( p  = 0.039). Caffeine supplementation improved high-intensity exercise tolerance despite greater-end exercise knee extensor phosphocreatine depletion and H + accumulation. Caffeine-induced increases in central motor drive and corticospinal excitability were attenuated at task failure. This may have been induced by the afferent feedback of the greater disturbance of the muscle milieu, resulting in a stronger inhibitory input to the spinal and supraspinal motor neurons. However, causality needs to be established through further experiments.

Production of hybrid lipid-based particles loaded with inorganic nanoparticles and active compounds for prolonged topical release.

PubMed

García-González, C A; Sampaio da Sousa, A R; Argemí, A; López Periago, A; Saurina, J; Duarte, C M M; Domingo, C

2009-12-01

The production of particulate hybrid carriers containing a glyceryl monostearate (Lumulse GMS-K), a waxy triglyceride (Cutina HR), silanized TiO(2) and caffeine were investigated with the aim of producing sunscreens with UV-radiation protection properties. Particles were obtained using the supercritical PGSS (Particles from Gas Saturated Solutions) technique. This method takes advantages of the lower melting temperatures of the lipids obtained from the dissolution of CO(2) in the bulk mixture. Experiments were performed at 13 MPa and 345 K, according to previous melting point measurements. Blends containing Lumulse GMS-K and Cutina HR lipids (50 wt%) were loaded with silanized TiO(2) and caffeine in percentile proportions of 6 and 4 wt%, respectively. The particles produced were characterized using several analytical techniques as follows: system crystallinity was checked by X-ray diffraction and differential scanning calorimetry, thermal stability by thermogravimetric analysis, and morphology by scanning and transmission electron microscopy. Further, the UV-shielding ability of TiO(2) after its dispersion in the lipidic matrix was assessed by solid UV-vis spectroscopy. Preliminary results indicated that caffeine-loaded solid lipid particles presented a two-step dissolution profile, with an initial burst of 60 wt% of the loaded active agent. Lipid blends loaded with TiO(2) and caffeine encompassed the UV-filter behavior of TiO(2) and the photoaging prevention properties of caffeine.

Fast and simultaneous determination of phenolic compounds and caffeine in teas, mate, instant coffee, soft drink and energetic drink by high-performance liquid chromatography using a fused-core column.

PubMed

Rostagno, M A; Manchón, N; D'Arrigo, M; Guillamón, E; Villares, A; García-Lafuente, A; Ramos, A; Martínez, J A

2011-01-31

A fast HPLC method with diode-array absorbance detector and fluorescence detector for the analysis of 19 phenolic acids, flavan-3-ols, flavones, flavonols and caffeine in different types of samples was developed. Using a C(18) reverse-phase fused-core column separation of all compounds was achieved in less than 5 min with an overall sample-to-sample time of 10 min. Evaluation of chromatographic performance revealed excellent reproducibility, resolution, selectivity and peak symmetry. Limits of detection for all analyzed compounds ranged from 0.5 to 211 μg L(-1), while limits of quantitation ranged between 1.5 and 704 μg L(-1). The developed method was used for the determination of analytes present in different samples, including teas (black, white, green), mate, coffee, cola soft drink and an energetic drink. Concentration of the analyzed compounds occurring in the samples ranged from 0.4 to 314 mg L(-1). Caffeine was the analyte found in higher concentrations in all samples. Phytochemical profiles of the samples were consistent with those reported in the literature. Copyright © 2010 Elsevier B.V. All rights reserved.

Corona plasma modification of polyamide 66 for the design of textile delivery systems for cosmetic therapy

NASA Astrophysics Data System (ADS)

Labay, C.; Canal, J. M.; Navarro, A.; Canal, C.

2014-10-01

Cosmetic and medical applications of technical textiles are a research expanding field. One of the added values of these new materials would be that they are suitable to contain and release active ingredients in a controlled manner. The influence of the initial state of the surface of polyamide 6.6 (PA66) fibers on the wetting properties of the fibers as well as on the incorporation of caffeine on the fibers and on its release kinetics from the fibers has been investigated. Comparison between industrially-finished PA66 fabrics and laboratory washed fabrics has been done to carry out this study. Furthermore, surface modification of the PA66 fibers by low temperature plasma has been studied regarding the modification of the physical, chemical and topographical properties of the textile fibers. Corona plasma treatment has been investigated to achieve surface modification in the first nanometers of polymer fibers surface in order to modulate the incorporation and the release of caffeine. It has been demonstrated that both initial state of the PA66 surface and prior plasma treatment of the PA66 fibers before the active principle incorporation condition caffeine release kinetics from the textile fibers. The final release percentage increases linearly with the C-O and Cdbnd O functional groups incorporated by plasma on the surface. It has also been established that the release amounts of caffeine achieved after 8 h from the PA66 fabric are in the same order of magnitude than topical doses of commercial gel-based formulations.

Variation of total aroma and polyphenol content of dark chocolate during three phase of conching.

PubMed

Albak, F; Tekin, A R

2016-01-01

Variation in the volatiles, total polyphenol, theobromine and caffein was investigated both qualitatively and quantitatively for all phases of conching with GC/MS/SPME, HPLC, GC/O, and UV-visible spectrophotometry. The volatile compounds being identified during the three phases consisted of aldehydes, ketones, pyrazines, acids, alcohols and esters. The number and concentration of these compounds were observed to be 31-25,681 ppb, 44-34,838 ppb and 44-29,809 ppb in the dry, pasty, and liquid phases respectively. The odor of dark chocolate was described as nutty, sweet, caramel, green and chocolate using olfactometry. The percent decrease in the concentration of total polyphenol, caffein and theobromine was observed to be only 3.0, 11.0, and 32.0 respectively.

Potential tracers for tracking septic tank effluent discharges in watercourses.

PubMed

Richards, Samia; Withers, Paul J A; Paterson, Eric; McRoberts, Colin W; Stutter, Marc

2017-09-01

Septic tank effluent (STE) contributes to catchment nutrient and pollutant loads. To assess the role of STE discharges in impairment of surface water, it is essential to identify the sources of pollution by tracing contaminants in watercourses. We examined tracers that were present in STE to establish their potential for identifying STE contamination in two stream systems (low and high dilution levels) against the background of upstream sources. The studied tracers were microbial, organic matter fluorescence, caffeine, artificial sweeteners and effluent chemical concentrations. The results revealed that tracer concentration ratios Cl/EC, Cl/NH 4 -N, Cl/TN, Cl/TSS, Cl/turbidity, Cl/total coliforms, Cl/sucralose, Cl/saccharin and Cl/Zn had potential as tracers in the stream with low dilution level (P < 0.05). Fluorescence spectroscopy could detect STE inputs through the presence of the tryptophan-like peak, but was limited to water courses with low level of dilution and was positively correlated with stream Escherichia coli (E. coli) and soluble reactive phosphorus (SRP). The results also suggested that caffeine and artificial sweeteners can be suitable tracers for effluent discharge in streams with low and high level of dilution. Caffeine and saccharin were positively correlated with faecal coliforms, E. coli, total P and SRP, indicating their potential to trace discharge of a faecal origin and to be a marker for effluent P. Caffeine and SRP had similar attenuation behaviour in the receiving stream waters suggesting caffeine's potential role as a surrogate indicator for the behaviour of P downstream of effluent inputs. Taken together, results suggest that a single tracer alone was not sufficient to evaluate STE contamination of watercourses, but rather a combination of multiple chemical and physical tracing approaches should be employed. A multiple tracing approach would help to identify individual and cumulative STE inputs that pose risks to stream waters in order to prioritise and target effective mitigation measures. Copyright © 2017 Elsevier Ltd. All rights reserved.

Caffeine Improves Left Hemisphere Processing of Positive Words

PubMed Central

Kuchinke, Lars; Lux, Vanessa

2012-01-01

A positivity advantage is known in emotional word recognition in that positive words are consistently processed faster and with fewer errors compared to emotionally neutral words. A similar advantage is not evident for negative words. Results of divided visual field studies, where stimuli are presented in either the left or right visual field and are initially processed by the contra-lateral brain hemisphere, point to a specificity of the language-dominant left hemisphere. The present study examined this effect by showing that the intake of caffeine further enhanced the recognition performance of positive, but not negative or neutral stimuli compared to a placebo control group. Because this effect was only present in the right visual field/left hemisphere condition, and based on the close link between caffeine intake and dopaminergic transmission, this result points to a dopaminergic explanation of the positivity advantage in emotional word recognition. PMID:23144893

Analysis of cocaine and its adulterants in drugs for international trafficking seized by the Brazilian Federal Police.

PubMed

Lapachinske, Silvio Fernandes; Okai, Guilherme Gonçalves; dos Santos, Ariana; de Bairros, André Valle; Yonamine, Mauricio

2015-02-01

Here, gas chromatography with nitrogen phosphorous detector (GC-NPD) method was developed and validated for the quantification of cocaine and adulterants (caffeine, 4-dimethylaminoantipyrine, levamisole, lidocaine and phenacetin) in illicit samples. The method was based on direct dilution of samples in methanol, sonication for 5 min and centrifugation. After appropriate dilution, an aliquot was injected into GC-MS in order to identify the active compounds and into GC-NPD for the analytes quantification. Bupivacaine was used as an internal standard. The method showed to be precise, accurate and linear over a range of 0.5-100% (weight/weight percentages) for all analytes, except phenacetin which showed a linear range between 2% and 100%. The method was successfully applied to 54 samples seized by the Brazilian Federal Police in the International Airport of Sao Paulo and mailing services during the year 2011. All the samples were associated with international trafficking and were apprehended while leaving the country. The purity of cocaine ranged from 16.5% to 91.4%. Cocaine was the only detected active compound in 29.6% of total samples. Among the identified cutting agents, levamisole was the most abundant (55.6% of the total samples) and relative concentrations (weight/weight percentages) ranged from 0.7% to 23%. Lidocaine, caffeine, phenacetin and 4-dimethylaminoantipyrine were also identified in these samples in minor concentrations. In contrast with what we initially hypothesized, drugs intended to international trafficking did not present high cocaine purity and most of the samples were laced with adulterants before leaving Brazil. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Extraction and preparation of high-aroma and low-caffeine instant green teas by the novel column chromatographic extraction method with gradient elution.

PubMed

Li, Qing-Rong; Wu, Min; Huang, Rui-Jie; Chen, Ya-Fei; Chen, Chan-Jian; Li, Hui; Ni, He; Li, Hai-Hang

2017-06-01

The lack of aroma and natural taste is a critical problem in production and consumption of instant green teas. A method to prepare instant green teas high in-natural-aroma and low-caffeine by the novel column chromatographic extraction with gradient elution is reported. This method simultaneously extracted aroma (or volatile) and non-aroma compounds from green tea. Green tea was loaded into columns with 2.0-fold of petroleum ether (PE): ethanol (8:2). After standing for 3 h until the aroma compounds dissolved, the column was sequentially eluted with 3.0-fold 40% ethanol and 3.5-fold water. The eluant was collected together and automatically separated into PE and ethanol aqueous phases. The aroma extracts was obtained by vacuum-evaporation of PE phase at 45 °C. The ethanol aqueous phase was vacuum-concentrated to aqueous and partially or fully decaffeinated with 4% or 9% charcoal at 70 °C. A regular instant green tea with epigallocatechin-3-gallate: caffeine of 3.5:1 and a low-caffeine instant green tea (less than 1% caffeine) with excellent aroma and taste were prepared, by combining the aroma and non-aroma extracts at a 1:10 ratio. This work provides a practical approach to solve the low-aroma and low-taste problems in the production of high quality instant green teas.

Development of a Two-Dimensional Model for Predicting Transdermal Permeation with the Follicular Pathway: Demonstration with a Caffeine Study.

PubMed

Kattou, Panayiotis; Lian, Guoping; Glavin, Stephen; Sorrell, Ian; Chen, Tao

2017-10-01

The development of a new two-dimensional (2D) model to predict follicular permeation, with integration into a recently reported multi-scale model of transdermal permeation is presented. The follicular pathway is modelled by diffusion in sebum. The mass transfer and partition properties of solutes in lipid, corneocytes, viable dermis, dermis and systemic circulation are calculated as reported previously [Pharm Res 33 (2016) 1602]. The mass transfer and partition properties in sebum are collected from existing literature. None of the model input parameters was fit to the clinical data with which the model prediction is compared. The integrated model has been applied to predict the published clinical data of transdermal permeation of caffeine. The relative importance of the follicular pathway is analysed. Good agreement of the model prediction with the clinical data has been obtained. The simulation confirms that for caffeine the follicular route is important; the maximum bioavailable concentration of caffeine in systemic circulation with open hair follicles is predicted to be 20% higher than that when hair follicles are blocked. The follicular pathway contributes to not only short time fast penetration, but also the overall systemic bioavailability. With such in silico model, useful information can be obtained for caffeine disposition and localised delivery in lipid, corneocytes, viable dermis, dermis and the hair follicle. Such detailed information is difficult to obtain experimentally.

Occurrence of pharmaceutically active compounds during 1-year period in wastewaters from four wastewater treatment plants in Seville (Spain).

PubMed

Santos, J L; Aparicio, I; Callejón, M; Alonso, E

2009-05-30

Several pharmaceutically active compounds have been monitored during 1-year period in influent and effluent wastewater from wastewater treatment plants (WWTPs) to evaluate their temporal evolution and removal from wastewater and to know which variables have influence in their removal rates. Pharmaceutical compounds monitored were four antiinflammatory drugs (diclofenac, ibuprofen, ketoprofen and naproxen), an antiepileptic drug (carbamazepine) and a nervous stimulant (caffeine). All of the pharmaceutically active compounds monitored, except diclofenac, were detected in influent and effluent wastewater. Mean concentrations measured in influent wastewater were 6.17, 0.48, 93.6, 1.83 and 5.41 microg/L for caffeine, carbamazepine, ibuprofen, ketoprofen and naproxen, respectively. Mean concentrations measured in effluent wastewater were 2.02, 0.56, 8.20, 0.84 and 2.10 microg/L for caffeine, carbamazepine, ibuprofen, ketoprofen and naproxen, respectively. Mean removal rates of the pharmaceuticals varied from 8.1% (carbamazepine) to 87.5% (ibuprofen). The existence of relationships between the concentrations of the pharmaceutical compounds, their removal rates, the characterization parameters of influent wastewaters and the WWTP control design parameters has been studied by means of statistical analysis (correlation and principal component analysis). With both statistical analyses, high correlations were obtained between the concentration of the pharmaceutical compounds and the characterization parameters of influent wastewaters; and between the removal rates of the pharmaceutical compounds, the removal rates of the characterization parameters of influent wastewaters and the WWTP hydraulic retention times. Principal component analysis showed the existence of two main components accounting for 76% of the total variability.

Combined effects of THC and caffeine on working memory in rats

PubMed Central

Panlilio, Leigh V; Ferré, Sergi; Yasar, Sevil; Thorndike, Eric B; Schindler, Charles W; Goldberg, Steven R

2012-01-01

BACKGROUND AND PURPOSE Cannabis and caffeine are two of the most widely used psychoactive substances. Δ9-Tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, induces deficits in short-term memory. Caffeine, a non-selective adenosine receptor antagonist, attenuates some memory deficits, but there have been few studies addressing the effects of caffeine and THC in combination. Here, we evaluate the effects of these drugs using a rodent model of working memory. EXPERIMENTAL APPROACH Rats were given THC (0, 1 and 3 mg·kg−1, i.p.) along with caffeine (0, 1, 3 and 10 mg·kg−1, i.p.), the selective adenosine A1-receptor antagonist CPT (0, 3 and 10 mg·kg−1) or the selective adenosine A2A-receptor antagonist SCH58261 (0 and 5 mg·kg−1) and were tested with a delayed non-matching-to-position procedure in which behaviour during the delay was automatically recorded as a model of memory rehearsal. KEY RESULTS THC alone produced memory deficits at 3 mg·kg−1. The initial exposure to caffeine (10 mg·kg−1) disrupted the established pattern of rehearsal-like behaviour, but tolerance developed rapidly to this effect. CPT and SCH58261 alone had no significant effects on rehearsal or memory. When a subthreshold dose of THC (1 mg·kg−1) was combined with caffeine (10 mg·kg−1) or CPT (10 mg·kg−1), memory performance was significantly impaired, even though performance of the rehearsal-like pattern was not significantly altered. CONCLUSION AND IMPLICATIONS Caffeine did not counteract memory deficits induced by THC but actually exacerbated them. These results are consistent with recent findings that adenosine A1 receptors modulate cannabinoid signalling in the hippocampus. LINKED ARTICLES This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7 PMID:21699509

Coffee, tea, and caffeine consumption and prevention of late-life cognitive decline and dementia: a systematic review.

PubMed

Panza, F; Solfrizzi, V; Barulli, M R; Bonfiglio, C; Guerra, V; Osella, A; Seripa, D; Sabbà, C; Pilotto, A; Logroscino, G

2015-03-01

A prolonged preclinical phase of more than two decades before the onset of dementia suggested that initial brain changes of Alzheimer's disease (AD) and the symptoms of advanced AD may represent a unique continuum. Given the very limited therapeutic value of drugs currently used in the treatment of AD and dementia, preventing or postponing the onset of AD and delaying or slowing its progression are becoming mandatory. Among possible reversible risk factors of dementia and AD, vascular, metabolic, and lifestyle-related factors were associated with the development of dementia and late-life cognitive disorders, opening new avenues for the prevention of these diseases. Among diet-associated factors, coffee is regularly consumed by millions of people around the world and owing to its caffeine content, it is the best known psychoactive stimulant resulting in heightened alertness and arousal and improvement of cognitive performance. Besides its short-term effect, some case-control and cross-sectional and longitudinal population-based studies evaluated the long-term effects on brain function and provided some evidence that coffee, tea, and caffeine consumption or higher plasma caffeine levels may be protective against cognitive impairment/decline and dementia. In particular, several cross-sectional and longitudinal population-based studies suggested a protective effect of coffee, tea, and caffeine use against late-life cognitive impairment/decline, although the association was not found in all cognitive domains investigated and there was a lack of a distinct dose-response association, with a stronger effect among women than men. The findings on the association of coffee, tea, and caffeine consumption or plasma caffeine levels with incident mild cognitive impairment and its progression to dementia were too limited to draw any conclusion. Furthermore, for dementia and AD prevention, some studies with baseline examination in midlife pointed to a lack of association, although other case-control and longitudinal population-based studies with briefer follow-up periods supported favourable effects of coffee, tea, and caffeine consumption against AD. Larger studies with longer follow-up periods should be encouraged, addressing other potential bias and confounding sources, so hopefully opening new ways for diet-related prevention of dementia and AD.

An in vivo model for studying the dynamics of intracellular free calcium changes in slow- and fast-twitch muscle fibres.

PubMed

Bátkai, S; Rácz, I B; Ivanics, T; Tóth, A; Hamar, J; Slaaf, D W; Reneman, R S; Ligeti, L

1999-10-01

The understanding of the regulation of the free cytosolic [Ca2+] ([Ca2+]i) in skeletal muscle is hampered by the lack of techniques for quantifying free [Ca2+]i in muscle fibres in situ. We describe a model for studying the dynamics of free [Ca2+]i in the fast-twitch extensor digitorum longus (EDL) and the slow-twitch soleus (SOL) muscles of the rat in vivo using caffeine superfusion to induce changes in free [Ca2+]i. We assumed that differences in sensitivity between the two muscle types for this substance reflect differences in intracellular Ca2+ handling in the fibres of which these muscles consist. The Indo-1 ratiometric method, using intravital microscopy with incident light, was adapted to measure free [Ca2+]i in vivo. Fluorescence images were collected by means of a digital camera. Caffeine superfusion at 37 degrees C for 2 min, at concentrations of 1, 2, 5, 10 or 20 mmol/l, induced a concentration-dependent increase in free [Ca2+]i and revealed differences in caffeine sensitivity between the muscle types, with the SOL being more sensitive. In a separate set of experiments the contracture threshold, as assessed by topical application of caffeine, was determined in both muscle types. EDL had a higher threshold for developing contracture than SOL. These finding are in agreement with previous in vitro studies. We may conclude that the dynamics of free [Ca2+]i can be assessed reliably in intact mammalian muscle in vivo.

Content Variation of Catechin Markers, Total Phenolics and Caffeine in Green Tea Dietary Supplements.

PubMed

Abourashed, Ehab A; Roberson, Cindy Leslie A; Elsharkawy, Nancy

2016-01-01

Green tea (Camellia sinensis) preparations are among the top selling products in the United States dietary supplements market. Numerous manufacturers claim different levels of specific catechin markers in their products while many others use total phenolic concentration instead, or not at all. Limited quality control results have been published for green tea dietary supplements over the past seven years. Thus, the goal of this work was to correlate determined levels of phenolics, catechins, and caffeine with manufacturer label claims for selected dietary supplement products (26 total) purchased in the United States. The Folin-Ciocalteu (FC) method was used to determine the total phenolic content while reversed-phase (RP) HPLC was used to quantify the major catechins: epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG), epigallocatechin gallate (EGCG). The developed HPLC method was validated for accuracy and precision. It utilized a C8 column with gradient elution of acetonitrile in 0.1% aqueous formic acid over 11 min total run time. Peak detection was performed at 280 nm. Caffeine was also included in the HPLC method as another non-phenolic alkaloid marker commonly found in green tea. Both methods showed a good correlation between the content of catechins and polyphenolic compounds in the selected products. The ranges of total catechins and polyphenol concentrations were 3.8-70.2% and 3.6-95.8%, respectively, while that of caffeine was 0.8-11.2%. The selected products displayed a wide range of marker levels. A lack of conformity in disclosing the actual levels of marker compounds was also noticed in the labeling of many products.

The association between pre-treatment maternal alcohol and caffeine intake and outcomes of assisted reproduction in a prospectively followed cohort.

PubMed

Abadia, L; Chiu, Y-H; Williams, P L; Toth, T L; Souter, I; Hauser, R; Chavarro, J E; Gaskins, A J

2017-09-01

Is pre-treatment alcohol and caffeine intake associated with infertility treatment outcomes among women undergoing ART? Low to moderate alcohol and caffeine intakes in the year prior to infertility treatment were not related to ART outcomes. Alcohol and caffeine intake have been found to be associated with infertility in some studies. Nevertheless, data on their relation with outcomes of infertility treatments are scarce and inconsistent. We included 300 women (493 ART cycles) from the Environment and Reproductive Health Study, an ongoing cohort study (2006-2016). Pre-treatment intakes of alcohol and caffeine were assessed retrospectively using a validated food frequency questionnaire. Intermediate and clinical endpoints of ART were abstracted from electronic medical records. Generalized linear mixed models with random intercepts to account for multiple ART cycles per woman were used to evaluate the association with ART outcomes adjusting for age, BMI, smoking status, infertility diagnosis, protocol type, race, dietary patterns, and calories, vitamin B12 and folate intake. Median (range) pre-treatment alcohol and caffeine intakes were 5.6 (0.0-85.8) g/day and 124.9 (0.3-642.2) mg/day, respectively. The adjusted percentage of initiated cycles resulting in live birth (95% CI) for women in increasing categories of pre-treatment alcohol intake was 34% (20, 52%) for non-consumers, 46% (36, 57%) for 0.1-6 g/day, 41% (29, 53%) for 6.1-12 g/day, 42% (31, 55%) for 12.1-24 g/day, and 41% (22, 63%) for >24 g/day (P, trend = 0.87). The adjusted percentage of cycles resulting in live birth (95% CI) for women in increasing categories of caffeine intake was 46% (36-57%) for <50 mg/day, 44% (29, 60%) for 50.1-100 mg/day, 42% (31, 53%) for 100.1-200 mg/day, 40% (28, 53%) for 200.1-300 mg/day and 40% (21, 63%) for >300 mg/day (P, trend = 0.34). When specific types of alcoholic and caffeinated beverages were evaluated, no relations with ART treatment outcomes were observed. Residual confounding by other diet and lifestyle factors cannot be ruled out owing to the observational nature of this study. It is also unclear how generalizable these results are to women who are conceiving without the assistance of ART. Our results provide reassurance that low to moderate intakes of alcohol (e.g. ≤12 g/day) and caffeine (e.g. <200 mg/day) in the year prior to infertility treatment initiation do not have an adverse effect on intermediate or clinical outcomes of ART. The authors are supported by National Institutes of Health (NIH) grants ES022955, R01ES009718, R01ES000002, P30DK46200 and L50-HD085359. No conflicts of interest to declare. NCT00011713. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

UV-B-induced damage to the lens in vitro: prevention by caffeine.

PubMed

Varma, Shambhu D; Hegde, Kavita R; Kovtun, Svitlana

2008-10-01

Ultraviolet (UV) irradiation is one of the significant risk factors in the genesis of cataracts. Pathogenetically, the process can be triggered by the intraocular generation of various reactive species of oxygen that are well known to be initiated by the penetration of light, especially of the UV frequencies. The contribution of UV exposure in the etiology of this disease is likely to increase further due to ozone depletion in the upper atmosphere. The present studies were undertaken to examine if the UV effects can be attenuated with the xanthine-based alkaloids primarily present in tea and coffee. We have examined this possibility by in vitro lens culture studies with caffeine. As expected, mice lenses incubated in Tyrode solution exposed to UV at 302 nm are physiologically damaged, as evidenced by the inhibition of the active transport of (86)Rb(+), an ion acting as a surrogate of the K(+). There was a simultaneous decrease in the levels of adenosine triphosphate and glutathione. The addition of caffeine to the medium prevented such deleterious effects. That caffeine and perhaps other xanthinoids have a protective effect against cataract formation induced by UV has hence been demonstrated for the first time.

Acute effects of tea consumption on attention and mood.

PubMed

Einöther, Suzanne J; Martens, Vanessa E

2013-12-01

Tea has historically been associated with mood and performance benefits, such as relaxation and concentration. This review summarizes the research on the acute effects of tea, and its ingredients theanine and caffeine, on attention and mood. Consistent with abundant research on the benefits of caffeine, the performance benefits of tea were identified in a number of studies, with particularly consistent evidence for improved attention. Tea consumption also consistently improved self-reported alertness and arousal, whereas effects on pleasure or relaxation were less consistent. In addition to the research on caffeine in real-life performance, 2 recent studies have provided a broader perspective on tea's effects on psychological function in that they showed beneficial effects in related areas such as work performance and creativity. These studies showed the validity of laboratory findings by supporting the idea that tea consumption has acute benefits on both mood and performance in real-life situations.

The acute effect of coffee on endothelial function and glucose metabolism following a glucose load in healthy human volunteers.

PubMed

Boon, Evan A J; Croft, Kevin D; Shinde, Sujata; Hodgson, Jonathan M; Ward, Natalie C

2017-09-20

A diet rich in plant polyphenols has been suggested to reduce the incidence of cardiovascular disease and type 2 diabetes mellitus, in part, via improvements in endothelial function. Coffee is a rich source of phenolic compounds including the phenolic acid, chlorogenic acid (CGA). The aim of the study was to investigate the effect of coffee as a whole beverage on endothelial function, blood pressure and blood glucose concentration. Twelve healthy men and women were recruited to a randomised, placebo-controlled, cross-over study, with three treatments tested: (i) 18 g of ground caffeinated coffee containing 300 mg CGA in 200 mL of hot water, (ii) 18 g of decaffeinated coffee containing 287 mg CGA in 200 mL of hot water, and (iii) 200 mL of hot water (control). Treatment beverages were consumed twice, two hours apart, with the second beverage consumed simultaneously with a 75 g glucose load. Blood pressure was recorded and the finger prick glucose test was performed at time = 0 and then every 30 minutes up to 2 hours. Endothelial function, assessed using flow-mediated dilatation (FMD) of the brachial artery, was measured at 1 hour and a blood sample taken at 2 hours to measure plasma nitrate/nitrite and 5-CGA concentrations. The FMD response was significantly higher in the caffeinated coffee group compared to both decaffeinated coffee and water groups (P < 0.001). There was no significant difference in the FMD response between decaffeinated coffee and water. Blood glucose concentrations and blood pressure were not different between the three treatment groups. In conclusion, the consumption of caffeinated coffee resulted in a significant improvement in endothelial function, but there was no evidence for benefit regarding glucose metabolism or blood pressure. Although the mechanism has yet to be elucidated the results suggest that coffee as a whole beverage may improve endothelial function, or that caffeine is the component of coffee responsible for improving FMD.

Artificial sweeteners, caffeine, and alcohol intoxication in bar patrons.

PubMed

Rossheim, Matthew E; Thombs, Dennis L

2011-10-01

Previous laboratory research on alcohol absorption has found that substitution of artificially sweetened alcohol mixers for sucrose-based mixers has a marked effect on the rate of gastric emptying, resulting in elevated blood alcohol concentrations. Studies conducted in natural drinking settings, such as bars, have indicated that caffeine ingestion while drinking is associated with higher levels of intoxication. To our knowledge, research has not examined the effects of alcohol mixers that contain both an artificial sweetener and caffeine, that is, diet cola. Therefore, we assessed the event-specific association between diet cola consumption and alcohol intoxication in bar patrons. We sought to determine whether putative increases in blood alcohol, produced by accelerated gastric emptying following diet cola consumption, as identified in the laboratory, also appear in a natural setting associated with impaired driving. We conducted a secondary analysis of data from 2 nighttime field studies that collected anonymous information from 413 randomly selected bar patrons in 2008 and 2010. Data sets were merged and recoded to distinguish between energy drink, regular cola, diet cola, and noncaffeinated alcohol mixers. Caffeinated alcohol mixers were consumed by 33.9% of the patrons. Cola-caffeinated mixed drinks were much more popular than those mixed with energy drinks. A large majority of regular cola-caffeinated mixed drink consumers were men (75%), whereas diet cola-caffeinated mixed drink consumers were more likely to be women (57%). After adjusting for the number of drinks consumed and other potential confounders, number of diet cola mixed drinks had a significant association with patron intoxication (β = 0.233, p < 0.0001). Number of drinks mixed with regular (sucrose-sweetened) cola and energy drinks did not have significant associations with intoxication (p > 0.05). Caffeine's effect on intoxication may be most pronounced when mixers are artificially sweetened, that is, lack sucrose which slows the rate of gastric emptying of alcohol. Risks associated with on-premise drinking may be reduced by greater attention given to types of mixers, particularly diet colas. Copyright © 2011 by the Research Society on Alcoholism.

Interaction between fed gastric media (Ensure Plus®) and different hypromellose based caffeine controlled release tablets: comparison and mechanistic study of caffeine release in fed and fasted media versus water using the USP dissolution apparatus 3.

PubMed

Franek, Frans; Holm, Per; Larsen, Frank; Steffansen, Bente

2014-01-30

The aim of the study was to investigate caffeine release in fed and fasted state media from three controlled release matrix tablets containing different HPMC viscosity grades. The biorelevant in vitro dissolution methods utilize the USP 3 dissolution apparatus and biorelevant media to simulate fed and fasted gastro-intestinal dissolution conditions. The effect of tablet reciprocation rate (dip speed) in dissolution media (10 and 15 dips per minute) and media (water, fed and fasted) on caffeine release rate from - and erosion rate of - 100, 4000 and 15,000 mPa s HPMC viscosity tablets was investigated using factorial designed experiments. Furthermore, the mechanism of release in Ensure Plus(®), a nutrition drink similar in composition to the FDA standard meal, was investigated by studying tablet swelling using texture analysis. Altering dip speed has negligible effect on release and erosion rates. Using fasted media instead of water slightly decreases caffeine release from 100 and 4000 mPa s HPMC viscosity tablets as well as erosion rates, while 15,000 mPa s tablets remain unaffected. Fed compared to fasted media decreases caffeine release rate, and the food effect is greater for the 100 mPa s viscosity tablets compared to the 4000 and 15,000 mPa s viscosity tablets. The investigation using texture analysis indicates that Ensure Plus(®) becomes rate-limiting for caffeine release from HPMC tablets by forming a hydrophobic barrier around the tablets. The barrier decreases tablet water permeation, which decreases erosion rate in 100 mPa s viscosity tablets, swelling in 15,000 mPa s viscosity tablets and caffeine release from both tablets. This observed interaction between Ensure Plus(®) and the HPMC tablets may translate into decreased drug release rate in the fed stomach, which may decrease the amount of drug available for absorption in the small intestine and thus reduce systemic drug exposure and maximum plasma concentration. Copyright © 2013 Elsevier B.V. All rights reserved.

Gender-specific increase in susceptibility to metabolic syndrome of offspring rats after prenatal caffeine exposure with post-weaning high-fat diet

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Jing; Luo, Hanwen; Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071

Prenatal caffeine exposure (PCE) alters the hypothalamic–pituitary–adrenocortical (HPA) axis-associated neuroendocrine metabolic programming and induces an increased susceptibility to metabolic syndrome (MS) in intrauterine growth retardation (IUGR) offspring rats. High-fat diet (HFD) is one of the main environmental factors accounting for the incidence of MS. In this study, we aimed to clarify the gender-specific increase in susceptibility to MS in offspring rats after PCE with post-weaning HFD. Maternal Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. The offspring rats with normal diet or HFD were euthanized at postnatal week 24, and blood samples were collected.more » Results showed that PCE not only reduced serum adrenocorticotropic hormone (ACTH) and corticosterone levels, but also enhanced serum glucose, triglyceride and total cholesterol (TCH) concentrations in the offspring rats. Moreover, several interactions among PCE, HFD and gender were observed by a three-way ANOVA analysis. In PCE offspring, HFD could aggravate the degree of increased serum triglyceride level. Meanwhile, serum corticosterone levels of females were decreased more obviously than those of males in PCE offspring. The results also revealed interactions between HFD and gender in the levels of serum ACTH, triglyceride and TCH, which were changed more evidently in female HFD offspring. These results indicate that HFD could exacerbate the dysfunction of lipid metabolism and the susceptibility to MS induced by PCE, and the female offspring are more sensitive to HFD-induced neuroendocrine metabolic dysfunction than their male counterparts. - Highlights: • Caffeine induced HPA axis dysfunction in offspring rats fed by high-fat diet (HFD). • Caffeine induced an increased susceptibility to metabolic syndrome. • HFD aggravated susceptibility to metabolic syndrome induced by caffeine. • Female was more sensitive to HFD-induced neuroendocrine metabolic dysfunction than male. • There were interactions among caffeine, high-fat diet and gender.« less

Caffeine-containing energy drink improves physical performance of elite rugby players during a simulated match.

PubMed

Del Coso, Juan; Ramírez, Juan A; Muñoz, Gloria; Portillo, Javier; Gonzalez-Millán, Cristina; Muñoz, Víctor; Barbero-Álvarez, José C; Muñoz-Guerra, Jesús

2013-04-01

The purpose of this study was to investigate the effectiveness of a caffeine-containing energy drink in enhancing rugby players' physical performance during a simulated match. A second purpose was to determine the urinary caffeine excretion derived from the energy drink intake. In a randomized and counterbalanced order, 26 elite rugby players (mean ± SD for age and body mass, 25 ± 2 y and 93 ± 15 kg) played 2 simulated rugby games (2 × 30 min) 60 min after ingesting (i) 3 mg of caffeine per kilogram of body mass in the form of an energy drink (Fure, ProEnergetics) or (ii) the same drink without caffeine (placebo). During the matches, the individual running distance and the instantaneous speed were measured, and the number of running actions above 20 km·h(-1) (i.e., sprints) were determined, using global positioning system devices. The number of impacts above 5 g during the matches was determined by accelerometry. The ingestion of the energy drink, compared with the placebo, increased the total distance covered during the match (4749 ± 589 vs 5139 ± 475 m, p < 0.05), the running distance covered at more than 20 km·h(-1) (184 ± 38 vs 208 ± 38 m, p < 0.05), and the number of sprints (10 ± 7 vs 12 ± 7, p < 0.05). The ingestion of the energy drink also resulted in a greater overall number of impacts (481 ± 352 vs 641 ± 366, p < 0.05) and a higher postexercise urine caffeine concentration (0.1 ± 0.1 vs 2.4 ± 0.9 μg·mL(-1), p < 0.05). The use of an energy drink with a caffeine dose equivalent to 3 mg·kg(-1) considerably enhanced the movement patterns of rugby players during a simulated match.

Effects of caffeine on performance and mood depend on the level of caffeine abstinence.

PubMed

Yeomans, Martin R; Ripley, Tamzin; Davies, Laura H; Rusted, Jennifer M; Rogers, Peter J

2002-11-01

Most studies of the effects of caffeine on performance have used regular caffeine consumers who are deprived at test. Thus the reported effects of caffeine could be explained through reversal of caffeine withdrawal. To test how preloading deprived caffeine consumers with 0, 1 or 2 mg/kg caffeine altered the subsequent ability of caffeine to modify mood and performance. Thirty moderate caffeine consumers were given a drink containing 0, 1 or 2 mg/kg caffeine at breakfast followed 60 min later by a second drink containing either 0 or 1 mg/kg caffeine. Performance on a measure of sustained attention and mood were measured before and after each drink. Administration of both 1 and 2 mg/kg caffeine at breakfast decreased reaction time and 1 mg/kg caffeine also increased performance accuracy on the sustained attention (RVIP) task relative to placebo. Both breakfast doses of caffeine also improved rated mental alertness. Similarly, 1 mg/kg caffeine administered 60 min after breakfast decreased reaction time and increased rated mental alertness in the group who had not been given caffeine at breakfast. However, this second dose of caffeine had no effect on subsequent performance or mood in the two groups who had received caffeine at breakfast. Caffeine reliably improved performance on a sustained attention task, and increased rated mental alertness, in moderate caffeine consumers who were tested when caffeine-deprived. However, caffeine had no such effects when consumers were no longer caffeine deprived. These data are consistent with the view that reversal of caffeine withdrawal is a major component of the effects of caffeine on mood and performance.

Habitual coffee consumption enhances attention and vigilance in hemodialysis patients.

PubMed

Nikić, Petar M; Andrić, Branislav R; Stojimirović, Biljana B; Trbojevic-Stanković, Jasna; Bukumirić, Zoran

2014-01-01

Coffee drinking is the main source of caffeine intake among adult population in the western world. It has been reported that low to moderate caffeine intake has beneficial effect on alertness and cognitive functions in healthy subjects. The aim of this study is to evaluate the impact of habitual coffee consumption on cognitive function in hemodialysis patients. In a cross-sectional study, 86 patients from a single-dialysis centre underwent assessment by the Montreal Cognitive Assessment tool and evaluation for symptoms of fatigue, mood, and sleep disorders by well-validated questionnaires. The habitual coffee use and the average daily caffeine intake were estimated by participants' response to a dietary questionnaire. Sixty-seven subjects (78%) consumed black coffee daily, mostly in low to moderate dose. Cognitive impairment was found in three-quarters of tested patients. Normal mental performance was more often in habitual coffee users (25% versus 16%). Regular coffee drinkers achieved higher mean scores on all tested cognitive domains, but a significant positive correlation was found only for items that measure attention and concentration (P = 0.024). Moderate caffeine intake by habitual coffee consumption could have beneficial impact on cognitive function in hemodialysis patients due to selective enhancement of attention and vigilance.

The effects of neurotoxins on web-geometry and web-building behaviour in Araneus diadematus Cl.

PubMed

Hesselberg, Thomas; Vollrath, Fritz

2004-09-15

The process of orb weaving and the resultant orb web constitute a good example of a complex behavioural pattern that is still governed by a relatively simple set of rules. We used the orb spider Araneus diadematus as a model organism to study the effect of the three neurotoxins (scopolamine, amphetamine, and caffeine) on the spider's behaviour. Scopolamine was given at two concentrations, with the lower one showing no effects but the higher one reducing web-building frequency; there also appeared to be a weak effect on web geometry. Amphetamine and caffeine, on the other hand, both resulted in significant changes in both building frequency and web geometry, compared to the controls. Amphetamine webs retained their size but showed an increase in spiral spacing and radius irregularity, as well as a decrease in building efficiency. Caffeine led to a general decrease in size and a slight increase in spiral spacing, as well as radius irregularity. Furthermore, caffeine caused webs to be rounder. Our observations suggest that these neurotoxins disturb different parts of the web-building programme presumably by affecting different actions in the spider's CNS.

Use of methylxanthine therapies for the treatment and prevention of apnea of prematurity.

PubMed

Schoen, Katherine; Yu, Tian; Stockmann, Chris; Spigarelli, Michael G; Sherwin, Catherine M T

2014-04-01

Apnea of prematurity (AOP) is a common complication of preterm birth, which affects more than 80 % of neonates with a birth weight less than 1,000 g. Methylxanthine therapies, including caffeine and theophylline, are a mainstay in the treatment and prevention of AOP. Despite their frequent use, little is known about the long-term safety and efficacy of these medications. In this review, we systematically evaluated the literature on neonatal methylxanthine therapies and found that caffeine is associated with fewer adverse effects and a wider therapeutic window when compared with theophylline. When used as a therapeutic agent, larger doses of caffeine citrate have been shown to improve acute neonatal outcomes when administered promptly, although further studies are needed to assess the long-term neurological consequences associated with the use of large loading doses. In a secondary analysis of data obtained from a randomized controlled trial, the prophylactic use of caffeine was associated with substantial cost savings and improved clinical outcomes. However, there remains a paucity of well-controlled, randomized clinical trials that have examined the use of caffeine as a prophylactic agent, and further prospective trials are needed to determine if caffeine is a safe and effective prophylactic agent. Additionally, measuring plasma concentrations longitudinally as a marker of therapeutic efficacy and/or toxicity has not been shown to be clinically useful in neonates who are responsive to treatment and exhibit no signs or symptoms of toxicity. However, in cases where toxicity is of concern or for neonates with congenital or pathophysiologic process that may alter the pharmacokinetics of these drugs, therapeutic drug monitoring may be warranted to monitor for methylxanthine toxicity.

Caffeine, coffee and tea intake and urinary estrogens and estrogen metabolites in premenopausal women

PubMed Central

Sisti, Julia S.; Hankinson, Susan E.; Caporaso, Neil E.; Gu, Fangyi; Tamimi, Rulla M.; Rosner, Bernard; Xu, Xia; Ziegler, Regina; Eliassen, A. Heather

2015-01-01

Background Prior studies have found weak inverse associations between breast cancer and caffeine and coffee intake, possibly mediated through their effects on sex hormones. Methods High-performance liquid chromatography/tandem mass spectrometry was used to quantify levels of 15 individual estrogens and estrogen metabolites (EM) among 587 premenopausal women in the Nurses’ Health Study II with mid-luteal phase urine samples and caffeine, coffee and/or tea intakes from self-reported food frequency questionnaires. Multivariate linear mixed models were used to estimate geometric means of individual EM, pathways and ratios by intake categories, and P-values for tests of linear trend. Results Compared to women in the lowest quartile of caffeine consumption, those in the top quartile had higher urinary concentrations of 16α-hydroxyestrone (28% difference; P-trend=0.01) and 16-epiestriol (13% difference; P-trend=0.04), and a decreased parent estrogens/2-, 4-, 16-pathway ratio (P-trend=0.03). Coffee intake was associated with higher 2-catechols, including 2-hydroxyestradiol (57% difference, ≥4 cups/day vs. ≤6 cups/week; P-trend=0.001) and 2-hydroxyestrone (52% difference; P-trend=0.001), and several ratio measures. Decaffeinated coffee was not associated with 2-pathway metabolism, but women in the highest (vs. lowest) category of intake (≥2 cups/day vs. ≤1–3 cups/month) had significantly lower levels of two 16-pathway metabolites, estriol (25% difference; P-trend=0.01) and 17-epiestriol (48% difference; Ptrend=0.0004). Tea intake was positively associated with 17-epiestriol (52% difference; Ptrend=0.01). Conclusion Caffeine and coffee intake were both associated with profiles of estrogen metabolism in premenopausal women. Impact Consumption of caffeine and coffee may alter patterns of premenopausal estrogen metabolism. PMID:26063478

Caffeine, coffee, and tea intake and urinary estrogens and estrogen metabolites in premenopausal women.

PubMed

Sisti, Julia S; Hankinson, Susan E; Caporaso, Neil E; Gu, Fangyi; Tamimi, Rulla M; Rosner, Bernard; Xu, Xia; Ziegler, Regina; Eliassen, A Heather

2015-08-01

Prior studies have found weak inverse associations between breast cancer and caffeine and coffee intake, possibly mediated through their effects on sex hormones. High-performance liquid chromatography/tandem mass spectrometry was used to quantify levels of 15 individual estrogens and estrogen metabolites (EM) among 587 premenopausal women in the Nurses' Health Study II with mid-luteal phase urine samples and caffeine, coffee, and/or tea intakes from self-reported food frequency questionnaires. Multivariate linear mixed models were used to estimate geometric means of individual EM, pathways, and ratios by intake categories, and P values for tests of linear trend. Compared with women in the lowest quartile of caffeine consumption, those in the top quartile had higher urinary concentrations of 16α-hydroxyestrone (28% difference; Ptrend = 0.01) and 16-epiestriol (13% difference; Ptrend = 0.04), and a decreased parent estrogens/2-, 4-, 16-pathway ratio (Ptrend = 0.03). Coffee intake was associated with higher 2-catechols, including 2-hydroxyestradiol (57% difference, ≥4 cups/day vs. ≤6 cups/week; Ptrend = 0.001) and 2-hydroxyestrone (52% difference; Ptrend = 0.001), and several ratio measures. Decaffeinated coffee was not associated with 2-pathway metabolism, but women in the highest (vs. lowest) category of intake (≥2 cups/day vs. ≤1-3 cups/month) had significantly lower levels of two 16-pathway metabolites, estriol (25% difference; Ptrend = 0.01) and 17-epiestriol (48% difference; Ptrend = 0.0004). Tea intake was positively associated with 17-epiestriol (52% difference; Ptrend = 0.01). Caffeine and coffee intake were both associated with profiles of estrogen metabolism in premenopausal women. Consumption of caffeine and coffee may alter patterns of premenopausal estrogen metabolism. ©2015 American Association for Cancer Research.

Caffeine, dibutyryl cyclic-AMP and heparin affect the chemotactic and phagocytotic activities of neutrophils for boar sperm in vitro.

PubMed

Li, J-C; Yamaguchi, S; Kondo, Y; Funahashi, H

2011-04-15

The objective was to examine the effects of caffeine, dibutyryl cyclic AMP, and heparin on the chemotaxis and/or phagocytosis of PMNs for porcine sperm. The chemotactic activity of PMNs, determined in a blind well chamber, increased (P < 0.05) when fresh serum was added to the medium (control containing BSA, 1109.5 cells/mm(2) vs serum, 1226.3 cells/mm(2)), regardless of the presence of sperm (control, 1121.1 cells/mm(2) vs serum, 1245.8 cells/mm(2)), whereas heat-inactivated serum did not affect activity (without sperm, 1099.4 cells/mm(2) and with sperm, 1132.6 cells/mm(2)). Regardless of live and dead sperm and of the origin of PMNs (boars vs sows), the phagocytotic activity of PMNs, as determined by co-culture of PMNs with sperm for 60 min, increased (P < 0.05) in the presence of fresh serum containing active complement (46.7 and 43.0%, respectively), but stimulation was decreased (P < 0.05) when 1 mM or higher concentrations of caffeine was added to the medium (from 40.7 to 20.8-31.6%). The origin of PMNs (sows vs boars) did not significantly affect phagocytotic activity. The percentage of PMNs that phagocytized polystyrene latex beads decreased when 2 mM caffeine was added to the medium containing porcine serum (from 43.7 to 21.5%). Serum-stimulated chemotactic activity of PMNs (1089.9 cells/mm(2)) was also reduced (P < 0.05) with 2 mM caffeine (942.5 cells/mm(2)). Furthermore, dibutyryl cAMP at ≥ 0.1 mM or heparin at ≥ 100 μg/mL decreased phagocytotic activity, in a concentration-dependent manner (P < 0.05). Supplementation of PMNs with heparin at 100 or 500 μg/mL decreased (P < 0.05) chemotactic activity in the presence of serum (from 1137.1 cells/mm(2) to 1008.8-1026.3 cells/mm(2)). We inferred that opsonization in the presence of active complement stimulated phagocytotic and chemotactic activities of PMNs, whereas supplementation with caffeine and dibutyryl cAMP (which could be associated with the intracellular cAMP level of PMNs) or adding heparin decreased serum-stimulated phagocytotic and chemotactic activities. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Caffeine improves the ability of serotonin-deficient (Pet-1−/−) mice to survive episodic asphyxia

PubMed Central

Cummings, Kevin J.; Commons, Kathryn G.; Trachtenberg, Felicia L.; Li, Aihua; Kinney, Hannah C.; Nattie, Eugene E.

2015-01-01

Background In neonatal rodents, serotonin (5-HT) neurons are critical for successful autoresuscitation. We hypothesized that caffeine, a respiratory stimulant, would hasten the onset of gasping and improve autoresuscitation in 5-HT-deficient, Pet-1−/− mice. Methods Using a head-out system and electrocardiogram, we measured respiratory and heart rate (HR) responses of Pet-1−/− rodents and their littermates during episodic asphyxia at postnatal days 8–9 (P8–9). After a baseline recording, we injected either vehicle or caffeine (i.p.) at doses of 1, 5, or 10 mg/ kg. We then induced 10 brief (~30 s) episodes of asphyxia, each interspersed with 5 min of room air to allow autoresuscitation. In addition to measuring survival, we measured the duration of hypoxic apnea (time to initiate gasping) and time to recover eupnea and HR. Results Caffeine had a dose-dependent effect of hastening the onset of gasping, recovery of breathing, and restoration of HR in Pet-1−/−(but not in wild-type) rodents, thereby improving survival across asphyxic episodes. Increased survival was strongly correlated with hastened onset of gasping. Conclusion Our data suggest that caffeine reduces mortality relating to asphyxia and 5-HT deficiency. These findings may be relevant for efforts to reduce the incidence of sudden infant death syndrome (SIDS), given that SIDS is associated with failed autoresuscitation and reduced brainstem 5-HT. PMID:23095976

Effects of caffeinated and decaffeinated coffee on biological risk factors for type 2 diabetes: a randomized controlled trial

PubMed Central

2011-01-01

Background Coffee consumption has been associated with a lower risk of type 2 diabetes in prospective cohort studies, but the underlying mechanisms remain unclear. The aim of this study was to evaluate the effects of regular and decaffeinated coffee on biological risk factors for type 2 diabetes. Methods Randomized parallel-arm intervention conducted in 45 healthy overweight volunteers who were nonsmokers and regular coffee consumers. Participants were assigned to consumption of 5 cups (177 mL each) per day of instant caffeinated coffee, decaffeinated coffee, or no coffee (i.e., water) for 8 weeks. Results Average age was 40 years and body mass index was 29.5 kg/m2. Compared with consuming no coffee, consumption of caffeinated coffee increased adiponectin (difference in change from baseline 1.4 μg/mL; 95% CI: 0.2, 2.7) and interleukin-6 (difference: 60%; 95% CI: 8, 138) concentrations and consumption of decaffeinated coffee decreased fetuin-A concentrations (difference: -20%; 95% CI: -35, -1). For measures of glucose tolerance, insulin sensitivity, and insulin secretion, no significant differences were found between treatment groups. Conclusions Although no changes in glycemia and/or insulin sensitivity were observed after 8 weeks of coffee consumption, improvements in adipocyte and liver function as indicated by changes in adiponectin and fetuin-A concentrations may contribute to beneficial metabolic effects of long-term coffee consumption. Trial Registration clinicaltrials.gov NCT00305097 PMID:21914162

Unusual way of suicide by carbon monoxide. Case Report.

PubMed

Zelený, Michal; Pivnička, Jan; Šindler, Martin; Kukleta, Pavel

2015-01-01

Authors discuss the case of a suicide of a 29-year-old man caused by carbon monoxide (CO) intoxication. What the authors found interesting was the unusual way of committing suicide that required good technical skills and expert knowledge. The level of carboxyhemoglobin (COHb) in the blood of the deceased man was routinely determined by the modified method by Blackmoore (1970), using gas chromatography/thermal conductivity detection. The level of saturation of the hemoglobin by CO in the collected blood sample is determined relatively to the same sample saturated to 100%. In the blood sample of the deceased man the lethal concentration of COHb of 76.5% was determined. Within the following examinations the blood alcohol concentration of 0.05 g.kg(-1) was determined. Further analysis revealed traces of sertraline, its metabolite N-desmethylsertraline, omeprazole and caffeine in the liver tissue, traces of N-desmethylsertraline, ibuprofen and caffeine in urine sample, and only traces of caffeine in the stomach content and blood samples were proved. To commit suicide the man used a sophisticated double container-system equipped with a timer for controlled generation of CO based on the chemical reaction of concentrated sulphuric acid and formic acid. The used timer was set by an electromechanical timer switch that triggered the fatal reaction of the acids while the man was sleeping. The authors discuss an unusual case of suicide by CO intoxication rarely seen in the area of forensic medicine and toxicology that is specific due to its sophisticated way of execution.

Caffeine withdrawal symptoms and self-administration following caffeine deprivation.

PubMed

Mitchell, S H; de Wit, H; Zacny, J P

1995-08-01

This study examined the effects of complete or partial caffeine deprivation on withdrawal symptomatology and self-administration of coffee in caffeine-dependent coffee drinkers. Nine habitual coffee drinkers abstained from dietary sources of caffeine for 33.5 h. Caffeine deprivation was manipulated by administering capsules containing 0%, 50%, or 100% of each subject's daily caffeine intake (complete, partial, and no deprivation conditions). Caffeine withdrawal symptomatology was measured using self-report questionnaires. Caffeine self-administration was measured using: i) the amount of coffee subjects earned on a series of concurrent random-ratio schedules that yielded coffee and money reinforcers; ii) the amount of earned coffee they consumed. Saliva samples revealed that subjects complied with the caffeine abstinence instructions. Caffeine withdrawal symptoms occurred reliably following complete caffeine deprivation, though not in the partial deprivation condition. Caffeine self-administration was not related to deprivation condition. We conclude that caffeine withdrawal symptomatology is not necessarily associated with increased caffeine consumption.

Evaluation of polar organic micropollutants as indicators for wastewater-related coastal water quality impairment.

PubMed

Nödler, Karsten; Tsakiri, Maria; Aloupi, Maria; Gatidou, Georgia; Stasinakis, Athanasios S; Licha, Tobias

2016-04-01

Results from coastal water pollution monitoring (Lesvos Island, Greece) are presented. In total, 53 samples were analyzed for 58 polar organic micropollutants such as selected herbicides, biocides, corrosion inhibitors, stimulants, artificial sweeteners, and pharmaceuticals. Main focus is the application of a proposed wastewater indicator quartet (acesulfame, caffeine, valsartan, and valsartan acid) to detect point sources and contamination hot-spots with untreated and treated wastewater. The derived conclusions are compared with the state of knowledge regarding local land use and infrastructure. The artificial sweetener acesulfame and the stimulant caffeine were used as indicators for treated and untreated wastewater, respectively. In case of a contamination with untreated wastewater the concentration ratio of the antihypertensive valsartan and its transformation product valsartan acid was used to further refine the estimation of the residence time of the contamination. The median/maximum concentrations of acesulfame and caffeine were 5.3/178 ng L(-1) and 6.1/522 ng L(-1), respectively. Their detection frequency was 100%. Highest concentrations were detected within the urban area of the capital of the island (Mytilene). The indicator quartet in the gulfs of Gera and Kalloni (two semi-enclosed embayments on the island) demonstrated different concentration patterns. A comparatively higher proportion of untreated wastewater was detected in the gulf of Gera, which is in agreement with data on the wastewater infrastructure. The indicator quality of the micropollutants to detect wastewater was compared with electrical conductivity (EC) data. Due to their anthropogenic nature and low detection limits, the micropollutants are superior to EC regarding both sensitivity and selectivity. The concentrations of atrazine, diuron, and isoproturon did not exceed the annual average of their environmental quality standards (EQS) defined by the European Commission. At two sampling locations irgarol 1051 exceeded its annual average EQS value but not the maximum allowable concentration of 16 ng L(-1). Copyright © 2016 Elsevier Ltd. All rights reserved.

Caffeine withdrawal and high-intensity endurance cycling performance.

PubMed

Irwin, Christopher; Desbrow, Ben; Ellis, Aleisha; O'Keeffe, Brooke; Grant, Gary; Leveritt, Michael

2011-03-01

In this study, we investigated the impact of a controlled 4-day caffeine withdrawal period on the effect of an acute caffeine dose on endurance exercise performance. Twelve well-trained and familiarized male cyclists, who were caffeine consumers (from coffee and a range of other sources), were recruited for the study. A double-blind placebo-controlled cross-over design was employed, involving four experimental trials. Participants abstained from dietary caffeine sources for 4 days before the trials and ingested capsules (one in the morning and one in the afternoon) containing either placebo or caffeine (1.5 mg · kg(-1) body weight · day(-1)). On day 5, capsules containing placebo or caffeine (3 mg · kg(-1) body weight) were ingested 90 min before completing a time trial, equivalent to one hour of cycling at 75% peak sustainable power output. Hence the study was designed to incorporate placebo-placebo, placebo-caffeine, caffeine-placebo, and caffeine-caffeine conditions. Performance time was significantly improved after acute caffeine ingestion by 1:49 ± 1:41 min (3.0%, P = 0.021) following a withdrawal period (placebo-placebo vs. placebo-caffeine), and by 2:07 ± 1:28 min (3.6%, P = 0.002) following the non-withdrawal period (caffeine-placebo vs. caffeine-caffeine). No significant difference was detected between the two acute caffeine trials (placebo-caffeine vs. caffeine-caffeine). Average heart rate throughout exercise was significantly higher following acute caffeine administration compared with placebo. No differences were observed in ratings of perceived exertion between trials. A 3 mg · kg(-1) dose of caffeine significantly improves exercise performance irrespective of whether a 4-day withdrawal period is imposed on habitual caffeine users.

Caffeine Consumption, Expectancies of Caffeine-Enhanced Performance, and Caffeinism Symptoms among University Students.

ERIC Educational Resources Information Center

Bradley, John R.; Petree, Allen

1990-01-01

Gathered self-report data on college students' (n=797) expectations of caffeine-enhanced performance, level of beverage caffeine consumed daily, and caffeinism signs experienced after consumption of caffeinated beverages. Results supported extending the expectancies model of substance use motivation from alcohol to caffeine. (Author/ABL)

Occurrence and preliminarily environmental risk assessment of selected pharmaceuticals in the urban rivers, China

PubMed Central

Zhou, Haidong; Ying, Tianqi; Wang, Xuelian; Liu, Jianbo

2016-01-01

Twelve selected pharmaceuticals including antibiotics, analgesics, antiepileptics and lipid regulators were analysed and detected in water samples collected from 18 sampling sections along the three main urban rivers in Yangpu District of Shanghai, China during four sampling campaigns. Besides, algal growth inhibition test was conducted to preliminarily assess the eco-toxicology induced by the target pharmaceuticals in the rivers. Mean levels for most of target compounds were generally below 100 ng/L at sampling sections, with the exception of caffeine and paracetamol presenting considerably high concentration. The detected pharmaceuticals in the urban rivers ranged from

Occurrence and preliminarily environmental risk assessment of selected pharmaceuticals in the urban rivers, China

NASA Astrophysics Data System (ADS)

Zhou, Haidong; Ying, Tianqi; Wang, Xuelian; Liu, Jianbo

2016-10-01

Twelve selected pharmaceuticals including antibiotics, analgesics, antiepileptics and lipid regulators were analysed and detected in water samples collected from 18 sampling sections along the three main urban rivers in Yangpu District of Shanghai, China during four sampling campaigns. Besides, algal growth inhibition test was conducted to preliminarily assess the eco-toxicology induced by the target pharmaceuticals in the rivers. Mean levels for most of target compounds were generally below 100 ng/L at sampling sections, with the exception of caffeine and paracetamol presenting considerably high concentration. The detected pharmaceuticals in the urban rivers ranged from

Intramuscular injection of malignant hyperthermia trigger agents induces hypermetabolism in susceptible and nonsusceptible individuals.

PubMed

Metterlein, Thomas; Schuster, Frank; Kranke, Peter; Roewer, Norbert; Anetseder, Martin

2010-01-01

A new minimally invasive metabolic test for the diagnosis of susceptibility for malignant hyperthermia measuring intramuscular p(CO(2)) and lactate following local application of caffeine and halothane in humans was recently proposed. The present study tested the hypothesis that a more simplified test protocol allows a differentiation between malignant hyperthermia susceptible (MHS) and malignant hyperthermia nonsusceptible (MHN) and control individuals. With approval of the local ethics committee and informed consent, microdialysis and p(CO(2)) probes with attached microtubing were placed into the lateral vastus muscle of six MHS, seven MHN and seven control individuals. Following equilibration, boluses of 500 microl caffeine 80 mmol l(-1) and halothane 10 vol% dissolved in soybean oil were injected locally. p(CO(2)) and lactate were measured spectrophotometrically. The maximal rate of p(CO(2)) increase was significantly higher in MHS than in MHN and control individuals following application of halothane and caffeine, respectively. Intramuscular caffeine injection leads to a significantly higher increase of local lactate levels in MHS than in MHN and control individuals, whereas halothane increased local lactate levels in all investigated groups. Haemodynamic and systemic metabolic parameters did not differ between the investigated groups. Local caffeine and halothane injection increased intramuscular metabolism in MHS individuals significantly more than in the two other groups. In contrast to previous investigations, direct injection of the concentrations of halothane described here increased lactate and p(CO(2)) even in MHN skeletal muscle.

The influence of alcohol, propylene glycol and 1,2-pentanediol on the permeability of hydrophilic model drug through excised pig skin.

PubMed

Duracher, Lucie; Blasco, Laurent; Hubaud, Jean-Claude; Vian, Laurence; Marti-Mestres, Gilberte

2009-06-05

Alcohol and glycol including 1,2-pentanediol, a new product in this field, were examined for their transdermal penetration enhancing in vitro properties using pig skin and caffeine as a model drug. In order to investigate a possible influence of these compounds, we followed diffusion from an aqueous solution with caffeine followed by a series of different vehicles, their compositions were: (1) in water as a control; (2) in propylene glycol/ethanol/water (25:25:48; v/v/v); (3) in 1,2-pentanediol/water (2.5:95.5, v/v); (4) in 1,2-pentanediol/water (5:93, v/v); in propylene glycol/water (5:93; v/v); and in ethanol/water (5:93; v/v). The stratum corneum/vehicle partition coefficients (K(m)), maximum flux (J), enhancement factor (EF), 24-h receptor concentration (Q(24h)) were determined and compared to control values (caffeine in water). Permeation was also expressed in percentage of the applied dose absorbed in the different compartments. In all test models, caffeine was released and penetrated into pig skin. The 1,2-pentanediol was presented as the most effective enhancer; with a low proportion of this compound (only 5%), caffeine penetrated the skin quicker and in a greater extent. While this compound showed promise as penetration enhancer, further study was required to determine its effectiveness with others drugs and its irritation potential.

Effects of carbohydrate-hydration strategies on glucose metabolism, sprint performance and hydration during a soccer match simulation in recreational players.

PubMed

Kingsley, Michael; Penas-Ruiz, Carlos; Terry, Chris; Russell, Mark

2014-03-01

This study compared the effects of three carbohydrate-hydration strategies on blood glucose concentration, exercise performance and hydration status throughout simulated soccer match-play. A randomized, double-blind and cross-over study design was employed. After familiarization, 14 recreational soccer players completed the soccer match simulation on three separate occasions. Participants consumed equal volumes of 9.6% carbohydrate-caffeine-electrolyte (∼ 6 mg/kg BW caffeine) solution with carbohydrate-electrolyte gels (H-CHO), 5.6% carbohydrate-electrolyte solution with electrolyte gels (CHO) or electrolyte solution and electrolyte gels (PL). Blood samples were taken at rest, immediately before exercise and every 15 min during exercise (first half: 15, 30, 45 min; second half: 60, 75, 90 min). Supplementation influenced blood glucose concentration (time × treatment interaction: p<0.001); however, none of the supplementation regimes were effective in preventing a drop in blood glucose at 60 min. Mean sprint speed was 3 ± 1% faster in H-CHO when compared with PL (treatment: p=0.047). Supplementation caused a 2.3 ± 0.5% increase in plasma osmolality in H-CHO (p<0.001) without change in CHO or PL. Similarly, mean sodium concentrations were 2.1 ± 0.4% higher in H-CHO when compared with PL (p=0.006). Combining high carbohydrate availability with caffeine resulted in improved sprint performance and elevated blood glucose concentrations throughout the first half and at 90 min of exercise; however, this supplementation strategy negatively influenced hydration status when compared with 5.6% carbohydrate-electrolyte and electrolyte solutions. Copyright © 2013 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Potassium-based algorithm allows correction for the hematocrit bias in quantitative analysis of caffeine and its major metabolite in dried blood spots.

PubMed

De Kesel, Pieter M M; Capiau, Sara; Stove, Veronique V; Lambert, Willy E; Stove, Christophe P

2014-10-01

Although dried blood spot (DBS) sampling is increasingly receiving interest as a potential alternative to traditional blood sampling, the impact of hematocrit (Hct) on DBS results is limiting its final breakthrough in routine bioanalysis. To predict the Hct of a given DBS, potassium (K(+)) proved to be a reliable marker. The aim of this study was to evaluate whether application of an algorithm, based upon predicted Hct or K(+) concentrations as such, allowed correction for the Hct bias. Using validated LC-MS/MS methods, caffeine, chosen as a model compound, was determined in whole blood and corresponding DBS samples with a broad Hct range (0.18-0.47). A reference subset (n = 50) was used to generate an algorithm based on K(+) concentrations in DBS. Application of the developed algorithm on an independent test set (n = 50) alleviated the assay bias, especially at lower Hct values. Before correction, differences between DBS and whole blood concentrations ranged from -29.1 to 21.1%. The mean difference, as obtained by Bland-Altman comparison, was -6.6% (95% confidence interval (CI), -9.7 to -3.4%). After application of the algorithm, differences between corrected and whole blood concentrations lay between -19.9 and 13.9% with a mean difference of -2.1% (95% CI, -4.5 to 0.3%). The same algorithm was applied to a separate compound, paraxanthine, which was determined in 103 samples (Hct range, 0.17-0.47), yielding similar results. In conclusion, a K(+)-based algorithm allows correction for the Hct bias in the quantitative analysis of caffeine and its metabolite paraxanthine.

Cognitive and psychomotor performance, mood, and pressor effects of caffeine after 4, 6 and 8 h caffeine abstinence.

PubMed

Heatherley, Susan V; Hayward, Robert C; Seers, Helen E; Rogers, Peter J

2005-04-01

Many studies have found that caffeine consumed after overnight caffeine abstinence improves cognitive performance and mood. Much less is known, however, about the effects of caffeine after shorter periods of caffeine abstinence. The aim of this study was to measure the effects on psychomotor and cognitive performance, mood, hand steadiness, blood pressure and heart rate of caffeine administration after periods of 4, 6, and 8 h of caffeine abstinence. Participants (n = 49, 27 female) were moderate to moderate-high caffeine consumers (mean daily intake 370 mg/day). Following overnight caffeine abstinence, a 'pre-dose' of caffeine (1.2 mg/kg) was administered at 9 A.M, 11 A.M or 1 P.M. The participants started a baseline battery of measurements at 4 P.M.: before receiving caffeine (1.2 mg/kg) or placebo at 5 P.M.: They then performed the battery of tests again, starting at 5:30 P.M. This was a double-blind, placebo-controlled, randomised study. Performance and mood measurements confirmed a psychostimulant action of caffeine (versus placebo), but only after 8 h of caffeine abstinence. Caffeine also increased blood pressure after 8-h abstinence, whereas hand steadiness was decreased and perception of task demand was increased by caffeine after 4 h, but not after 6- and 8-h abstinence. A second cup-of-coffee equivalent dose of caffeine only reliably affected cognitive performance and mood after an 8-h interval between doses, but not after shorter intervals (when caffeine had some adverse effects). These results show that, apart from caffeine consumption soon after waking, the daily pattern of caffeine intake of many typical caffeine consumers is not well explained by the short-term psychostimulant effects of caffeine.

3,5-Di-t-butyl catechol is a potent human ryanodine receptor 1 activator, not suitable for the diagnosis of malignant hyperthermia susceptibility.

PubMed

Lacava, Caterina; Michalek-Sauberer, Andrea; Kraft, Birgit; Sgaragli, Giampietro; Sipos, Elisabeth; Höller, Carmen; Kress, Hans Georg; Fusi, Fabio; Weigl, Lukas G

2012-07-01

3,5-Di-t-butyl catechol (DTCAT) releases Ca(2+) from rat skeletal muscle sarcoplasmic reticulum (SR) vesicles. Hence, it is a candidate for use as a substitute for halothane or caffeine in the in vitro contracture test for the diagnosis of susceptibility to malignant hyperthermia (MH). To characterize the effect of DTCAT at cell level, Ca(2+) release experiments were performed on cultured, human skeletal muscle myotubes using the fluorescent Ca(2+) indicator fura2-AM. DTCAT was also assayed in the in vitro contracture test on human skeletal muscle bundles obtained from individuals diagnosed susceptible (MHS), normal (MHN) or equivocal for halothane (MHEH) and compared to the standard test substances caffeine and halothane. DTCAT increased, in a concentration-dependent manner and with a higher efficacy as compared to caffeine, the free, intracellular Ca(2+) levels of cultured MHN and MHS skeletal muscle myotubes. This effect was similar in both types of myotubes and involved the release of Ca(2+) from SR stores as well as Ca(2+)-influx from the extracellular space. Inhibition of ryanodine receptors either with ryanodine or with ruthenium red markedly reduced DTCAT-induced increase in intracellular Ca(2+) concentration while abolishing that induced by caffeine. In MHN skeletal muscle bundles, DTCAT induced contractures with an EC(50) value of 160 ± 91 μM. However, the sensitivity of MHS or MHEH muscles to DTCAT was similar to that of MHN muscles. In conclusion, DTCAT is not suitable for the diagnosis of MH susceptibility due to its failure to discriminate between MHN and MHS muscles. Copyright © 2012 Elsevier Ltd. All rights reserved.

Caffeine Reinforces Flavor Preference and Behavior in Moderate Users but Not in Low Caffeine Users

ERIC Educational Resources Information Center

Dack, Charlotte; Reed, Phil

2009-01-01

The study examined the role of caffeine consumption in caffeine reinforcement. Previous findings have shown that caffeine reinforced flavor preference in moderate caffeine consumers who are caffeine deprived. However, most of these studies have employed rating procedures only, and have not shown the effectiveness of caffeine to reinforce behaviors…

Determination of myoglobin based on its enzymatic activity by stopped-flow spectrophotometry

NASA Astrophysics Data System (ADS)

Zheng, Qi; Liu, Zhihong; Cai, Ruxiu

2005-04-01

A new method has been developed for the determination of myoglobin (Mb) based on its enzymatic activity for the oxidation of o-phenylenediamine (OPDA) with hydrogen peroxide. Stopped-flow spectrophotometry was used to study the kinetic behavior of the oxidation reaction. The catalytic activity of Mb was compared to other three kinds of catalyst. The time dependent absorbance of the reaction product, 2,3-diamimophenazine (DAPN), at a wavelength of 426 nm was recorded. The initial reaction rate obtained at 40 °C was found to be proportional to the concentration of Mb in the range of 1.0 × 10 -6 to 4.0 × 10 -9 mol L -1. The detection limit of Mb was found to be 9.93 × 10 -10 mol L -1. The relative standard deviations were within 5% for the determination of different concentrations of Mb. Excess of bovine serum albumin (BSA), Ca(II), Mg(II), Cu(II), glucose, caffeine, lactose and uric acid did not interfere.

Interactions Between Energy Drink Consumption and Sleep Problems: Associations with Alcohol Use Among Young Adolescents.

PubMed

Marmorstein, Naomi R

2017-09-01

Background: Energy drink consumption and sleep problems are both associated with alcohol use among adolescents. In addition, caffeine consumption (including energy drinks) is associated with sleep problems. However, information about how these three constructs may interact is limited. The goal of this study was to examine potential interactions between energy drink consumption and sleep problems in the concurrent prediction of alcohol use among young adolescents. Coffee and soda consumption were also examined for comparison. Methods: Participants from the Camden Youth Development Study were included ( n  = 127; mean age = 13.1; 68% Hispanic, 29% African American) and questionnaire measures of frequency of caffeinated beverage consumption (energy drinks, coffee, and soda), sleep (initial insomnia, sleep disturbances, daytime fatigue, and sleep duration), and alcohol consumption were used. Regression analyses were conducted to examine interactions between caffeinated beverage consumption and sleep in the concurrent prediction of alcohol use. Results: Energy drink consumption interacted with initial insomnia and daytime fatigue to concurrently predict particularly frequent alcohol use among those with either of these sleep-related problems and energy drink consumption. The pattern of results for coffee consumption was similar for insomnia but reached only a trend level of significance. Results of analyses examining soda consumption were nonsignificant. Conclusions: Young adolescents who both consume energy drinks and experience initial insomnia and/or daytime fatigue are at particularly high risk for alcohol use. Coffee consumption appears to be associated with similar patterns. Longitudinal research is needed to explain the developmental pathways by which these associations emerge, as well as mediators and moderators of these associations.

Effects of low doses of caffeine on cognitive performance, mood and thirst in low and higher caffeine consumers.

PubMed

Smit, H J; Rogers, P J

2000-10-01

Caffeine is present in many widely consumed drinks and some foods. In the fairly extensive literature on the psychostimulant effects of caffeine, there are few dose-response studies and even fewer studies of the effects of doses of caffeine lower than 50 mg (the range of the amounts of caffeine contained in, for example, a typical serving of tea or cola). This study measured the effects of 0, 12.5, 25, 50 and 100 mg caffeine on cognitive performance, mood and thirst in adults with low and moderate to high habitual caffeine intakes. This was a double-blind, within-subjects study. Following overnight caffeine abstinence, participants (n=23) completed a test battery once before and three times after placebo or caffeine administration. The test battery consisted of two performance tests, a long duration simple reaction time task and a rapid visual information processing task, and a mood questionnaire (including also an item on thirst). Effects on performance and mood confirmed a psychostimulant action of caffeine. All doses of caffeine significantly affected cognitive performance, and the dose-response relationships for these effects were rather flat. The effects on performance were more marked in individuals with a higher level of habitual caffeine intake, whereas caffeine increased thirst only in low caffeine consumers. After overnight caffeine abstinence, caffeine can significantly affect cognitive performance, mood and thirst at doses within and even lower than the range of amounts of caffeine contained in a single serving of popular caffeine-containing drinks. Regular caffeine consumers appear to show substantial tolerance to the thirst-increasing but not to the performance and mood effects of caffeine.

Absence of reinforcing, mood and psychomotor performance effects of caffeine in habitual non-consumers of caffeine.

PubMed

Rogers, Peter J; Martin, James; Smith, Chloe; Heatherley, Susan V; Smit, Hendrik J

2003-04-01

The extent to which the measured (and felt) psychostimulant effects of caffeine represent a real benefit of caffeine consumption or merely withdrawal reversal is unclear. Results showing positive psychostimulant effects of acute caffeine administration in habitual non-consumers of caffeine would provide evidence for a net benefit of caffeine unconfounded by withdrawal. To compare the mood, alerting, psychomotor and reinforcing effects of caffeine in caffeine non-consumers and acutely (overnight) withdrawn caffeine consumers. In experiment 1, these participants consumed two differently flavoured drinks, one containing 100 mg caffeine and the other containing no caffeine. Each drink was consumed on 4 separate days in semi-random order, and self-ratings of mood and alertness were completed before and after drink consumption. On day 9, both drinks contained 50 mg caffeine and drink preference (choice) and intake were assessed. In experiment 2, mood, alertness and performance on a long-duration simple reaction time task were assessed before and after administration of 100 mg or placebo in a single test session. Prior to receiving caffeine, the (overnight withdrawn) caffeine consumers were less alert and more tense than the non-consumers. Caffeine only had significant reinforcing, mood and psychomotor performance effects in the caffeine consumers. The reinforcing effect of caffeine was evident from an effect on drink intake, but drink choice was unaffected. Caffeine increased self-rated alertness of both caffeine consumers and non-consumers; however, for some of the non-consumers this was associated with a worsening of performance. These results support the hypothesis that the psychostimulant and related effects of caffeine are due largely to withdrawal reversal.

The Combined Effects of Alcohol, Caffeine and Expectancies on Subjective Experience, Impulsivity and Risk-Taking

PubMed Central

Heinz, Adrienne J.; de Wit, Harriet; Lilje, Todd C.; Kassel, Jon D.

2013-01-01

Caffeinated alcoholic beverage (CAB) consumption is a rapidly growing phenomenon among young adults and is associated with a variety of health-risk behaviors. The current study examined whether either caffeinated alcohol or the expectation of receiving caffeinated alcohol altered affective, cognitive and behavioral outcomes hypothesized to contribute to risk behavior. Young adult social drinkers (N=146) participated in a single session where they received alcohol (peak Breath Alcohol Content = .088 g/dL, SD = .019; equivalent to about 4 standard drinks) and were randomly assigned to one of four further conditions 1) no caffeine, no caffeine expectancy, 2) caffeine and caffeine expectancy, 3) no caffeine but caffeine expectancy, 4) caffeine but no caffeine expectancy. Participants’ habitual CAB consumption was positively correlated with measures of impulsivity and risky behavior, independently of study drugs. Administration of caffeine (mean dose = 220 mg, SD = 38; equivalent to about 2.75 Red Bulls) in the study reduced subjective ratings of intoxication and reversed the decrease in desire to continue drinking, regardless of expectancy. Caffeine also reduced the effect of alcohol on inhibitory reaction time (faster incorrect responses). Participants not expecting caffeine were less attentive after alcohol, whereas participants expecting caffeine were not, regardless of caffeine administration. Alcohol decreased response accuracy in all participants except those who both expected and received caffeine. Findings suggest that CABs may elevate risk for continued drinking by reducing perceived intoxication, and by maintaining the desire to continue drinking. Simply expecting to consume caffeine may reduce the effects of alcohol on inattention, and either expecting or consuming caffeine may protect against other alcohol-related performance decrements. Caffeine, when combined with alcohol, has both beneficial and detrimental effects on mechanisms known to contribute to risky behavior. PMID:23750693

Caffeine as a model drug of dependence: recent developments in understanding caffeine withdrawal, the caffeine dependence syndrome, and caffeine negative reinforcement.

PubMed

Griffiths, R R; Chausmer, A L

2000-11-01

Caffeine is an excellent model compound for understanding drugs of abuse/dependence. The results of self-administration and choice studies in humans clearly demonstrate the reinforcing effects of low and moderate doses of caffeine. Caffeine reinforcement has been demonstrated in about 45% of normal subjects with histories of moderate and heavy caffeine use. Recent studies provide compelling evidence that caffeine physical dependence potentiates the reinforcing effects of caffeine through the mechanism of withdrawal symptom avoidance. Tolerance to the subjective and sleep-disrupting effects of caffeine in humans has been demonstrated. Physical dependence as reflected in a withdrawal syndrome in humans has been repeatedly demonstrated in adults and recently demonstrated in children. Withdrawal severity is an increasing function of caffeine maintenance dose, with withdrawal occurring at doses as low as 100 mg per day. Increased cerebral blood flow may be the physiological mechanism for caffeine withdrawal headache. Case studies in adults and adolescents clearly demonstrate that some individuals meet DSM-IV diagnostic criteria for a substance dependence syndrome on caffeine, including feeling compelled to continue caffeine use despite desires and recommendations to the contrary. Survey data suggest that 9% to 30% percent of caffeine consumers may be caffeine dependent according to DSM-IV criteria.

Caffeine and caffeine sodium benzoate have a sunscreen effect, enhance UVB-induced apoptosis, and inhibit UVB-induced skin carcinogenesis in SKH-1 mice.

PubMed

Lu, Yao-Ping; Lou, You-Rong; Xie, Jian-Guo; Peng, Qing-Yun; Zhou, Sherry; Lin, Yong; Shih, Weichung Joe; Conney, Allan H

2007-01-01

Topical application of caffeine sodium benzoate (caffeine-SB) immediately after UVB irradiation of SKH-1 mice enhanced UVB-induced apoptosis by a 2- to 3-fold greater extent than occurred after the topical application of an equimolar amount of caffeine. Although topical application of caffeine-SB or caffeine enhanced UVB-induced apoptosis, both substances were inactive on non-UVB-treated normal skin. Topical application of caffeine-SB or caffeine (each has UVB absorption properties) 0.5 h before irradiation with a high dose of UVB decreased UVB-induced thymine dimer formation and sunburn lesions (sunscreen effect). Caffeine-SB was more active than an equimolar amount of caffeine in exerting a sunscreen effect. In additional studies, caffeine-SB strongly inhibited the formation of tumors in UVB-pretreated 'high-risk mice' and in tumor-bearing mice, and the growth of UVB-induced tumors was also inhibited. Caffeine-SB and caffeine are the first examples of compounds that have both a sunscreen effect and enhance UVB-induced apoptosis. Our studies suggest that caffeine-SB and caffeine may be good agents for inhibiting the formation of sunlight-induced skin cancer.

A comparison of the effects of caffeine following abstinence and normal caffeine use.

PubMed

Addicott, Merideth A; Laurienti, Paul J

2009-12-01

Caffeine typically produces positive effects on mood and performance. However, tolerance may develop following habitual use, and abrupt cessation can result in withdrawal symptoms, such as fatigue. This study investigated whether caffeine has a greater stimulant effect in a withdrawn state compared to a normal caffeinated state, among moderate daily caffeine consumers. Using a within-subjects design, 17 caffeine consumers (mean +/- sd = 375 +/- 101 mg/day) ingested placebo or caffeine (250 mg) following 30-h of caffeine abstention or normal dietary caffeine use on four separate days. Self-reported mood and performance on choice reaction time, selective attention, and memory tasks were measured. Caffeine had a greater effect on mood and choice reaction time in the abstained state than in the normal caffeinated state, but caffeine improved selective attention and memory in both states. Although improvements in mood and reaction time may best explained as relief from withdrawal symptoms, other performance measures showed no evidence of withdrawal and were equally sensitive to an acute dose of caffeine in the normal caffeinated state.

A comparison of the effects of caffeine following abstinence and normal caffeine use

PubMed Central

Addicott, Merideth A.

2010-01-01

Rationale Caffeine typically produces positive effects on mood and performance. However, tolerance may develop following habitual use, and abrupt cessation can result in withdrawal symptoms, such as fatigue. This study investigated whether caffeine has a greater stimulant effect in a withdrawn state compared to a normal caffeinated state, among moderate daily caffeine consumers. Materials and methods Using a within-subjects design, 17 caffeine consumers (mean±sd=375±101 mg/day) ingested placebo or caffeine (250 mg) following 30-h of caffeine abstention or normal dietary caffeine use on four separate days. Self-reported mood and performance on choice reaction time, selective attention, and memory tasks were measured. Results Caffeine had a greater effect on mood and choice reaction time in the abstained state than in the normal caffeinated state, but caffeine improved selective attention and memory in both states. Conclusions Although improvements in mood and reaction time may best explained as relief from withdrawal symptoms, other performance measures showed no evidence of withdrawal and were equally sensitive to an acute dose of caffeine in the normal caffeinated state. PMID:19777214

Combined effects of THC and caffeine on working memory in rats.

PubMed

Panlilio, Leigh V; Ferré, Sergi; Yasar, Sevil; Thorndike, Eric B; Schindler, Charles W; Goldberg, Steven R

2012-04-01

Cannabis and caffeine are two of the most widely used psychoactive substances. Δ(9) -Tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, induces deficits in short-term memory. Caffeine, a non-selective adenosine receptor antagonist, attenuates some memory deficits, but there have been few studies addressing the effects of caffeine and THC in combination. Here, we evaluate the effects of these drugs using a rodent model of working memory. Rats were given THC (0, 1 and 3 mg·kg(-1) , i.p.) along with caffeine (0, 1, 3 and 10 mg·kg(-1) , i.p.), the selective adenosine A(1) -receptor antagonist CPT (0, 3 and 10 mg·kg(-1) ) or the selective adenosine A(2A) -receptor antagonist SCH58261 (0 and 5 mg·kg(-1) ) and were tested with a delayed non-matching-to-position procedure in which behaviour during the delay was automatically recorded as a model of memory rehearsal. THC alone produced memory deficits at 3 mg·kg(-1) . The initial exposure to caffeine (10 mg·kg(-1) ) disrupted the established pattern of rehearsal-like behaviour, but tolerance developed rapidly to this effect. CPT and SCH58261 alone had no significant effects on rehearsal or memory. When a subthreshold dose of THC (1 mg·kg(-1) ) was combined with caffeine (10 mg·kg(-1) ) or CPT (10 mg·kg(-1) ), memory performance was significantly impaired, even though performance of the rehearsal-like pattern was not significantly altered. Caffeine did not counteract memory deficits induced by THC but actually exacerbated them. These results are consistent with recent findings that adenosine A(1) receptors modulate cannabinoid signalling in the hippocampus. This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7. Published 2011. This article is a U.S. Government work and is in the public domain in the USA.

The cAMP-induced G protein subunits dissociation monitored in live Dictyostelium cells by BRET reveals two activation rates, a positive effect of caffeine and potential role of microtubules.

PubMed

Tariqul Islam, A F M; Yue, Haicen; Scavello, Margarethakay; Haldeman, Pearce; Rappel, Wouter-Jan; Charest, Pascale G

2018-08-01

To study the dynamics and mechanisms controlling activation of the heterotrimeric G protein Gα2βγ in Dictyostelium in response to stimulation by the chemoattractant cyclic AMP (cAMP), we monitored the G protein subunit interaction in live cells using bioluminescence resonance energy transfer (BRET). We found that cAMP induces the cAR1-mediated dissociation of the G protein subunits to a similar extent in both undifferentiated and differentiated cells, suggesting that only a small number of cAR1 (as expressed in undifferentiated cells) is necessary to induce the full activation of Gα2βγ. In addition, we found that treating cells with caffeine increases the potency of cAMP-induced Gα2βγ activation; and that disrupting the microtubule network but not F-actin inhibits the cAMP-induced dissociation of Gα2βγ. Thus, microtubules are necessary for efficient cAR1-mediated activation of the heterotrimeric G protein. Finally, kinetics analyses of Gα2βγ subunit dissociation induced by different cAMP concentrations indicate that there are two distinct rates at which the heterotrimeric G protein subunits dissociate when cells are stimulated with cAMP concentrations above 500 nM versus only one rate at lower cAMP concentrations. Quantitative modeling suggests that the kinetics profile of Gα2βγ subunit dissociation results from the presence of both uncoupled and G protein pre-coupled cAR1 that have differential affinities for cAMP and, consequently, induce G protein subunit dissociation through different rates. We suggest that these different signaling kinetic profiles may play an important role in initial chemoattractant gradient sensing. Copyright © 2018 Elsevier Inc. All rights reserved.

Acute effects of caffeine in volunteers with different patterns of regular consumption.

PubMed

Hewlett, Paul; Smith, Andrew

2006-04-01

The effects of caffeine on mood and performance are well established. One explanation of these effects is that caffeine removes negative effects induced by prior caffeine withdrawal. This was tested here by comparing effects of caffeine in withdrawn consumers and non-consumers (who by definition were not withdrawn). The present study aimed to determine whether caffeine withdrawal influenced mood and performance by comparing regular consumers who had been withdrawn from caffeine overnight with non-consumers. Following this the effects of acute caffeine challenges were compared in withdrawn consumers and non-consumers. In addition, comparisons were made between those with higher and lower caffeine consumption. One hundred seventy-six volunteers participated in the study. Regular caffeine consumption was assessed by questionnaire and this showed that 56 of the sample did not regularly consume caffeinated beverages. Volunteers were instructed to abstain from caffeine overnight and then completed a baseline session measuring mood and a range of cognitive functions at 08.00 the next day. Following this approximately half of the volunteers were given 1 mg/kg caffeine in a milkshake or water (in the 'no caffeine' condition they were given just the milkshake or water) and the test battery repeated one hour later. A second test battery was carried out at 12.00 and a second caffeine challenge at 13.00. A final test session was carried out at 15.00. The baseline data revealed little evidence of effects of caffeine withdrawal on performance and mood. In contrast to this, caffeine produced a number of significant improvements in performance. There were some differences in the effects of caffeine on regular and non-consumers, with caffeine tending to reduce reaction time in regular consumers while the opposite was true for non-consumers. The present results show little evidence of effects of caffeine withdrawal on performance. In contrast, caffeine challenge produced improvements in aspects of performance and these were often not modified by regular caffeine consumption patterns. The differences in effects of caffeine that were observed between non-consumers and regular consumers were in functions that were unaffected by caffeine withdrawal. These findings show that the observed beneficial effects of caffeine cannot be interpreted in terms of a reversal of caffeine withdrawal. Copyright (c) 2006 John Wiley & Sons, Ltd.

Quantification of the interceptor action of caffeine on the in vitro biological effect of the anti-tumour agent topotecan.

PubMed

Evstigneev, M P; Mosunov, A A; Evstigneev, V P; Parkes, H G; Davies, D B

2011-08-01

Using published in vitro data on the dependence of the percentage of apoptosis induced by the anti-cancer drug topotecan in a leukaemia cell line on the concentration of added caffeine, and a general model of competitive binding in a system containing two aromatic drugs and DNA, it has been shown to be possible to quantify the relative change in the biological effect just using a set of component concentrations and equilibrium constants of the complexation of the drugs. It is also proposed that a general model of competitive binding and parameterization of that model may potentially be applied to any system of DNA-targeting aromatic drugs under in vitro conditions. The main reasons underpinning the proposal are the general feature of the complexation of aromatic drugs with DNA and their interaction in physiological media via hetero-association.

Mapping the pharmacological modulation of brain oxygen metabolism: The effects of caffeine on absolute CMRO2 measured using dual calibrated fMRI.

PubMed

Merola, Alberto; Germuska, Michael A; Warnert, Esther Ah; Richmond, Lewys; Helme, Daniel; Khot, Sharmila; Murphy, Kevin; Rogers, Peter J; Hall, Judith E; Wise, Richard G

2017-07-15

This study aims to map the acute effects of caffeine ingestion on grey matter oxygen metabolism and haemodynamics with a novel MRI method. Sixteen healthy caffeine consumers (8 males, age=24.7±5.1) were recruited to this randomised, double-blind, placebo-controlled study. Each participant was scanned on two days before and after the delivery of an oral caffeine (250mg) or placebo capsule. Our measurements were obtained with a newly proposed estimation approach applied to data from a dual calibration fMRI experiment that uses hypercapnia and hyperoxia to modulate brain blood flow and oxygenation. Estimates were based on a forward model that describes analytically the contributions of cerebral blood flow (CBF) and of the measured end-tidal partial pressures of CO 2 and O 2 to the acquired dual-echo GRE signal. The method allows the estimation of grey matter maps of: oxygen extraction fraction (OEF), CBF, CBF-related cerebrovascular reactivity (CVR) and cerebral metabolic rate of oxygen consumption (CMRO 2 ). Other estimates from a multi inversion time ASL acquisition (mTI-ASL), salivary samples of the caffeine concentration and behavioural measurements are also reported. We observed significant differences between caffeine and placebo on average across grey matter, with OEF showing an increase of 15.6% (SEM±4.9%, p<0.05) with caffeine, while CBF and CMRO 2 showed differences of -30.4% (SEM±1.6%, p<0.01) and -18.6% (SEM±2.9%, p<0.01) respectively with caffeine administration. The reduction in oxygen metabolism found is somehow unexpected, but consistent with a hypothesis of decreased energetic demand, supported by previous electrophysiological studies reporting reductions in spectral power with EEG. Moreover the maps of the physiological parameters estimated illustrate the spatial distribution of changes across grey matter enabling us to localise the effects of caffeine with voxel-wise resolution. CBF changes were widespread as reported by previous findings, while changes in OEF were found to be more restricted, leading to unprecedented mapping of significant CMRO 2 reductions mainly in frontal gyrus, parietal and occipital lobes. In conclusion, we propose the estimation framework based on our novel forward model with a dual calibrated fMRI experiment as a viable MRI method to map the effects of drugs on brain oxygen metabolism and haemodynamics with voxel-wise resolution. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Analysis of some selected catechins and caffeine in green tea by high performance liquid chromatography.

PubMed

El-Shahawi, M S; Hamza, A; Bahaffi, S O; Al-Sibaai, A A; Abduljabbar, T N

2012-10-15

Green tea seems to have a positive impact on health due to the catechins-found as flavanols. Thus, the present study was aimed to develop a low cost reversed phase high performance liquid chromatographic (HPLC) method for simultaneous determination of flavanol contents, namely catechin (C), epicatechin (EC), epigallocatechin (EGC), epicatechin 3-gallate (ECG) and epigallocatechin 3-gallate (EGCG) and caffeine in 29 commercial green tea samples available in a Saudi Arabian local market. A C-18 reversed-phase column, acetonitrile-trifluoroacetic acid as a mobile phase, coupled with UV detector at 205 nm, was successfully used for precise analysis of the tested analytes in boiled water of digested tea leaves. The average values of N (No. of theoretical plates), HETP (height equivalent of theoretical plates) and R(s) (separation factor) (at 10 μg ml(-1) of the catechins EC, EGC, EGCG and ECG) were 2.6×10(3)±1.2×10(3), 1.7×10(-3)±4.7×10(-4) cm and 1.7±5.53×10(-2), respectively. The developed HPLC method demonstrated excellent performance, with low limits of detection (LOD) and quantification (LOQ) of the tested catechins of 0.004-0.05 μg ml(-1) and 0.01-0.17 μg ml(-1), respectively, and recovery percentages of 96-101%. The influence of infusion time (5-30 min) and temperature on the content of the flavanols was investigated by HPLC. After a 5 min infusion of the tea leaves, the average concentrations of caffeine, catechin, EC, EGC, ECG and EGCG were found to be in the ranges 0.086-2.23, 0.113-2.94, 0.58-10.22, 0.19-24.9, 0.22-13.9 and 1.01-43.3 mg g(-1), respectively. The contents of caffeine and catechins followed the sequence: EGCG>EGC>ECG>EC>C>caffeine. The method was applied satisfactorily for the analysis of (+)-catechin, even at trace and ultra trace concentrations of catechins. The method was rapid, accurate, reproducible and ideal for routine analysis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Characterization of Individuals Seeking Treatment for Caffeine Dependence

PubMed Central

Juliano, Laura M.; Evatt, Daniel P.; Richards, Brian D.; Griffiths, Roland R.

2013-01-01

Previous investigations have identified individuals who meet criteria for DSM-IV-TR substance dependence as applied to caffeine, but there is little research on treatments for caffeine dependence. This study aimed to thoroughly characterize individuals who are seeking treatment for problematic caffeine use. Ninety-four individuals who identified as being psychologically or physically dependent on caffeine, or who had tried unsuccessfully to modify caffeine consumption participated in a face-to-face diagnostic clinical interview. They also completed measures concerning caffeine use and quitting history, reasons for seeking treatment, and standardized self-report measures of psychological functioning. Caffeine treatment seekers (mean age 41 yrs, 55% women) consumed an average of 548 mg caffeine per day. The primary source of caffeine was coffee for 50% of the sample and soft drinks for 37%. Eighty-eight percent reported prior serious attempts to modify caffeine use (mean 2.7 prior attempts) and 43% reported being advised by a medical professional to reduce or eliminate caffeine. Ninety-three percent met criteria for caffeine dependence when generic DSM-IV-TR substance dependence criteria were applied to caffeine use. The most commonly endorsed criteria were withdrawal (96%), persistent desire or unsuccessful efforts to control use (89%), and use despite knowledge of physical or psychological problems caused by caffeine (87%). The most common reasons for wanting to modify caffeine use were health-related (59%) and not wanting to be dependent on caffeine (35%). This investigation reveals that there are individuals with problematic caffeine use who are seeking treatment, and suggests that there is a need for effective caffeine dependence treatments. PMID:22369218

Rapid determination of phenolic compounds and alkaloids of carob flour by improved liquid chromatography tandem mass spectrometry.

PubMed

Ortega, Nàdia; Macià, Alba; Romero, Maria-Paz; Trullols, Esther; Morello, Jose-Ramón; Anglès, Neus; Motilva, Maria-Jose

2009-08-26

An improved chromatographic method was developed using ultra-performance liquid chromatography-tandem mass spectrometry to identify and quantify phenolic compounds and alkaloids, theobromine and caffeine, in carob flour samples. The developed method has been validated in terms of speed, sensitivity, selectivity, peak efficiency, linearity, reproducibility, limits of detection, and limits of quantification. The chromatographic method allows the identification and quantification of 20 phenolic compounds, that is, phenolic acids, flavonoids, and their aglycone and glucoside forms, together with the determination of the alkaloids, caffeine and theobromine, at low concentration levels all in a short analysis time of less than 20 min.

Tracking acidic pharmaceuticals, caffeine, and triclosan through the wastewater treatment process.

PubMed

Thomas, Paul M; Foster, Gregory D

2005-01-01

Pharmaceuticals are a class of emerging contaminants whose fate in the wastewater treatment process has received increasing attention in past years. Acidic pharmaceuticals (ibuprofen, naproxen, mefenamic acid, ketoprofen, and diclofenac), caffeine, and the antibacterial triclosan were quantified at four different steps of wastewater treatment from three urban wastewater treatment plants. The compounds were extracted from wastewater samples on Waters Oasis hydrophilic-lipophilic balance solid-phase extraction columns, silylated, and analyzed by gas chromatography-mass spectrometry. For the chemicals studied, it was found that the majority of the influent load was removed during secondary treatment (51-99%), yielding expected surface water concentrations of 13 to 56 ng/L.

Effects of caffeine or RX821002 in rats with a neonatal ventral hippocampal lesion

PubMed Central

Sandner, Guy; Angst, Marie-Josée; Guiberteau, Thierry; Guignard, Blandine; Nehlig, Astrid

2014-01-01

Rats with a neonatal ventral hippocampal lesion (NVHL) are used to model schizophrenia. They show enhanced locomotion and difficulties in learning after puberty. Such behavioral modifications are strengthened by dopaminergic psychostimulant drugs, which is also relevant for schizophrenia because illustrating its dopaminergic facet. But it remains questionable that only dopaminergic drugs elicit such effects. The behavioral effects could simply represent a non specific arousal, in which case NVHL rats should also be hyper-responsive to other vigilance enhancing drugs. We administered an adenosine (caffeine) or an adrenaline receptor antagonist, (RX821002) at doses documented to modify alertness of rats, respectively 5 mg/kg and 1 mg/kg. Rats were selected prior to the experiments using magnetic resonance imaging (MRI). Each group contained typical and similar NVHL lesions. They were compared to sham lesioned rats. We evaluated locomotion in a new environment and the capacity to remember a visual or acoustic cue that announced the occurrence of food. Both caffeine and RX82100 enhanced locomotion in the novel environment, particularly in NVHL rats. But, RX82100 had a biphasic effect on locomotion, consisting of an initial reduction preceding the enhancement. It was independent of the lesion. Caffeine did not modify the learning performance of NVHL rats. But, RX821002 was found to facilitate learning. Patients tend to intake much more caffeine than healthy people, which has been interpreted as a means to counter some cognitive deficits. This idea was not validated with the present results. But adrenergic drugs could be helpful for attenuating some of their cognitive deficits. PMID:24478661

Effects of caffeine in overnight-withdrawn consumers and non-consumers.

PubMed

Smith, Andrew P; Christopher, Gary; Sutherland, David

2006-01-01

A number of recent studies have suggested that caffeine only improves mood and cognitive performance in regular caffeine consumers who are caffeine withdrawn at test (the "withdrawal hypothesis"). This can be tested by investigating the effects of caffeine in non-consumers of caffeine. To compare the effects of 2 mg/kg caffeine on mood and cognitive performance in overnight-withdrawn consumers and non-consumers of caffeine. Twenty-five overnight-withdrawn consumers and twenty-five non-consumers of caffeine were tested in a within-subjects design where they were given a drink containing 2 mg/kg caffeine on one test day and placebo on another test day. The order of conditions (caffeine/placebo) was counterbalanced. Mood and performance measures were taken before and after each drink, and pre-drink measures were used as covariates in the analysis of post-drink measures. Analysis of baseline scores revealed no significant effects of caffeine withdrawal. Caffeine generally improved mood and cognitive performance, relative to placebo, in both subjects groups. These effects did not differ significantly between groups apart from three measures (fewer lapses of attention and ratings of alertness and anxiety) where the effects of caffeine were larger in the non-consumers. The present study revealed no negative effects of caffeine withdrawal. Beneficial effects of caffeine were observed in both withdrawn consumers and in non-consumers. Therefore, the withdrawal hypothesis is not an adequate explanation for the effects of caffeine.

Ca2+ cycling between sarcoplasmic reticulum and mitochondria in rabbit cardiac myocytes.

PubMed Central

Bassani, J W; Bassani, R A; Bers, D M

1993-01-01

1. Shortening and intracellular Ca2+ (Ca2+i) transients were measured in isolated rabbit ventricular myocytes during paired contractures induced by rapid application of 10 mM caffeine. 2. Caffeine-induced contractures relax despite maintained presence of caffeine. In control solution, a second phasic caffeine contracture failed to appear, unless the sarcoplasmic reticulum (SR) was refilled by a series of electrically stimulated twitches during the interval between caffeine exposures. 3. The relaxation of caffeine-induced contractures in 0 Na(+)-0 Ca2+ solution has previously been shown to rely on mitochondrial Ca2+ uptake and sarcolemmal Ca2(+)-ATPase. Thus, a second caffeine contracture (T2) while still in 0 Na(+)-0 Ca2+ was greatly reduced compared to the first one (T1). However, the amplitude of T2 increased exponentially with the time interval, attaining a maximum of approximately 50% of T1 for an interval of 180-300 s, with a time constant (tau) of 41.2 s. Similar results were found for Ca2+i transients (tau = 45 s). 4. Inhibition of the mitochondrial Ca2+ uptake by the oxidative phosphorylation uncoupler, FCCP during T1 dramatically depressed T2. On the other hand, inhibition of the sarcolemmal Ca2(+)-ATPase (by increasing extracellular Ca2+ concentration, [Ca2+]o) resulted in increase of T2. Spermine inclusion during T1 also increased T2, possibly by an increase of mitochondrial Ca2+ uptake. 5. We conclude that Ca2+ taken up by mitochondria during the decline of T1 moves back to the SR after caffeine is removed, with a tau approximately 40 s. 6. Partial intracellular Na+ depletion by prolonged (3 min) perfusion with 0 Na(+)-0 Ca2+ solution before T1 (a) accelerated relaxation and [Ca2+]i decline during T1, and (b) slowed, but did not abolish, the recovery of T2 as the interval was increased. This effect was particularly pronounced when choline was used instead of Li+ as the Na+ substitute. 7. We further conclude that the mitochondrial Na(+)-Ca2+ antiporter influences the rate of net Ca2+ uptake by mitochondria and is also important in Ca2+ efflux from mitochondria during rest. PMID:8387590

Ca2+ cycling between sarcoplasmic reticulum and mitochondria in rabbit cardiac myocytes.

PubMed

Bassani, J W; Bassani, R A; Bers, D M

1993-01-01

1. Shortening and intracellular Ca2+ (Ca2+i) transients were measured in isolated rabbit ventricular myocytes during paired contractures induced by rapid application of 10 mM caffeine. 2. Caffeine-induced contractures relax despite maintained presence of caffeine. In control solution, a second phasic caffeine contracture failed to appear, unless the sarcoplasmic reticulum (SR) was refilled by a series of electrically stimulated twitches during the interval between caffeine exposures. 3. The relaxation of caffeine-induced contractures in 0 Na(+)-0 Ca2+ solution has previously been shown to rely on mitochondrial Ca2+ uptake and sarcolemmal Ca2(+)-ATPase. Thus, a second caffeine contracture (T2) while still in 0 Na(+)-0 Ca2+ was greatly reduced compared to the first one (T1). However, the amplitude of T2 increased exponentially with the time interval, attaining a maximum of approximately 50% of T1 for an interval of 180-300 s, with a time constant (tau) of 41.2 s. Similar results were found for Ca2+i transients (tau = 45 s). 4. Inhibition of the mitochondrial Ca2+ uptake by the oxidative phosphorylation uncoupler, FCCP during T1 dramatically depressed T2. On the other hand, inhibition of the sarcolemmal Ca2(+)-ATPase (by increasing extracellular Ca2+ concentration, [Ca2+]o) resulted in increase of T2. Spermine inclusion during T1 also increased T2, possibly by an increase of mitochondrial Ca2+ uptake. 5. We conclude that Ca2+ taken up by mitochondria during the decline of T1 moves back to the SR after caffeine is removed, with a tau approximately 40 s. 6. Partial intracellular Na+ depletion by prolonged (3 min) perfusion with 0 Na(+)-0 Ca2+ solution before T1 (a) accelerated relaxation and [Ca2+]i decline during T1, and (b) slowed, but did not abolish, the recovery of T2 as the interval was increased. This effect was particularly pronounced when choline was used instead of Li+ as the Na+ substitute. 7. We further conclude that the mitochondrial Na(+)-Ca2+ antiporter influences the rate of net Ca2+ uptake by mitochondria and is also important in Ca2+ efflux from mitochondria during rest.

Caffeine enhanced measurement of mutagenesis by low levels of [gamma]-irradiation in human lymphocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Puck, T.P.; Johnson, R.; Waldren, C.A.

1993-09-01

The well-known action of caffeine in synergizing mutagenesis (including chromosome aberrations) of agents like ionizing radiation by inhibition of cellular repair processes has been incorporated into a rapid procedure for detection of mutagenicity with high sensitivity. Effects of 5-10 rads of [gamma]-irradiation, which approximate the human lifetime dose accumulation from background radiation, can be detected in a two-day procedure using an immortalized human WBC culture. Chromosomally visible lesions are scored on cells incubated for 2 h after irradiation in the presence and absence of 1.0 mg/ml of caffeine. An eightfold amplification of scorable lesions is achieved over the action ofmore » radiation alone. This approach provides a closer approximation to absolute mutagenicity unmitigated by repair processes, which can vary in different situations. It is proposed that mutagenesis testing of this kind, using caffiene or other repair-inhibitory agents, be employed to identify mutagens in their effective concentrations to which human populations may be exposed; to detect agents such as caffeine that may synergize mutagenic actions and pose epidemiologic threats; and to discover effective anti-mutagens. Information derived from the use of such procedures may help prevent cancer and newly acquired genetic disease.« less

Calcium-Binding Properties of Sarcoplasmic Reticulum As Influenced by ATP, Caffeine, Quinine, and Local Anesthetics

PubMed Central

Carvalho, Arselio P.

1968-01-01

Calcium retained at binding sites of the sarcoplasmic reticulum membranes isolated from rabbit skeletal muscle requires 10-5 – 10-4 M ATP to exchange with 45Ca added to the medium. The ATP requirement for Ca exchangeability was observed with respect to the "intrinsic" Ca of the reticulum membranes and the fraction of Ca that is "actively" bound in the presence of ATP. Furthermore, a concentration of free Ca in the medium higher than 10-8 M is required for ATP to promote Ca exchangeability. This exchangeability is not influenced by caffeine, quinine, procaine, and tetracaine, and Ca that is either nonexchangeable (in the absence of ATP) or exchangeable (in the presence of ATP) is released by 1–5 mM quinine or tetracaine, but neither caffeine (6 mM) nor procaine (2–5 mM) has this effect. Quinine or tetracaine also releases Ca and Mg bound passively to the reticulum membranes. A possible role of ATP in maintaining the integrity of cellular membranes is discussed, and the effects of caffeine, quinine, and of local anesthetics on the binding of Ca by the isolated reticulum are related to the effects of these agents on 45Ca fluxes and on the twitch output observed in whole muscles. PMID:19873636

Determination of caffeine, theobromine and theophylline in Mate beer and Mate soft drinks by high-performance thin-layer chromatography.

PubMed

Oellig, Claudia; Schunck, Jacob; Schwack, Wolfgang

2018-01-19

Mate beer and Mate soft drinks are beverages produced from the dried leaves of Ilex paraguariensis (Yerba Mate). In Yerba Mate, the xanthine derivatives caffeine, theobromine and theophylline, also known as methylxanthines, are important active components. The presented method for the determination of caffeine, theobromine and theophylline in Mate beer and Mate soft drinks by high-performance thin-layer chromatography with ultraviolet detection (HPTLC-UV) offers a fully automated and sensitive determination of the three methylxanthines. Filtration of the samples was followed by degassing, dilution with acetonitrile in the case of Mate beers for protein precipitation, and centrifugation before the extracts were analyzed by HPTLC-UV on LiChrospher silica gel plates with fluorescence indicator and acetone/toluene/chloroform (4:3:3, v/v/v) as the mobile phase. For quantitation, the absorbance was scanned at 274nm. Limits of detection and quantitation were 1 and 4ng/zone, respectively, for caffeine, theobromine and theophylline. With recoveries close to 100% and low standard deviations reliable results were guaranteed. Experimental Mate beers as well as Mate beers and Mate soft drinks from the market were analyzed for their concentrations of methylxanthines. Copyright © 2017 Elsevier B.V. All rights reserved.

Habitual Coffee Consumption Enhances Attention and Vigilance in Hemodialysis Patients

PubMed Central

Nikić, Petar M.; Andrić, Branislav R.; Stojimirović, Biljana B.; Trbojevic-Stanković, Jasna; Bukumirić, Zoran

2014-01-01

Objective. Coffee drinking is the main source of caffeine intake among adult population in the western world. It has been reported that low to moderate caffeine intake has beneficial effect on alertness and cognitive functions in healthy subjects. The aim of this study is to evaluate the impact of habitual coffee consumption on cognitive function in hemodialysis patients. Methods. In a cross-sectional study, 86 patients from a single-dialysis centre underwent assessment by the Montreal Cognitive Assessment tool and evaluation for symptoms of fatigue, mood, and sleep disorders by well-validated questionnaires. The habitual coffee use and the average daily caffeine intake were estimated by participants' response to a dietary questionnaire. Results. Sixty-seven subjects (78%) consumed black coffee daily, mostly in low to moderate dose. Cognitive impairment was found in three-quarters of tested patients. Normal mental performance was more often in habitual coffee users (25% versus 16%). Regular coffee drinkers achieved higher mean scores on all tested cognitive domains, but a significant positive correlation was found only for items that measure attention and concentration (P = 0.024). Conclusions. Moderate caffeine intake by habitual coffee consumption could have beneficial impact on cognitive function in hemodialysis patients due to selective enhancement of attention and vigilance. PMID:24895603

Simultaneous pharmacokinetics evaluation of human cytochrome P450 probes, caffeine, warfarin, omeprazole, metoprolol and midazolam, in common marmosets (Callithrix jacchus).

PubMed

Uehara, Shotaro; Inoue, Takashi; Utoh, Masahiro; Toda, Akiko; Shimizu, Makiko; Uno, Yasuhiro; Sasaki, Erika; Yamazaki, Hiroshi

2016-01-01

1. Pharmacokinetics of human cytochrome P450 probes (caffeine, racemic warfarin, omeprazole, metoprolol and midazolam) composite, after single intravenous and oral administrations at doses of 0.20 and 1.0 mg kg(-1), respectively, to four male common marmosets were investigated. 2. The plasma concentrations of caffeine and warfarin decreased slowly in a monophasic manner but those of omeprazole, metoprolol and midazolam decreased extensively after intravenous and oral administrations, in a manner that approximated those as reported for pharmacokinetics in humans. 3. Bioavailabilities were ∼100% for caffeine and warfarin, but <25% for omeprazole and metoprolol. Bioavailability of midazolam was 4% in marmosets, presumably because of contribution of marmoset P450 3A4 expressed in small intestine and liver, with a high catalytic efficiency for midazolam 1'-hydroxylation as evident in the recombinant system. 4. These results suggest that common marmosets, despite their rapid clearance of some human P450 probe substrates, could be an experimental model for humans and that marmoset P450s have functional characteristics that differ from those of human and/or cynomolgus monkey P450s in some aspects, indicating their importance in modeling in P450-dependent drug metabolism studies in marmosets and of further studies.

Effects of repeated doses of caffeine on performance and alertness: new data and secondary analyses.

PubMed

Hewlett, Paul; Smith, Andrew

2007-08-01

The effects of caffeine on mood and performance are well established. Some authors suggest that caffeine merely reverses effects of caffeine withdrawal rather than having direct behavioural effects. It has also been suggested that withdrawal may be removed by a first dose of caffeine and further doses have little subsequent effect. These issues are examined here. The present study aimed to determine whether caffeine withdrawal influenced mood and performance by comparing regular consumers who had been withdrawn from caffeine overnight with non-consumers. Following this repeated caffeine doses were administered to test the claim that repeated dosing has no extra effect on mood or performance. Secondary analyses of data collected after a day of normal caffeine consumption were also carried out to examine some alternative explanations of their results which showed effects of caffeine after a day of normal caffeine consumption. One hundred and twenty volunteers participated in the study. Regular caffeine consumption was assessed by questionnaire and this showed that 36 of the volunteers did not regularly consume caffeinated beverages. Volunteers were instructed to abstain from caffeine overnight and then completed a baseline session measuring mood and a range of cognitive functions at 08.00 the next day. Following this volunteers were given 0, or 1 mg/kg caffeine in a milkshake, glucose solution or water (at 09:00), followed by a second 0 or 1 mg/kg caffeine dose (at 09:40) and the test battery repeated at 10:00. The baseline data showed no effect of overnight caffeine withdrawal on mood or performance. In contrast, caffeine challenge improved vigilance performance and prevented decreases in alertness induced by completion of the task battery. The magnitude of these effects increased as a function of the number of doses of caffeine given. Secondary analyses of data from Christopher et al. (2003) also confirmed that effects of caffeine did not depend on length of withdrawal. The present findings show no effect of overnight caffeine withdrawal on mood and performance. Caffeine challenge did have the predicted effect on alertness and vigilance, with the size of the effects increasing with caffeine dose. These findings suggest that the effects of caffeine are not due to reversal of effects of withdrawal, a view confirmed by secondary analyses of data collected after a day of normal caffeine consumption. Copyright 2007 John Wiley & Sons, Ltd.

Drugs and personal care products as ubiquitous pollutants: occurrence and distribution of clofibric acid, caffeine and DEET in the North Sea.

PubMed

Weigel, Stefan; Kuhlmann, Jan; Hühnerfuss, Heinrich

2002-08-05

An analytical method is presented, which allows the simultaneous extraction of neutral and acidic compounds from 20-L seawater samples at ambient pH (approximately 8.3). It is based on a solid-phase extraction by means of a polystyrene-divinylbenzene sorbent and gas chromatographic-mass spectrometric detection, and provides detection limits in the lower pg/L range. The method was applied to the screening of samples from different North Sea areas for clofibric acid, diclofenac, ibuprofen, ketoprofen, propyphenazone, caffeine and N,N-diethyl-3-toluamide (DEET). Whereas clofibric acid, caffeine and DEET showed to be present throughout the North Sea in concentrations of up to 1.3, 16 and 1.1 ng/L, respectively, propyphenazone could only be detected after further clean-up. Diclofenac and ibuprofen were found in the estuary of the river Elbe (6.2 and 0.6 ng/L, respectively) but in none of the marine samples. Ketoprofen was below the detection limit in all samples.

Effects of caffeine deprivation on taste and mood.

PubMed

Brauer, L.H.; Buican, B.; de Wit, H.

1994-04-01

Despite its ubiquitous consumption in the natural environment, caffeine has not been a reliable reinforcer in laboratory settings. The reinforcing effects of caffeine are greater in caffeine-dependent subjects relative to non-dependent subjects, but the mechanism underlying this difference remains unclear. We hypothesized that deprivation from caffeine would produce alterations in subjective ratings of stimuli commonly associated with caffeine consumption. Specifically, we hypothesized that hedonic ratings of the coffee taste would be selectively enhanced following caffeine deprivation. Twelve regular caffeine users received acute doses of caffeine (300mg) or placebo after 33h of caffeine deprivation or non-deprivation. They rated the taste of coffee and sucrose, saccharin, and quinine solutions on intensity, bitterness, sweetness, pleasantness, and unpleasantness. Contrary to our hypothesis, subjects' ratings of the pleasantness of the coffee taste were not significantly altered by caffeine deprivation. However, subjects' ratings of the bitterness and sweetness of the coffee taste and ratings of the sucrose solution were altered by caffeine. Implications of these data for caffeine self-administration are discussed.

Effects of caffeine and caffeine withdrawal on mood and cognitive performance degraded by sleep restriction.

PubMed

Rogers, Peter J; Heatherley, Susan V; Hayward, Robert C; Seers, Helen E; Hill, Joanne; Kane, Marian

2005-06-01

It has been suggested that caffeine is most likely to benefit mood and performance when alertness is low. To measure the effects of caffeine on psychomotor and cognitive performance, mood, blood pressure and heart rate in sleep-restricted participants. To do this in a group of participants who had also been previously deprived of caffeine for 3 weeks, thereby potentially removing the confounding effects of acute caffeine withdrawal. Participants were moderate to moderate-high caffeine consumers who were provided with either decaffeinated tea and/or coffee for 3 weeks (LTW) or regular tea and/or coffee for 3 weeks (overnight caffeine-withdrawn participants, ONW). Then, following overnight caffeine abstinence, they were tested on a battery of tasks assessing mood, cognitive performance, etc. before and after receiving caffeine (1.2 mg/kg) or on another day after receiving placebo. Final analyses were based on 17 long-term caffeine-withdrawn participants (LTW) and 17 ONW participants whose salivary caffeine levels on each test day confirmed probable compliance with the instructions concerning restrictions on consumption of caffeine-containing drinks. Acute caffeine withdrawal (ONW) had a number of negative effects, including impairment of cognitive performance, increased headache, and reduced alertness and clear-headedness. Caffeine (versus placebo) did not significantly improve cognitive performance in LTW participants, although it prevented further deterioration of performance in ONW participants. Caffeine increased tapping speed (but tended to impair hand steadiness), increased blood pressure, and had some effects on mood in both groups. The findings provide strong support for the withdrawal reversal hypothesis. In particular, cognitive performance was found to be affected adversely by acute caffeine withdrawal and, even in the context of alertness lowered by sleep restriction, cognitive performance was not improved by caffeine in the absence of these withdrawal effects. Different patterns of effects (or lack of effects) of caffeine and caffeine withdrawal were found for other variables, but overall these results also suggest that there is little benefit to be gained from caffeine consumption.

Investigation of pharmaceuticals, personal care products and endocrine disrupting chemicals in a tropical urban catchment and the influence of environmental factors.

PubMed

You, Luhua; Nguyen, Viet Tung; Pal, Amrita; Chen, Huiting; He, Yiliang; Reinhard, Martin; Gin, Karina Yew-Hoong

2015-12-01

Previous studies showed the presence of multiple emerging organic contaminants (EOCs) in urban surface waters of Singapore even though there are no obvious direct wastewater discharges. In this study, we investigated the occurrence and distribution of 17 pharmaceuticals and personal care products (PPCPs) and endocrine disruptive compounds (EDCs) in a tropical urban catchment of Singapore. Monthly samples were collected from a reservoir and its 5 upstream tributaries during a 16-month period. Analysis of samples showed all sites had measurable PPCP and EDC concentrations, with caffeine (33.9-2980 ng/L), salicylic acid (5-838 ng/L), acetaminophen (<4-485.5 ng/L), BPA (<2-919.5 ng/L) and DEET (13-270 ng/L) being the most abundant. Marked differences in concentrations of target analytes between the reservoir and upstream tributaries were observed, and were tentatively attributed to the spatial differences in source inputs, water dilution capacity as well as natural attenuation of EOCs. Significant correlations between EOCs and conductivity, dissolved oxygen, chlorophyll a, turbidity, nutrients and cumulative precipitation were observed. These factors appeared to affect the distribution and attenuation of EOCs, depending on their physicochemical properties. Rainfall also influenced the temporal distribution of caffeine, BPA, triclosan, fipronil and DEET in the reservoir. Ecological risk assessment showed that caffeine, acetaminophen, estrone, BPA, triclosan and fipronil may warrant further survey. In particular, BPA levels exceeded the literature-based Predicted No-Effect Concentration (PNEC) value, highlighting the need for source control and/or water remediation in this urban catchment. Copyright © 2015 Elsevier B.V. All rights reserved.

Fewer but heavier caffeine consumers in schizophrenia: a case-control study.

PubMed

Gurpegui, Manuel; Aguilar, M Carmen; Martínez-Ortega, José M; Jurado, Dolores; Diaz, Francisco J; Quintana, Hernando M; de Leon, Jose

2006-09-01

According to the literature, there is an association between schizophrenia and caffeine consumption, but it is not clear whether schizophrenia is associated with either higher prevalence of daily caffeine intake or the amount consumed. In this study we compared our previously published schizophrenia patients (n=250) with a control sample (n=290) after controlling for demographic variables and tobacco and alcohol consumption. Current caffeine intake was less frequent in schizophrenia patients (59%, 147/250) than in controls (70%, 204/290). In the multivariate analyses, caffeine intake was less frequent at an older age and in schizophrenia patients, and more frequent in smokers and alcohol users. Among caffeine consumers, heavy caffeine intake (> or =200 mg/day) was significantly associated with schizophrenia (64%, 94/147 in schizophrenia versus 36%, 73/204 in controls), as well as older age and smoking. Daily amount of caffeine intake and smoked cigarettes correlated significantly in the schizophrenia group but not in the control group; the correlation of caffeine intake with nicotine dependence was low and non-significant in both groups. The association between current smoking and heavy caffeine intake may be partly explained by a pharmacokinetic effect: tobacco smoke compounds induce caffeine metabolism by the cytochrome P450 1A2. Although schizophrenia by itself may be associated with heavy caffeine intake in caffeine users, part of this association was explained by the association between schizophrenia and smoking. The relationship between caffeine and alcohol intake appeared to be more complex; alcohol and caffeine use were significantly associated, but within caffeine users alcohol was associated with less frequent heavy caffeine consumption among smokers. In future studies, the measurement of plasma caffeine levels will help both to better define heavy caffeine intake and to control for smoking pharmacokinetic effects.

Characterization of individuals seeking treatment for caffeine dependence.

PubMed

Juliano, Laura M; Evatt, Daniel P; Richards, Brian D; Griffiths, Roland R

2012-12-01

Previous investigations have identified individuals who meet criteria for Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR; American Psychiatric Association, 2000) substance dependence as applied to caffeine, but there is little research on treatments for caffeine dependence. This study aimed to thoroughly characterize individuals who are seeking treatment for problematic caffeine use. Ninety-four individuals who identified as being psychologically or physically dependent on caffeine, or who had tried unsuccessfully to modify caffeine consumption participated in a face-to-face diagnostic clinical interview. They also completed measures concerning caffeine use and quitting history, reasons for seeking treatment, and standardized self-report measures of psychological functioning. Caffeine treatment seekers (mean age 41 years, 55% women) consumed an average of 548 mg caffeine per day. The primary source of caffeine was coffee for 50% of the sample and soft drinks for 37%. Eighty-eight percent reported prior serious attempts to modify caffeine use (mean 2.7 prior attempts), and 43% reported being advised by a medical professional to reduce or eliminate caffeine. Ninety-three percent met criteria for caffeine dependence when generic DSM-IV-TR substance dependence criteria were applied to caffeine use. The most commonly endorsed criteria were withdrawal (96%), persistent desire or unsuccessful efforts to control use (89%), and use despite knowledge of physical or psychological problems caused by caffeine (87%). The most common reasons for wanting to modify caffeine use were health-related (59%) and not wanting to be dependent on caffeine (35%). This investigation reveals that there are individuals with problematic caffeine use who are seeking treatment and suggests that there is a need for effective caffeine dependence treatments. 2013 APA, all rights reserved

[Caffeine--common ingredient in a diet and its influence on human health].

PubMed

Wierzejska, Regina

2012-01-01

Caffeine is widely consumed by people of all ages. In the last period a market of caffeine-containing products, particularly energy drinks and food supplements increased. Caffeine for years is under discussion, whether has positive whether adverse impact on health. Children are a group of special anxieties. Caffeine is a stimulant of central nervous system and therefore is probably the most commonly used psychoactive substance in the world. The physiological effect of caffeine and the lack of nutrition value causes a great interest its impact on health, especially with reference to the risk of cardiovascular diseases. Results of scientific research are not clear. The influence of caffeine on the human body is conditioned with the individual metabolism of caffeine which also depends on many endogenic and environmental factors. According to the current knowledge moderate caffeine intake by healthy adults at a dose level of 400 mg a day is not associated with adverse effects, but it also depends on other health determinants of a lifestyle. Excessive caffeine consumption can cause negative health consequences such as psychomotor agitation, insomnia, headache, gastrointestinal complaints. Adverse effect of caffeine intoxication is classified in World Health Organization's International Classification of Diseases (ICD-10). Metabolism of caffeine by pregnant woman is slowed down. Caffeine and its metabolites pass freely across the placenta into a fetus. For this reason pregnant women should limit caffeine intake. Children and adolescents should also limit daily caffeine consumption. It results from the influence of caffeine on the central nervous system in the period of rapid growth and the final stage of brain development, calcium balance and sleep duration. Average daily caffeine consumption in European countries ranging from 280-490 mg. The highest caffeine intake is in Scandinavian countries what results from the great consumption of the coffee. As far as caffeine consumption by Polish population is concerned there is very few data in this subject so far. In the nineties of the previous century it was 141 mg per day, whereas according to recent survey daily caffeine intake by women from the Warsaw region was 251 mg and 15% of examined women consumed an excessive quantity of caffeine (> or = 400 mg). Smokers consume more caffeine than nonsmokers, similarly to persons with mental illnesses. With reference to the caffeine consumption it should be underline that caffeine content in coffee and tea beverages varies greatly depending on the method of brewing whereas the content of caffeine in many brands of energy drinks can much vary. This should be taken into account in the daily caffeine intake.

Caffeine Content Labeling: A Missed Opportunity for Promoting Personal and Public Health

PubMed Central

Kole, Jon

2013-01-01

Current regulation of caffeine-containing products is incoherent, fails to protect consumers' interests, and should be modified in multiple ways. We make the case for one of the regulatory reforms that are needed: all consumable products containing added caffeine should be required by the Food and Drug Administration (FDA) to include caffeine quantity on their labels. Currently, no foods or beverages that contain caffeine are required to include caffeine content on their labels. Strengthening these lax labeling requirements could prevent direct caffeine-induced harm, protect those most vulnerable to caffeine-related side effects, and enhance consumer autonomy and effective caffeine use. Consumers have an interest in regulating their intake of caffeine and thus, ought to know how much caffeine their foods and beverages contain. PMID:24761278

Clinical importance of caffeine dependence and abuse.

PubMed

Ogawa, Naoshi; Ueki, Hirofumi

2007-06-01

Caffeine is the most widely consumed psychoactive substance and is a legal stimulant that is readily available to children. Caffeine has occasionally been considered a drug of abuse and the potential for dependence on caffeine has been debated. Presently, due to a paucity of clinical evidence on caffeine dependence or abuse, no such diagnosis is included in the Diagnostic and Statistical Manual of Mental Disorder-fourth edition. The authors present two cases of abuse or dependence on the caffeine contained in 'eutrophic' (energy/nutritional) beverages or caffeine preparations, followed by a review of clinical studies demonstrating evidence that some people can manifest a clinical syndrome of caffeine dependence or abuse. The cases suggest that caffeine can produce a clinical dependence syndrome similar to those produced by other psychoactive substances and has a potential for abuse. In a recent study using a structured interview and the Diagnostic and Statistical Manual of Mental Disorder-fourth edition criteria for substance dependence and abuse, a subset of the general population was found to demonstrate caffeine dependence or caffeine abuse. Therefore, the authors propose that companies or businesses manufacturing or marketing caffeine or products containing caffeine must meet the following guidelines: (i) clearly indicate the caffeine content of products containing comparatively higher quantities of caffeine; (ii) warn that such products should be avoided by infants and children wherever possible, and inform adult consumers about the precise quantity of caffeine that is considered safe for consumption; and (iii) clearly state that consuming large quantities of caffeine and the long-term use of caffeine carry health risks.

The Effects of Caffeine Use on Driving Safety Among Truck Drivers Who Are Habitual Caffeine Users.

PubMed

Heaton, Karen; Griffin, Russell

2015-08-01

The purpose of this study was to describe caffeine use among a group of habitual caffeine users, truck drivers, and to explore the associations between caffeine use and critical safety events by age in the naturalistic work setting. A secondary analysis of existing data from the Naturalistic Truck Driving Study was conducted. Analyses focused on the association between sleep and caffeine consumption by duty status, comparisons of sleep and caffeine use by age, and the associations between caffeine use and safety-critical events (SCEs). Findings indicated differences in caffeine use by duty status. However, no difference in sleep time by duty status, or between sleep time and caffeine use was found regardless of when the caffeine was consumed during the 5 hours prior to sleep. Sleep time did not vary significantly by age, although increasing age was associated with decreased caffeine use. Overall, a 6% reduction in the rate of SCEs per eight ounces of caffeinated beverage consumed was found. This study makes a unique scientific contribution because it uses real-time observations of truckers in the naturalistic work setting. It also does not involve caffeine withdrawal but rather an investigation of the effects of the naturalistic consumption of caffeine on sleep and driving performance. Findings suggest that caffeine use among habitual users offers a protective effect for safety-critical driving events. Occupational health nurses may use this information to counsel workers in the use of caffeine to enhance driving safety. © 2015 The Author(s).

Sensitization to caffeine and cross-sensitization to amphetamine: influence of individual response to caffeine.

PubMed

Simola, Nicola; Cauli, Omar; Morelli, Micaela

2006-09-15

The present study evaluated the ability of a subchronic intermittent administration of caffeine to induce a sensitized motor response and correlated the individual susceptibility of rats to acute caffeine to the development of sensitization. Moreover, individual susceptibility to caffeine and development of motor behaviour sensitization were correlated to the behavioural response obtained after a challenge with amphetamine. To this end, rats were subdivided in "low" and "high" responders according to their individual susceptibility to acute caffeine established on the basis of the motor activity observed after the first caffeine administration. "Low" and "high" responder rats were then repeatedly and intermittently treated with caffeine (15 mg/kg, i.p.), or vehicle, every other day for fourteen days. Three days after treatment discontinuation, behavioural activation induced by acute amphetamine (0.5 mg/kg, s.c.) was measured in vehicle- and caffeine-pretreated rats. Subchronic caffeine resulted in motor sensitization of a variable degree among rats and no difference were observed between "low" and "high" responders. Moreover, caffeine pretreatment potentiated the behavioural effects of amphetamine according to the degree of caffeine sensitization but not to individual susceptibility to acute caffeine. These results demonstrate that individual susceptibility to acute caffeine does not influence the modifications in caffeine motor effects produced by its subchronic administration and does not affect the enhancement of acute behavioural effects of amphetamine in caffeine-pretreated rats, rather sensitization to subchronic caffeine administration critically influences the behavioural effects of amphetamine.

Effect of Carbohydrate and Caffeine Ingestion on Badminton Performance.

PubMed

Clarke, Neil D; Duncan, Michael J

2016-01-01

To investigate the effect of ingesting carbohydrate and caffeine solutions on measures that are central to success in badminton. Twelve male badminton players performed a badminton serve-accuracy test, coincidence-anticipation timing (CAT), and a choice reaction-time sprint test 60 min before exercise. Participants then consumed 7 mL/kg body mass of either water (PLA), 6.4% carbohydrate solution (CHO), a solution containing a caffeine dose of 4 mg/kg, or 6.4% carbohydrate and 4 mg/kg caffeine (C+C). All solutions were flavored with orange-flavored concentrate. During the 33-min fatigue protocol, participants were provided with an additional 3 mL/kg body mass of solution, which was ingested before the end of the protocol. As soon as the 33-min fatigue protocol was completed, all measures were recorded again. Short-serve accuracy was improved after the ingestion of CHO and C+C compared with PLA (P = .001, η(p)(2) = .50). Long-serve accuracy was improved after the ingestion of C+C compared with PLA (P < .001, η(p)(2) = .53). Absolute error in CAT demonstrated smaller deteriorations after the ingestion of C+C compared with PLA (P < .05; slow, η(p)(2) = .41; fast, η(p)(2) = .31). Choice reaction time improved in all trials with the exception of PLA, which demonstrated a reduction (P < .001, η(p)(2) = .85), although C+C was faster than all trials (P < .001, η(p)(2) = .76). These findings suggest that the ingestion of a caffeinated carbohydrate solution before and during a badminton match can maintain serve accuracy, anticipation timing, and sprinting actions around the court.

Effects of alcohol mixed with energy drink and alcohol alone on subjective intoxication.

PubMed

Ulbrich, Andrea; Hemberger, Sophie Helene; Loidl, Alexandra; Dufek, Stephanie; Pablik, Eleonore; Fodor, Sugarka; Herle, Marion; Aufricht, Christoph

2013-12-01

Recent studies suggest that the combination of caffeine-containing drinks together with alcohol might reduce the subjective feelings of alcohol intoxication-the so-called "masking effect". In this study, we aimed to review the effects of alcohol in combination with caffeine or energy drink with special focus on the "masking effect". Fifty-two healthy male volunteers were analysed concerning breath alcohol concentration and subjective sensations of intoxication using a 18 item Visual Analogue Scale in a randomised, double-blinded, controlled, four treatments cross-over trial after consumption of (A) placebo, (B) alcohol (vodka 37.5% at a dose of 46.5 g ethanol), (C) alcohol in combination with caffeine at a dose of 80 mg (equivalent to one 250 ml can of energy drink) and (D) alcohol in combination with energy drink at a dose of 250 ml (one can). Primary variables were headache, weakness, salivation and motor coordination. Out of four primary variables, weakness and motor coordination showed a statistically significant difference between alcohol and non-alcohol group, out of 14 secondary variables, five more variables (dizziness, alterations in sight, alterations in walking, agitation and alterations in speech) also showed significant differences due mainly to contrasts with the non-alcohol group. In none of these end points, could a statistically significant effect be found for the additional ingestion of energy drink or caffeine on the subjective feelings of alcohol intoxication. This within-subjects study does not confirm the presence of a "masking effect" when combining caffeine or energy drink with alcohol.

Caffeine addiction: Need for awareness and research and regulatory measures.

PubMed

Jain, Shobhit; Srivastava, Adya Shanker; Verma, Raghunath Prasad; Maggu, Gaurav

2017-02-04

Caffeine consumption has been constantly growing in India especially among children and youngsters. Addictive potential of caffeine has long been reported, still there is lack of awareness about caffeine abuse in India. There is an intense need for appropriate public health regulatory measures and awareness about addictive potential & harms related to caffeine. To the best of our knowledge this is first case from India highlighting several important issues with progressive caffeine abuse resulting in dependence leading to physical, psychological, academic and social consequences; psychotic symptoms during intoxication; predisposing factors as impulsivity and novelty seeking traits in pre-morbid personality; psychosis in family; poor awareness of health hazards even among medical professionals. Widely variable caffeine containing products are available but caffeine content or its safety limit is not mentioned on caffeine products in India. Due to harmful consequences, legal availability to children, growing consumption of caffeine products, it is utmost essential to recognize caffeine as addictive substance and impose regulatory measures on sale, advertisement, maximum caffeine content, health consequences and safety limits of caffeine containing products. Further school teachers, parents and medical practitioners need to be made aware of health hazards of caffeine. Caffeine use shall always be enquired from patients presenting with psychiatric complaints. Further research and survey are required on caffeine use and related problems. Copyright © 2017 Elsevier B.V. All rights reserved.

The effect of an acute ingestion of Turkish coffee on reaction time and time trial performance.

PubMed

Church, David D; Hoffman, Jay R; LaMonica, Michael B; Riffe, Joshua J; Hoffman, Mattan W; Baker, Kayla M; Varanoske, Alyssa N; Wells, Adam J; Fukuda, David H; Stout, Jeffrey R

2015-01-01

The purpose of this study was to examine the ergogenic benefits of Turkish coffee consumed an hour before exercise. In addition, metabolic, cardiovascular, and subjective measures of energy, focus and alertness were examined in healthy, recreationally active adults who were regular caffeine consumers (>200 mg per day). Twenty males (n = 10) and females (n = 10), age 24.1 ± 2.9 y; height 1.70 ± 0.09 m; body mass 73.0 ± 13.0 kg (mean ± SD), ingested both Turkish coffee [3 mg · kg(-1) BW of caffeine, (TC)], and decaffeinated Turkish coffee (DC) in a double-blind, randomized, cross-over design. Performance measures included a 5 km time trial, upper and lower body reaction to visual stimuli, and multiple object tracking. Plasma caffeine concentrations, blood pressure (BP), heart rate and subjective measures of energy, focus and alertness were assessed at baseline (BL), 30-min following coffee ingestion (30+), prior to endurance exercise (PRE) and immediately-post 5 km (IP). Metabolic measures [VO2, V E , and respiratory exchange rate (RER)] were measured during the 5 km. Plasma caffeine concentrations were significantly greater during TC (p < 0.001) at 30+, PRE, and IP compared to DC. Significantly higher energy levels were reported at 30+ and PRE for TC compared to DC. Upper body reaction performance (p = 0.023) and RER (p = 0.019) were significantly higher for TC (85.1 ± 11.6 "hits," and 0.98 ± 0.05 respectively) compared to DC (81.2 ± 13.7 "hits," and 0.96 ± 0.05, respectively). Although no significant differences (p = 0.192) were observed in 5 km run time, 12 of the 20 subjects ran faster (p = 0.012) during TC (1662 ± 252 s) compared to DC (1743 ± 296 s). Systolic BP was significantly elevated during TC in comparison to DC. No other differences (p > 0.05) were noted in any of the other performance or metabolic measures. Acute ingestion of TC resulted in a significant elevation in plasma caffeine concentrations within 30-min of consumption. TC ingestion resulted in significant performance benefits in reaction time and an increase in subjective feelings of energy in habitual caffeine users. No significant differences were noted in time for the 5 km between trials, however 60 % of the participants performed the 5 km faster during the TC trial and were deemed responders. When comparing TC to DC in responders only, significantly faster times were noted when consuming TC compared to DC. No significant benefits were noted in measures of cognitive function.

Differential sensitivity to perchlorate and caffeine of tetracaine-resistant Ca2+ release in frog skeletal muscle.

PubMed

Píriz, Nazira; Brum, Gustavo; Pizarro, Gonzalo

2006-01-01

In voltage clamped frog skeletal muscle fibres 0.2 mM tetracaine strongly suppresses Ca(2+) release. After this treatment Ca(2+) release flux lacks its characteristic initial peak and the remaining steady component is strongly reduced when compared with the control condition. We studied the effect of two agonists of Ca(2+) release on these tetracaine treated fibres. 8 mM ClO(4)(-) added after tetracaine potentiated release flux from 0.11 +/- 0.03 mM s(-1) to 0.34 +/- 0.07 mM s(-1) (n = 6) although without recovery of the peak at any test voltage. The voltage dependence of the increased release was shifted towards more negative potentials (approximately -10 mV). The effects of ClO(4)(-) on charge movement under these conditions showed the previously described characteristic changes consisting in a left shift of its voltage dependence (approximately -9 mV) together with a slower kinetics, both at the ON and OFF transients. Caffeine at 0.5 mM in the presence of the same concentration of tetracaine failed to potentiate release flux independently of the test voltage applied. When the cut ends of the fibre were exposed to a 10 mM BAPTA intracellular solution, in the absence of tetracaine, the peak was progressively abolished. Under these conditions caffeine potentiated release restoring the peak (from 0.63 +/- 0.12 mM s(-1) to 1.82 +/- 0.23 mM s(-1)) with no effect on charge movement. Taken together the present results suggest that tetracaine is blocking a Ca(2+) sensitive component of release flux. It is speculated that the suppressed release includes a component that is dependent on Ca(2+) and mainly mediated by the activation of the beta ryanodine receptors (the RyR3 equivalent isoform). These receptors are located parajunctionally in the frog and are not interacting with the dihydropyridine receptor.

Caffeine Consumption by College Undergraduates.

ERIC Educational Resources Information Center

Loke, Wing Hong

1988-01-01

Surveyed 542 undergraduates concerning their caffeine consumption. Found that subjects consumed less caffeine than average caffeine-drinking population. Coffee was main beverage used. Subjects reported drinking more caffeine when preparing for examinations. Suggests that caffeine may have some beneficial effects on learning. (Author/NB)

The Taste of Caffeine

PubMed Central

Tordoff, Michael G.

2017-01-01

Many people avidly consume foods and drinks containing caffeine, despite its bitter taste. Here, we review what is known about caffeine as a bitter taste stimulus. Topics include caffeine's action on the canonical bitter taste receptor pathway and caffeine's action on noncanonical receptor-dependent and -independent pathways in taste cells. Two conclusions are that (1) caffeine is a poor prototypical bitter taste stimulus because it acts on bitter taste receptor-independent pathways, and (2) caffeinated products most likely stimulate “taste” receptors in nongustatory cells. This review is relevant for taste researchers, manufacturers of caffeinated products, and caffeine consumers. PMID:28660093

Anxiogenic effects of caffeine on panic and depressed patients.

PubMed

Lee, M A; Flegel, P; Greden, J F; Cameron, O G

1988-05-01

Caffeine increases anxiety in people with anxiety disorders. To determine whether caffeine exerts a similar effect in depression, the authors compared retrospective reports of caffeine intake and symptoms produced by caffeine ingestion in patients with panic disorder, patients with major depression, and control subjects. Panic patients consumed less caffeine and reported more symptoms than depressed or control subjects. Although depressed patients did not differ from control subjects in caffeine intake or most symptoms, more depressed patients reported that caffeine induced anxiety. These data support prior reports that panic patients have increased sensitivity to caffeine; some depressed patients may also have increased sensitivity.

Consumption of caffeinated beverages and the awareness of their caffeine content among Dutch students.

PubMed

Mackus, Marlou; van de Loo, Aurora J A E; Benson, Sarah; Scholey, Andrew; Verster, Joris C

2016-08-01

The purpose of the current study was to examine the knowledge of caffeine content of a variety of caffeinated beverages among Dutch university students. A pencil-and-paper survey was conducted among N = 800 Dutch students. Most participants (87.8%) reported consuming caffeinated beverages during the past 24 h. Their mean ± SD past 24-h caffeine intake from beverages was 144.2 ± 169.5 mg (2.2 ± 3.0 mg/kg bw). Most prevalent sources of caffeine were coffee beverages (50.8%) and tea (34.8%), followed by energy drink (9.2%), cola (4.7%), and chocolate milk (0.5%). Participants had poor knowledge on the relative caffeine content of caffeinated beverages. That is, they overestimated the caffeine content of energy drinks and cola, and underestimated the caffeine content of coffee beverages. If caffeine consumption is a concern, it is important to inform consumers about the caffeine content of all caffeine containing beverages, including coffee and tea. The current findings support previous research that the most effective way to reduce caffeine intake is to limit the consumption of coffee beverages and tea. Copyright © 2016 Elsevier Ltd. All rights reserved.

Caffeine dependence in combination with a family history of alcoholism as a predictor of continued use of caffeine during pregnancy.

PubMed

Svikis, Dace S; Berger, Nathan; Haug, Nancy A; Griffiths, Roland R

2005-12-01

The purpose of the study was to examine whether caffeine dependence and a family history of alcoholism are associated with continued use of caffeine during pregnancy. Forty-four women seeking obstetrical care in an office-based practice completed questionnaires and provided saliva samples at three prenatal visits occurring 2-3, 3-4, and 7 months postconception. On visit 1, the patients received the physician's instructions to stop using caffeine. Structured interviews were used to assign a diagnosis of caffeine dependence (lifetime) and to identify family history of alcoholism. Outcome measures included self-reported levels of caffeine use and saliva caffeine levels at the three prenatal visits. Although most women eliminated or substantially reduced their caffeine consumption between pregnancy awareness and prenatal visit 1, those with a lifetime diagnosis of caffeine dependence and a family history of alcoholism had higher levels of caffeine use and lower rates of abstinence throughout pregnancy. Saliva caffeine levels confirmed these effects. Withdrawal symptoms, functional impairment, and craving were cited as reasons they failed to eliminate or cut back on caffeine use. Fifty percent of the women with both a lifetime diagnosis of caffeine dependence and a family history of alcoholism continued to use caffeine in amounts (>300 mg/day) greater than those considered safe during pregnancy, compared to none of the women without caffeine dependence and a family history of alcoholism. Women with a lifetime diagnosis of caffeine dependence and a family history of alcoholism also reported higher rates of past cigarette smoking and problematic alcohol use. Caffeine-dependent women with a family history of alcoholism were not able to follow their physician's advice to reduce or eliminate caffeine consumption during pregnancy, despite their wanting to do so. This subgroup may require more intensive intervention to ensure caffeine abstinence and may be at greater risk for abuse of or dependence on other drugs.

Caffeine use and dependence in adolescents: one-year follow-up.

PubMed

Oberstar, Joel V; Bernstein, Gail A; Thuras, Paul D

2002-01-01

The objectives were to conduct a 1-year follow-up of daily caffeine-using adolescents to further describe caffeine dependence symptoms and to determine whether caffeine dependence is associated with other substance dependence disorders. Twenty-one of 36 (58.3%) adolescents who participated in a study of caffeine dependence returned for follow-up. The previous study was a case series of adolescents who consumed caffeine daily and met some Diagnostic and Statistical Manual of Mental Disorders (fourth edition) substance dependence criteria as applied to caffeine. At follow-up, caffeine consumption from beverages was 179.9 +/- 151.8 mg/day. Of the 21 teenagers, 23.8% (n = 5) met criteria for caffeine dependence. Four of these participants developed caffeine dependence during the follow-up period. Other substance dependence disorders were not overrepresented in the caffeine dependent group compared to the caffeine nondependent group. The most commonly reported withdrawal symptoms in dependent teenagers (at baseline and follow-up combined) were feeling drowsy/tired, fatigued, or sluggish/slowed down (83.3% each) and headache (75.0%). Caffeine dependence occurs in some adolescents who drink caffeine daily and is marked by symptoms similar to those found in adults.

Sources and transport of contaminants of emerging concern: A two-year study of occurrence and spatiotemporal variation in a mixed land use watershed.

PubMed

Fairbairn, David J; Karpuzcu, M Ekrem; Arnold, William A; Barber, Brian L; Kaufenberg, Elizabeth F; Koskinen, William C; Novak, Paige J; Rice, Pamela J; Swackhamer, Deborah L

2016-05-01

The occurrence and spatiotemporal variation of 26 contaminants of emerging concern (CECs) were evaluated in 68 water samples in 2011-2012 in the Zumbro River watershed, Minnesota, U.S.A. Samples were collected across a range of seasonal/hydrological conditions from four stream sites that varied in associated land use and presence of an upstream wastewater treatment plant (WWTP). Selected CECs included human/veterinary pharmaceuticals, personal care products, pesticides, phytoestrogens, and commercial/industrial compounds. Detection frequencies and concentrations varied, with atrazine, metolachlor, acetaminophen, caffeine, DEET, and trimethoprim detected in more than 70% of samples, acetochlor, mecoprop, carbamazepine, and daidzein detected in 30%-50% of samples, and 4-nonylphenol, cotinine, sulfamethoxazole, erythromycin, tylosin, and carbaryl detected in 10%-30% of samples. The remaining target CECs were not detected in water samples. Three land use-associated trends were observed for the detected CECs. Carbamazepine, 4-nonylphenol, erythromycin, sulfamethoxazole, tylosin, and carbaryl profiles were WWTP-dominated, as demonstrated by more consistent loading and significantly greater concentrations downstream of the WWTP and during low-flow seasons. In contrast, acetaminophen, trimethoprim, DEET, caffeine, cotinine, and mecoprop patterns demonstrated both seasonally-variable non-WWTP-associated and continual WWTP-associated influences. Surface water studies of CECs often target areas near WWTPs. This study suggests that several CECs often characterized as effluent-associated have additional important sources such as septic systems or land-applied biosolids. Finally, agricultural herbicide (atrazine, acetochlor, and metolachlor) profiles were strongly influenced by agricultural land use and seasonal application-runoff, evident by significantly greater concentrations and loadings at upstream sites and in early summer when application and precipitation rates are greatest. Our results indicate that CEC monitoring studies should consider a range of land uses, seasonality, and transport pathways in relation to concentrations and loadings. This knowledge can augment CEC monitoring programs to result in more accurate source, occurrence, and ecological risk characterizations, more precisely targeted mitigation initiatives, and ultimately, enhanced environmental decision-making. Copyright © 2016 Elsevier B.V. All rights reserved.

Caffeine as an opioid analgesic adjuvant in fibromyalgia

PubMed Central

Scott, J Ryan; Hassett, Afton L; Brummett, Chad M; Harris, Richard E; Clauw, Daniel J; Harte, Steven E

2017-01-01

Background Caffeine’s properties as an analgesic adjuvant with nonsteroidal anti-inflammatory drugs/acetaminophen are well documented. However, little clinical research has explored caffeine’s effects on opioid analgesia. This study assessed the effects of caffeine consumption on pain and other symptoms in opioid-using and nonusing chronic pain patients meeting the survey criteria for fibromyalgia. Materials and methods Patients presenting to a university-based pain clinic completed validated self-report questionnaires assessing symptoms. Patients (N=962) meeting the fibromyalgia survey criteria were stratified by opioid use and further split into groups based on caffeine amount consumed per day (no caffeine, or low, moderate, high caffeine). Analysis of covariance with Dunnett’s post hoc testing compared pain and symptom severity between the no caffeine group and the caffeine consuming groups. Results In opioid users, caffeine consumption had modest but significant effects on pain, catastrophizing, and physical function. Lower levels of pain interference were associated with low and moderate caffeine use compared to no caffeine intake. Lower pain catastrophizing and higher physical function were observed in all caffeine dose groups, relative to the no caffeine group. Lower pain severity and depression were observed only in the moderate caffeine group. In opioid nonusers, low caffeine intake was associated with higher physical function; however, no other significant effects were observed. Conclusion Caffeine consumption was associated with decreased pain and symptom severity in opioid users, but not in opioid nonusers, indicating caffeine may act as an opioid adjuvant in fibromyalgia-like chronic pain patients. These data suggest that caffeine consumption concomitant with opioid analgesics could provide therapeutic benefits not seen with opioids or caffeine alone. PMID:28814895

Association of the Anxiogenic and Alerting Effects of Caffeine with ADORA2A and ADORA1 Polymorphisms and Habitual Level of Caffeine Consumption

PubMed Central

Rogers, Peter J; Hohoff, Christa; Heatherley, Susan V; Mullings, Emma L; Maxfield, Peter J; Evershed, Richard P; Deckert, Jürgen; Nutt, David J

2010-01-01

Caffeine, a widely consumed adenosine A1 and A2A receptor antagonist, is valued as a psychostimulant, but it is also anxiogenic. An association between a variant within the ADORA2A gene (rs5751876) and caffeine-induced anxiety has been reported for individuals who habitually consume little caffeine. This study investigated whether this single nucleotide polymorphism (SNP) might also affect habitual caffeine intake, and whether habitual intake might moderate the anxiogenic effect of caffeine. Participants were 162 non-/low (NL) and 217 medium/high (MH) caffeine consumers. In a randomized, double-blind, parallel groups design they rated anxiety, alertness, and headache before and after 100 mg caffeine and again after another 150 mg caffeine given 90 min later, or after placebo on both occasions. Caffeine intake was prohibited for 16 h before the first dose of caffeine/placebo. Results showed greater susceptibility to caffeine-induced anxiety, but not lower habitual caffeine intake (indeed coffee intake was higher), in the rs5751876 TT genotype group, and a reduced anxiety response in MH vs NL participants irrespective of genotype. Apart from the almost completely linked ADORA2A SNP rs3761422, no other of eight ADORA2A and seven ADORA1 SNPs studied were found to be clearly associated with effects of caffeine on anxiety, alertness, or headache. Placebo administration in MH participants decreased alertness and increased headache. Caffeine did not increase alertness in NL participants. With frequent consumption, substantial tolerance develops to the anxiogenic effect of caffeine, even in genetically susceptible individuals, but no net benefit for alertness is gained, as caffeine abstinence reduces alertness and consumption merely returns it to baseline. PMID:20520601

Interaction of caffeine with the SOS response pathway in Escherichia coli.

PubMed

Whitney, Alyssa K; Weir, Tiffany L

2015-01-01

Previous studies have highlighted the antimicrobial activity of caffeine, both individually and in combination with other compounds. A proposed mechanism for caffeine's antimicrobial effects is inhibition of bacterial DNA repair pathways. The current study examines the influence of sub-lethal caffeine levels on the growth and morphology of SOS response pathway mutants of Escherichia coli. Growth inhibition after treatment with caffeine and methyl methane sulfonate (MMS), a mutagenic agent, was determined for E. coli mutants lacking key genes in the SOS response pathway. The persistence of caffeine's effects was explored by examining growth and morphology of caffeine and MMS-treated bacterial isolates in the absence of selective pressure. Caffeine significantly reduced growth of E. coli recA- and uvrA-mutants treated with MMS. However, there was no significant difference in growth between umuC-isolates treated with MMS alone and MMS in combination with caffeine after 48 h of incubation. When recA-isolates from each treatment group were grown in untreated medium, bacterial isolates that had been exposed to MMS or MMS with caffeine showed increased growth relative to controls and caffeine-treated isolates. Morphologically, recA-isolates that had been treated with caffeine and both caffeine and MMS together had begun to display filamentous growth. Caffeine treatment further reduced growth of recA- and uvrA-mutants treated with MMS, despite a non-functional SOS response pathway. However, addition of caffeine had very little effect on MMS inhibition of umuC-mutants. Thus, growth inhibition of E. coli with caffeine treatment may be driven by caffeine interaction with UmuC, but also appears to induce damage by additional mechanisms as evidenced by the additive effects of caffeine in recA- and uvrA-mutants.

Transition metal modified and partially calcined inorganic-organic pillared clays for the adsorption of salicylic acid, clofibric acid, carbamazepine, and caffeine from water.

PubMed

Cabrera-Lafaurie, Wilman A; Román, Félix R; Hernández-Maldonado, Arturo J

2012-11-15

Pharmaceutical and Personal Care Products (PPCPs) are considered emerging contaminants, and their efficient removal from water is going to be a challenging endeavor. Microporous adsorbent materials, including pillared clays, could offer a potential solution if tailored properly. Although pillared clays have been employed previously for the removal of organics, the effective removal of PPCPs will only be possible if their surface and textural properties are manipulated from the bottom-up. This work presents the use of modified inorganic-organic pillared clays (IOCs) for the adsorption of salicylic acid, clofibric acid, carbamazepine, and caffeine. The IOCs have been modified with Co(2+), Cu(2+), or Ni(2+) to induce complexation-like adsorbate-adsorbent interactions at ambient conditions, in an attempt to provide an efficient and yet reversible driving force in the sub-ppm concentration range. Furthermore, the IOCs were partially calcined to increase effective surface area by an order of magnitude while preserving some hydrophobicity. In general, the Ni(2+) IOCs exhibited the greatest interaction with salicylic and clofibric acids, respectively, while the Co(2+) adsorbents excelled at adsorbing caffeine at low concentrations. All of the metal-modified IOCs showed comparable adsorption capacities for the case of carbamazepine, probably due to the lack of availability of particular functional groups in this adsorbate. Copyright © 2012 Elsevier Inc. All rights reserved.

The use of biochemical responses to assess ecotoxicological effects of Pharmaceutical and Personal Care Products (PPCPs) after injection in the mussel Elliptio complanata.

PubMed

Martín-Díaz, M Laura; Gagné, François; Blaise, Christian

2009-09-01

A biomarker approach was undertaken using the mussel Elliptio complanata to assess the ecotoxicological effects after injection of a range concentration (0-10mM) of three different PPCPs: carbamazepine, caffeine, methotrexate; and an effluent extract (C8) from St. Lawrence wastewaters treatment plant (Montreal, Canada). A battery of biomarkers, involving oxidative stress and genotoxicity responses: glutation-S-transferase (GST), ethoxyresorufin O-deethylase (EROD), dibenzylflourescein dealkylase (DBF), xanthine oxidoreductase (XOR) activities, lipid peroxidation (LPO) and DNA damage were determined in gonad and digestive gland tissues after 48 h of injection. Results showed an induction of the oxidative metabolism with increasing pharmaceutical concentration in those mussels injected with the PPCPs and the effluent extract. Phase I detoxification enzymes were significantly induced (p<0.05), concretely DBF activity was significantly induced after caffeine, carbamazipine and C8 injection; and EROD activity after C8 and methotrexate injection. Oxidative stress induction only lead to lipid peroxidation (p<0.05) in organisms injected with carbamazepine and caffeine and DNA damage in organisms injected with methotrexate (p<0.05). EROD and DBF enzymatic activities have been found to be suitable biomarkers to determine bioavailability of pharmaceuticals. LPO and DNA damage to determine possible associated adverse effects. Nevertheless, their validation in realistic exposure scenarios and under exposure conditions should be performed in future research.

Differential responsiveness to caffeine and perceived effects of caffeine in moderate and high regular caffeine consumers.

PubMed

Attwood, A S; Higgs, S; Terry, P

2007-03-01

Individual differences in responsiveness to caffeine occur even within a caffeine-consuming population, but the factors that mediate differential responsiveness remain unclear. To compare caffeine's effects on performance and mood in a group of high vs moderate consumers of caffeine and to examine the potential role of subjective awareness of the effects of caffeine in mediating any differential responsiveness. Two groups of regular caffeine consumers (<200 mg/day and >200 mg/day) attended two sessions at which mood and cognitive functions were measured before and 30 min after consumption of 400-mg caffeine or placebo in a capsule. Cognitive tests included visual information processing, match-to-sample visual search (MTS) and simple and choice reaction times. Post-session questionnaires asked participants to describe any perceived effect of capsule consumption. High consumers, but not moderate consumers, demonstrated significantly faster simple and choice reaction times after caffeine relative to placebo. These effects were not attributable to obvious group differences in withdrawal or tolerance because there were no group differences in baseline mood or in reports of negative affect after caffeine. Instead, the high consumers were more likely to report experiencing positive effects of caffeine, whereas the moderate consumers were more likely to report no effect. The sensitivity of caffeine consumers to the mood- and performance-enhancing effects of caffeine is related to their levels of habitual intake. High caffeine consumers are more likely than moderate consumers to perceive broadly positive effects of caffeine, and this may contribute to their levels of use.

Occurrence and risk assessment of pharmaceutically active compounds in wastewater treatment plants. A case study: Seville city (Spain).

PubMed

Santos, J L; Aparicio, I; Alonso, E

2007-05-01

The occurrence of four anti-inflammatory drugs (diclofenac, ibuprofen, ketoprofen and naproxen), an antiepileptic drug (carbamazepine) and a nervous stimulant (caffeine) in influent and effluent samples from four wastewater treatment plants (WWTPs) in Seville was evaluated. Removal rates in the WWTPs and risk assessment of the pharmaceutically active compounds have been studied. Analytical determination was carried out by high performance liquid chromatography (HPLC) with diode array (DAD) and fluorescence (Fl) detectors after sample clean up and concentration by solid phase extraction. All pharmaceutically active compounds, except diclofenac, were detected not only in wastewater influents but also in wastewater effluents. Mean concentrations of caffeine, carbamazepine, ketoprofen and naproxen ranged between 0.28-11.44 microg l(-1) and 0.21-2.62 microg l(-1) in influent and effluent wastewater, respectively. Ibuprofen was present in the highest concentrations in the range 12.13-373.11 microg l(-1) and 0.78-48.24 microg l(-1) in influent and effluent wastewater, respectively. Removal rates of the pharmaceuticals ranged between 6 and 98%. Risk quotients, expressed as ratios between the measured environmental concentration (MEC) and the predicted no effect concentrations (PNEC) were higher than 1 for ibuprofen and naproxen in influent wastewater and for ibuprofen in effluent wastewater.

Caffeine promotes wakefulness via dopamine signaling in Drosophila

PubMed Central

Nall, Aleksandra H.; Shakhmantsir, Iryna; Cichewicz, Karol; Birman, Serge; Hirsh, Jay; Sehgal, Amita

2016-01-01

Caffeine is the most widely-consumed psychoactive drug in the world, but our understanding of how caffeine affects our brains is relatively incomplete. Most studies focus on effects of caffeine on adenosine receptors, but there is evidence for other, more complex mechanisms. In the fruit fly Drosophila melanogaster, which shows a robust diurnal pattern of sleep/wake activity, caffeine reduces nighttime sleep behavior independently of the one known adenosine receptor. Here, we show that dopamine is required for the wake-promoting effect of caffeine in the fly, and that caffeine likely acts presynaptically to increase dopamine signaling. We identify a cluster of neurons, the paired anterior medial (PAM) cluster of dopaminergic neurons, as the ones relevant for the caffeine response. PAM neurons show increased activity following caffeine administration, and promote wake when activated. Also, inhibition of these neurons abrogates sleep suppression by caffeine. While previous studies have focused on adenosine-receptor mediated mechanisms for caffeine action, we have identified a role for dopaminergic neurons in the arousal-promoting effect of caffeine. PMID:26868675

Beliefs, Behaviors, and Contexts of Adolescent Caffeine Use: A Focus Group Study.

PubMed

Ludden, Alison B; O'Brien, Elizabeth M; Pasch, Keryn E

2017-07-29

Caffeinated products are widely available to adolescents, and consumption of caffeine products-energy drinks and coffee in particular-is on the rise in this age group (Branum, Rossen, & Schoendorf, 2014). Yet, little is known about the psychosocial context of caffeine use. Previous studies on adolescent caffeine use have focused on caffeine's acute physiological effects, rather than the psychosocial contexts and beliefs regarding different types of caffeinated beverages (e.g., coffee, energy drinks, soda). The current research examines the contexts and beliefs associated with adolescents' use of caffeinated beverages (e.g., coffee, energy drinks, soda) using a focus group approach. Eleven focus group interviews (49 total participants) addressed adolescents' motivations for and patterns of caffeine use; they were transcribed and axial coding was used to identify common themes. Coffee and energy drinks were perceived to be the most popular caffeinated beverages. Reasons for consuming caffeine included the effect of caffeine as a stimulant, the pleasant feelings experienced when drinking it, and the fact that caffeine was available. As for contexts, coffee was consumed in more diverse social contexts than other caffeinated beverages. Friends and sports were the most popular contexts for energy drink use. The present findings inform adolescent health promotion efforts and provide researchers and practitioners alike detailed information in adolescents' own words about how and why they use caffeine. Adolescents' beliefs about caffeinated products are not uniform; the reasons adolescents articulate regarding their use of coffee, soda, and energy drinks are different across contexts and beverage type.

Expectation of having consumed caffeine can improve performance and mood.

PubMed

Dawkins, Lynne; Shahzad, Fatima-Zahra; Ahmed, Suada S; Edmonds, Caroline J

2011-12-01

We explored whether caffeine, and expectation of having consumed caffeine, affects attention, reward responsivity and mood using double-blinded methodology. 88 participants were randomly allocated to 'drink-type' (caffeinated/decaffeinated coffee) and 'expectancy' (told caffeinated/told decaffeinated coffee) manipulations. Both caffeine and expectation of having consumed caffeine improved attention and psychomotor speed. Expectation enhanced self-reported vigour and reward responsivity. Self-reported depression increased at post-drink for all participants, but less in those receiving or expecting caffeine. These results suggest caffeine expectation can affect mood and performance but do not support a synergistic effect. Copyright © 2011 Elsevier Ltd. All rights reserved.

The Odorant ( R)-Citronellal Attenuates Caffeine Bitterness by Inhibiting the Bitter Receptors TAS2R43 and TAS2R46.

PubMed

Suess, Barbara; Brockhoff, Anne; Meyerhof, Wolfgang; Hofmann, Thomas

2018-03-14

Sensory studies showed the volatile fraction of lemon grass and its main constituent, the odor-active citronellal, to significantly decrease the perceived bitterness of a black tea infusion as well as caffeine solutions. Seven citronellal-related derivatives were synthesized and shown to inhibit the perceived bitterness of caffeine in a structure-dependent manner. The aldehyde function at carbon 1, the ( R)-configuration of the methyl-branched carbon 3, and a hydrophobic carbon chain were found to favor the bitter inhibitory activity of citronellal; for example, even low concentrations of 25 ppm were observed to reduce bitterness perception of caffeine solution (6 mmol/L) by 32%, whereas ( R)-citronellic acid (100 pm) showed a reduction of only 21% and ( R)-citronellol (100 pm) was completely inactive. Cell-based functional experiments, conducted with the human bitter taste receptors TAS2R7, TAS2R10, TAS2R14, TAS2R43, and TAS2R46 reported to be sensitive to caffeine, revealed ( R)-citronellal to completely block caffeine-induced calcium signals in TAS2R43-expressing cells, and, to a lesser extent, in TAS2R46-expressing cells. Stimulation of TAS2R43-expressing cells with structurally different bitter agonists identified ( R)-citronellal as a general allosteric inhibitor of TAS2R43. Further structure/activity studies indicated 3-methyl-branched aliphatic aldehydes with a carbon chain of ≥4 C atoms as best TAS2R43 antagonists. Whereas odor-taste interactions have been mainly interpreted in the literature to be caused by a central neuronal integration of odors and tastes, rather than by peripheral events at the level of reception, the findings of this study open up a new dimension regarding the interaction of the two chemical senses.

AMPKα2 deficiency uncovers time dependency in the regulation of contraction-induced palmitate and glucose uptake in mouse muscle.

PubMed

Abbott, Marcia J; Bogachus, Lindsey D; Turcotte, Lorraine P

2011-07-01

AMP-activated protein kinase (AMPK) is a fuel sensor in skeletal muscle with multiple downstream signaling targets that may be triggered by increases in intracellular Ca(2+) concentration ([Ca(2+)]). The purpose of this study was to determine whether increases in intracellular [Ca(2+)] induced by caffeine act solely via AMPKα(2) and whether AMPKα(2) is essential to increase glucose uptake, fatty acid (FA) uptake, and FA oxidation in contracting skeletal muscle. Hindlimbs from wild-type (WT) or AMPKα(2) dominant-negative (DN) transgene mice were perfused during rest (n = 11), treatment with 3 mM caffeine (n = 10), or muscle contraction (n = 11). Time-dependent effects on glucose and FA uptake were uncovered throughout the 20-min muscle contraction perfusion period (P < 0.05). Glucose uptake rates did not increase in DN mice during muscle contraction until the last 5 min of the protocol (P < 0.05). FA uptake rates were elevated at the onset of muscle contraction and diminished by the end of the protocol in DN mice (P < 0.05). FA oxidation rates were abolished in the DN mice during muscle contraction (P < 0.05). The DN transgene had no effect on caffeine-induced FA uptake and oxidation (P > 0.05). Glucose uptake rates were blunted in caffeine-treated DN mice (P < 0.05). The DN transgene resulted in a greater use of intramuscular triglycerides as a fuel source during muscle contraction. The DN transgene did not alter caffeine- or contraction-mediated changes in the phosphorylation of Ca(2+)/calmodulin-dependent protein kinase I or ERK1/2 (P > 0.05). These data suggest that AMPKα(2) is involved in the regulation of substrate uptake in a time-dependent manner in contracting muscle but is not necessary for regulation of FA uptake and oxidation during caffeine treatment.

Effects of green tea catechins with or without caffeine on glycemic control in adults: a meta-analysis of randomized controlled trials.

PubMed

Zheng, Xin-Xin; Xu, Yan-Lu; Li, Shao-Hua; Hui, Rutai; Wu, Yong-Jian; Huang, Xiao-Hong

2013-04-01

The effect of green tea catechins (GTCs) with or without caffeine on glycemic control is controversial. We aimed to identify and quantify the effects of GTCs or GTC-caffeine mixtures on glucose metabolism in adults. A comprehensive literature search was conducted to identify relevant trials of GTCs with or without caffeine on markers of glycemic control [fasting blood glucose (FBG), fasting blood insulin (FBI), glycated hemoglobin (Hb A1c), and homeostatic model assessment of insulin resistance (HOMA-IR)]. Weighted mean differences were calculated for net changes by using fixed-effects models. Prespecified subgroup analyses were performed to explore the influence of covariates on net changes in FBG and FBI concentrations. Twenty-two eligible randomized controlled trials with 1584 subjects were identified. Pooled analyses showed that FBG (-1.48 mg/dL; 95% CI: -2.57, -0.40 mg/dL) decreased significantly with GTCs with or without caffeine, whereas FBI (0.04 μU/mL; 95% CI: -0.36, 0.45 μU/mL), Hb A1c (-0.04%; 95% CI: -0.15, 0.08%), and HOMA-IR (-0.05; 95% CI: -0.37, 0.26) did not. Subgroup analyses indicated that the glucose-lowering effect was apparent when the duration of follow-up was over a median of 12 wk. Overall, no significant heterogeneity was detected for FBG, FBI, Hb A1c, or HOMA-IR. The meta-analysis showed that the administration of GTCs with or without caffeine resulted in a significant reduction in FBG. The limited data available on GTCs did not support a positive effect on FBI, Hb A1c, or HOMA-IR. Thus, more large and well-designed trials are needed in the future. This trial was registered at http://www.crd.york.ac.uk/prospero as CRD42012002139.

Caffeine dependence in teenagers.

PubMed

Bernstein, Gail A; Carroll, Marilyn E; Thuras, Paul D; Cosgrove, Kelly P; Roth, Megan E

2002-03-01

This study identifies and characterizes symptoms of caffeine dependence in adolescents. Thirty-six adolescents who consumed caffeine daily and had some features of caffeine dependence on telephone screen were scheduled for outpatient evaluation. Evaluation included the Diagnostic Interview Schedule for Children-IV-Youth Version (DISC-IV) and modified DISC-IV questions that assessed caffeine dependence based on DSM-IV substance dependence criteria. Of 36 subjects, 41.7% (n=15) reported tolerance to caffeine, 77.8% (n=28) described withdrawal symptoms after cessation or reduction of caffeine intake, 38.9% (n=14) reported desire or unsuccessful attempts to control use, and 16.7% (n=6) endorsed use despite knowledge of physical or psychological problems associated with caffeine. There was no significant difference in the amount of caffeine consumed daily by caffeine dependent versus non-dependent teenagers. These findings are important due to the vast number of adolescents who drink caffeinated beverages.

Cognitive and mood improvements of caffeine in habitual consumers and habitual non-consumers of caffeine.

PubMed

Haskell, Crystal F; Kennedy, David O; Wesnes, Keith A; Scholey, Andrew B

2005-06-01

The cognitive and mood effects of caffeine are well documented. However, the majority of studies in this area involve caffeine-deprived, habitual caffeine users. It is therefore unclear whether any beneficial findings are due to the positive effects of caffeine or to the alleviation of caffeine withdrawal. The present placebo-controlled, double-blind, balanced crossover study investigated the acute cognitive and mood effects of caffeine in habitual users and habitual non-users of caffeine. Following overnight caffeine withdrawal, 24 habitual caffeine consumers (mean=217 mg/day) and 24 habitual non-consumers (20 mg/day) received a 150 ml drink containing either 75 or 150 mg of caffeine or a matching placebo, at intervals of > or =48 h. Cognitive and mood assessments were undertaken at baseline and 30 min post-drink. These included the Cognitive Drug Research computerised test battery, two serial subtraction tasks, a sentence verification task and subjective visual analogue mood scales. There were no baseline differences between the groups' mood or performance. Following caffeine, there were significant improvements in simple reaction time, digit vigilance reaction time, numeric working memory reaction time and sentence verification accuracy, irrespective of group. Self-rated mental fatigue was reduced and ratings of alertness were significantly improved by caffeine independent of group. There were also group effects for rapid visual information processing false alarms and spatial memory accuracy with habitual consumers outperforming non-consumers. There was a single significant interaction of group and treatment effects on jittery ratings. Separate analyses of each groups' responses to caffeine revealed overlapping but differential responses to caffeine. Caffeine tended to benefit consumers' mood more while improving performance more in the non-consumers. These results do not support a withdrawal alleviation model. Differences in the patterns of responses to caffeine by habitual consumers and habitual non-consumers may go some way to explaining why some individuals become caffeine consumers.

Caffeine's implications for women's health and survey of obstetrician-gynecologists' caffeine knowledge and assessment practices.

PubMed

Anderson, Britta L; Juliano, Laura M; Schulkin, Jay

2009-09-01

Caffeine has relevance for women's health and pregnancy, including significant associations with spontaneous abortion and low birth weight. According to scientific data, pregnant women and women of reproductive age should be advised to limit their caffeine consumption. This article reviews the implications of caffeine for women's psychological and physical health, and presents data on obstetrician-gynecologists' (ob-gyns) knowledge and practices pertaining to caffeine. Ob-gyns (N = 386) who are members of the American College of Obstetricians and Gynecologists' Collaborative Ambulatory Research Network responded to a 21-item survey about caffeine. Although most knew that caffeine is passed through breast milk, only 24.8% were aware that caffeine metabolism significantly slows as pregnancy progresses. Many respondents were not aware of the caffeine content of commonly used products, such as espresso and Diet Coke, with 14.3% and 57.8% indicating amounts within an accurate range, respectively. Furthermore, ob-gyns did not take into account large differences in caffeine content across different caffeinated beverages with most recommending one to two servings of coffee or tea or soft drinks per day. There was substantial inconsistency in what was considered to be "high levels" of maternal caffeine consumption, with only 31.6% providing a response. When asked to indicate the risk that high levels of caffeine have on various pregnancy outcomes, responses were not consistent with scientific data. For example, respondents overestimated the relative risk of stillbirths and underestimated the relative risk of spontaneous abortion. There was great variability in assessment and advice practices pertaining to caffeine. More than half advise their pregnant patients to consume caffeine under certain circumstances, most commonly to alleviate headache and caffeine withdrawal. The data suggest that ob-gyns could benefit from information about caffeine and its relevance to their clinical practice. The development of clinical practice guidelines for caffeine may prove to be useful.

Psychostimulant and Other Effects of Caffeine in 9- to 11-Year-Old Children

ERIC Educational Resources Information Center

Heatherley, Susan V.; Hancock, Katie M. F.; Rogers, Peter J.

2006-01-01

Background: Recent research on adults suggests that "beneficial" psychostimulant effects of caffeine are found only in the context of caffeine deprivation; that is, caffeine improves psychomotor and cognitive performance in habitual caffeine consumers following caffeine withdrawal. Furthermore, no net benefit is gained because…

A Survey of Caffeine Use and Associated Side Effects in a College Population.

ERIC Educational Resources Information Center

Johnson-Greene, Douglas; And Others

1988-01-01

Surveyed 270 college students concerning their caffeine consumption. Results suggest there is identifiable group using excessive amounts of caffeine. Identified several deleterious effects possibly related to caffeine use. Approximately 75 percent of caffeine users surveyed rarely sought information on caffeine content of products or avoided…

Caffeine and psychiatric symptoms: a review.

PubMed

Broderick, Pamela; Benjamin, Ashley B

2004-12-01

Caffeine is a widely used psychoactive substance that has the potential to contribute to many psychiatric symptoms. This review article aims to address the specific research studies and case reports that relate caffeine to psychiatric symptoms. Caffeine can cause anxiety symptoms in normal individuals, especially in vulnerable patients, like those with pre-existing anxiety disorders. Caffeine use is also associated with symptoms of depression due to either a self-medication theory, or a theory that caffeine itself causes changes in mood. Psychosis can be induced in normal individuals ingesting caffeine at toxic doses, and psychotic symptoms can also be worsened in schizophrenic patients using caffeine. Sleep and symptoms of ADHD may be altered by caffeine as well. Prevention of caffeine-induced psychiatric symptoms is possible by recognizing, educating, and treating patients using a tapering approach.

Mountain Dew or mountain don't?: a pilot investigation of caffeine use parameters and relations to depression and anxiety symptoms in 5th- and 10th-grade students.

PubMed

Luebbe, Aaron M; Bell, Debora J

2009-08-01

Caffeine, the only licit psychoactive drug available to minors, may have a harmful impact on students' health and adjustment, yet little is known about its use or effects on students, especially from a developmental perspective. Caffeine use in 5th- and 10th-grade students was examined in a cross-sectional design, and relations and potential mediators of caffeine use to depression and anxiety symptoms were investigated. Children (n = 135) and adolescents (n = 79) completed a measure of naturalistic use of caffeinated and noncaffeinated beverages. Furthermore, daily availability, perceived benefits, and stimulating, psychological, and withdrawal effects of caffeinated and noncaffeinated beverages were assessed. Measures of depression and anxiety were also administered. Fifth and 10th graders used caffeine frequently. Depression was positively related to caffeine use for both cohorts, though mediated by caffeine withdrawal effects. Surprisingly, anxiety was unrelated to use. Fifth graders reported less daily access to caffeine, but more psychological and stimulating effects of caffeine than 10th graders. Although both children and adolescents experience negative caffeine-related outcomes, intake is seemingly not greatly limited in either cohort. In particular, youth appear vulnerable to increased depressive symptoms with increasing caffeine consumption. Implications for school policy regarding students' caffeine use are discussed.

Genome-wide association study of caffeine metabolites provides new insights to caffeine metabolism and dietary caffeine-consumption behavior.

PubMed

Cornelis, Marilyn C; Kacprowski, Tim; Menni, Cristina; Gustafsson, Stefan; Pivin, Edward; Adamski, Jerzy; Artati, Anna; Eap, Chin B; Ehret, Georg; Friedrich, Nele; Ganna, Andrea; Guessous, Idris; Homuth, Georg; Lind, Lars; Magnusson, Patrik K; Mangino, Massimo; Pedersen, Nancy L; Pietzner, Maik; Suhre, Karsten; Völzke, Henry; Bochud, Murielle; Spector, Tim D; Grabe, Hans J; Ingelsson, Erik

2016-12-15

Caffeine is the most widely consumed psychoactive substance in the world and presents with wide interindividual variation in metabolism. This variation may modify potential adverse or beneficial effects of caffeine on health. We conducted a genome-wide association study (GWAS) of plasma caffeine, paraxanthine, theophylline, theobromine and paraxanthine/caffeine ratio among up to 9,876 individuals of European ancestry from six population-based studies. A single SNP at 6p23 (near CD83) and several SNPs at 7p21 (near AHR), 15q24 (near CYP1A2) and 19q13.2 (near CYP2A6) met GW-significance (P < 5 × 10-8) and were associated with one or more metabolites. Variants at 7p21 and 15q24 associated with higher plasma caffeine and lower plasma paraxanthine/caffeine (slow caffeine metabolism) were previously associated with lower coffee and caffeine consumption behavior in GWAS. Variants at 19q13.2 associated with higher plasma paraxanthine/caffeine (slow paraxanthine metabolism) were also associated with lower coffee consumption in the UK Biobank (n = 94 343, P < 1.0 × 10-6). Variants at 2p24 (in GCKR), 4q22 (in ABCG2) and 7q11.23 (near POR) that were previously associated with coffee consumption in GWAS were nominally associated with plasma caffeine or its metabolites. Taken together, we have identified genetic factors contributing to variation in caffeine metabolism and confirm an important modulating role of systemic caffeine levels in dietary caffeine consumption behavior. Moreover, candidate genes identified encode proteins with important clinical functions that extend beyond caffeine metabolism. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Safety of Ingested Caffeine: A Comprehensive Review

PubMed Central

Temple, Jennifer L.; Bernard, Christophe; Lipshultz, Steven E.; Czachor, Jason D.; Westphal, Joslyn A.; Mestre, Miriam A.

2017-01-01

Caffeine is the most widely consumed psychoactive drug in the world. Natural sources of caffeine include coffee, tea, and chocolate. Synthetic caffeine is also added to products to promote arousal, alertness, energy, and elevated mood. Over the past decade, the introduction of new caffeine-containing food products, as well as changes in consumption patterns of the more traditional sources of caffeine, has increased scrutiny by health authorities and regulatory bodies about the overall consumption of caffeine and its potential cumulative effects on behavior and physiology. Of particular concern is the rate of caffeine intake among populations potentially vulnerable to the negative effects of caffeine consumption: pregnant and lactating women, children and adolescents, young adults, and people with underlying heart or other health conditions, such as mental illness. Here, we review the research into the safety and safe doses of ingested caffeine in healthy and in vulnerable populations. We report that, for healthy adults, caffeine consumption is relatively safe, but that for some vulnerable populations, caffeine consumption could be harmful, including impairments in cardiovascular function, sleep, and substance use. We also identified several gaps in the literature on which we based recommendations for the future of caffeine research. PMID:28603504

Effects of caffeine on persistence and reinstatement of nicotine-seeking behavior in rats: interaction with nicotine-associated cues

PubMed Central

Jernigan, Courtney

2013-01-01

Rationale Caffeine and nicotine are the most commonly co-used psychostimulants. However, it is still unclear whether caffeine exposure enhances nicotine-seeking behavior. Objective The present study examined the effects of caffeine on nicotine-seeking in rats trained to self-administer nicotine with and without presession administration of caffeine. Methods Male Sprague–Dawley rats were trained to intravenously self-administer nicotine (0.03 mg/kg/infusion, freebase) on a fixed ratio 5 schedule of reinforcement and associate a stimulus cue with each nicotine administration. Five minutes before the sessions, the rats received an intraperitoneal administration of caffeine (5 mg/kg). Extinction tests were conducted under four conditions: presession caffeine administration, response-contingent presentation of nicotine cues, neither condition, or both conditions. Reinstatement tests were conducted after responding was extinguished by withholding presession caffeine, nicotine, and its cues. A separate group of rats trained without presession caffeine exposure was also subjected to the reinstatement tests. Results In the rats trained with presession caffeine exposure, continued caffeine administration sustained nicotine-seeking responses and interacted with nicotine cues to significantly delay the extinction of nicotine-seeking behavior. Readministration of caffeine after extinction effectively reinstated nicotine-seeking behavior. In caffeine-naive rats, caffeine administration did not reinstate extinguished nicotine-seeking behavior but significantly potentiated the cue-induced reinstatement of nicotine-seeking. Conclusion These data demonstrate that caffeine administration sustained and reinstated nicotine-seeking behavior, possibly via its acquired discriminative-stimulus properties predictive of nicotine availability. These findings suggest that smokers who attempt to quit may benefit from stopping caffeine consumption. PMID:21947355

Common Psychiatric Disorders and Caffeine Use, Tolerance, and Withdrawal: An Examination of Shared Genetic and Environmental Effects

PubMed Central

Bergin, Jocilyn E.; Kendler, Kenneth S.

2012-01-01

Background Previous studies examined caffeine use and caffeine dependence and risk for the symptoms, or diagnosis, of psychiatric disorders. The current study aimed to determine if generalized anxiety disorder (GAD), panic disorder, phobias, major depressive disorder (MDD), anorexia nervosa (AN), or bulimia nervosa (BN) shared common genetic or environmental factors with caffeine use, caffeine tolerance, or caffeine withdrawal. Method Using 2,270 women from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, bivariate Cholesky decomposition models were used to determine if any of the psychiatric disorders shared genetic or environmental factors with caffeine use phenotypes. Results GAD, phobias, and MDD shared genetic factors with caffeine use, with genetic correlations estimated to be 0.48, 0.25, and 0.38, respectively. Removal of the shared genetic and environmental parameter for phobias and caffeine use resulted in a significantly worse fitting model. MDD shared unique environmental factors (environmental correlation = 0.23) with caffeine tolerance; the genetic correlation between AN and caffeine tolerance and BN and caffeine tolerance were 0.64 and 0.49, respectively. Removal of the genetic and environmental correlation parameters resulted in significantly worse fitting models for GAD, phobias, MDD, AN, and BN, which suggested that there was significant shared liability between each of these phenotypes and caffeine tolerance. GAD had modest genetic correlations with caffeine tolerance, 0.24, and caffeine withdrawal, 0.35. Conclusions There was suggestive evidence of shared genetic and environmental liability between psychiatric disorders and caffeine phenotypes. This might inform us about the etiology of the comorbidity between these phenotypes. PMID:22854069

Common psychiatric disorders and caffeine use, tolerance, and withdrawal: an examination of shared genetic and environmental effects.

PubMed

Bergin, Jocilyn E; Kendler, Kenneth S

2012-08-01

Previous studies examined caffeine use and caffeine dependence and risk for the symptoms, or diagnosis, of psychiatric disorders. The current study aimed to determine if generalized anxiety disorder (GAD), panic disorder, phobias, major depressive disorder (MDD), anorexia nervosa (AN), or bulimia nervosa (BN) shared common genetic or environmental factors with caffeine use, caffeine tolerance, or caffeine withdrawal. Using 2,270 women from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, bivariate Cholesky decomposition models were used to determine if any of the psychiatric disorders shared genetic or environmental factors with caffeine use phenotypes. GAD, phobias, and MDD shared genetic factors with caffeine use, with genetic correlations estimated to be 0.48, 0.25, and 0.38, respectively. Removal of the shared genetic and environmental parameter for phobias and caffeine use resulted in a significantly worse fitting model. MDD shared unique environmental factors (environmental correlation=0.23) with caffeine tolerance; the genetic correlation between AN and caffeine tolerance and BN and caffeine tolerance were 0.64 and 0.49, respectively. Removal of the genetic and environmental correlation parameters resulted in significantly worse fitting models for GAD, phobias, MDD, AN, and BN, which suggested that there was significant shared liability between each of these phenotypes and caffeine tolerance. GAD had modest genetic correlations with caffeine tolerance, 0.24, and caffeine withdrawal, 0.35. There was suggestive evidence of shared genetic and environmental liability between psychiatric disorders and caffeine phenotypes. This might inform us about the etiology of the comorbidity between these phenotypes.

Characteristic of theophylline imprinted monolithic column and its application for determination of xanthine derivatives caffeine and theophylline in green tea.

PubMed

Sun, Han-wen; Qiao, Feng-xia; Liu, Guang-yu

2006-11-17

Theophylline imprinted monolithic columns were designed and prepared for rapid separation of a homologous series of xanthine derivatives, caffeine, and theophylline by an in situ thermal-initiated copolymerization technique. Caffeine and theophylline were fully separated both under isocratic and gradient elutions on this kind of monolithic molecularly imprinted polymers (MIP) column. The broad peak showed in isocratic elution could be improved in gradient elution. Some chromatographic conditions such as mobile phase composition, flow rate, and the temperature on the retention times were investigated. Hydrogen bonding interaction and hydrophobic interaction played an important role in the retention and separation. The binding capacity was evaluated by static adsorption and Scatchard analysis, which showed that the dissociation constant (KD) and the maximum binding capacity (Qmax) were 1.50 mol/L, and 236 micromol/g for high affinity binding site, and 7.97 mol/L and 785 micromol/g for lower affinity binding site, respectively. Thermodynamic data (DeltaDeltaH and DeltaDeltaS) obtained by Van't Hoff plots revealed an enthalpy-controlled separation. The morphological characteristics of monolithic MIP were investigated by scanning electron microscope, which showed that both mesopores and macropores were formed in the monolith. The present monolithic MIP column was successfully applied for the quantitative determination of caffeine and theophylline in different kinds of green tea.

The Combined Effect of Caffeine and Ornithine on the Mood of Healthy Office Workers

PubMed Central

Misaizu, Akane; Kokubo, Takeshi; Tazumi, Kyoko; Kanayama, Masaya; Miura, Yutaka

2014-01-01

Caffeine is widely consumed and well known for stimulating the central nervous system. When developing new foods and beverages that contain caffeine, it is important to explore the potential synergistic effects of consuming amino acids and other food ingredients with caffeine on humans. Given the physiological pathways affected by the amino acid ornithine, consumption of ornithine with caffeine may have synergistic effects. The purpose of the present study was to examine the effect of consuming caffeine with ornithine in humans. The study used a randomized, placebo-controlled, double-blinded crossover design. The subjects were all healthy office workers who ingested the placebo, 100 mg caffeine, or 100 mg caffeine plus 200 mg ornithine in the morning and completed questionnaires about their mood. Office workers who consumed the combination of caffeine and ornithine had higher mood ratings 8 h after consumption than office workers who consumed caffeine alone. The results of the present study suggest that there is a unique synergistic effect between caffeine and ornithine on the mood of healthy office workers and that ornithine may potentiate the effects of caffeine. PMID:25580405

Caffeine Use in Children: What we know, what we have left to learn, and why we should worry

PubMed Central

Temple, Jennifer L.

2009-01-01

Caffeine is a widely used psychoactive substance in both adults and children that is legal, easy to obtain, and socially acceptable to consume. Although once relatively restricted to use among adults, caffeine-containing drinks are now consumed regularly by children. In addition, some caffeine-containing beverages are specifically marketed to children as young as four years of age. Unfortunately, our knowledge of the effects of caffeine use on behavior and physiology of children remains understudied and poorly understood. The purpose of this article is to review what is known about caffeine use in children and adolescents, to discuss why children and adolescents may be particularly vulnerable to the negative effects of caffeine, and to propose how caffeine consumption within this population may potentiate the rewarding properties of other substances. The following topics are reviewed: 1) tolerance and addiction to caffeine 2) sensitization and cross-sensitization to the effects of caffeine 3) caffeine self-administration and reinforcing value and 4) conditioning of preferences for caffeine-containing beverages in both adults and children. PMID:19428492

The distribution dynamics and desorption behaviour of mobile pharmaceuticals and caffeine to combined sewer sediments.

PubMed

Hajj-Mohamad, M; Darwano, H; Duy, S Vo; Sauvé, S; Prévost, M; Arp, H P H; Dorner, S

2017-01-01

Pharmaceuticals are discharged to the environment from wastewater resource recovery facilities, sewer overflows, and illicit sewer connections. To understand the fate of pharmaceuticals, there is a need to better understand their sorption dynamics to suspended sediments (SS) and settled sediments (StS) in sewer systems. In this study, such sorption dynamics to both SS and StS were assessed using a batch equilibrium method under both static and dynamic conditions. Experiments were performed with natively occurring and artificially modified concentrations of sewer pharmaceuticals (acetaminophen, theophylline, carbamazepine, and a metabolite of carbamazepine) and caffeine. Differences in apparent distribution coefficients, K d,app , between SS and StS were related to differences in their organic carbon (OC) content, and the practice of artificially modifying the concentration. K d,app values of modified contaminant concentrations and high OC sediments were substantially higher. Pseudo-second order desorption rates for these mobile compounds were also quantified. Successive flushing events to simulate the addition of stormwater to sewer networks revealed that aqueous concentrations would not necessarily decrease, because the added water will rapidly return to equilibrium concentrations with the sediments. Sorption and desorption kinetics must be considered in addition to dilution, to avoid underestimating the influence of dilution on concentrations of pharmaceuticals discharged to the environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Caffeine Sodium Benzoate for Electroconvulsive Therapy Augmentation.

PubMed

Bozymski, Kevin M; Potter, Teresa G; Venkatachalam, Vasu; Pandurangi, Ananda K; Crouse, Ericka L

2018-05-15

Because of an ongoing manufacturer shortage of injectable caffeine sodium benzoate (CSB), patients at our health system were given CSB compounded in-house to increase seizure response during electroconvulsive therapy (ECT). Therefore, we aimed to evaluate its effectiveness and safety as an ECT augmentation agent. Medical records of patients who received compounded CSB at Virginia Commonwealth University Health System were reviewed to identify adults receiving it as part of an index ECT treatment course between June 2012 and December 2016. The primary outcome was change in electroencephalogram seizure duration from pre-caffeine session to initial caffeine session. Data were also collected on demographics, motor seizure duration, maximum heart rate, mean arterial pressure, and concurrent medication use for these sessions and the last caffeine session. Seven-one patients were included in the study, predominantly white females with a mean age of 58.6 years. The most common indication for ECT was major depressive disorder resistant to pharmacotherapy (71.8%), followed by catatonia associated with another mental disorder (19.7%). Electroencephalogram seizure duration increased by 24.1 seconds on average with first CSB use (P < 0.0001), allowing 24 more patients overall to achieve goal of at least 30 seconds (P < 0.0001). No clinically significant changes in maximum heart rate or mean arterial pressure were observed, nor did any patients require an abortive agent for prolonged seizure. Five patients (7%) discontinued CSB prematurely: 4 related to adverse effects and 1 secondary to ineffectiveness. We confirm results of prior studies of the utility of CSB and add that compounded CSB is effective for ECT augmentation, maintaining effectiveness throughout the index course with minimal safety concerns.

Caffeine alleviates the deterioration of Ca2+ release mechanisms and fragmentation of in vitro aged mouse eggs

PubMed Central

Zhang, Nan; Wakai, Takuya; Fissore, Rafael. A.

2011-01-01

The developmental competence of mammalian eggs is compromised by postovulatory aging. We and others found that in these eggs the intracellular calcium ([Ca2+]i) responses required for egg activation and initiation of development are altered. Nevertheless, the mechanism(s) underlying this defective Ca2+ release is not well known. Here, we investigated if the function of IP3R1, the major Ca2+ release channel at fertilization, was undermined in in vitro aged mouse eggs. We found that in aged eggs IP3R1 displayed reduced function, as many of the changes acquired during maturation that enhance IP3R1 Ca2+ conductivity such as phosphorylation, receptor reorganization and increased Ca2+ store content ([Ca2+]ER) were lost with increasing postovulatory time. IP3R1 fragmentation, possibly associated with the activation of caspase-3, was also observed in these eggs. Many of these changes were prevented when the postovulatory aging of eggs was carried out in the presence of caffeine, which minimized the decline in IP3R1 function and maintained [Ca2+]ER content. Caffeine also maintained mitochondrial membrane potential as measured by JC-1 fluorescence. We therefore conclude that [Ca2+]i responses in aged eggs are undermined by reduced IP3R1 sensitivity, decreased [Ca2+]ER and compromised mitochondrial function, and that addition of caffeine ameliorates most of these aging-associated changes. Understanding the molecular basis of the protective effects of caffeine will be useful in elucidating, and possibly reversing, the signaling pathway(s) compromised by in vitro culture of eggs. PMID:22095868

Energy drink use frequency among an international sample of people who use drugs: Associations with other substance use and well-being.

PubMed

Peacock, Amy; Bruno, Raimondo; Ferris, Jason; Winstock, Adam

2017-05-01

The study aims were to identify: i.) energy drink (ED), caffeine tablet, and caffeine intranasal spray use amongst a sample who report drug use, and ii.) the association between ED use frequency and demographic profile, drug use, hazardous drinking, and wellbeing. Participants (n=74,864) who reported drug use completed the online 2014 Global Drug Survey. They provided data on demographics, ED use, and alcohol and drug use, completed the Alcohol Use Disorders Identification Test (AUDIT) and Personal Wellbeing Index (PWI), and reported whether they wished to reduce alcohol use. Lifetime ED, caffeine tablet and intranasal caffeine spray use were reported by 69.2%, 24.5% and 4.9%. Median age of ED initiation was 16 years. For those aged 16-37, median years using EDs increased from 4 to 17 years of consumption, where it declined thereafter. Greater ED use frequency was associated with: being male; under 21 years of age; studying; and past year caffeine tablet/intranasal spray, tobacco, cannabis, amphetamine, MDMA, and cocaine use. Past year, infrequent (1-4days) and frequent (≥5days) past month ED consumers reported higher AUDIT scores and lower PWI scores than lifetime abstainers; past month consumers were less likely to report a desire to reduce alcohol use. ED use is part of a complex interplay of drug use, alcohol problems, and poorer personal wellbeing, and ED use frequency may be a flag for current/future problems. Prospective research is required exploring where ED use fits within the trajectory of other alcohol and drug use. Copyright © 2017 Elsevier B.V. All rights reserved.

The influence of CYP1A2 genotype in the blood pressure response to caffeine ingestion is affected by physical activity status and caffeine consumption level.

PubMed

Soares, Rogerio Nogueira; Schneider, Augusto; Valle, Sandra Costa; Schenkel, Paulo Cavalheiro

2018-03-06

This study aimed to investigate whether the influence of CYP1A2 genotype in the blood pressure (BP) response to caffeine ingestion was affected by physical activity status and habitual caffeine consumption. Thirty-seven participants (19-50 years old) took place in the study and were categorized according to i) genotype: CYP1A2 (AA) "fast metabolizer", and CYP1A2 (AC) "slow metabolizer"; ii) physical activity level: sedentary (S) and physically active (A); and iii) caffeine consumption level: non-habitual caffeine consumer (NC) and habitual heavy caffeine consumer (C). All groups had BP assessed before (basal) and 1 hourh after (post) caffeine ingestion (6 mg·kg -1 ). It was observed that AC genotype individuals had increased basal-DBP and post-caffeine SBP when compared to AA individuals. Additionally, acute caffeine ingestion increased SBP only in the AC group. It was also found that physical activity only modulated the BP responses to acute caffeine ingestion in AC individuals. Furthermore, the results indicated that the habitual heavy caffeine consumers AC individuals had increased basal-DBP when compared to the AA ones. Our results suggest that the influence of CYP1A2 genotype in the basal and post-caffeine BP response to caffeine ingestion is modified by physical activity status and caffeine consumption level. Copyright © 2018 Elsevier Inc. All rights reserved.

Chronic caffeine produces sexually dimorphic effects on amphetamine-induced behavior, anxiety and depressive-like behavior in adolescent rats.

PubMed

Turgeon, Sarah M; Townsend, Shannon E; Dixon, Rushell S; Hickman, Emma T; Lee, Sabrina M

2016-04-01

Caffeine consumption has been increasing rapidly in adolescents; however, most research on the behavioral effects of caffeine has been conducted in adults. Two experiments were conducted in which adolescent male and female rats were treated with a moderate dose of caffeine (0.25 g/l) in their drinking water beginning on P26-28. In the first experiment, animals were maintained on caffeinated drinking water or normal tap water for 14 days and were then tested for behavioral and striatal c-Fos response to amphetamine (1.5 mg/kg). In the second experiment, rats were maintained on caffeinated drinking water or normal tap water beginning on P28 and were tested for novel object recognition, anxiety in the light/dark test (L/D) and elevated plus maze (EPM), and depressive like behavior in the forced swim test (FST) beginning on the 14th day of caffeine exposure. Caffeine decreased amphetamine-induced rearing in males, but had no effect in females; however, this behavioral effect was not accompanied by changes in striatal c-Fos, which was increased by amphetamine but not altered by caffeine. No effects of caffeine were observed on novel object recognition or elevated plus maze behavior. However, in the L/D test, there was a sex by caffeine interaction on time spent in the light driven by a caffeine-induced increase in light time in the males but not the females. On the pretest day of the FST, sex by caffeine interactions were observed for swimming and struggling; caffeine decreased struggling behavior and increased swimming behavior in males and caffeine-treated females demonstrated significantly more struggling and significantly less swimming than caffeine-treated males. A similar pattern was observed on the test day in which caffeine decreased immobility overall and increased swimming. These data reveal sex dependent effects of caffeine on behavior in adolescent rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Caffeine consumption, sleep, and affect in the natural environments of depressed youth and healthy controls.

PubMed

Whalen, Diana J; Silk, Jennifer S; Semel, Mara; Forbes, Erika E; Ryan, Neal D; Axelson, David A; Birmaher, Boris; Dahl, Ronald E

2008-05-01

Sleep problems are a cardinal symptom of depression in children and adolescents and caffeine use is a prevalent and problematic issue in youth; yet little is known about caffeine use and its effects on sleep in youth with depression. We examined caffeine use and its relation to sleep and affect in youth's natural environments. Thirty youth with major depressive disorder (MDD) and 23 control youth reported on caffeine use, sleep, and affect in their natural environment using ecological momentary assessment at baseline and over 8 weeks, while MDD youth received treatment. Youth with MDD reported more caffeine use and sleep problems relative to healthy youth. Youth with MDD reported more anxiety on days they consumed caffeine. Caffeine use among youth with MDD decreased across treatment, but sleep complaints remained elevated. Findings suggest that both sleep quality and caffeine use are altered in pediatric depression; that caffeine use, but not sleep problems, improves with treatment; and that caffeine may exacerbate daily anxiety among youth with depression.

Performance effects and metabolic consequences of caffeine and caffeinated energy drink consumption on glucose disposal.

PubMed

Shearer, Jane; Graham, Terry E

2014-10-01

This review documents two opposing effects of caffeine and caffeine-containing energy drinks, i.e., their positive effects on athletic performance and their negative impacts on glucose tolerance in the sedentary state. Analysis of studies examining caffeine administration prior to performance-based exercise showed caffeine improved completion time by 3.6%. Similar analyses following consumption of caffeine-containing energy drinks yielded positive, but more varied, benefits, which were likely due to the diverse nature of the studies performed, the highly variable composition of the beverages consumed, and the range of caffeine doses administered. Conversely, analyses of studies administering caffeine prior to either an oral glucose tolerance test or insulin clamp showed a decline in whole-body glucose disposal of ~30%. The consequences of this resistance are unknown, but there may be implications for the development of a number of chronic diseases. Both caffeine-induced performance enhancement and insulin resistance converge with the primary actions of caffeine on skeletal muscle. © 2014 International Life Sciences Institute.

Caffeine Use Disorder: A Review of the Evidence and Future Implications.

PubMed

Addicott, Merideth A

2014-09-01

The latest edition of the Diagnostic and Statistical Manual (DSM-5) has introduced new provisions for caffeine-related disorders. Caffeine Withdrawal is now an officially recognized diagnosis, and criteria for caffeine use disorder have been proposed for additional study. caffeine use disorder is intended to be characterized by cognitive, behavioral, and physiological symptoms indicative of caffeine use despite significant caffeine-related problems, similar to other Substance Use Disorders. However, since nonproblematic caffeine use is so common and widespread, it may be difficult for some health professionals to accept that caffeine use can result in the same types of pathological behaviors caused by alcohol, cocaine, opiates, or other drugs of abuse. Yet there is evidence that some individuals are psychologically and physiologically dependent on caffeine, although the prevalence and severity of these problems is unknown. This article reviews the recent changes to the DSM, the concerns regarding these changes, and some potential impacts these changes could have on caffeine consumers.

Effect of caffeine on the intraocular pressure in patients with primary open angle glaucoma

PubMed Central

Chandra, Peeyush; Gaur, Ajit; Varma, Shambhu

2011-01-01

Purpose Coffee and tea are very common nonalcoholic beverages. However, their intake, particularly that of coffee, has been suggested to increase intraocular pressure (IOP) in patients with open angle glaucoma/ocular hypertension. The causative agent has been suggested to be their caffeine content. The objective of this study was to determine if this represents a direct caffeine effect. This study was therefore done using pure caffeine applied directly to the eyes. Methods The study was conducted with five human volunteers with open angle glaucoma/ ocular hypertension. IOP was measured using a Perkins applanation tonometer. Eye drops of 1% caffeine were prepared in-home. Following the initial (basal) measurement of the IOP, 50 μL of the eye drop preparation was instilled in the eye at 0-, 4-, and 6-hour intervals. IOPs were measured 30 minutes after each instillation. A second study was also undertaken following the first. In this study, the same patients instilled the eye drops three times per day for 1 week at home and then returned to the clinic on day 7. They were then again treated with caffeine eye drops as above and IOPs measured. Results In the 1-day study, the mean basal IOP was 23.6 ± 2.80 mmHg. Thirty minutes after instillation of the drops as described, the pressures were 23.2 ± 1.93, 22.2 ± 1.99, and 22.6 ± 2.31. The basal reading was taken at 10 am and another reading was then taken at 10.30 am. Additional eye drops were instilled at 2 and 8 pm and readings taken 30 minutes after each instillation. In the 1 week study, the basal value was 22.6 ± 2.32. After instillation of the drops as above the values were 23 ± 2.16, 22.4 ± 2.27, and 23 ± 1.94. Conclusion Administration of caffeine into the eyes of patients did not have any effect on IOP and it remained relatively unchanged. This was true in the 1-day study as well as in the 1-week study. A cumulative effect was not visible. The results therefore demonstrate that caffeine has no significant effect on IOP in patients with glaucoma. Any effects reported in coffee drinkers may therefore be related to other constituents in coffee, known to be generated pyrolytically from endogenous constituents of coffee beans by roasting at relatively high temperature, combined with the osmotic effects imposed by adequate fluid intake, known to be common in glaucoma patients. PMID:22140308

Stress, Coping and Coffee Consumption

DTIC Science & Technology

1991-08-30

Henry and Stephens (1980) have found evidence for this role for caffeine as an intensifier for stress effects on plasma renin, corticosterone , and...have learned a lot. Vll TABLE OF CONTENTS Introduction Stress, coping and perceived control Stress Coping Perceived control Effects of caffeine...Central nervous system effects of caffeine Mood effects of caffeine Health effects of caffeine cardiovascular effects caffeine and

Psychostimulant and other effects of caffeine in 9- to 11-year-old children.

PubMed

Heatherley, Susan V; Hancock, Katie M F; Rogers, Peter J

2006-02-01

Recent research on adults suggests that "beneficial" psychostimulant effects of caffeine are found only in the context of caffeine deprivation; that is, caffeine improves psychomotor and cognitive performance in habitual caffeine consumers following caffeine withdrawal. Furthermore, no net benefit is gained because performance is merely restored to "baseline" levels. The effects of caffeine in children is an under-researched area, with only a handful of studies being carried out in the US where children's consumption of caffeine appears to be lower on average than in the UK. Twenty-six children aged between 9 and 11 years completed a double-blind, placebo-controlled study. Habitual caffeine consumers (mean daily caffeine intake = 109 mg) and non/low-consumers (12 mg) were tested on two separate days following overnight caffeine abstinence. On each day measures of cognitive performance (a number search task), and self-rated mood and physical symptoms, including alertness and headache, were taken before and after administration of 50 mg of caffeine, or placebo. At baseline (before treatment), the habitual consumers showed poorer performance on the cognitive test than did the non/low-consumers, although no significant differences in mood or physical symptoms were found between the two groups. There were significant habit by treatment (caffeine vs. placebo) interactions for accuracy of performance and headache, and a significant main effect of treatment for alertness. Post hoc comparisons showed that caffeine administration improved the consumers' accuracy on the cognitive test (to near the level displayed by the non/low-consumers at baseline), but that it had no significant effect on the non/low-consumers' performance. In the consumers, caffeine prevented an increase in headache that occurred after placebo, and it increased alertness relative to placebo. Again, however, caffeine did not significantly affect levels of headache or alertness in the non/low-consumers. These results suggest that, like adults, children probably derive little or no benefit from habitual caffeine intake, although negative symptoms associated with overnight caffeine withdrawal are avoided or rapidly reversed by subsequent caffeine consumption.

Administration of Caffeine in Alternate Forms.

PubMed

Wickham, Kate A; Spriet, Lawrence L

2018-03-01

There has been recent interest in the ergogenic effects of caffeine delivered in low doses (~ 200 mg or ~ 3 mg/kg body mass) and administered in forms other than capsules, coffee and sports drinks, including chewing gum, bars, gels, mouth rinses, energy drinks and aerosols. Caffeinated chewing gum is absorbed quicker through the buccal mucosa compared with capsule delivery and absorption in the gut, although total caffeine absorption over time is not different. Rapid absorption may be important in many sporting situations. Caffeinated chewing gum improved endurance cycling performance, and there is limited evidence that repeated sprint cycling and power production may also be improved. Mouth rinsing with caffeine may stimulate nerves with direct links to the brain, in addition to caffeine absorption in the mouth. However, caffeine mouth rinsing has not been shown to have significant effects on cognitive performance. Delivering caffeine with mouth rinsing improved short-duration, high-intensity, repeated sprinting in normal and depleted glycogen states, while the majority of the literature indicates no ergogenic effect on aerobic exercise performance, and resistance exercise has not been adequately studied. Studies with caffeinated energy drinks have generally not examined the individual effects of caffeine on performance, making conclusions about this form of caffeine delivery impossible. Caffeinated aerosol mouth and nasal sprays may stimulate nerves with direct brain connections and enter the blood via mucosal and pulmonary absorption, although little support exists for caffeine delivered in this manner. Overall, more research is needed examining alternate forms of caffeine delivery including direct measures of brain activation and entry of caffeine into the blood, as well as more studies examining trained athletes and female subjects.

Caffeine and theanine exert opposite effects on attention under emotional arousal.

PubMed

Giles, Grace E; Mahoney, Caroline R; Brunyé, Tad T; Taylor, Holly A; Kanarek, Robin B

2017-01-01

Tea is perceived as more relaxing than coffee, even though both contain caffeine. L-theanine in tea may account for the difference. Consumed together, caffeine and theanine exert similar cognitive effects to that of caffeine alone, but exert opposite effects on arousal, in that caffeine accentuates and theanine mitigates physiological and felt stress responses. We evaluated whether caffeine and theanine influenced cognition under emotional arousal. Using a double-blind, repeated-measures design, 36 participants received 4 treatments (200 mg caffeine + 0 mg theanine, 0 mg caffeine + 200 mg theanine, 200 mg caffeine + 200 mg theanine, 0 mg caffeine + 0 mg theanine) on separate days. Emotional arousal was induced by highly arousing negative film clips and pictures. Mood, salivary cortisol, and visual attention were evaluated. Caffeine accentuated global processing of visual attention on the hierarchical shape task (p < 0.05), theanine accentuated local processing (p < 0.05), and the combination did not differ from placebo. Caffeine reduced flanker conflict difference scores on the Attention Network Test (p < 0.05), theanine increased difference scores (p < 0.05), and the combination did not differ from placebo. Thus, under emotional arousal, caffeine and theanine exert opposite effects on certain attentional processes, but when consumed together, they counteract the effects of each other.

Electrogenic Na+/Ca2+ Exchange

PubMed Central

Danaceau, Jonathan P.; Lucero, Mary T.

2000-01-01

Olfactory receptor neurons (ORNs) from the squid, Lolliguncula brevis, respond to the odors l-glutamate or dopamine with increases in internal Ca2+ concentrations ([Ca2+]i). To directly asses the effects of increasing [Ca2+]i in perforated-patched squid ORNs, we applied 10 mM caffeine to release Ca2+ from internal stores. We observed an inward current response to caffeine. Monovalent cation replacement of Na+ from the external bath solution completely and selectively inhibited the caffeine-induced response, and ruled out the possibility of a Ca2+-dependent nonselective cation current. The strict dependence on internal Ca2+ and external Na+ indicated that the inward current was due to an electrogenic Na+/Ca2+ exchanger. Block of the caffeine-induced current by an inhibitor of Na+/Ca2+ exchange (50–100 μM 2′,4′-dichlorobenzamil) and reversibility of the exchanger current, further confirmed its presence. We tested whether Na+/Ca2+ exchange contributed to odor responses by applying the aquatic odor l-glutamate in the presence and absence of 2′,4′-dichlorobenzamil. We found that electrogenic Na+/Ca2+ exchange was responsible for ∼26% of the total current associated with glutamate-induced odor responses. Although Na+/Ca2+ exchangers are known to be present in ORNs from numerous species, this is the first work to demonstrate amplifying contributions of the exchanger current to odor transduction. PMID:10828249

Non-destructive analysis of sucrose, caffeine and trigonelline on single green coffee beans by hyperspectral imaging.

PubMed

Caporaso, Nicola; Whitworth, Martin B; Grebby, Stephen; Fisk, Ian D

2018-04-01

Hyperspectral imaging (HSI) is a novel technology for the food sector that enables rapid non-contact analysis of food materials. HSI was applied for the first time to whole green coffee beans, at a single seed level, for quantitative prediction of sucrose, caffeine and trigonelline content. In addition, the intra-bean distribution of coffee constituents was analysed in Arabica and Robusta coffees on a large sample set from 12 countries, using a total of 260 samples. Individual green coffee beans were scanned by reflectance HSI (980-2500nm) and then the concentration of sucrose, caffeine and trigonelline analysed with a reference method (HPLC-MS). Quantitative prediction models were subsequently built using Partial Least Squares (PLS) regression. Large variations in sucrose, caffeine and trigonelline were found between different species and origin, but also within beans from the same batch. It was shown that estimation of sucrose content is possible for screening purposes (R 2 =0.65; prediction error of ~0.7% w/w coffee, with observed range of ~6.5%), while the performance of the PLS model was better for caffeine and trigonelline prediction (R 2 =0.85 and R 2 =0.82, respectively; prediction errors of 0.2 and 0.1%, on a range of 2.3 and 1.1% w/w coffee, respectively). The prediction error is acceptable mainly for laboratory applications, with the potential application to breeding programmes and for screening purposes for the food industry. The spatial distribution of coffee constituents was also successfully visualised for single beans and this enabled mapping of the analytes across the bean structure at single pixel level. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Caffeine Increases Anaerobic Work and Restores Cycling Performance following a Protocol Designed to Lower Endogenous Carbohydrate Availability

PubMed Central

Silva-Cavalcante, Marcos David; Correia-Oliveira, Carlos Rafaell; Santos, Ralmony Alcantara; Lopes-Silva, João Paulo; Lima, Hessel Marani; Bertuzzi, Romulo; Duarte, Marcos; Bishop, David John; Lima-Silva, Adriano Eduardo

2013-01-01

The purpose this study was to examine the effects of caffeine ingestion on performance and energy expenditure (anaerobic and aerobic contribution) during a 4-km cycling time trial (TT) performed after a carbohydrate (CHO) availability-lowering exercise protocol. After preliminary and familiarization trials, seven amateur cyclists performed three 4-km cycling TT in a double-blind, randomized and crossover design. The trials were performed either after no previous exercise (CON), or after a CHO availability-lowering exercise protocol (DEP) performed in the previous evening, followed by either placebo (DEP-PLA) or 5 mg.kg−1 of caffeine intake (DEP-CAF) 1 hour before the trial. Performance was reduced (−2.1%) in DEP-PLA vs CON (421.0±12.3 vs 412.4±9.7 s). However, performance was restored in DEP-CAF (404.6±17.1 s) compared with DEP-PLA, while no differences were found between DEP-CAF and CON. The anaerobic contribution was increased in DEP-CAF compared with both DEP-PLA and CON (67.4±14.91, 47. 3±14.6 and 55.3±14.0 W, respectively), and this was more pronounced in the first 3 km of the trial. Similarly, total anaerobic work was higher in DEP-CAF than in the other conditions. The integrated electromyographic activity, plasma lactate concentration, oxygen uptake, aerobic contribution and total aerobic work were not different between the conditions. The reduction in performance associated with low CHO availability is reversed with caffeine ingestion due to a higher anaerobic contribution, suggesting that caffeine could access an anaerobic “reserve” that is not used under normal conditions. PMID:23977198

Effects of caffeine on alcohol reinforcement: beverage choice, self-administration, and subjective ratings.

PubMed

Sweeney, Mary M; Meredith, Steven E; Evatt, Daniel P; Griffiths, Roland R

2017-03-01

Combining alcohol and caffeine is associated with increased alcohol consumption, but no prospective experimental studies have examined whether added caffeine increases alcohol consumption. This study examined how caffeine alters alcohol self-administration and subjective reinforcing effects in healthy adults. Thirty-one participants completed six double-blind alcohol self-administration sessions: three sessions with alcohol only (e.g., beverage A) and three sessions with alcohol and caffeine (e.g., beverage B). Participants chose which beverage to consume on a subsequent session (e.g., beverage A or B). The effects of caffeine on overall beverage choice, number of self-administered drinks, subjective ratings (e.g., Biphasic Alcohol Effects Scale), and psychomotor performance were examined. A majority of participants (65%) chose to drink the alcohol beverage containing caffeine on their final self-administration session. Caffeine did not increase the number of self-administered drinks. Caffeine significantly increased stimulant effects, decreased sedative effects, and attenuated decreases in psychomotor performance attributable to alcohol. Relative to nonchoosers, caffeine choosers reported overall lower stimulant ratings and reported greater drinking behavior prior to the study. Although caffeine did not increase the number of self-administered drinks, most participants chose the alcohol beverage containing caffeine. Given the differences in subjective ratings and pre-existing differences in self-reported alcohol consumption for caffeine choosers and nonchoosers, these data suggest that decreased stimulant effects of alcohol and heavier self-reported drinking may predict subsequent choice of combined caffeine and alcohol beverages. These predictors may identify individuals who would benefit from efforts to reduce risk behaviors associated with combining alcohol and caffeine.

Trends in Caffeine Intake Among US Children and Adolescents

PubMed Central

Branum, Amy M.; Rossen, Lauren M.; Schoendorf, Kenneth C.

2016-01-01

BACKGROUND AND OBJECTIVE Physicians and policy makers are increasingly interested in caffeine intake among children and adolescents in the advent of increasing energy drink sales. However, there have been no recent descriptions of caffeine or energy drink intake in the United States. We aimed to describe trends in caffeine intake over the past decade among US children and adolescents. METHODS We assessed trends and demographic differences in mean caffeine intake among children and adolescents by using the 24-hour dietary recall data from the 1999–2010 NHANES. In addition, we described the proportion of caffeine consumption attributable to different beverages, including soda, energy drinks, and tea. RESULTS Approximately 73% of children consumed caffeine on a given day. From 1999 to 2010, there were no significant trends in mean caffeine intake overall; however, caffeine intake decreased among 2- to 11-year-olds (P < .01) and Mexican-American children (P = .003). Soda accounted for the majority of caffeine intake, but this contribution declined from 62% to 38% (P < .001). Coffee accounted for 10% of caffeine intake in 1999–2000 but increased to nearly 24% of intake in 2009–2010 (P < .001). Energy drinks did not exist in 1999–2000 but increased to nearly 6% of caffeine intake in 2009–2010. CONCLUSIONS Mean caffeine intake has not increased among children and adolescents in recent years. However, coffee and energy drinks represent a greater proportion of caffeine intake as soda intake has declined. These findings provide a baseline for caffeine intake among US children and young adults during a period of increasing energy drink use. PMID:24515508

Effects of caffeine on alcohol reinforcement: Beverage choice, self-administration, and subjective ratings

PubMed Central

Sweeney, Mary M.; Meredith, Steven E.; Evatt, Daniel P.; Griffiths, Roland R.

2017-01-01

Rationale Combining alcohol and caffeine is associated with increased alcohol consumption, but no prospective experimental studies have examined whether added caffeine increases alcohol consumption. Objectives This study examined how caffeine alters alcohol self-administration and subjective reinforcing effects in healthy adults. Methods Thirty-one participants completed six double-blind alcohol self-administration sessions: three sessions with alcohol only (e.g., Beverage A) and three sessions with alcohol and caffeine (e.g., Beverage B). Participants chose which beverage to consume on a subsequent session (e.g., Beverage A or B). Effects of caffeine on overall beverage choice, number of self-administered drinks, subjective ratings (e.g., Biphasic Alcohol Effects Scale), and psychomotor performance were examined. Results A majority of participants (65%) chose to drink the alcohol beverage containing caffeine on their final self-administration session. Caffeine did not increase the number of self-administered drinks. Caffeine significantly increased stimulant effects, decreased sedative effects, and attenuated decreases in psychomotor performance attributable to alcohol. Relative to nonchoosers, caffeine choosers reported overall lower stimulant ratings, and reported greater drinking behavior prior to the study. Conclusions Although caffeine did not increase the number of self-administered drinks, most participants chose the alcohol beverage containing caffeine. Given the differences in subjective ratings and pre-existing differences in self-reported alcohol consumption for caffeine choosers and nonchoosers, these data suggest decreased stimulant effects of alcohol and heavier self-reported drinking may predict subsequent choice of combined caffeine and alcohol beverages. These predictors may identify individuals who would benefit from efforts to reduce risk behaviors associated with combining alcohol and caffeine. PMID:28108773

Reinforcing effects of caffeine in coffee and capsules.

PubMed

Griffiths, R R; Bigelow, G E; Liebson, I A

1989-09-01

In a residential research ward the reinforcing and subjective effects of caffeine were studied under double-blind conditions in volunteer subjects with histories of heavy coffee drinking. In Experiment 1, 6 subjects had 13 opportunities each day to self-administer either a caffeine (100 mg) or a placebo capsule for periods of 14 to 61 days. All subjects developed a clear preference for caffeine, with intake of caffeine becoming relatively stable after preference had been attained. Preference for caffeine was demonstrated whether or not preference testing was preceded by a period of 10 to 37 days of caffeine abstinence, suggesting that a recent history of heavy caffeine intake (tolerance/dependence) was not a necessary condition for caffeine to function as a reinforcer. In Experiment 2, 6 subjects had 10 opportunities each day to self-administer a cup of coffee or (on different days) a capsule, dependent upon completing a work requirement that progressively increased and then decreased over days. Each day, one of four conditions was studied: caffeinated coffee (100 mg/cup), decaffeinated coffee, caffeine capsules (100 mg/capsule), or placebo capsules. Caffeinated coffee maintained the most self-administration, significantly higher than decaffeinated coffee and placebo capsules but not different from caffeine capsules. Both decaffeinated coffee and caffeine capsules were significantly higher than placebo capsules but not different from each other. In both experiments, subject ratings of "linking" of coffee or capsules covaried with the self-administration measures. These experiments provide the clearest demonstrations to date of the reinforcing effects of caffeine in capsules and in coffee.

Reinforcing effects of caffeine in coffee and capsules.

PubMed Central

Griffiths, R R; Bigelow, G E; Liebson, I A

1989-01-01

In a residential research ward the reinforcing and subjective effects of caffeine were studied under double-blind conditions in volunteer subjects with histories of heavy coffee drinking. In Experiment 1, 6 subjects had 13 opportunities each day to self-administer either a caffeine (100 mg) or a placebo capsule for periods of 14 to 61 days. All subjects developed a clear preference for caffeine, with intake of caffeine becoming relatively stable after preference had been attained. Preference for caffeine was demonstrated whether or not preference testing was preceded by a period of 10 to 37 days of caffeine abstinence, suggesting that a recent history of heavy caffeine intake (tolerance/dependence) was not a necessary condition for caffeine to function as a reinforcer. In Experiment 2, 6 subjects had 10 opportunities each day to self-administer a cup of coffee or (on different days) a capsule, dependent upon completing a work requirement that progressively increased and then decreased over days. Each day, one of four conditions was studied: caffeinated coffee (100 mg/cup), decaffeinated coffee, caffeine capsules (100 mg/capsule), or placebo capsules. Caffeinated coffee maintained the most self-administration, significantly higher than decaffeinated coffee and placebo capsules but not different from caffeine capsules. Both decaffeinated coffee and caffeine capsules were significantly higher than placebo capsules but not different from each other. In both experiments, subject ratings of "linking" of coffee or capsules covaried with the self-administration measures. These experiments provide the clearest demonstrations to date of the reinforcing effects of caffeine in capsules and in coffee. PMID:2794839

Placebo caffeine reduces withdrawal in abstinent coffee drinkers.

PubMed

Mills, Llewellyn; Boakes, Robert A; Colagiuri, Ben

2016-04-01

Expectancies have been shown to play a role in the withdrawal syndrome of many drugs of addiction; however, no studies have examined the effects of expectancies across a broad range of caffeine withdrawal symptoms, including craving. The purpose of the current study was to use caffeine as a model to test the effect of expectancy on withdrawal symptoms, specifically whether the belief that one has ingested caffeine is sufficient to reduce caffeine withdrawal symptoms and cravings in abstinent coffee drinkers. We had 24-h abstinent regular coffee drinkers complete the Caffeine Withdrawal Symptom Questionnaire (CWSQ) before and after receiving decaffeinated coffee. One-half of the participants were led to believe the coffee was regular caffeinated coffee (the 'Told Caffeine' condition) and one-half were told that it was decaffeinated (the 'Told Decaf' condition). Participants in the Told Caffeine condition reported a significantly greater reduction in the factors of cravings, fatigue, lack of alertness and flu-like feelings of the CWSQ, than those in the Told Decaf condition. Our results indicated that the belief that one has consumed caffeine can affect caffeine withdrawal symptoms, especially cravings, even when no caffeine was consumed. © The Author(s) 2016.

Effects of repeated doses of caffeine on mood and performance of alert and fatigued volunteers.

PubMed

Smith, Andrew; Sutherland, David; Christopher, Gary

2005-11-01

Evidence for behavioural effects of caffeine is well documented in the literature. It is associated with increased subjective alertness, improved reaction time and enhanced encoding of new information. These effects are most prominent in low arousal situations. However, there is an ongoing debate as to whether such changes are in fact improvements or merely a reversal of the negative effects of a period of caffeine withdrawal (e.g. overnight abstinence). To avoid such a confound this study included multiple doses of caffeine which were administered under double-blind conditions to participants who had ingested their normal daily quota of caffeine. In the present study participants were fatigued by carrying out a prolonged testing schedule in the evening. Sixty volunteers, all regular caffeine consumers, took part in the study. They attended for three sessions on separate days. They were instructed to consume normal amounts of caffeinated beverages. Consumption was measured by a diary and saliva samples were taken and caffeine assays conducted. A baseline test session was carried out at 18.00h and following this a double blind placebo controlled caffeine challenge (1.5mg/kg) conducted. The test battery was repeated twice approximately 30 minutes after the caffeine challenge. Following this another drink was administered and the test battery repeated twice more. On one test session volunteers had placebo in both drinks, in another they had caffeine in both drinks and another caffeine in the first and placebo in the second. Order of conditions was balanced across subjects. The results showed that caffeine led to a more positive mood and improved performance on a number of tasks. Different effects of caffeine were seen depending on the person's level of arousal. Linear effects of caffeine dose were also observed. This is evidence against the argument that behavioural changes due to caffeine are merely the reversal of negative effects of a long period of caffeine abstinence. The findings are discussed in relation to both noradrenergic and cholinergic neurotransmitter systems.

Porcine malignant hyperthermia susceptibility: hypersensitive calcium-release mechanism of skeletal muscle sarcoplasmic reticulum.

PubMed Central

O'Brien, P J

1986-01-01

This study tested the hypothesis that calcium-release from sarcoplasmic reticulum isolated from malignant hyperthermia swine had abnormal concentration-dependency on release modulators. Halothane stimulated half-maximal calcium-release at similar concentrations for malignant hyperthermia and control sarcoplasmic reticulum (0.10 +/- 0.04 mM). However, concentrations causing half-maximal calcium-release were lower for malignant hyperthermia sarcoplasmic reticulum (P less than 0.001) by an order of magnitude for Ca2+ (28.1 +/- 8.3 versus 1.23 +/- 0.45 nM), adenosine triphosphate (0.33 +/- 0.09 versus 0.023 +/- 0.014 mM) and caffeine (7.79 +/- 1.56 versus 0.80 +/- 0.44 mM). Half-maximal inhibition by Mg2+ occurred at threefold higher concentrations for malignant hyperthermia sarcoplasmic reticulum (0.23 +/- 0.02 versus 0.78 +/- 0.17 mM). The Ca2+-sensitivity curves for calcium-release by sarcoplasmic reticulum isolated from heterozygotes for the malignant hyperthermia-defect were indistinguishable from the averages of the curves for controls and malignant hyperthermia-homozygotes. Results of this study suggest that malignant hyperthermia is initiated due to a hypersensitive calcium-release mechanism which is inherited in an autosomal, codominant pattern and may be diagnosed using calcium-release sensitivity-tests on isolated sarcoplasmic reticulum. Images Fig. 1. PMID:3742367

Design, formulation and evaluation of caffeine chewing gum.

PubMed

Aslani, Abolfazl; Jalilian, Fatemeh

2013-01-01

Caffeine which exists in drinks such as coffee as well as in drug dosage forms in the global market is among the materials that increase alertness and decrease fatigue. Compared to other forms of caffeine, caffeine gum can create faster and more prominent effects. In this study, the main goal is to design a new formulation of caffeine gum with desirable taste and assess its physicochemical properties. Caffeine gum was prepared by softening of gum bases and then mixing with other formulation ingredients. To decrease the bitterness of caffeine, sugar, aspartame, liquid glucose, sorbitol, manitol, xylitol, and various flavors were used. Caffeine release from gum base was investigated by mechanical chewing set. Content uniformity test was also performed on the gums. The gums were evaluated in terms of organoleptic properties by the Latin-Square design at different stages. After making 22 formulations of caffeine gums, F11 from 20 mg caffeine gums and F22 from 50 mg caffeine gums were chosen as the best formulation in organoleptic properties. Both types of gum released about 90% of their own drug content after 30 min. Drug content of 20 and 50 mg caffeine gum was about 18.2-21.3 mg and 45.7-53.6 mg respectively. In this study, 20 and 50 mg caffeine gums with suitable and desirable properties (i.e., good taste and satisfactory release) were formulated. The best flavor for caffeine gum was cinnamon. Both kinds of 20 and 50 mg gums succeeded in content uniformity test.

Reversal of caffeine withdrawal by ingestion of a soft beverage.

PubMed

Watson, J M; Lunt, M J; Morris, S; Weiss, M J; Hussey, D; Kerr, D

2000-05-01

Followlng regular use, acute cessation of caffeine is associated with a characteristic withdrawal syndrome. Despite this, caffeine remains popular with its consumers. The aim of this study was to examine the physiologic and psychologic effects of small caffeine doses, administered in the form of a market-leading soft drink, on healthy women who were acutely withdrawn from caffeine. After 48-h abstinence and overnight fast, 11 healthy (22 to 40 years) female volunteers, all regular caffeine users (daily consumption 143 to 773 mg) consumed using a double-blind. randomized, controlled cross-over design either 2 tins of regular or caffeine-free Diet Coke. On both visits a Mars bar was eaten to prevent hypoglycaemia. Thus, the caffeine load was 76 or 10 mg respectively. Following ingestion of regular Diet Coke, there was a l0% fall in middle cerebral artery velocity (95% CI [6%-l4%], p < 0.005 versus caffeine free) and improvement in feelings of pleasure (p < 0.046) and energy (p < 0.037). Intellectual function (4-choice reaction time) was unaffected by caffeine status. On both visits, ingestion of Diet Coke induced a pressor response (maximum rise in systolic pressure +15+/- 2 mm Hg with caffeine and +l2 +/- 2 mm Hg with caffeine-free beverage, both p < 0.001 compared with baseline). In conclusion, in women acutely withdrawn from caffeine, ingestion of a popular soft beverage containing modest amounts of caffeine is associated with demonstrable physiologic and psychologic effects.

Pre-existent expectancy effects in the relationship between caffeine and performance.

PubMed

Elliman, Nicola A; Ash, Jennifer; Green, Michael W

2010-10-01

The present study investigated the impact of pre-existent expectancy regarding the effects of the caffeine load of a drink and the perception of the caffeine content on subjective mood and vigilance performance. Caffeine deprived participants (N=25) were tested in four conditions (within subjects design), using a 2×2 design, with caffeine load and information regarding the caffeine content of the drink. In two sessions, they were given caffeinated coffee and in two were given decaffeinated coffee. Within these two conditions, on one occasion they were given accurate information about the drink and on the other they were given inaccurate information about the drink. Mood and vigilance performance were assessed post ingestion. Caffeine was found to enhance performance, but only when participants were accurately told they were receiving it. When decaffeinated coffee was given, performance was poorer, irrespective of expectancy. However, when caffeine was given, but participants were told it was decaffeinated coffee, performance was as poor as when no caffeine had been administered. There were no easily interpretable effects on mood. The pharmacological effects of caffeine appear to act synergistically with expectancy.

Caffeine Consumption, Sleep, and Affect in the Natural Environments of Depressed Youth and Healthy Controls*

PubMed Central

Whalen, Diana J.; Silk, Jennifer S.; Semel, Mara; Forbes, Erika E.; Ryan, Neal D.; Axelson, David A.; Birmaher, Boris; Dahl, Ronald E.

2008-01-01

Objective Sleep problems are a cardinal symptom of depression in children and adolescents and caffeine use is a prevalent and problematic issue in youth; yet little is known about caffeine use and its effects on sleep in youth with depression. We examined caffeine use and its relation to sleep and affect in youth’s natural environments. Methods Thirty youth with major depressive disorder (MDD) and 23 control youth reported on caffeine use, sleep, and affect in their natural environment using ecological momentary assessment at baseline and over 8 weeks, while MDD youth received treatment. Results Youth with MDD reported more caffeine use and sleep problems relative to healthy youth. Youth with MDD reported more anxiety on days they consumed caffeine. Caffeine use among youth with MDD decreased across treatment, but sleep complaints remained elevated. Conclusions Findings suggest that both sleep quality and caffeine use are altered in pediatric depression; that caffeine use, but not sleep problems, improves with treatment; and that caffeine may exacerbate daily anxiety among youth with depression. PMID:17947257

Legitimacy of concerns about caffeine and energy drink consumption.

PubMed

Wesensten, Nancy J

2014-10-01

Whether caffeine and energy drink consumption presents a critical emerging health problem is not currently known. Available evidence suggests that energy drink consumption represents a change in the ways in which individuals in the United States consume caffeine but that the amount of caffeine consumed daily has not appreciably increased. In the present review, the question of whether Americans are sleep deprived (a potential reason for using caffeine) is briefly explored. Reported rates of daily caffeine consumption (based on beverage formulation) and data obtained from both civilian and military populations in the United States are examined, the efficacy of ingredients other than caffeine in energy drinks is discussed, and the safety and side effects of caffeine are addressed, including whether evidence supports the contention that excessive caffeine/energy drink consumption induces risky behavior. The available evidence suggests that the main legitimate concern regarding caffeine and energy drink use is the potential negative impact on sleep but that, otherwise, there is no cause for concern regarding caffeine use in the general population. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

A comparative study of ICH validated novel spectrophotometric techniques for resolving completely overlapping spectra of quaternary mixtures

NASA Astrophysics Data System (ADS)

Ali, Nouruddin W.; Abdelwahab, Nada S.; Abdelkawy, M.; Emam, Aml A.

2016-02-01

A pharmaceutically marketed mixture of Yohimbine, Alpha-tocopheryl acetate, Niacin, and Caffeine co-formulated as a promising therapy for erectile dysfunction. Simultaneous determination of the aforementioned pharmaceutical formulation without prior separation steps was applied using mean centering of ratio spectra and triple divisor spectrophotometric methods. Mean centering of ratio spectra method depended on using the mean centered ratio spectra in three successive steps which eliminated the derivative steps and so the signal to noise ratio was improved. The absorption spectra of the prepared solutions were measured in the wavelength range of 215-300 nm in the concentration ranges of 1-15, 3-15, 1-20, and 3-15 μg mL- 1 for Yohimbine, Alpha-tocopheryl acetate, Niacin, and Caffeine, respectively. The amplitudes of the mean centered third ratio spectra were measured at 250 nm and 268 nm for Yohimbine and Alpha-tocopheryl acetate, respectively and at peak to peak 272-273 and 262-263 nm for Niacin and Caffeine, respectively. In triple divisor method each drug in the quaternary mixture was determined by dividing the spectrum of the quaternary mixture by a standard spectrum of a mixture containing equal concentrations of the other three drugs. First derivative of these ratio spectra was obtained where determination could be achieved without any interference from the other three drugs. Amplitudes of 1-15, 3-15, 1-15, and 3-15 μg mL- 1 were used for selective determination of Yohimbine, Alpha-tocopheryl acetate, Niacin, and Caffeine, respectively. Laboratory prepared mixtures were analyzed by the developed novel methods to investigate their selectivity also, Super Act® capsules were successfully analyzed to ensure absence of interference from additives. The developed methods were validated according to the ICH guidelines. The proposed methods were statistically compared with each other and with the reported methods; using student t-test, F-test, and one way ANOVA, where no significant difference was found with respect to accuracy and precision.

Post-fusion treatment with MG132 increases transcription factor expression in somatic cell nuclear transfer embryos in pigs.

PubMed

You, Jinyoung; Lee, Joohyeong; Kim, Jinyoung; Park, Junhong; Lee, Eunsong

2010-02-01

The objective of this study was to examine the effect of post-fusion treatment of somatic cell nuclear transfer (SCNT) oocytes with the proteasomal inhibitor MG132 on maturation promoting factor (MPF) activity, nuclear remodeling, embryonic development, and gene expression of cloned pig embryos. Immediately after electrofusion, SCNT oocytes were treated with MG132 and/or caffeine for 2 hr, vanadate for 0.5 hr, or vanadate for 0.5 hr followed by MG132 for 1.5 hr. Of the MG132 concentrations tested (0-5 microM), the 1 microM concentration showed a higher rate of blastocyst formation (25.9%) than 0 (14.2%), 0.5 (16.9%), and 5 microM (16.9%). Post-fusion treatment with MG132, caffeine, and both MG132 and caffeine improved blastocyst formation (22.1%, 21.4%, and 24.4%, respectively), whereas vanadate treatment inhibited blastocyst formation (6.5%) compared to the control (11.1%). When examined 2 hr after fusion and 1 hr after activation, MPF activity remained at a higher (P < 0.05) level in SCNT oocytes that were treated post-fusion with caffeine and/or MG132, but it was decreased by vanadate. The rate of oocytes showing premature chromosome condensation was not altered by MG132 but was decreased by vanadate treatment. In addition, formation of single pronuclei was increased by MG132 compared to control and vanadate treatment. MG132-treated embryos showed increased expression of POU5F1, DPPA2, DPPA3, DPPA5, and NDP52l1 genes compared to control embryos. Our results demonstrate that post-fusion treatment of SCNT oocytes with MG132 prevents MPF degradation and increases expression of transcription factors in SCNT embryos, which are necessary for normal development of SCNT embryos. (c) 2009 Wiley-Liss, Inc.