International society of sports nutrition position stand: caffeine and performance

PubMed Central

2010-01-01

Position Statement: The position of The Society regarding caffeine supplementation and sport performance is summarized by the following seven points: 1.) Caffeine is effective for enhancing sport performance in trained athletes when consumed in low-to-moderate dosages (~3-6 mg/kg) and overall does not result in further enhancement in performance when consumed in higher dosages (≥ 9 mg/kg). 2.) Caffeine exerts a greater ergogenic effect when consumed in an anhydrous state as compared to coffee. 3.) It has been shown that caffeine can enhance vigilance during bouts of extended exhaustive exercise, as well as periods of sustained sleep deprivation. 4.) Caffeine is ergogenic for sustained maximal endurance exercise, and has been shown to be highly effective for time-trial performance. 5.) Caffeine supplementation is beneficial for high-intensity exercise, including team sports such as soccer and rugby, both of which are categorized by intermittent activity within a period of prolonged duration. 6.) The literature is equivocal when considering the effects of caffeine supplementation on strength-power performance, and additional research in this area is warranted. 7.) The scientific literature does not support caffeine-induced diuresis during exercise, or any harmful change in fluid balance that would negatively affect performance. PMID:20205813

The Effects of Low Dose Buccal Administered Caffeine on RPE and Pain during an Upper Body Muscle Endurance Test and Lower Body Anaerobic Test

ERIC Educational Resources Information Center

Bellar, David M.; Judge, Lawrence W.; Kamimori, Gary H.; Glickman, Ellen L.

2012-01-01

To date there have been a number of studies that have assessed the effects of caffeine on Rated Perceived Exertion (RPE) and Pain Scale scores during continuous exercise. Presently there is little information about the effects of caffeine on RPE and Pain Scale scores during short term, anaerobic and muscle endurance activity. The purpose of the…

Caffeine provokes adverse interactions with 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) and related psychostimulants: mechanisms and mediators

PubMed Central

Vanattou-Saïfoudine, N; McNamara, R; Harkin, A

2012-01-01

Concomitant consumption of caffeine with recreational psychostimulant drugs of abuse can provoke severe acute adverse reactions in addition to longer term consequences. The mechanisms by which caffeine increases the toxicity of psychostimulants include changes in body temperature regulation, cardiotoxicity and lowering of the seizure threshold. Caffeine also influences the stimulatory, discriminative and reinforcing effects of psychostimulant drugs. In this review, we consider our current understanding of such caffeine-related drug interactions, placing a particular emphasis on an adverse interaction between caffeine and the substituted amphetamine, 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’), which has been most recently described and characterized. Co-administration of caffeine profoundly enhances the acute toxicity of MDMA in rats, as manifested by high core body temperature, tachycardia and increased mortality. In addition, co-administration of caffeine enhances the long-term serotonergic neurotoxicity induced by MDMA. Observations to date support an interactive model of drug-induced toxicity comprising MDMA-related enhancement of dopamine release coupled to a caffeine-mediated antagonism of adenosine receptors in addition to inhibition of PDE. These experiments are reviewed together with reports of caffeine-related drug interactions with cocaine, d-amphetamine and ephedrine where similar mechanisms are implicated. Understanding the underlying mechanisms will guide appropriate intervention strategies for the management of severe reactions and potential for increased drug-related toxicity, resulting from concomitant caffeine consumption. PMID:22671762

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.

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.

Radiation enhanced reactivation of herpes simplex virus: effect of caffeine.

PubMed

Hellman, K B; Lytle, C D; Bockstahler, L E

1976-09-01

Ultaviolet enhanced (Weigle) reactivation of UV-irradiated herpes simplex virus in UV-irradiated CV-1 monkey kidney cell monolayers was decreased by caffeine. X-ray enhanced reactivation of UV-irradiated virus in X-irradiated monolayers (X-ray reactivation) and UV- or X-ray-inactivated capacity of the cells to support unirradiated virus plaque formation were unaffected by caffeine. The results suggest that a caffeine-sensitive process is necessary for the expression of Weigle reactivation for herpes virus. Since cafeine did not significantly affect X-ray reactivation, different mechanisms may be responsible for the expression of Weigle reactivation and X-ray reactivation.

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

Effect of different protocols of caffeine intake on metabolism and endurance performance.

PubMed

Cox, Gregory R; Desbrow, Ben; Montgomery, Paul G; Anderson, Megan E; Bruce, Clinton R; Macrides, Theodore A; Martin, David T; Moquin, Angela; Roberts, Alan; Hawley, John A; Burke, Louise M

2002-09-01

Competitive athletes completed two studies of 2-h steady-state (SS) cycling at 70% peak O(2) uptake followed by 7 kJ/kg time trial (TT) with carbohydrate (CHO) intake before (2 g/kg) and during (6% CHO drink) exercise. In Study A, 12 subjects received either 6 mg/kg caffeine 1 h preexercise (Precaf), 6 x 1 mg/kg caffeine every 20 min throughout SS (Durcaf), 2 x 5 ml/kg Coca-Cola between 100 and 120 min SS and during TT (Coke), or placebo. Improvements in TT were as follows: Precaf, 3.4% (0.2-6.5%, 95% confidence interval); Durcaf, 3.1% (-0.1-6.5%); and Coke, 3.1% (-0.2-6.2%). In Study B, eight subjects received 3 x 5 ml/kg of different cola drinks during the last 40 min of SS and TT: decaffeinated, 6% CHO (control); caffeinated, 6% CHO; decaffeinated, 11% CHO; and caffeinated, 11% CHO (Coke). Coke enhanced TT by 3.3% (0.8-5.9%), with all trials showing 2.2% TT enhancement (0.5-3.8%; P < 0.05) due to caffeine. Overall, 1) 6 mg/kg caffeine enhanced TT performance independent of timing of intake and 2) replacing sports drink with Coca-Cola during the latter stages of exercise was equally effective in enhancing endurance performance, primarily due to low intake of caffeine (approximately 1.5 mg/kg).

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: a potential complexing agent for solubility and dissolution enhancement of celecoxib.

PubMed

Shakeel, Faiyaz; Faisal, Mohammed S

2010-01-01

Complexation of caffeine with the drug celecoxib was used to enhance its solubility as well as in vitro dissolution in the present investigation. Caffeine was extracted from tea leaves using the sublimation method. A molecular complex (1:1) of caffeine-celecoxib was prepared using the solubility method. The solubility of celecoxib in distilled water and the caffeine complex was determined using a HPLC method at a wavelength of 250 nm. Dissolution studies of pure celecoxib, a marketed capsule (Celebrex), and the complex were performed using USP dissolution apparatus I for pure celecoxib and the complex and apparatus II for the capsule in distilled water. The highest solubility (48.32 mg/mL) as well as percent dissolution (90.54%) of celecoxib was obtained with the caffeine-celecoxib complex. The results for solubility and dissolution were highly significant as compared to pure celecoxib and the marketed capsule (p < 0.01). These results suggest that caffeine is a promising complexing agent for solubility as well as dissolution enhancement of the poorly soluble drug celecoxib.

Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain.

PubMed

Volkow, N D; Wang, G-J; Logan, J; Alexoff, D; Fowler, J S; Thanos, P K; Wong, C; Casado, V; Ferre, S; Tomasi, D

2015-04-14

Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A2A receptors (A2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [(11)C]raclopride (DA D2/D3 receptor radioligand sensitive to endogenous DA) to assess if caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300 mg p.o.) significantly increased the availability of D2/D3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D2/D3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D2/D3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D2/D3 receptor availability. Instead, we interpret our findings to reflect an increase in D2/D3 receptor levels in striatum with caffeine (or changes in affinity). The association between increases in D2/D3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D2/D3 receptors.

Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain

PubMed Central

Volkow, N D; Wang, G-J; Logan, J; Alexoff, D; Fowler, J S; Thanos, P K; Wong, C; Casado, V; Ferre, S; Tomasi, D

2015-01-01

Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A2A receptors (A2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [11C]raclopride (DA D2/D3 receptor radioligand sensitive to endogenous DA) to assess if caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300 mg p.o.) significantly increased the availability of D2/D3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D2/D3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D2/D3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D2/D3 receptor availability. Instead, we interpret our findings to reflect an increase in D2/D3 receptor levels in striatum with caffeine (or changes in affinity). The association between increases in D2/D3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D2/D3 receptors. PMID:25871974

Caffeine increases striatal dopamine D 2/D 3 receptor availability in the human brain

DOE PAGES

Volkow, N. D.; Wang, G. -J.; Logan, J.; ...

2015-04-14

Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A 2A receptors (A 2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [ 11C]raclopride (DA D 2/D 3 receptor radioligand sensitive to endogenous DA) to assess ifmore » caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300mg p.o.) significantly increased the availability of D 2/D 3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D 2/D 3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D 2/D 3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D 2/D 3 receptor availability. Instead, we interpret our findings to reflect an increase in D 2/D 3 receptor levels in striatum with caffeine (or changes in affinity). Furthermore, the association between increases in D 2/D 3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D 2/D 3 receptors.« less

Differential effects of caffeine on hair shaft elongation, matrix and outer root sheath keratinocyte proliferation, and transforming growth factor-β2/insulin-like growth factor-1-mediated regulation of the hair cycle in male and female human hair follicles in vitro.

PubMed

Fischer, T W; Herczeg-Lisztes, E; Funk, W; Zillikens, D; Bíró, T; Paus, R

2014-11-01

Caffeine reportedly counteracts the suppression of hair shaft production by testosterone in organ-cultured male human hair follicles (HFs). We aimed to investigate the impact of caffeine (i) on additional key hair growth parameters, (ii) on major hair growth regulatory factors and (iii) on male vs. female HFs in the presence of testosterone. Microdissected male and female human scalp HFs were treated in serum-free organ culture for 120 h with testosterone alone (0·5 μg mL(-1)) or in combination with caffeine (0·005-0·0005%). The following effects on hair shaft elongation were evaluated by quantitative (immuno)histomorphometry: HF cycling (anagen-catagen transition); hair matrix keratinocyte proliferation; expression of a key catagen inducer, transforming growth factor (TGF)-β2; and expression of the anagen-prolonging insulin-like growth factor (IGF)-1. Caffeine effects were further investigated in human outer root sheath keratinocytes (ORSKs). Caffeine enhanced hair shaft elongation, prolonged anagen duration and stimulated hair matrix keratinocyte proliferation. Female HFs showed higher sensitivity to caffeine than male HFs. Caffeine counteracted testosterone-enhanced TGF-β2 protein expression in male HFs. In female HFs, testosterone failed to induce TGF-β2 expression, while caffeine reduced it. In male and female HFs, caffeine enhanced IGF-1 protein expression. In ORSKs, caffeine stimulated cell proliferation, inhibited apoptosis/necrosis, and upregulated IGF-1 gene expression and protein secretion, while TGF-β2 protein secretion was downregulated. This study reveals new growth-promoting effects of caffeine on human hair follicles in subjects of both sexes at different levels (molecular, cellular and organ). © 2014 British Association of Dermatologists.

Caffeine increases striatal dopamine D 2/D 3 receptor availability in the human brain

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

Volkow, N. D.; Wang, G. -J.; Logan, J.

Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A 2A receptors (A 2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [ 11C]raclopride (DA D 2/D 3 receptor radioligand sensitive to endogenous DA) to assess ifmore » caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300mg p.o.) significantly increased the availability of D 2/D 3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D 2/D 3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D 2/D 3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D 2/D 3 receptor availability. Instead, we interpret our findings to reflect an increase in D 2/D 3 receptor levels in striatum with caffeine (or changes in affinity). Furthermore, the association between increases in D 2/D 3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D 2/D 3 receptors.« less

Caffeine Toxicity Due to Supplement Use in Caffeine--Naïve Individual: A Cautionary Tale.

PubMed

Lystrup, Robert M; Leggit, Jeffery C

2015-08-01

Thousands of military members self-medicate with dietary supplements containing unknown quantities of pharmacologically active compounds. These poorly regulated substances can cause real harm to the military population, especially when they contain stimulants such as caffeine. When taken regularly, caffeine has several performance-enhancing benefits. However, when used excessively or in vulnerable populations, caffeine can cause several unwanted side effects such as nervousness, sensory disturbances, insomnia, arrhythmia, excitability, inattentiveness, restlessness, mood changes, gastrointestinal disturbances, and even psychosis. Vulnerable patients include the caffeine-naïve, physiologically stressed, young, and mentally ill patients. One such case describes a caffeine-naïve service member who suffered an adverse reaction after taking an allegedly moderate dose of caffeine from a pill he obtained from a teammate. This case highlights the importance of supplement awareness among service members, increased provider vigilance, third party verification, and enhanced regulation on the approval and marketing of dietary supplements. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

Investigation of the binding sites and orientation of caffeine on human serum albumin by surface-enhanced Raman scattering and molecular docking

NASA Astrophysics Data System (ADS)

Wang, Weinan; Zhang, Wei; Duan, Yaokai; Jiang, Yong; Zhang, Liangren; Zhao, Bing; Tu, Pengfei

2013-11-01

Fluorescence, normal Raman and surface-enhanced Raman scattering (SERS) were introduced to explore the absorptive geometry of caffeine on Human Serum Albumin (HSA) at physiological condition. The molecular docking was also employed to make a better understanding of the interaction between caffeine and HSA as well as to elucidate the detailed information of the major binding site. The results showed that caffeine could bind to HSA via the hydrophobic force of aromatic stacking and the main binding group on caffeine could be the pyrimidine ring. In addition, a consecutive set of changes in the orientation of caffeine molecule had been demonstrated during the process of caffeine binding to HSA, and the primary binding site was considered to be a hydrophobic cavity formed by Leu198, Lys199, Ser202, Phe211, Trp214, Val344, Ser454 and Leu481 in domain II.

Enhancement of nootropic effect of duloxetine and bupropion by caffeine in mice.

PubMed

Kale, Pravin Popatrao; Addepalli, Veeranjaneyulu

2015-01-01

The existing evidence suggests an association between depression and memory impairment. The objective of present study was to assess the effect of low dose caffeine with duloxetine and bupropion on memory. Mice were divided randomly into seven groups. Intra-peritoneal treatment of normal saline (10 ml/kg), caffeine (10 mg/kg), duloxetine (10 mg/kg), bupropion alone (10 mg/kg), caffeine + duloxetine (5 mg/kg, each), caffeine + bupropion (5 mg/kg, each), and bupropion + duloxetine (5 mg/kg, each) were given to groups I-VII, respectively. Elevated plus maze was used to evaluate transfer latency (TL) and Morris water maze was used to estimate the time spent in target quadrant. Caffeine with duloxetine treated group was better than other combination treated groups in terms of a significant decrease in TL and increase in the time spent in target quadrant recorded. Combining lower dose of caffeine with duloxetine may enhance cognitive benefits than respective monotherapies.

Caffeine: sleep and daytime sleepiness.

PubMed

Roehrs, Timothy; Roth, Thomas

2008-04-01

Caffeine is one of the most widely consumed psychoactive substances and it has profound effects on sleep and wake function. Laboratory studies have documented its sleep-disruptive effects. It clearly enhances alertness and performance in studies with explicit sleep deprivation, restriction, or circadian sleep schedule reversals. But, under conditions of habitual sleep the evidence indicates that caffeine, rather then enhancing performance, is merely restoring performance degraded by sleepiness. The sleepiness and degraded function may be due to basal sleep insufficiency, circadian sleep schedule reversals, rebound sleepiness, and/or a withdrawal syndrome after the acute, over-night, caffeine discontinuation typical of most studies. Studies have shown that caffeine dependence develops at relatively low daily doses and after short periods of regular daily use. Large sample and population-based studies indicate that regular daily dietary caffeine intake is associated with disturbed sleep and associated daytime sleepiness. Further, children and adolescents, while reporting lower daily, weight-corrected caffeine intake, similarly experience sleep disturbance and daytime sleepiness associated with their caffeine use. The risks to sleep and alertness of regular caffeine use are greatly underestimated by both the general population and physicians.

Action of caffeine on x-irradiated HeLa cells. VII. Evidence that caffeine enhances expression of potentially lethal radiation damage

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

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

1984-12-01

HeLa cells irradiated with 2 Gy of 220-kV X rays suffer a 60-70% loss of colony-forming ability which is increased to 90% by postirradiation treatment with 10 mM caffeine for 6 hr. The detailed postirradiation patterns of cell death and sister-cell fusion in such cultures and in cultures in which the colony-forming ability was brought to about the same level by treatment with a larger (4 Gy) X-ray dose alone or by longer (48 hr) treatment with 10 mM caffeine alone were recorded by time-lapse cinemicrography. Because the patterns of cell death and fusion differ radically in irradiated and inmore » caffeine-treated cultures, the response of the additional cells killed by the combined treatment can be identified as X-ray induced rather than caffeine induced. The appearance of cultures after several days of incubation confirms the similarity of the post-treatment patterns of proliferation in cultures suffering enhanced killing to those occurring in cultures treated with larger doses of X rays alone. It is concluded that x rays do not sensitize cells to caffeine, but rather that caffeine enhanced the expression of potentially lethal radiation-induced damage.« less

Use of coffee, caffeinated drinks and caffeine tablets for cognitive enhancement in pupils and students in Germany.

PubMed

Franke, A G; Christmann, M; Bonertz, C; Fellgiebel, A; Huss, M; Lieb, K

2011-11-01

Substance use for cognitive enhancement (CE) is a topic of increasing importance. There are only few data about substances, prevalence rates and factors associated with CE. The aim of this study was to assess first data about the use of coffee, caffeinated drinks and caffeine tablets for CE at school and university. A self-report questionnaire was developed to analyze 1 547 pupils and students about their use of coffee, caffeine tablets, and caffeinated drinks for CE and factors associated with this use. Lifetime, past-year, and past-month prevalence for the use of coffee for CE was 53.2%, 8.5%, and 6.3%, for the use of caffeinated drinks 39%, 10.7%, and 6.3%, and for the use of caffeine tablets 10.5%, 3.8%, and 0.8%. Use of caffeinated substances for CE was influenced by gender and school grades. The use of coffee and caffeinated drinks for CE was found to be widespread in the surveyed population. Although the use of caffeine tablets was found to be smaller than the above-mentioned means, it still indicates a relatively high disposition for using tablets for purposes of CE. © Georg Thieme Verlag KG Stuttgart · New York.

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.

Caffeine Use and Extroversion.

ERIC Educational Resources Information Center

Landrum, R. Eric; Meliska, Charles J.

Some research on the stimulant effect of caffeine suggests that the amount of behavioral enhancement produced by caffeine may depend on subjects' prior experience with the task and the drug. A study was undertaken to test whether prior experience with a task while under the influence of caffeine would facilitate performance of that task. Male…

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…

Conditioned Reinforcement and Locomotor Activating Effects of Caffeine and Ethanol Combinations in Mice

PubMed Central

Hilbert, Megan L.T.; May, Christina E.; Griffin, William C.

2013-01-01

A growing trend among ethanol drinkers, especially young adults, is to combine caffeinated energy drinks with ethanol during a drinking episode. The primary active ingredient of these mixers is caffeine, which may significantly interact with ethanol. We tested the two hypotheses that caffeine would enhance ethanol-conditioned place preference and also enhance ethanol-stimulated locomotor activity. The interactive pharmacology of ethanol and caffeine was examined in C57BL/6J (B6) mice in a conditioned place preference procedure with 1.75 g/kg ethanol and 3 mg/kg caffeine. Additionally, we used B6 mice to evaluate ethanol/caffeine combinations on locomotor activity using 3 doses of ethanol (1.75, 2.5 and 3.25 g/kg) and 2 two doses of caffeine (3 and 15 mg/kg). Both ethanol and caffeine administered alone increased preference for the drug paired side, though the effect of caffeine was more modest than that of ethanol. The drug combination produced significant place preference itself, but this was not greater than that for ethanol alone. Additionally, the combination of caffeine and ethanol significantly increased locomotion compared to giving either drug alone. The effect was strongest with a stimulatory dose of ethanol (1.75 g/kg) and waned with increasing doses of ethanol. Thus, combinations of caffeine and ethanol had significant conditioned reinforcing and locomotor activating effects in mice. PMID:23872371

Effects of a combination of 3,4-methylenedioxymeth amphetamine and caffeine on real time stimulated dopamine release in the rat striatum: Studies using fast cyclic voltammetry.

PubMed

O'Connor, J J; O'Boyle, K M; Lowry, J P

2018-04-15

It is well documented that caffeine exacerbates the hyperthermia associated with acute exposure to 3,4-methylenedioxymethamphetamine (MDMA) in rats. Previous reports have also indicated that MDMA-related enhancement of dopamine release is exacerbated in the presence of caffeine. In the present study we have examined whether the effects of MDMA on real-time stimulated dopamine release, in the absence of uptake inhibition, are accentuated in the presence of caffeine. Isolated striatal slices from adult male Wistar rats were treated acutely with MDMA, caffeine, or a combination, and their effects on single and 5pulse stimulated dopamine release monitored using the technique of fast cyclic voltammetry. Caffeine at 10 or 100μM had no significant effect on single pulse stimulated dopamine release. However 100μM caffeine caused a significant peak increase in 5pulse stimulated dopamine release. Both 1 and 30μM MDMA gave rise to a significant increase in both single and 5-pulse dopamine release and reuptake. A combination of 100μM caffeine and 1 or 30μM MDMA did not significantly enhance the effects of MDMA on single or 5pulse dopamine release and reuptake when compared to that applied alone. Utilizing single action potential dependent dopamine release, these results do not demonstrate a caffeine-enhanced MDMA-induced dopamine release. Copyright © 2017 Elsevier B.V. All rights reserved.

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

The effect of caffeine on skeletal muscle anabolic signaling and hypertrophy.

PubMed

Moore, Timothy M; Mortensen, Xavier M; Ashby, Conrad K; Harris, Alexander M; Kump, Karson J; Laird, David W; Adams, Aaron J; Bray, Jeremy K; Chen, Ting; Thomson, David M

2017-06-01

Caffeine is a widely consumed stimulant with the potential to enhance physical performance through multiple mechanisms. However, recent in vitro findings have suggested that caffeine may block skeletal muscle anabolic signaling through AMP-activated protein kinase (AMPK)-mediated inhibition of mechanistic target of rapamycin (mTOR) signaling pathway. This could negatively affect protein synthesis and the capacity for muscle growth. The primary purpose of this study was to assess the effect of caffeine on in vivo AMPK and mTOR pathway signaling, protein synthesis, and muscle growth. In cultured C2C12 muscle cells, physiological levels of caffeine failed to impact mTOR activation or myoblast proliferation or differentiation. We found that caffeine administration to mice did not significantly enhance the phosphorylation of AMPK or inhibit signaling proteins downstream of mTOR (p70S6k, S6, or 4EBP1) or protein synthesis after a bout of electrically stimulated contractions. Skeletal muscle-specific knockout of LKB1, the primary AMPK activator in skeletal muscle, on the other hand, eliminated AMPK activation by contractions and enhanced S6k, S6, and 4EBP1 activation before and after contractions. In rats, the addition of caffeine did not affect plantaris hypertrophy induced by the tenotomy of the gastrocnemius and soleus muscles. In conclusion, caffeine administration does not impair skeletal muscle load-induced mTOR signaling, protein synthesis, or muscle hypertrophy.

Enhancement of nootropic effect of duloxetine and bupropion by caffeine in mice

PubMed Central

Kale, Pravin Popatrao; Addepalli, Veeranjaneyulu

2015-01-01

Objective: The existing evidence suggests an association between depression and memory impairment. The objective of present study was to assess the effect of low dose caffeine with duloxetine and bupropion on memory. Materials and Methods: Mice were divided randomly into seven groups. Intra-peritoneal treatment of normal saline (10 ml/kg), caffeine (10 mg/kg), duloxetine (10 mg/kg), bupropion alone (10 mg/kg), caffeine + duloxetine (5 mg/kg, each), caffeine + bupropion (5 mg/kg, each), and bupropion + duloxetine (5 mg/kg, each) were given to groups I-VII, respectively. Elevated plus maze was used to evaluate transfer latency (TL) and Morris water maze was used to estimate the time spent in target quadrant. Results: Caffeine with duloxetine treated group was better than other combination treated groups in terms of a significant decrease in TL and increase in the time spent in target quadrant recorded. Conclusion: Combining lower dose of caffeine with duloxetine may enhance cognitive benefits than respective monotherapies. PMID:25878382

Effects of Caffeine on Olfactory Learning in Crickets.

PubMed

Sugimachi, Seigo; Matsumoto, Yukihisa; Mizunami, Makoto; Okada, Jiro

2016-10-01

Caffeine is a plant-derived alkaloid that is generally known as a central nervous system (CNS) stimulant. In order to examine the effects of caffeine on higher CNS functions in insects, we used an appetitive olfactory learning paradigm for the cricket Gryllus bimaculatus. Crickets can form significant long-term memories (LTMs) after repetitive training sessions, during which they associate a conditioned stimulus (CS: odor) with an unconditioned stimulus (US: reward). Administration of hemolymphal injections of caffeine established LTM after only single-trial conditioning over a wide range of caffeine dosages (1.6 µµg/kg to 39 mg/kg). We investigated the physiological mechanisms underlying this enhancement of olfactory learning performance pharmacologically, focusing on three major physiological roles of caffeine: 1) inhibition of phosphodiesterase (PDE), 2) agonism of ryanodine receptors, and 3) antagonism of adenosine receptors. Application of drugs relevant to these actions resulted in significant effects on LTM formation. These results suggest that externally applied caffeine enhances LTM formation in insect olfactory learning via multiple cellular mechanisms.

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.

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.

A Comparison of Blue Light and Caffeine Effects on Cognitive Function and Alertness in Humans

PubMed Central

Beaven, C. Martyn; Ekström, Johan

2013-01-01

The alerting effects of both caffeine and short wavelength (blue) light have been consistently reported. The ability of blue light to enhance alertness and cognitive function via non-image forming neuropathways have been suggested as a non-pharmacological countermeasure for drowsiness across a range of occupational settings. Here we compare and contrast the alerting and psychomotor effects of 240 mg of caffeine and a 1-h dose of ~40 lx blue light in a non-athletic population. Twenty-one healthy subjects performed a computer-based psychomotor vigilance test before and after each of four randomly assigned trial conditions performed on different days: white light/placebo; white light/240 mg caffeine; blue light/placebo; blue light/240 mg caffeine. The Karolinska Sleepiness Scale was used to assess subjective measures of alertness. Both the caffeine only and blue light only conditions enhanced accuracy in a visual reaction test requiring a decision and an additive effect was observed with respect to the fastest reaction times. However, in a test of executive function, where a distraction was included, caffeine exerted a negative effect on accuracy. Furthermore, the blue light only condition consistently outperformed caffeine when both congruent and incongruent distractions were presented. The visual reactions in the absence of a decision or distraction were also enhanced in the blue light only condition and this effect was most prominent in the blue-eyed participants. Overall, blue light and caffeine demonstrated distinct effects on aspects of psychomotor function and have the potential to positively influence a range of settings where cognitive function and alertness are important. Specifically, despite the widespread use of caffeine in competitive sporting environments, the possible impact of blue light has received no research attention. PMID:24282477

Caffeine may enhance orthodontic tooth movement through increasing osteoclastogenesis induced by periodontal ligament cells under compression.

PubMed

Yi, Jianru; Yan, Boxi; Li, Meile; Wang, Yu; Zheng, Wei; Li, Yu; Zhao, Zhihe

2016-04-01

Caffeine is the kernel component of coffee and has multiple effects on bone metabolism. Here we aimed to investigate the effects of caffeine intake on orthodontic tooth movement (OTM). (1) In the in vivo study, two groups comprising 15 randomly assigned rats each underwent orthodontic treatment. One group ingested caffeine at 25mg/kg body weight per day and the other, plain water. After 3 weeks, the degree of tooth movement and effect on the periodontium were assessed. (2) In the in vitro study, we established a model mimicking the essential bioprocess of OTM, which contained a periodontal ligament tissue model (PDLtm), and a co-culture system of osteoblasts (OBs) and osteoclast precursors (pre-OCs). After being subjected to static compressive force with or without caffeine administration, the conditioned media from the PDLtm were used for the OB/pre-OC co-cultures to induce osteoclastogenesis. (1) In vivo, the caffeine group displayed a significantly greater rate of tooth movement than the control. The alveolar bone mineral density and bone volume fraction were similar between the two groups; however, immunohistochemical staining showed that the caffeine group had significantly more TRAP(+) osteoclasts and higher RANKL expression in the compressed periodontium. (2) In vitro, caffeine at 0.01mM significantly enhanced the compression-induced expression of RANKL and COX-2, as well as prostaglandin E2 production in the PDLtm. Furthermore, the "caffeine+compression"-conditioned media induced significantly more TRAP(+) OC formation when compared with compression alone. Daily intake of caffeine, at least at some specific dosage, may enhance OTM through increasing osteoclastogenesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Effects of Caffeine on Vertical Jump Height and Execution in Collegiate Athletes.

PubMed

Bloms, Lucas P; Fitzgerald, John S; Short, Martin W; Whitehead, James R

2016-07-01

Bloms, LP, Fitzgerald, JS, Short, MW, and Whitehead, JR. The effects of caffeine on vertical jump height and execution in collegiate athletes. J Strength Cond Res 30(7): 1855-1861, 2016-Caffeine ingestion elicits a variety of physiological effects that may be beneficial to maximal-intensity exercise performance, although its effectiveness and physical mechanism of action enhancing ballistic task performance are unclear. The purpose of this study was to examine the effects of caffeine ingestion on vertical jump height and jump execution in Division I collegiate athletes. The study used a single-blind, randomized, crossover design. Athletes (n = 25) consumed either caffeine (5 mg·kg) or placebo. After a 60-minute waiting period, athletes performed 3 squat jumps (SJ) and 3 countermovement jumps (CMJ) while standing on a force platform. Jump height and execution variables were calculated from mechanography data. In comparison with placebo, caffeine increased SJ height (32.8 ± 6.2 vs. 34.5 ± 6.7 cm; p = 0.001) and CMJ height (36.4 ± 6.9 vs. 37.9 ± 7.4 cm; p = 0.001). Peak force (p = 0.032) and average rate of force development (p = 0.037) were increased during the CMJ in the caffeine trail compared with the control. Time to half peak force was the only execution variable improved with caffeine (p = 0.019) during the SJ. It seems that caffeine affects both height and execution of jumping. Our data indicate that the physical mechanism of jump enhancement is increased peak force production or rate of force development during jumping depending on technique. The physical mechanism of jump enhancement suggests that the ergogenic effects of caffeine may transfer to other ballistic tasks involving the lower-body musculature in collegiate athletes.

Caffeine ingestion enhances Wingate performance: a meta-analysis.

PubMed

Grgic, Jozo

2018-03-01

The positive effects of caffeine ingestion on aerobic performance are well-established; however, recent findings are suggesting that caffeine ingestion might also enhance components of anaerobic performance. A commonly used test of anaerobic performance and power output is the 30-second Wingate test. Several studies explored the effects of caffeine ingestion on Wingate performance, with equivocal findings. To elucidate this topic, this paper aims to determine the effects of caffeine ingestion on Wingate performance using meta-analytic statistical techniques. Following a search through PubMed/MEDLINE, Scopus, and SportDiscus ® , 16 studies were found meeting the inclusion criteria (pooled number of participants = 246). Random-effects meta-analysis of standardized mean differences (SMD) for peak power output and mean power output was performed. Study quality was assessed using the modified version of the PEDro checklist. Results of the meta-analysis indicated a significant difference (p = .005) between the placebo and caffeine trials on mean power output with SMD values of small magnitude (0.18; 95% confidence interval: 0.05, 0.31; +3%). The meta-analysis performed for peak power output indicated a significant difference (p = .006) between the placebo and caffeine trials (SMD = 0.27; 95% confidence interval: 0.08, 0.47 [moderate magnitude]; +4%). The results from the PEDro checklist indicated that, in general, studies are of good and excellent methodological quality. This meta-analysis adds on to the current body of evidence showing that caffeine ingestion can also enhance components of anaerobic performance. The results presented herein may be helpful for developing more efficient evidence-based recommendations regarding caffeine supplementation.

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.

Enhanced Brain Amyloid-β Clearance by Rifampicin and Caffeine as a Possible Protective Mechanism Against Alzheimer’s Disease

PubMed Central

Qosa, Hisham; Abuznait, Alaa H.; Hill, Ronald A.; Kaddoumi, Amal

2014-01-01

Rifampicin and caffeine are widely used drugs with reported protective effect against Alzheimer’s disease (AD). However, the mechanism underlying this effect is incompletely understood. In this study, we have hypothesized that enhanced amyloid-β (Aβ) clearance from the brain across the blood-brain barrier (BBB) of wild-type mice treated with rifampicin or caffeine is caused by both drugs potential to upregulate low-density lipoprotein receptor related protein-1 (LRP1) and/or P-glycoprotein (P-gp) at the BBB. Expression studies of LRP1 and P-gp in brain endothelial cells and isolated mice brain microvessels following treatment with rifampicin or caffeine demonstrated both drugs as P-gp inducers, and only rifampicin as an LRP1 inducer. Also, brain efflux index (BEI%) studies conducted on C57BL/6 mice treated with either drug to study alterations in Aβ clearance demonstrated the BEI% of Aβ in rifampicin (82.4 ± 4.3%) and caffeine (80.4 ± 4.8%) treated mice were significantly higher than those of control mice (62.4 ±6.1%, p <0.01). LRP1 and P-gp inhibition studies confirmed the importance of both proteins to the clearance of Aβ, and that enhanced clearance following drugs treatment was caused by LRP1 and/or P-gp upregulation at the mouse BBB. Furthermore, our results provided evidence for the presence of a yet to be identified transporter/receptor that plays significant role in Aβ clearance and is upregulated by caffeine and rifampicin. In conclusion, our results demonstrated the upregulation of LRP1 and P-gp at the BBB by rifampicin and caffeine enhanced brain Aβ clearance, and this effect could explain, at least in part, the protective effect of rifampicin and caffeine against AD. PMID:22504320

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.

Effects of Adolescent Caffeine Consumption on Cocaine Sensitivity

PubMed Central

O'Neill, Casey E; Levis, Sophia C; Schreiner, Drew C; Amat, Jose; Maier, Steven F; Bachtell, Ryan K

2015-01-01

Caffeine is the most commonly used psychoactive substance, and consumption by adolescents has risen markedly in recent years. We identified the effects of adolescent caffeine consumption on cocaine sensitivity and determined neurobiological changes within the nucleus accumbens (NAc) that may underlie caffeine-induced hypersensitivity to cocaine. Male Sprague-Dawley rats consumed caffeine (0.3 g/l) or water for 28 days during adolescence (postnatal day 28–55; P28–P55) or adulthood (P67–P94). Testing occurred in the absence of caffeine during adulthood (P62–82 or P101–121). Cocaine-induced and quinpirole (D2 receptor agonist)-induced locomotion was enhanced in rats that consumed caffeine during adolescence. Adolescent consumption of caffeine also enhanced the development of a conditioned place preference at a sub-threshold dose of cocaine (7.5 mg/kg, i.p.). These behavioral changes were not observed in adults consuming caffeine for an equivalent period of time. Sucrose preferences were not altered in rats that consumed caffeine during adolescence, suggesting there are no differences in natural reward. Caffeine consumption during adolescence reduced basal dopamine levels and augmented dopamine release in the NAc in response to cocaine (5 mg/kg, i.p.). Caffeine consumption during adolescence also increased the expression of the dopamine D2 receptor, dopamine transporter, and adenosine A1 receptor and decreased adenosine A2A receptor expression in the NAc. Consumption of caffeine during adulthood increased adenosine A1 receptor expression in the NAc, but no other protein expression changes were observed. Together these findings suggest that caffeine consumption during adolescence produced changes in the NAc that are evident in adulthood and may contribute to increases in cocaine-mediated behaviors. PMID:25328052

The pH dependent Raman spectroscopic study of caffeine

NASA Astrophysics Data System (ADS)

Kang, Jian; Gu, Huaimin; Zhong, Liang; Hu, Yongjun; Liu, Fang

2011-02-01

First of all the surface enhanced Raman spectroscopy (SERS) and normal Raman spectra of caffeine aqueous solution were obtained at different pH values. In order to obtain the detailed vibrational assignments of the Raman spectroscopy, the geometry of caffeine molecule was optimized by density functional theory (DFT) calculation. By comparing the SERS of caffeine with its normal spectra at different pH values; it is concluded that pH value can dramatically affect the SERS of caffeine, but barely affect the normal Raman spectrum of caffeine aqueous solution. It can essentially affect the reorientation of caffeine molecule to the Ag colloid surface, but cannot impact the vibration of functional groups and chemical bonds in caffeine molecule.

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

Effects of dietary caffeine on mood when rested and sleep restricted.

PubMed

James, Jack E; Gregg, M Elizabeth

2004-07-01

Prolonged use of caffeine can lead to physical dependence evidenced by characteristic withdrawal symptoms during abstinence. Debate exists as to whether mood enhancement by caffeine represents a net effect or merely the restoration of abstinence-induced mood decrements. One aim of this study was to determine the net effects on mood of dietary caffeine compared with prolonged abstinence. In addition, the study aimed to determine whether caffeine restores mood degraded by a non-caffeine source, namely, sleep restriction. A double-blind placebo-controlled cross-over design was employed in which 48 male and female volunteers alternated weekly between ingesting placebo and caffeine (1.75 mg/kg) three times daily for 4 consecutive weeks, while being either rested or sleep restricted. Mood was assessed using a computerized version of the profile of mood states (POMS), giving scores for overall mood and six mood dimensions. Gender had small effects on mood, whereas all mood dimensions were markedly adversely affected by sleep restriction. Caffeine had no significant net enhancing effects on mood when participants were rested, and produced no net restorative effects when mood was degraded by sleep restriction. On the contrary, caffeine-induced decrements in mood were observed during both conditions of rest and sleep restriction. Copyright 2004 John Wiley & Sons, Ltd.

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.

Chronic Caffeine Treatment Protects Against α-Synucleinopathy by Reestablishing Autophagy Activity in the Mouse Striatum.

PubMed

Luan, Yanan; Ren, Xiangpeng; Zheng, Wu; Zeng, Zhenhai; Guo, Yingzi; Hou, Zhidong; Guo, Wei; Chen, Xingjun; Li, Fei; Chen, Jiang-Fan

2018-01-01

Despite converging epidemiological evidence for the inverse relationship of regular caffeine consumption and risk of developing Parkinson's disease (PD) with animal studies demonstrating protective effect of caffeine in various neurotoxin models of PD, whether caffeine can protect against mutant α-synuclein (α-Syn) A53T-induced neurotoxicity in intact animals has not been examined. Here, we determined the effect of chronic caffeine treatment using the α-Syn fibril model of PD by intra-striatal injection of preformed A53T α-Syn fibrils. We demonstrated that chronic caffeine treatment blunted a cascade of pathological events leading to α-synucleinopathy, including pSer129α-Syn-rich aggregates, apoptotic neuronal cell death, microglia, and astroglia reactivation. Importantly, chronic caffeine treatment did not affect autophagy processes in the normal striatum, but selectively reversed α-Syn-induced defects in macroautophagy (by enhancing microtubule-associated protein 1 light chain 3, and reducing the receptor protein sequestosome 1, SQSTM1/p62) and chaperone-mediated autophagy (CMA, by enhancing LAMP2A). These findings support that caffeine-a strongly protective environment factor as suggested by epidemiological evidence-may represent a novel pharmacological therapy for PD by targeting autophagy pathway.

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.

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

Activation of Peripheral κ-Opioid Receptors Normalizes Caffeine Effects Modified in Nicotine-Dependent Rats during Nicotine Withdrawal.

PubMed

Sudakov, S K; Bogdanova, N G

2016-10-01

The study examined the effect of peripheral (intragastric) ICI-204,448, an agonist of gastric κ-opioid receptors, on the psychostimulating and anxiolytic effects of caffeine in nicotinedependent rats at the stage of nicotine withdrawal. In these rats, the effects of caffeine (10 mg/kg) were perverted. In nicotine-dependent rats, caffeine produced an anxiolytic effect accompanied by pronounced stimulation of motor activity, in contrast to anxiogenic effect induced by caffeine in intact rats without nicotine dependence. During nicotine withdrawal, nicotine-dependent rats demonstrated enhanced sensitivity to nicotine. Intragastric administration of κ-opioid receptor agonist ICI-204,448 normalized the effect of caffeine in nicotinedependent rats. We have previously demonstrated that activation of peripheral κ-opioid receptors inhibited central κ-opioid activity and eliminated manifestations of nicotine withdrawal syndrome in nicotine-dependent rats, e.g. metabolism activation, stimulation of motor activity, and enhancement of food consumption. In its turn, inhibition of central κ-opioid structures activates the brain adenosine system, which can attenuate the caffeine-induced effects in nicotine-dependent rats.

Caffeine Concentrations in Coffee, Tea, Chocolate, and Energy Drink Flavored E-liquids

PubMed Central

Lisko, Joseph G.; Lee, Grace E.; Kimbrell, J. Brett; Rybak, Michael E.; Valentin-Blasini, Liza; Watson, Clifford H.

2017-01-01

Introduction Most electronic cigarettes (e-cigarettes) contain a solution of propylene glycol/glycerin and nicotine, as well as flavors. E-cigarettes and their associated e-liquids are available in numerous flavor varieties. A subset of the flavor varieties include coffee, tea, chocolate, and energy drink, which, in beverage form, are commonly recognized sources of caffeine. Recently, some manufacturers have begun marketing e-liquid products as energy enhancers that contain caffeine as an additive. Methods A Gas Chromatography-Mass Spectrometry (GC-MS) method for the quantitation of caffeine in e-liquids was developed, optimized and validated. The method was then applied to assess caffeine concentrations in 44 flavored e-liquids from cartridges, disposables, and refill solutions. Products chosen were flavors traditionally associated with caffeine (ie, coffee, tea, chocolate, and energy drink), marketed as energy boosters, or labeled as caffeine-containing by the manufacturer. Results Caffeine was detected in 42% of coffee-flavored products, 66% of tea-flavored products, and 50% of chocolate-flavored e-liquids (limit of detection [LOD] – 0.04 μg/g). Detectable caffeine concentrations ranged from 3.3 μg/g to 703 μg/g. Energy drink-flavored products did not contain detectable concentrations of caffeine. Eleven of 12 products marketed as energy enhancers contained caffeine, though in widely varying concentrations (31.7 μg/g to 9290 μg/g). Conclusions E-liquid flavors commonly associated with caffeine content like coffee, tea, chocolate, and energy drink often contained caffeine, but at concentrations significantly lower than their dietary counterparts. Estimated daily exposures from all e-cigarette products containing caffeine were much less than ingestion of traditional caffeinated beverages like coffee. Implications This study presents an optimized and validated method for the measurement of caffeine in e-liquids. The method is applicable to all e-liquid matrices and could potentially be used to ensure regulatory compliance for those geographic regions that forbid caffeine in e-cigarette products. The application of the method shows that caffeine concentrations and estimated total caffeine exposure from e-cigarette products is significantly lower than oral intake from beverages. However, because very little is known about the effects of caffeine inhalation, e-cigarette users should proceed with caution when using caffeine containing e-cigarette products. Further research is necessary to determine associated effects from inhaling caffeine. PMID:27613945

The acute effects of a caffeine-containing supplement on strength, muscular endurance, and anaerobic capabilities.

PubMed

Beck, Travis W; Housh, Terry J; Schmidt, Richard J; Johnson, Glen O; Housh, Dona J; Coburn, Jared W; Malek, Moh H

2006-08-01

The purpose of this study was to examine the acute effects of a caffeine-containing supplement on upper- and lower-body strength and muscular endurance as well as anaerobic capabilities. Thirty-seven resistance-trained men (mean +/- SD, age: 21 +/- 2 years) volunteered to participate in this study. On the first laboratory visit, the subjects performed 2 Wingate Anaerobic Tests (WAnTs) to determine peak power (PP) and mean power (MP), as well as tests for 1 repetition maximum (1RM), dynamic constant external resistance strength, and muscular endurance (TOTV; total volume of weight lifted during an endurance test with 80% of the 1RM) on the bilateral leg extension (LE) and free-weight bench press (BP) exercises. Following a minimum of 48 hours of rest, the subjects returned to the laboratory for the second testing session and were randomly assigned to 1 of 2 groups: a supplement group (SUPP; n = 17), which ingested a caffeine-containing supplement, or a placebo group (PLAC; n = 20), which ingested a cellulose placebo. One hour after ingesting either the caffeine-containing supplement or the placebo, the subjects performed 2 WAnTs and were tested for 1RM strength and muscular endurance on the LE and BP exercises. The results indicated that there was a significant (p < 0.05) increase in BP 1RM for the SUPP group, but not for the PLAC group. The caffeine-containing supplement had no effect, however, on LE 1RM, LE TOTV, BP TOTV, PP, and MP. Thus, the caffeine-containing supplement may be an effective supplement for increasing upper-body strength and, therefore, could be useful for competitive and recreational athletes who perform resistance training.

Cognition-Enhancing Drugs and Their Appropriateness for Aviation and Ground Troops: A Meta-Analysis

DTIC Science & Technology

2010-12-01

individuals is not approved by the Food and Drug Administration (FDA). Current indications include narcolepsy, obstructive sleep apnea/hypopnea syndrome, and...to caffeine and perceived effects of caffeine in moderate and high regular caffeine consumers . Psychopharmacology. 190: 469-477...J. 2004. The effect of caffeinated tube food on cognitive performance during fatigue/circadian desynchronosis. Brooks City-Base, TX

Dietary caffeine, performance and mood: enhancing and restorative effects after controlling for withdrawal reversal.

PubMed

James, Jack E; Gregg, M Elizabeth; Kane, Marian; Harte, Frances

2005-01-01

This study aimed to determine whether sustained (i.e. dietary) use of caffeine has net effects on performance and mood compared with sustained abstinence, and whether dietary caffeine restores performance and mood adversely affected by sleep restriction. Participants (n = 96) alternated weekly between ingesting placebo and caffeine (1.75 mg/kg) three times daily for 4 consecutive weeks, while either rested or sleep restricted. Performance involved either a single task requiring sustained vigilance or a varied battery of brief psychomotor and cognitive tasks, and mood was assessed using the Profile of Mood States. Caffeine had no significant net enhancing effects for either performance or mood when participants were rested, and produced no net restorative effects when performance and mood were degraded by sleep restriction. Copyright 2005 S. Karger AG, Basel

Extraction and removal of caffeine from green tea by ultrasonic-enhanced supercritical fluid.

PubMed

Tang, Wei-Qiang; Li, Di-Cai; Lv, Yang-Xiao; Jiang, Jian-Guo

2010-05-01

Low-caffeine or caffeine-removed tea and its products are widely welcomed on market in recent years. In the present study, we adopt ultrasonic-enhanced supercritical fluid extraction process to remove caffeine from green tea. An orthogonal experiment (L16 (4(5))) was applied to optimize the best removal conditions. Extraction pressure, extraction time, power of ultrasound, moisture content, and temperature were the main factors to influence the removal rate of caffeine from green tea. The 5 factors chosen for the present investigation were based on the results of a single-factor test. The optimum removal conditions were determined as follows: extraction pressure of 30 MPa, temperature at 55 degrees C, time of 4 h, 30% moisture content, and ultrasound power of 100 W. Chromatogram and ultraviolet analysis of raw material and decaffeinates suggests that under optimized conditions, the caffeine of green tea was effectively removed and minished without damaging the structure of active ingredients in green tea.

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.

Stimulatory effect of oral administration of tea, coffee or caffeine on UVB-induced apoptosis in the epidermis of SKH-1 mice

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

Conney, Allan H.; Zhou, Sherry; Lee Maojung

Oral administration of green tea or a caffeine solution, but not decaffeinated green tea, inhibits UVB-induced complete carcinogenesis in SKH-1 mice. Oral administration of green tea, coffee or a caffeine solution for 2 weeks enhanced UVB-induced increases in apoptosis in the epidermis, but these treatments had no effect in non-UVB treated normal epidermis. Our results suggest that administration of green tea, coffee and caffeine may inhibit UVB-induced carcinogenesis - at least in part - by enhancing UVB-induced apoptosis. Plasma levels of caffeine observed after its oral administration at cancer-preventive dose levels were within the range observed in moderate coffee drinkers.more » Topical applications of caffeine to mice previously treated with UVB for 20 weeks (high risk mice without tumors) inhibited the formation of tumors and stimulated apoptosis in the tumors but not in areas of the epidermis away from tumors. The selective effects of caffeine administration to stimulate UVB-induced apoptosis or apoptosis in tumors but not in normal epidermis or in areas of the epidermis away from tumors is of considerable interest, but the reasons for the selective effects of caffeine on apoptosis in DNA damaged tissues are unknown. Further studies are needed to determine mechanisms of these effects of caffeine and to determine the effects of caffeine administration on sunlight-induced actinic keratoses and squamous cell carcinomas in humans.« less

Caffeine in the management of patients with headache.

PubMed

Lipton, Richard B; Diener, Hans-Christoph; Robbins, Matthew S; Garas, Sandy Yacoub; Patel, Ketu

2017-10-24

Caffeinated headache medications, either alone or in combination with other treatments, are widely used by patients with headache. Clinicians should be familiar with their use as well as the chemistry, pharmacology, dietary and medical sources, clinical benefits, and potential safety issues of caffeine. In this review, we consider the role of caffeine in the over-the-counter treatment of headache. The MEDLINE and Cochrane databases were searched by combining "caffeine" with the terms "headache," "migraine," and "tension-type." Studies that were not placebo-controlled or that involved medications available only with a prescription, as well as those not assessing patients with migraine and/or tension-type headache (TTH), were excluded. Compared with analgesic medication alone, combinations of caffeine with analgesic medications, including acetaminophen, acetylsalicylic acid, and ibuprofen, showed significantly improved efficacy in the treatment of patients with TTH or migraine, with favorable tolerability in the vast majority of patients. The most common adverse events were nervousness (6.5%), nausea (4.3%), abdominal pain/discomfort (4.1%), and dizziness (3.2%). This review provides evidence for the role of caffeine as an analgesic adjuvant in the acute treatment of primary headache with over-the-counter drugs, caffeine doses of 130 mg enhance the efficacy of analgesics in TTH and doses of ≥100 mg enhance benefits in migraine. Additional studies are needed to assess the relationship between caffeine dosing and clinical benefits in patients with TTH and migraine.

Caffeine restores regional brain activation in acute hypoglycaemia in healthy volunteers.

PubMed

Rosenthal, M J; Smith, D; Yaguez, L; Giampietro, V; Kerr, D; Bullmore, E; Brammer, M; Williams, S C R; Amiel, S A

2007-07-01

Caffeine enhances counterregulatory responses to acute hypoglycaemia. Our aim was to explore its effects on cortical function, which are not known at present. Regional brain activation during performance of the four-choice reaction time (4CRT) at different levels of complexity was measured using functional magnetic resonance imaging (fMRI) at euglycaemia (5 mmol/l) and hypoglycaemia (2.6 mmol/l) in the presence and absence of caffeine in six healthy right-handed men. During hypoglycaemia, caffeine enhanced adrenaline responses to hypoglycaemia (2.5 +/- 0.7 nmol/l to 4.0 +/- 1.0 nmol/l, P = 0.01) and restored the brain activation response to the non-cued 4CRT, the linear increases in regional brain activation associated with increased task complexity and the ability to respond to a cue that were lost in hypoglycaemia alone. Caffeine can sustain regional brain activation patterns lost in acute hypoglycaemia, with some restoration of cortical function and enhanced adrenaline responsiveness. A methodology has been established that may help in the development of therapies to protect against severe hypoglycaemia in insulin therapy for patients with diabetes and problematic hypoglycaemia.

Modulatory effects of caffeine on oxidative stress and anxiety-like behavior in ovariectomized rats.

PubMed

Caravan, Ionut; Sevastre Berghian, Alexandra; Moldovan, Remus; Decea, Nicoleta; Orasan, Remus; Filip, Gabriela Adriana

2016-09-01

Menopause is accompanied by enhanced oxidative stress and behavioral changes, effects attenuated by antioxidants. The aim of this study was to evaluate the effects of caffeine on behavior and oxidative stress in an experimental model of menopause. Female rats were divided into the following groups: sham-operated (CON), sham-operated and caffeine-treated (CAF), ovariectomized (OVX), ovariectomized and caffeine-treated (OVX+CAF). Caffeine (6 mg/kg) and vehicle were administered for 21 days (subchronic) and 42 days (chronic), using 2 experimental subsets. Behavioral tests and oxidative stress parameters in the blood, whole brain, and hippocampus were assessed. The subchronic administration of caffeine decreased the lipid peroxidation and improved the antioxidant defense in the blood and brain. The GSH/GGSG ratio in the brain was improved by chronic administration, with reduced activities of antioxidant enzymes and enhanced nitric oxide and malondialdehyde levels. In particular, the lipid peroxidation in the hippocampus decreased in both experiments. The rats became hyperactive after 21 days of treatment, but no effect was observed after chronic administration. In both experimental subsets, caffeine had anxiolytic effects as tested in elevated plus maze. The administration of low doses of caffeine, for a short period of time, may be a new therapeutic approach to modulating the oxidative stress and anxiety in menopause.

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 Promotes Global Spatial Processing in Habitual and Non-Habitual Caffeine Consumers

PubMed Central

Giles, Grace E.; Mahoney, Caroline R.; Brunyé, Tad T.; Taylor, Holly A.; Kanarek, Robin B.

2013-01-01

Information processing is generally biased toward global cues, often at the expense of local information. Equivocal extant data suggests that arousal states may accentuate either a local or global processing bias, at least partially dependent on the nature of the manipulation, task, and stimuli. To further differentiate the conditions responsible for such equivocal results we varied caffeine doses to alter physiological arousal states and measured their effect on tasks requiring the retrieval of local versus global spatial knowledge. In a double-blind, repeated-measures design, non-habitual (Experiment 1; N = 36, M = 42.5 ± 28.7 mg/day caffeine) and habitual (Experiment 2; N = 34, M = 579.5 ± 311.5 mg/day caffeine) caffeine consumers completed four test sessions corresponding to each of four caffeine doses (0, 100, 200, 400 mg). During each test session, participants consumed a capsule containing one of the three doses of caffeine or placebo, waited 60 min, and then completed two spatial tasks, one involving memorizing maps and one spatial descriptions. A spatial statement verification task tested local versus global spatial knowledge by differentially probing memory for proximal versus distal landmark relationships. On the map learning task, results indicated that caffeine enhanced memory for distal (i.e., global) compared to proximal (i.e., local) comparisons at 100 (marginal), 200, and 400 mg caffeine in non-habitual consumers, and marginally beginning at 200 mg caffeine in habitual consumers. On the spatial descriptions task, caffeine enhanced memory for distal compared to proximal comparisons beginning at 100 mg in non-habitual but not habitual consumers. We thus provide evidence that caffeine-induced physiological arousal amplifies global spatial processing biases, and these effects are at least partially driven by habitual caffeine consumption. PMID:24146646

Caffeine suppresses exercise-enhanced long-term and location memory in middle-aged rats: Involvement of hippocampal Akt and CREB signaling.

PubMed

Cechella, José L; Leite, Marlon R; da Rocha, Juliana T; Dobrachinski, Fernando; Gai, Bibiana M; Soares, Félix A A; Bresciani, Guilherme; Royes, Luiz F F; Zeni, Gilson

2014-11-05

The cognitive function decline is closely related with brain changes generated by age. The ability of caffeine and exercise to prevent memory impairment has been reported in animal models and humans. The purpose of the present study was to investigate whether swimming exercise and caffeine administration enhance memory in middle-aged Wistar rats. Male Wistar rats (18months) received caffeine at a dose of 30mg/kg, 5days per week by a period of 4weeks. Animals were subjected to swimming training with a workload (3% of body weight, 20min per day for 4weeks). After 4weeks, the object recognition test (ORT) and the object location test (OLT) were performed. The results of this study demonstrated that caffeine suppressed exercise-enhanced long-term (ORT) and spatial (OLT) memory in middle-aged and this effect may be related to a decrease in hippocampal p-CREB signaling. This study also provided evidence that the effects of this protocol on memory were not accompanied by alterations in the levels of activated Akt. The [(3)H] glutamate uptake was reduced in hippocampus of rats administered with caffeine and submitted to swimming protocol. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Caffeine Concentrations in Coffee, Tea, Chocolate, and Energy Drink Flavored E-liquids.

PubMed

Lisko, Joseph G; Lee, Grace E; Kimbrell, J Brett; Rybak, Michael E; Valentin-Blasini, Liza; Watson, Clifford H

2017-04-01

Most electronic cigarettes (e-cigarettes) contain a solution of propylene glycol/glycerin and nicotine, as well as flavors. E-cigarettes and their associated e-liquids are available in numerous flavor varieties. A subset of the flavor varieties include coffee, tea, chocolate, and energy drink, which, in beverage form, are commonly recognized sources of caffeine. Recently, some manufacturers have begun marketing e-liquid products as energy enhancers that contain caffeine as an additive. A Gas Chromatography-Mass Spectrometry (GC-MS) method for the quantitation of caffeine in e-liquids was developed, optimized and validated. The method was then applied to assess caffeine concentrations in 44 flavored e-liquids from cartridges, disposables, and refill solutions. Products chosen were flavors traditionally associated with caffeine (ie, coffee, tea, chocolate, and energy drink), marketed as energy boosters, or labeled as caffeine-containing by the manufacturer. Caffeine was detected in 42% of coffee-flavored products, 66% of tea-flavored products, and 50% of chocolate-flavored e-liquids (limit of detection [LOD] - 0.04 µg/g). Detectable caffeine concentrations ranged from 3.3 µg/g to 703 µg/g. Energy drink-flavored products did not contain detectable concentrations of caffeine. Eleven of 12 products marketed as energy enhancers contained caffeine, though in widely varying concentrations (31.7 µg/g to 9290 µg/g). E-liquid flavors commonly associated with caffeine content like coffee, tea, chocolate, and energy drink often contained caffeine, but at concentrations significantly lower than their dietary counterparts. Estimated daily exposures from all e-cigarette products containing caffeine were much less than ingestion of traditional caffeinated beverages like coffee. This study presents an optimized and validated method for the measurement of caffeine in e-liquids. The method is applicable to all e-liquid matrices and could potentially be used to ensure regulatory compliance for those geographic regions that forbid caffeine in e-cigarette products. The application of the method shows that caffeine concentrations and estimated total caffeine exposure from e-cigarette products is significantly lower than oral intake from beverages. However, because very little is known about the effects of caffeine inhalation, e-cigarette users should proceed with caution when using caffeine containing e-cigarette products. Further research is necessary to determine associated effects from inhaling caffeine. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Understanding adolescent caffeine use: connecting use patterns with expectancies, reasons, and sleep.

PubMed

Bryant Ludden, Alison; Wolfson, Amy R

2010-06-01

Little is known about adolescents' caffeine use, yet caffeinated soda, and more recently coffee and energy drinks, are part of youth culture. This study examines adolescents' caffeine use and, using cluster analysis, identifies three groups of caffeine users who differed in their reasons for use, expectancies, and sleep behaviors. In this high school student sample (N = 197), 95% of participants reported recent caffeine use-most often soda-where typical first use of the day was in the evening. Results reveal that adolescents in the mixed use and high soda use groups consumed similar amounts of soda, reporting significantly more use than the low caffeine use group. In contrast with high soda users, mixed users drank more coffee, expected more dependence symptoms and energy enhancement from caffeine, and were more likely to report getting up early, daytime sleepiness, and using caffeine to get through the day.

Discriminative Stimulus Effects of Binary Drug Mixtures: Studies with Cocaine, MDPV, and Caffeine.

PubMed

Collins, Gregory T; Abbott, Megan; Galindo, Kayla; Rush, Elise L; Rice, Kenner C; France, Charles P

2016-10-01

Illicit drug preparations often include more than one pharmacologically active compound. For example, cocaine and synthetic cathinones [e.g., 3,4-methylenedioxypyrovalerone (MDPV)] are often mixed with caffeine before sale. Caffeine is likely added to these preparations because it is inexpensive and legal; however, caffeine might also mimic or enhance some of the effects of cocaine or MDPV. In these studies, male Sprague-Dawley rats were trained to discriminate 10 mg/kg cocaine from saline, and the discriminative stimulus effects of cocaine, caffeine, and MDPV were evaluated alone and as binary mixtures (cocaine and caffeine, MDPV and caffeine, and cocaine and MDPV) at fixed-dose ratios of 3:1, 1:1, and 1:3 relative to the dose of each drug that produced 50% cocaine-appropriate responding. Dose-addition analyses were used to determine the nature of the drug-drug interactions for each mixture (e.g., additive, supra-additive, or subadditive). Although additive interactions were observed for most mixtures, supra-additive interactions were observed at the 50% effect level for the 1:1 mixture of cocaine and caffeine and at the 80% effect level for all three mixtures of cocaine and caffeine, as well as for the 3:1 and 1:3 mixtures of cocaine and MDPV. These results demonstrate that with respect to cocaine-like discriminative stimulus effects, caffeine can function as a substitute in drug preparations containing either cocaine or MDPV, with enhancements of cocaine-like effects possible under certain conditions. Further research is needed to determine whether similar interactions exist for other abuse-related or toxic effects of drug preparations, including cocaine, synthetic cathinones, and caffeine. U.S. Government work not protected by U.S. copyright.

Caffeine intake and abstract reasoning among 1374 unselected men and women from general population. Role of the -163C>A polymorphism of CYP1A2 gene.

PubMed

Casiglia, Edoardo; Tikhonoff, Valérie; Albertini, Federica; Favaro, Jacopo; Montagnana, Martina; Danese, Elisa; Finatti, Francesco; Benati, Marco; Mazza, Alberto; Dal Maso, Lucia; Spinella, Paolo; Palatini, Paolo

2017-08-01

The possible effect of caffeine as an enhancer of cognitive performance, particularly that on abstract reasoning, has never been studied in an epidemiological setting, especially in relation to -163C>A polymorphism of CYP1A2 gene, largely controlling caffeine metabolism. Aim of this study was to ascertain whether in general population free chronic caffeine intake modifies abstract reasoning, and if this effect is influenced by the above mentioned genotype, by age, schooling, ethanol intake and smoking habits. We studied 1374 unselected men and women aged 51 ± 15 years (range 18-89) from a general population. Daily caffeine intake deriving from coffee, tea, chocolate or cola was calculated from an anamnestic questionnaire and from a 7-day dietary diary. Abstract reasoning was measured in the frame of a neuropsychological assessment as the ability to find a concept linking two words indicating objects or actions and explaining how they were connected. In age-schooling-adjusted linear regression, the higher the caffeine intake, the better the abstraction score. Abstract reasoning depended on caffeine in the -163C>A CC homozygous only (so-called slow metabolizers), where it was higher in the 3rd tertile of caffeine intake. Age and ethanol reduced while smoking and schooling enhanced this association. The interaction term between caffeine and the -163C>A polymorphism was accepted in linear regressions. Caffeine consumption resulted innocuous for the A-carriers (so-called fast metabolizers). In general population, a positive association between caffeine intake and abstract reasoning exists in the CC homozygous of the -163C>A polymorphism of CYP1A2 gene. Copyright © 2017 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

Discriminative Stimulus Effects of Binary Drug Mixtures: Studies with Cocaine, MDPV, and Caffeine

PubMed Central

Abbott, Megan; Galindo, Kayla; Rush, Elise L.; Rice, Kenner C.; France, Charles P.

2016-01-01

Illicit drug preparations often include more than one pharmacologically active compound. For example, cocaine and synthetic cathinones [e.g., 3,4-methylenedioxypyrovalerone (MDPV)] are often mixed with caffeine before sale. Caffeine is likely added to these preparations because it is inexpensive and legal; however, caffeine might also mimic or enhance some of the effects of cocaine or MDPV. In these studies, male Sprague-Dawley rats were trained to discriminate 10 mg/kg cocaine from saline, and the discriminative stimulus effects of cocaine, caffeine, and MDPV were evaluated alone and as binary mixtures (cocaine and caffeine, MDPV and caffeine, and cocaine and MDPV) at fixed-dose ratios of 3:1, 1:1, and 1:3 relative to the dose of each drug that produced 50% cocaine-appropriate responding. Dose-addition analyses were used to determine the nature of the drug-drug interactions for each mixture (e.g., additive, supra-additive, or subadditive). Although additive interactions were observed for most mixtures, supra-additive interactions were observed at the 50% effect level for the 1:1 mixture of cocaine and caffeine and at the 80% effect level for all three mixtures of cocaine and caffeine, as well as for the 3:1 and 1:3 mixtures of cocaine and MDPV. These results demonstrate that with respect to cocaine-like discriminative stimulus effects, caffeine can function as a substitute in drug preparations containing either cocaine or MDPV, with enhancements of cocaine-like effects possible under certain conditions. Further research is needed to determine whether similar interactions exist for other abuse-related or toxic effects of drug preparations, including cocaine, synthetic cathinones, and caffeine. PMID:27493274

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.

Sleep Deprivation Impairs and Caffeine Enhances My Performance, but Not Always Our Performance.

PubMed

Faber, Nadira S; Häusser, Jan A; Kerr, Norbert L

2017-02-01

What effects do factors that impair or enhance performance in individuals have when these individuals act in groups? We provide a framework, called the GIE ("Effects of Grouping on Impairments and Enhancements") framework, for investigating this question. As prominent examples for individual-level impairments and enhancements, we discuss sleep deprivation and caffeine. Based on previous research, we derive hypotheses on how they influence performance in groups, specifically process gains and losses in motivation, individual capability, and coordination. We conclude that the effect an impairment or enhancement has on individual-level performance is not necessarily mirrored in group performance: grouping can help or hurt. We provide recommendations on how to estimate empirically the effects individual-level performance impairments and enhancements have in groups. By comparing sleep deprivation to stress and caffeine to pharmacological cognitive enhancement, we illustrate that we cannot readily generalize from group results on one impairment or enhancement to another, even if they have similar effects on individual-level performance.

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 Enhances Real-World Language Processing: Evidence from a Proofreading Task

ERIC Educational Resources Information Center

Brunye, Tad T.; Mahoney, Caroline R.; Rapp, David N.; Ditman, Tali; Taylor, Holly A.

2012-01-01

Caffeine has become the most prevalently consumed psychostimulant in the world, but its influences on daily real-world functioning are relatively unknown. The present work investigated the effects of caffeine (0 mg, 100 mg, 200 mg, 400 mg) on a commonplace language task that required readers to identify and correct 4 error types in extended…

Effect of caffeine contained in a cup of coffee on microvascular function in healthy subjects.

PubMed

Noguchi, Katsuhiko; Matsuzaki, Toshihiro; Sakanashi, Mayuko; Hamadate, Naobumi; Uchida, Taro; Kina-Tanada, Mika; Kubota, Haruaki; Nakasone, Junko; Sakanashi, Matao; Ueda, Shinichiro; Masuzaki, Hiroaki; Ishiuchi, Shogo; Ohya, Yusuke; Tsutsui, Masato

2015-02-01

Recent epidemiological studies have demonstrated that coffee drinking is associated with reduced mortality of cardiovascular disease. However, its precise mechanisms remain to be clarified. In this study, we examined whether single ingestion of caffeine contained in a cup of coffee improves microvascular function in healthy subjects. A double-blind, placebo-controlled, crossover study was performed in 27 healthy volunteers. A cup of either caffeinated or decaffeinated coffee was drunk by the subjects, and reactive hyperemia of finger blood flow was assessed by laser Doppler flowmetry. In an interval of more than 2 days, the same experimental protocol was repeated with another coffee in a crossover manner. Caffeinated coffee intake slightly but significantly elevated blood pressure and decreased finger blood flow as compared with decaffeinated coffee intake. There was no significant difference in heart rate between caffeinated and decaffeinated coffee intake. Importantly, caffeinated coffee intake significantly enhanced post-occlusive reactive hyperemia of finger blood flow, an index of microvascular endothelial function, compared with decaffeinated coffee intake. These results provide the first evidence that caffeine contained in a cup of coffee enhances microvascular function in healthy individuals. Copyright © 2015 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

Sleep Deprivation Impairs and Caffeine Enhances My Performance, but Not Always Our Performance

PubMed Central

Faber, Nadira S.; Häusser, Jan A.; Kerr, Norbert L.

2016-01-01

What effects do factors that impair or enhance performance in individuals have when these individuals act in groups? We provide a framework, called the GIE ("Effects of Grouping on Impairments and Enhancements”) framework, for investigating this question. As prominent examples for individual-level impairments and enhancements, we discuss sleep deprivation and caffeine. Based on previous research, we derive hypotheses on how they influence performance in groups, specifically process gains and losses in motivation, individual capability, and coordination. We conclude that the effect an impairment or enhancement has on individual-level performance is not necessarily mirrored in group performance: grouping can help or hurt. We provide recommendations on how to estimate empirically the effects individual-level performance impairments and enhancements have in groups. By comparing sleep deprivation to stress and caffeine to pharmacological cognitive enhancement, we illustrate that we cannot readily generalize from group results on one impairment or enhancement to another, even if they have similar effects on individual-level performance. PMID:26468077

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.

Evaluation of anticancer effects and enhanced doxorubicin cytotoxicity of xanthine derivatives using canine hemangiosarcoma cell lines.

PubMed

Motegi, Tomoki; Katayama, Masaaki; Uzuka, Yuji; Okamura, Yasuhiko

2013-10-01

Methylxanthine derivatives increase cAMP and are known to have diuretic, cardiac, and central nervous system stimulatory effects. Moreover, caffeine inhibits the development of tumors induced by various carcinogens. The aim of this work was to elucidate the anticancer effects on apoptosis of xanthine derivatives alone and with doxorubicin in canine hemangiosarcoma cells. Xanthine derivatives with or without doxorubicin were administered to cells, and the effects were investigated by measuring tumor cell proliferation, cell death (cytotoxicity) induction, and apoptosis by the expression of annexin V or caspase 3/7. Both caffeine and theophylline induced apoptosis, and the treated cells expressed annexin V and caspase 3/7. Both drugs enhanced doxorubicin-induced cytotoxicity; however, hypoxanthine showed no effect. These results indicate that theophylline is similar to caffeine; both drugs may enhance doxorubicin-induced cytotoxicity by inhibiting ATM/ATR kinases. Our data suggest that caffeine and theophylline have anticancer effects and can improve the treatment effect in canine hemangiosarcoma patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

Caffeine enhances real-world language processing: evidence from a proofreading task.

PubMed

Brunyé, Tad T; Mahoney, Caroline R; Rapp, David N; Ditman, Tali; Taylor, Holly A

2012-03-01

Caffeine has become the most prevalently consumed psychostimulant in the world, but its influences on daily real-world functioning are relatively unknown. The present work investigated the effects of caffeine (0 mg, 100 mg, 200 mg, 400 mg) on a commonplace language task that required readers to identify and correct 4 error types in extended discourse: simple local errors (misspelling 1- to 2-syllable words), complex local errors (misspelling 3- to 5-syllable words), simple global errors (incorrect homophones), and complex global errors (incorrect subject-verb agreement and verb tense). In 2 placebo-controlled, double-blind studies using repeated-measures designs, we found higher detection and repair rates for complex global errors, asymptoting at 200 mg in low consumers (Experiment 1) and peaking at 400 mg in high consumers (Experiment 2). In both cases, covariate analyses demonstrated that arousal state mediated the relationship between caffeine consumption and the detection and repair of complex global errors. Detection and repair rates for the other 3 error types were not affected by caffeine consumption. Taken together, we demonstrate that caffeine has differential effects on error detection and repair as a function of dose and error type, and this relationship is closely tied to caffeine's effects on subjective arousal state. These results support the notion that central nervous system stimulants may enhance global processing of language-based materials and suggest that such effects may originate in caffeine-related right hemisphere brain processes. Implications for understanding the relationships between caffeine consumption and real-world cognitive functioning are discussed. PsycINFO Database Record (c) 2012 APA, all rights reserved.

Effect of caffeine on induction of endogenous type C virus in mouse cells in vitro

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

Niwa, O.; Sugahara, T.

1981-08-01

The effect of caffeine on the expression of murine endogenous virus in mouse cells induced by radiation and chemicals was studied. Postirradiation treatment of K-BALB cells with caffeine enhanced cell killing as well as the induction of xenotropic virus after ultraviolet light irradiation. The degree of enhancement for the virus induction was comparable to that for cell killing. On the other hand, colony-forming ability and the expression of xenotropic virus of K-BALB cells after X-irradiation were unaffected by caffeine. These data suggest a linear relationship between the degree of endogenous virus expression and the amount of lethal damages after irradiation.more » For induction by halogenated pyrimidines, a 24-hr incubation of AKR2B cells with caffeine after 5-iodo-2'-deoxyuridine treatment resulted in marked suppression of the expression of ecotropic virus. On the contrary, in K-BALB cells, caffeine exerted only a small effect on 5-iodo-2'-deoxyuridine-induced expression of ecotropic and xenotropic viruses. These results indicate that, although using the same inducing agent, the pathway of endogenous virus induction may be different for AKR2B cells and for K-BALB cells.« less

Caffeine enhances and accelerates the expression of sensitization induced by coca paste indicating its relevance as a main adulterant.

PubMed

Prieto, José P; Galvalisi, Martín; López-Hill, Ximena; Meikle, María N; Abin-Carriquiry, Juan A; Scorza, Cecilia

2015-08-01

Caffeine is an active adulterant found in several drugs of abuse including coca paste (CP). We had previously demonstrated that caffeine potentiated the acute stimulant effect induced by CP seized samples. The role of caffeine in the expression of sensitization elicited by a CP seized sample (CP1) was here evaluated. CP1 (equivalent dose of 10 mg/kg of cocaine), cocaine (pure, 10 mg/kg), a combination of cocaine 10 mg/kg plus caffeine 2.5 mg/kg (CP1-surrogate) and saline (control) were intraperitoneally injected in male rats under two different sensitization schedules. Ambulatory locomotion was recorded in 58 animals. After five daily CP1 injections and 5 days of withdrawal, CP1-challenged animals displayed a more robust sensitization than cocaine-treated animals. When a 3 injections-regime of CP1-surrogate or cocaine was assayed, only CP1-surrogate was able to elicit sensitization. Caffeine enhances and accelerates the CP1-induced sensitization. Results may shed light on the fast and high dependence observed in CP users. © American Academy of Addiction Psychiatry.

Removal of caffeine from green tea by microwave-enhanced vacuum ice water extraction.

PubMed

Lou, Zaixiang; Er, Chaojuan; Li, Jing; Wang, Hongxin; Zhu, Song; Sun, Juntao

2012-02-24

In order to selectively remove caffeine from green tea, a microwave-enhanced vacuum ice water extraction (MVIE) method was proposed. The effects of MVIE variables including extraction time, microwave power, and solvent to solid radio on the removal yield of caffeine and the loss of total phenolics (TP) from green tea were investigated. The optimized conditions were as follows: solvent (mL) to solid (g) ratio was 10:1, microwave extraction time was 6 min, microwave power was 350 W and 2.5 h of vacuum ice water extraction. The removal yield of caffeine by MVIE was 87.6%, which was significantly higher than that by hot water extraction, indicating a significant improvement of removal efficiency. Moreover, the loss of TP of green tea in the proposed method was much lower than that in the hot water extraction. After decaffeination by MVIE, the removal yield of TP tea was 36.2%, and the content of TP in green tea was still higher than 170 mg g(-1). Therefore, the proposed microwave-enhanced vacuum ice water extraction was selective, more efficient for the removal of caffeine. The main phenolic compounds of green tea were also determined, and the results indicated that the contents of several catechins were almost not changed in MVIE. This study suggests that MVIE is a new and good alternative for the removal of caffeine from green tea, with a great potential for industrial application. Copyright © 2011 Elsevier B.V. All rights reserved.

Enhancing physical performance in elite junior tennis players with a caffeinated energy drink.

PubMed

Gallo-Salazar, César; Areces, Francisco; Abián-Vicén, Javier; Lara, Beatriz; Salinero, Juan José; Gonzalez-Millán, Cristina; Portillo, Javier; Muñoz, Victor; Juarez, Daniel; Del Coso, Juan

2015-04-01

The aim of this study was to investigate the effectiveness of a caffeinated energy drink to enhance physical performance in elite junior tennis players. In 2 different sessions separated by 1 wk, 14 young (16 ± 1 y) elite-level tennis players ingested 3 mg caffeine per kg body mass in the form of an energy drink or the same drink without caffeine (placebo). After 60 min, participants performed a handgrip-strength test, a maximal-velocity serving test, and an 8 × 15-m sprint test and then played a simulated singles match (best of 3 sets). Instantaneous running speed during the matches was assessed using global positioning (GPS) devices. Furthermore, the matches were videotaped and notated afterward. In comparison with the placebo drink, the ingestion of the caffeinated energy drink increased handgrip force by ~4.2% ± 7.2% (P = .03) in both hands, the running pace at high intensity (46.7 ± 28.5 vs 63.3 ± 27.7 m/h, P = .02), and the number of sprints (12.1 ± 1.7 vs 13.2 ± 1.7, P = .05) during the simulated match. There was a tendency for increased maximal running velocity during the sprint test (22.3 ± 2.0 vs 22.9 ± 2.1 km/h, P = .07) and higher percentage of points won on service with the caffeinated energy drink (49.7% ± 9.8% vs 56.4% ± 10.0%, P = .07) in comparison with the placebo drink. The energy drink did not improve ball velocity during the serving test (42.6 ± 4.8 vs 42.7 ± 5.0 m/s, P = .49). The preexercise ingestion of caffeinated energy drinks was effective to enhance some aspects of physical performance of elite junior tennis players.

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.

Non-ionic surfactant based vesicular drug delivery system for topical delivery of caffeine for treatment of cellulite: design, formulation, characterization, histological anti-cellulite activity, and pharmacokinetic evaluation.

PubMed

Teaima, Mahmoud H; Abdelhalim, Sally A; El-Nabarawi, Mohamed A; Attia, Dalia A; Helal, Doaa A

2018-01-01

Cellulite is a common topographical alteration where skin acquires an orange peel or mattress appearance with alterations in adipose tissue and microcirculation. This work aims to develop and evaluate a topical niosomal gel formulae with good permeation to reach the subcutaneous fat layer. Several caffeine niosomal dispersions were prepared and incorporated into gel formulae using Carbopol 940 polymer, chemical penetration enhancers, and iontophoresis, then the prepared gels were applied onto the skin of rats and anticellulite activity of caffeine from the prepared gels compared to that of the commercial product Cellu Destock ® was evaluated by histological study of the skin and measurement of plasma level of caffeine passing through the skin using liquid chromatography (LC/MS-MS). Results of histology revealed reduction of size and thickness of fatty layer of rat skin in the following order: FVII > FXIV > Cellu Destock ®  > FVII + Iontophoresis > FXIV + Iontophoresis. Pharmacokinetic results of caffeine in plasma revealed that C max , T max , and AUC 0-12h decreased in the following order: FXIV > FVII > Cellu Destock ® . These results conclude that incorporation of caffeine niosomal dispersion into gel matrix with penetration enhancers and iontophoresis resulted in improvement in penetration of caffeine through the skin into the underlying fatty layer in treatment of cellulite.

Espresso coffees, caffeine and chlorogenic acid intake: potential health implications.

PubMed

Crozier, Thomas W M; Stalmach, Angelique; Lean, Michael E J; Crozier, Alan

2012-01-01

HPLC analysis of 20 commercial espresso coffees revealed 6-fold differences in caffeine levels, a 17-fold range of caffeoylquinic acid contents, and 4-fold differences in the caffeoylquinic acid : caffeine ratio. These variations reflect differences in batch-to-batch bean composition, possible blending of arabica with robusta beans, as well as roasting and grinding procedures, but the predominant factor is likely to be the amount of beans used in the coffee-making/barista processes. The most caffeine in a single espresso was 322 mg and a further three contained >200 mg, exceeding the 200 mg day(-1) upper limit recommended during pregnancy by the UK Food Standards Agency. This snap-shot of high-street expresso coffees suggests the published assumption that a cup of strong coffee contains 50 mg caffeine may be misleading. Consumers at risk of toxicity, including pregnant women, children and those with liver disease, may unknowingly ingest excessive caffeine from a single cup of espresso coffee. As many coffee houses prepare larger volume coffees, such as Latte and Cappuccino, by dilution of a single or double shot of expresso, further study on these products is warranted. New data are needed to provide informative labelling, with attention to bean variety, preparation, and barista methods.

Effects of dilute aqueous NaCl solution on caffeine aggregation

NASA Astrophysics Data System (ADS)

Sharma, Bhanita; Paul, Sandip

2013-11-01

The effect of salt concentration on association properties of caffeine molecule was investigated by employing molecular dynamics simulations in isothermal-isobaric ensemble of eight caffeine molecules in pure water and three different salt (NaCl) concentrations, at 300 K temperature and 1 atm pressure. The concentration of caffeine was taken almost at the solubility limit. With increasing salt concentration, we observe enhancement of first peak height and appearance of a second peak in the caffeine-caffeine distribution function. Furthermore, our calculated solvent accessible area values and cluster structure analyses suggest formation of higher order caffeine cluster on addition of salt. The calculated hydrogen bond properties reveal that there is a modest decrease in the average number of water-caffeine hydrogen bonds on addition of NaCl salt. Also observed are: (i) decrease in probability of salt contact ion pair as well as decrease in the solvent separated ion pair formation with increasing salt concentration, (ii) a modest second shell collapse in the water structure, and (iii) dehydration of hydrophobic atomic sites of caffeine on addition of NaCl.

Effects of dilute aqueous NaCl solution on caffeine aggregation

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

Sharma, Bhanita; Paul, Sandip, E-mail: sandipp@iitg.ernet.in

The effect of salt concentration on association properties of caffeine molecule was investigated by employing molecular dynamics simulations in isothermal-isobaric ensemble of eight caffeine molecules in pure water and three different salt (NaCl) concentrations, at 300 K temperature and 1 atm pressure. The concentration of caffeine was taken almost at the solubility limit. With increasing salt concentration, we observe enhancement of first peak height and appearance of a second peak in the caffeine-caffeine distribution function. Furthermore, our calculated solvent accessible area values and cluster structure analyses suggest formation of higher order caffeine cluster on addition of salt. The calculated hydrogenmore » bond properties reveal that there is a modest decrease in the average number of water-caffeine hydrogen bonds on addition of NaCl salt. Also observed are: (i) decrease in probability of salt contact ion pair as well as decrease in the solvent separated ion pair formation with increasing salt concentration, (ii) a modest second shell collapse in the water structure, and (iii) dehydration of hydrophobic atomic sites of caffeine on addition of NaCl.« less

Effects of caffeine and carbohydrate mouth rinses on repeated sprint performance.

PubMed

Beaven, C Martyn; Maulder, Peter; Pooley, Adrian; Kilduff, Liam; Cook, Christian

2013-06-01

Our purpose was to examine the effectiveness of carbohydrate and caffeine mouth rinses in enhancing repeated sprint ability. Previously, studies have shown that a carbohydrate mouth rinse (without ingestion) has beneficial effects on endurance performance that are related to changes in brain activity. Caffeine ingestion has also demonstrated positive effects on sprint performance. However, the effects of carbohydrate or caffeine mouth rinses on intermittent sprints have not been examined previously. Twelve males performed 5 × 6-s sprints interspersed with 24 s of active recovery on a cycle ergometer. Twenty-five milliliters of either a noncaloric placebo, a 6% glucose, or a 1.2% caffeine solution was rinsed in the mouth for 5 s prior to each sprint in a double-blinded and balanced cross-over design. Postexercise maximal heart rate and perceived exertion were recorded, along with power measures. A second experiment compared a combined caffeine-carbohydrate rinse with carbohydrate only. Compared with the placebo mouth rinse, carbohydrate substantially increased peak power in sprint 1 (22.1 ± 19.5 W; Cohen's effect size (ES), 0.81), and both caffeine (26.9 ± 26.9 W; ES, 0.71) and carbohydrate (39.1 ± 25.8 W; ES, 1.08) improved mean power in sprint 1. Experiment 2 demonstrated that a combination of caffeine and carbohydrate improved sprint 1 power production compared with carbohydrate alone (36.0 ± 37.3 W; ES, 0.81). We conclude that carbohydrate and (or) caffeine mouth rinses may rapidly enhance power production, which could have benefits for specific short sprint exercise performance. The ability of a mouth-rinse intervention to rapidly improve maximal exercise performance in the absence of fatigue suggests a central mechanism.

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 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

Effects of dietary caffeine on EEG, performance and mood when rested and sleep restricted.

PubMed

Keane, Michael A; James, Jack E

2008-12-01

Until recently, little account had been taken of the confounding effects of caffeine withdrawal and withdrawal reversal when examining the net effects of dietary caffeine. By including a manipulation involving sleep restriction, the present study aimed to extend recent findings from research in which caffeine withdrawal and withdrawal reversal were controlled. The main aims of the study were to examine the net effects of caffeine, as well as its potential restorative effects following sleep restriction, on EEG, performance and mood. A randomised cross-over design was used in which 15 participants alternated weekly between ingesting placebo and caffeine (1.75 mg/kg) three times daily for four consecutive weeks following either usual sleep or sleep restriction. EEG activity was measured at 32 sites during eyes closed, eyes open and performance of a vigilance task. Modest effects of caffeine were found in the delta and beta bandwidths, but no main effects of caffeine were observed in the theta or alpha bandwidths. Overall, the effects of caffeine on EEG activity were relatively few, weak and inconsistent, and no evidence was found of net restorative effects of caffeine for any outcome variables. The findings do not support the use of caffeine as a means for enhancing human function or as an antidote to the negative effects of sleep loss.

The effect of caffeine ingestion on mood state and bench press performance to failure.

PubMed

Duncan, Michael J; Oxford, Samuel W

2011-01-01

Research has suggested that caffeine enhances aerobic performance. The evidence for high-intensity, short-term exercise, particularly resistance exercise is mixed and has not fully examined the psychological changes that occur after this mode of exercise with caffeine ingestion. This study examined the effect of caffeine (5 mg · kg(-1)) vs. placebo on bench press exercise to failure and the mood state response pre to postexercise. Thirteen moderately trained men (22.7 ± 6.0 years) completed 2 laboratory visits, after determination of 1 repetition maximum (1RM) on the bench press, where they performed bench press repetitions to failure at a load of 60% 1RM. Mood state was assessed 60 minutes pre and immediately post-substance ingestion. Borg's rating of perceived exertion (RPE) and peak blood lactate (PBla) were assessed after each test, and peak heart rate (PHR) was determined using heart rate telemetry. Participants completed significantly more repetitions to failure (p = 0.031) and lifted significantly greater weight (p = 0.027) in the caffeine condition compared to the placebo condition. The PHR (p = 0.0001) and PBla (p = 0.002) were higher after caffeine ingestion. The RPE was not different across conditions (p = 0.082). Mood state scores for vigor were greater (p = 0.001) and fatigue scores lower (p = 0.04) in the presence of caffeine. Fatigue scores were greater postexercise (p = 0.001) compared to scores pre exercise across conditions. Caffeine ingestion enhances performance in short-term, resistance exercise to failure and may favorably change the mood state response to exercise compared to a placebo.

Caffeine-enhanced survival of radiation-sensitive, repair-deficient Chinese hamster cells

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

Utsumi, H.; Elkind, M.M.

1983-11-01

A clone of V79 Chinese hamster cells (V79-AL162/S-10) with unique properties has been isolated after a challenge of parental cells (V79-AL162) with 1 mM ouabain. Compared with parental cells, or with other clones isolated after the ouabain challenge, these cells form smaller colonies, are more sensitive to both x rays and fission-spectrum neutrons, and respond atypically to a postirradiation treatment with caffeine. Their enhanced response to x rays results mainly from a large reduction in the shoulder of their survival curve, probably because in late S phase, the most resistant phase in the cell cycle, the survival curve of thesemore » cells has a reduced shoulder width. Caffeine, and to a lesser extent theophylline, added to the colony-forming medium immediately after exposure appreciably increases the width of the shoulder of these sensitive cells, whereas caffeine has the opposite effect on the response of normal V79 cells. Thus the unique response of the V79-AL162/S-10 cells to a radiation posttreatment with caffeine (increased survival) results from a net increase in their ability to repair damage that is otherwise lethal; caffeine treatment ordinarly prevents normal V79 cells from repairing damage that is only potentially lethal.« less

Enhancing physical performance in male volleyball players with a caffeine-containing energy drink.

PubMed

Del Coso, Juan; Pérez-López, Alberto; Abian-Vicen, Javier; Salinero, Juan Jose; Lara, Beatriz; Valadés, David

2014-11-01

There are no scientific data about the effects of caffeine intake on volleyball performance. The aim of this study was to investigate the effect of a caffeine-containing energy drink to enhance physical performance in male volleyball players. A double-blind, placebo-controlled, randomized experimental design was used. In 2 different sessions separated by 1 wk, 15 college volleyball players ingested 3 mg of caffeine per kg of body mass in the form of an energy drink or the same drink without caffeine (placebo). After 60 min, participants performed volleyball-specific tests: standing spike test, maximal squat jump (SJ), maximal countermovement jump (CMJ), 15-s rebound jump test (15RJ), and agility T-test. Later, a simulated volleyball match was played and recorded. In comparison with the placebo drink, the ingestion of the caffeinated energy drink increased ball velocity in the spike test (73 ± 9 vs 75 ± 10 km/h, P < .05) and the mean jump height in SJ (31.1 ± 4.3 vs 32.7 ± 4.2 cm, P < .05), CMJ (35.9 ± 4.6 vs 37.7 ± 4.4 cm, P < .05), and 15RJ (29.0 ± 4.0 vs 30.5 ± 4.6 cm, P < .05). The time to complete the agility test was significantly reduced with the caffeinated energy drink (10.8 ± 0.7 vs 10.3 ± 0.4 s, P < .05). In addition, players performed successful volleyball actions more frequently (24.6% ± 14.3% vs 34.3% ± 16.5%, P < .05) with the ingestion of the caffeinated energy drink than with the placebo drink during the simulated game. A caffeine-containing energy drink, with a dose equivalent to 3 mg of caffeine per kg body mass, might be an effective ergogenic aid to improve physical performance and accuracy in male volleyball players.

Prenatal caffeine ingestion induces transgenerational neuroendocrine metabolic programming alteration in second generation rats

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

Luo, Hanwen; Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071; Deng, Zixin

Our previous studies have demonstrated that prenatal caffeine ingestion induces an increased susceptibility to metabolic syndrome with alterations of glucose and lipid metabolic phenotypes in adult first generation (F1) of intrauterine growth retardation (IUGR) rats, and the underlying mechanism is originated from a hypothalamic–pituitary–adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration in utero. This study aims to investigate the transgenerational effects of this programming alteration in adult second generation (F2). Pregnant Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. Four groups in F2 were set according to the cross-mating between control and caffeine-induced IUGR rats.more » F2 were subjected to a fortnight ice water swimming stimulus on postnatal month 4, and blood samples were collected before and after stress. Results showed that the majority of the activities of HPA axis and phenotypes of glucose and lipid metabolism were altered in F2. Particularly, comparing with the control group, caffeine groups had an enhanced corticosterone levels after chronic stress. Compared with before stress, the serum glucose levels were increased in some groups whereas the triglyceride levels were decreased. Furthermore, total cholesterol gain rates were enhanced but the high-density lipoprotein-cholesterol gain rates were decreased in most caffeine groups after stress. These transgenerational effects were characterized partially with gender and parental differences. Taken together, these results indicate that the reproductive and developmental toxicities and the neuroendocrine metabolic programming mechanism by prenatal caffeine ingestion have transgenerational effects in rats, which may help to explain the susceptibility to metabolic syndrome and associated diseases in F2. - Highlights: • Caffeine-induced neuroendocrine metabolic programming of HPA has hereditary effect. • Caffeine-induced reproductive and developmental toxicities in F1 have hereditary effect. • Caffeine-induced programming of HPA axis in F2 has gender and parental differences.« less

Caffeine Induces a Stimulant Effect and Increases Dopamine Release in the Nucleus Accumbens Shell Through the Pulmonary Inhalation Route of Administration in Rats.

PubMed

Galvalisi, Martín; Prieto, José Pedro; Martínez, Marcela; Abin-Carriquiry, Juan Andrés; Scorza, Cecilia

2017-01-01

Oral, intraperitoneal, or intravenous have been the common routes of administration used to study the behavioral and neurochemical pharmacology of caffeine, one of the most widely used psychoactive substances worldwide. We have reported that caffeine is an active adulterant frequently found in coca-paste (CP)-seized samples, a highly addictive form of smokable cocaine. The role of caffeine in the psychostimulant and neurochemical effects induced by CP remains under study. No preclinical animal studies have been performed so far to characterize the effects of caffeine when it is administered through the pulmonary inhalation route. Caffeine (10, 25, and 50 mg) was volatilized and rats were exposed to one inhalation session of its vapor. The stimulant effect was automatically recorded and plasmatic levels of caffeine were measured. Caffeine capability (50 mg) to increase extracellular dopamine (DA) levels in nucleus accumbens shell was also studied by in vivo microdialysis in non-anesthetized animals. A dose-dependent stimulant effect induced by volatilized caffeine was observed and this effect was directly related with caffeine plasmatic levels. A significant increase in the extracellular DA was achieved after 50 mg of volatilized caffeine exposure. This is the first report showing pharmacological acute effects of caffeine through the pulmonary inhalation route of administration and suggests that this could be a condition under which caffeine can elevate its weak reinforcing effect and even enhance the psychostimulant effect and abuse liability of smokable adulterated psychostimulant drugs.

Subjective, behavioral, and physiological effects of acute caffeine in light, nondependent caffeine users.

PubMed

Childs, Emma; de Wit, Harriet

2006-05-01

Caffeine produces mild psychostimulant effects that are thought to underlie its widespread use. However, the direct effects of caffeine are difficult to evaluate in regular users of caffeine because of tolerance and withdrawal. Indeed, some researchers hypothesize that the psychostimulant effects of caffeine are due largely to the reversal of withdrawal and question whether there are direct effects of caffeine consumption upon mood, alertness, or mental performance in nondependent individuals. This study investigated the physiological, subjective, and behavioral effects of 0, 50, 150, and 450 mg caffeine in 102 light, nondependent caffeine users. Using a within-subjects design, subjects participated in four experimental sessions, in which they received each of the four drug conditions in random order under double blind conditions. Participants completed subjective effects questionnaires and vital signs were measured before and at repeated time points after drug administration. Forty minutes after the capsules were ingested, subjects completed behavioral tasks that included tests of sustained attention, short-term memory, psychomotor performance, and behavioral inhibition. Caffeine significantly increased blood pressure, and produced feelings of arousal, positive mood, and high. Caffeine increased the number of hits and decreased reaction times in a vigilance task, but impaired performance on a memory task. We confirm that acute doses of caffeine, at levels typically found in a cup of coffee, produce stimulant-like subjective effects and enhance performance in light, nondependent caffeine users. These findings support the idea that the drug has psychoactive effects even in the absence of withdrawal.

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.

Caffeine prevents changes in muscle caused by high-intensity interval training.

PubMed

Vieira, Juliano M; Gutierres, Jessié M; Carvalho, Fabiano B; Pereira, Luciane B; Oliveira, Liziele S; Morsch, Vera Maria; Schetinger, Maria Rosa C; Rodrigues, Marília V; Leitemperger, Jossiele; Loro, Vânia; Krewer, Cristina C; Vencato, Marina S; Spanevello, Roselia M

2017-05-01

The use of ergogenic substances such as caffeine has become a strategy to enhance sports performance. In the present study we evaluated the effects of high-intensity interval training (HIIT) associated with caffeine intake on acetylcholinesterase (AChE) and Ca 2+ ATPase activity and glycogen levels in the muscles of rats were evaluated. The animals were divided in groups: control, caffeine 4 or 8mg/kg, HIIT, HIIT plus caffeine 4 or caffeine 8mg/kg. Our results showed a decrease in glycogen levels in muscle in all trained groups after acute session exercise, while that an increase in glycogen levels was observed in all groups in relation to control in chronic exercise protocol. HIIT increases the thickness of the left ventricle and the Ca 2+ -ATPase activity and decrease the AChE activity in gastrocnemius muscle. Caffeine treatment prevents changes in enzymes activities as well as left ventricular hypertrophy adaptation induced by HIIT. Our findings suggest that caffeine modulates crucial pathways for muscle contraction in HIIT. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The paradox of caffeine-zolpidem interaction: a network analysis.

PubMed

Myslobodsky, Michael

2009-10-01

A widely prescribed and potent short-acting hypnotic, zolpidem has become the mainstay for the treatment of middle-of-the-night sleeplessness. It is expected to be antagonized by caffeine. Paradoxically, in some cases caffeine appears to slightly enhance zolpidem sedation. The pharmacokinetic and pharmacodynamic nature of this odd effect remains unexplored. The purpose of this study is to reproduce a hypothetical molecular network recruited by caffeine when co-administered with zolpidem using Ingenuity Pathway Analysis. Thus generated, network drew attention to several possible contributors to caffeine sedation, such as tachykinin precursor 1, cannabinoid, and GABA receptors. The present overview is centered on the possibility that caffeine potentiation of zolpidem sedation does not involve a centralized interaction of specific neurotransmitters, but rather is contributed by its antioxidant capacity. It is proposed that by modifying the cellular redox state, caffeine ultimately reduces the pool of reactive oxygen species, thereby increasing the bioavailability of endogenous melatonin for interaction with zolpidem. This side effect of caffeine encourages further studies of multiple antioxidants as an attractive way to potentially increasing somnolence.

The effect of caffeine and albuterol on body composition and metabolic rate

PubMed Central

Liu, Ann G.; Arceneaux, Kenneth P.; Chu, Jessica T.; Jacob, Gregory; Schreiber, Allyson L.; Tipton, Russell C.; Yu, Ying; Johnson, William D.; Greenway, Frank L.; Primeaux, Stefany D.

2015-01-01

Objective Caffeine and ephedrine was an effective combination therapy for weight loss until ephedrine was removed from the market due to safety concerns. We investigated the combination of caffeine and albuterol as a possibly safer alternative to ephedrine. Design and Methods In a series of experiments using cultured adipocytes, rat models, and humans, we evaluated the effects of caffeine and albuterol on lipolysis, metabolic rate, food intake, and body composition. Results Both caffeine and albuterol enhanced lipolysis in cultured adipocytes. Acute treatment of humans with caffeine and/or albuterol increased resting metabolic rate. Longer-term studies of rats revealed a trend for increased metabolic rate with albuterol treatment. There was increased lean mass gain concurrent with decreased fat mass gain with caffeine/albuterol treatment that was greater than albuterol treatment alone. Conclusions In rats, albuterol with caffeine produced significantly greater increases in lean body mass and reductions in fat mass without changes in food intake after 4-8 weeks of treatment. Since caffeine and albuterol are approved for the treatment of asthma in children and adolescents at the doses tested and change body composition without changing food intake, this combination may deserve further exploration for use in treating pediatric obesity. PMID:26239482

The effects of caffeine in women during aerobic-dance bench stepping.

PubMed

Ahrens, Jennifer N; Lloyd, Lisa K; Crixell, Sylvia H; Walker, John L

2007-02-01

People of all ages and fitness levels participate regularly in aerobic-dance bench stepping (ADBS) to increase fitness and control body weight. Any reasonable method for enhancing the experience or effectiveness of ADBS would be beneficial. This study examined the acute effects of a single dose of caffeine on physiological responses during ADBS in women. When compared with a placebo, neither a 3- nor a 6-mg/kg dose of caffeine altered physiological responses or rating of perceived exertion (RPE) in 20 women (age 19-28 y) of average fitness level, not habituated to caffeine, while they performed an ADBS routine. Since neither dose of caffeine had any effect on VO2, VCO2, minute ventilation, respiratory-exchange ratio, rate of energy expenditure, heart rate, or RPE during ADBS exercise, it would not be prudent for a group exercise leader to recommend caffeine to increase energy cost or decrease perception of effort in an ADBS session. Furthermore, caffeine ingestion should not interfere with monitoring intensity using heart rate or RPE during ADBS.

Synergistic induction of cytogenetic damage by the homo-aza-steroidal ester of p-bis(2-chloroethyl)aminophenylacetic acid in combination with caffeine in human lymphocytes in vitro and in Ehrlich ascites tumour cells in vivo.

PubMed

Petrou, C; Mourelatos, D; Dozi-Vassiliades, J; Catsoulacos, P

1990-02-01

We studied the effects of caffeine alone or in combination with homo-aza-steroidal ester of p-bis(2-chloroethyl)aminophenylacetic acid (ASE, NSC 290205) on the frequency of SCEs and lymphocyte proliferation kinetics. Caffeine was found to act synergistically with ASE on the induction of SCEs when the two components were administered in combination. Caffeine was also found to act synergistically with ASE in inducing cell-division delays. Enhanced cytogenetic damage by ASE was observed when Ehrlich ascites tumour cells (EAT cells) were exposed in vivo to caffeine. ASE alone or in combination with caffeine caused a dose-dependent increase in SCE rates and cell-division delays. SCEs were demonstrated in EAT-bearing mice, by the i.p. injection of BrdUrd adsorbed onto activated charcoal, 1 h after the i.p. injection of ASE and/or caffeine.

Exercise and sport performance with low doses of caffeine.

PubMed

Spriet, Lawrence L

2014-11-01

Caffeine is a popular work-enhancing supplement that has been actively researched since the 1970s. The majority of research has examined the effects of moderate to high caffeine doses (5-13 mg/kg body mass) on exercise and sport. These caffeine doses have profound effects on the responses to exercise at the whole-body level and are associated with variable results and some undesirable side effects. Low doses of caffeine (<3 mg/kg body mass, ~200 mg) are also ergogenic in some exercise and sport situations, although this has been less well studied. Lower caffeine doses (1) do not alter the peripheral whole-body responses to exercise; (2) improve vigilance, alertness, and mood and cognitive processes during and after exercise; and (3) are associated with few, if any, side effects. Therefore, the ergogenic effect of low caffeine doses appears to result from alterations in the central nervous system. However, several aspects of consuming low doses of caffeine remain unresolved and suffer from a paucity of research, including the potential effects on high-intensity sprint and burst activities. The responses to low doses of caffeine are also variable and athletes need to determine whether the ingestion of ~200 mg of caffeine before and/or during training and competitions is ergogenic on an individual basis.

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

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

Caffeine Citrate Dosing Adjustments to Assure Stable Caffeine Concentrations in Preterm Neonates.

PubMed

Koch, Gilbert; Datta, Alexandre N; Jost, Kerstin; Schulzke, Sven M; van den Anker, John; Pfister, Marc

2017-12-01

To identify dosing strategies that will assure stable caffeine concentrations in preterm neonates despite changing caffeine clearance during the first 8 weeks of life. A 3-step simulation approach was used to compute caffeine doses that would achieve stable caffeine concentrations in the first 8 weeks after birth: (1) a mathematical weight change model was developed based on published weight distribution data; (2) a pharmacokinetic model was developed based on published models that accounts for individual body weight, postnatal, and gestational age on caffeine clearance and volume of distribution; and (3) caffeine concentrations were simulated for different dosing regimens. A standard dosing regimen of caffeine citrate (using a 20 mg/kg loading dose and 5 mg/kg/day maintenance dose) is associated with a maximal trough caffeine concentration of 15 mg/L after 1 week of treatment. However, trough concentrations subsequently exhibit a clinically relevant decrease because of increasing clearance. Model-based simulations indicate that an adjusted maintenance dose of 6 mg/kg/day in the second week, 7 mg/kg/day in the third to fourth week and 8 mg/kg/day in the fifth to eighth week assures stable caffeine concentrations with a target trough concentration of 15 mg/L. To assure stable caffeine concentrations during the first 8 weeks of life, the caffeine citrate maintenance dose needs to be increased by 1 mg/kg every 1-2 weeks. These simple adjustments are expected to maintain exposure to stable caffeine concentrations throughout this important developmental period and might enhance both the short- and long-term beneficial effects of caffeine treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Separate and joint effects of alcohol and caffeine on conflict monitoring and adaptation.

PubMed

Bailey, Kira; Amlung, Michael T; Morris, David H; Price, Mason H; Von Gunten, Curtis; McCarthy, Denis M; Bartholow, Bruce D

2016-04-01

Caffeine is commonly believed to offset the acute effects of alcohol, but some evidence suggests that cognitive processes remain impaired when caffeine and alcohol are coadministered. No previous study has investigated the separate and joint effects of alcohol and caffeine on conflict monitoring and adaptation, processes thought to be critical for self-regulation. This was the purpose of the current study. Healthy, young adult social drinkers recruited from the community completed a flanker task after consuming one of four beverages in a 2 × 2 experimental design: Alcohol + caffeine, alcohol + placebo caffeine, placebo alcohol + caffeine, or placebo alcohol + placebo caffeine. Accuracy, response time, and the amplitude of the N2 component of the event-related potential (ERP), a neural index of conflict monitoring, were examined as a function of whether or not conflict was present (i.e., whether or not flankers were compatible with the target) on both the previous trial and the current trial. Alcohol did not abolish conflict monitoring or adaptation. Caffeine eliminated conflict adaptation in sequential trials but also enhanced neural conflict monitoring. The combined effect of alcohol and caffeine was apparent only in how previous conflict affected the neural conflict monitoring response. Together, the findings suggest that caffeine leads to exaggeration of attentional resource utilization, which could provide short-term benefits but lead to problems conserving resources for when they are most needed.

Caffeine Enhances Memory Performance in Young Adults during Their Non-optimal Time of Day

PubMed Central

Sherman, Stephanie M.; Buckley, Timothy P.; Baena, Elsa; Ryan, Lee

2016-01-01

Many college students struggle to perform well on exams in the early morning. Although students drink caffeinated beverages to feel more awake, it is unclear whether these actually improve performance. After consuming coffee (caffeinated or decaffeinated), college-age adults completed implicit and explicit memory tasks in the early morning and late afternoon (Experiment 1). During the morning, participants ingesting caffeine demonstrated a striking improvement in explicit memory, but not implicit memory. Caffeine did not alter memory performance in the afternoon. In Experiment 2, participants engaged in cardiovascular exercise in order to examine whether increases in physiological arousal similarly improved memory. Despite clear increases in physiological arousal, exercise did not improve memory performance compared to a stretching control condition. These results suggest that caffeine has a specific benefit for memory during students’ non-optimal time of day – early morning. These findings have real-world implications for students taking morning exams. PMID:27895607

Caffeine and adenosine.

PubMed

Ribeiro, Joaquim A; Sebastião, Ana M

2010-01-01

Caffeine causes most of its biological effects via antagonizing all types of adenosine receptors (ARs): A1, A2A, A3, and A2B and, as does adenosine, exerts effects on neurons and glial cells of all brain areas. In consequence, caffeine, when acting as an AR antagonist, is doing the opposite of activation of adenosine receptors due to removal of endogenous adenosinergic tonus. Besides AR antagonism, xanthines, including caffeine, have other biological actions: they inhibit phosphodiesterases (PDEs) (e.g., PDE1, PDE4, PDE5), promote calcium release from intracellular stores, and interfere with GABA-A receptors. Caffeine, through antagonism of ARs, affects brain functions such as sleep, cognition, learning, and memory, and modifies brain dysfunctions and diseases: Alzheimer's disease, Parkinson's disease, Huntington's disease, Epilepsy, Pain/Migraine, Depression, Schizophrenia. In conclusion, targeting approaches that involve ARs will enhance the possibilities to correct brain dysfunctions, via the universally consumed substance that is caffeine.

Confocal Raman microscopy and multivariate statistical analysis for determination of different penetration abilities of caffeine and propylene glycol applied simultaneously in a mixture on porcine skin ex vivo.

PubMed

Mujica Ascencio, Saul; Choe, ChunSik; Meinke, Martina C; Müller, Rainer H; Maksimov, George V; Wigger-Alberti, Walter; Lademann, Juergen; Darvin, Maxim E

2016-07-01

Propylene glycol is one of the known substances added in cosmetic formulations as a penetration enhancer. Recently, nanocrystals have been employed also to increase the skin penetration of active components. Caffeine is a component with many applications and its penetration into the epidermis is controversially discussed in the literature. In the present study, the penetration ability of two components - caffeine nanocrystals and propylene glycol, applied topically on porcine ear skin in the form of a gel, was investigated ex vivo using two confocal Raman microscopes operated at different excitation wavelengths (785nm and 633nm). Several depth profiles were acquired in the fingerprint region and different spectral ranges, i.e., 526-600cm(-1) and 810-880cm(-1) were chosen for independent analysis of caffeine and propylene glycol penetration into the skin, respectively. Multivariate statistical methods such as principal component analysis (PCA) and linear discriminant analysis (LDA) combined with Student's t-test were employed to calculate the maximum penetration depths of each substance (caffeine and propylene glycol). The results show that propylene glycol penetrates significantly deeper than caffeine (20.7-22.0μm versus 12.3-13.0μm) without any penetration enhancement effect on caffeine. The results confirm that different substances, even if applied onto the skin as a mixture, can penetrate differently. The penetration depths of caffeine and propylene glycol obtained using two different confocal Raman microscopes are comparable showing that both types of microscopes are well suited for such investigations and that multivariate statistical PCA-LDA methods combined with Student's t-test are very useful for analyzing the penetration of different substances into the skin. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of caffeine and aspirin on light resistance training performance, perceived exertion, and pain perception.

PubMed

Hudson, Geoffrey M; Green, J Matt; Bishop, Phillip A; Richardson, Mark T

2008-11-01

This study compared independent effects of caffeine and aspirin on muscular endurance (repetitions), heart rate (HR), perceived exertion (RPE), and perceived pain index (PPI) during light resistance training bouts performed to volitional failure. It was hypothesized that the hypoalgesic properties of these ergogenic aids would decrease pain perception and potentially result in enhanced performance. College-aged men (n = 15) participated in a within-subjects, double-blind study with three independent, counterbalanced sessions wherein aspirin (10 mg x kg(-1)), caffeine (6 mg x kg(-1)), or matched placebo were ingested 1 hour before exercise, and RPE, HR, PPI, and repetitions (per set and total per exercise) were recorded at 100% of individual, predetermined, 12-repetition maximum for leg extensions (LE) and seated arm curls (AC). Repeated-measures analyses of variance were used for between-trial comparisons. Caffeine resulted in significantly greater (p < 0.05) HR (LE and AC), total repetitions (LE), and repetitions in set 1 (LE and AC) compared with aspirin and placebo. Aspirin resulted in significantly higher PPI in set 1 (LE). In LE, 47% of participants' performance exceeded the predetermined effect size (>or= 5 repetitions) for total repetitions, with 53% exceeding the effect size (>or= 2 repetitions) for repetitions in set 1 with caffeine (vs. placebo). In AC, 53% (total repetitions) and 47% (set 1 repetitions) of participants exceeded effect sizes with caffeine (vs. placebo), with only 13% experiencing decrements in performance (total repetitions). Aspirin also produced a higher PPI and RPE overall and in set 1 (vs. placebo). This study demonstrates that caffeine significantly enhanced resistance training performance in LE and AC, whereas aspirin did not. Athletes may improve their resistance training performance by acute ingestion of caffeine. As with most ergogenic aids, our analyses indicate that individual responses vary greatly.

Capillary electrophoresis for caffeine and pyroglutamate determination in coffees study of the in vivo effect on learning and locomotor activity in mice.

PubMed

Maeso, N; del Castillo, C; Cornejo, L; García-Acicollar, M; Alguacil, L F; Barbas, C

2006-06-16

In a preliminary study pyroglutamate showed to be over 10 times increased in some lyophilised coffees with respect to brewed or filtered coffees, and probably that increase is related to some stage of the industrial process. Pyroglutamate is known to have a number of remarkable cognitive enhancing effects, which could be also related to the properties of coffee traditionally associated to caffeine. Pyroglutamate improves memory and learning and has anti-anxiety effects in rats. Therefore, a method has been developed and validated for the simultaneous determination of caffeine and pyroglutamate in coffee by capillary electrophoresis. Separation conditions employed MECK conditions with 50 mM borate buffer at pH 9.5 with 130 mM SDS. The applied potential was 10 kV and detection was performed at 200 nm. Afterwards, 10 soluble coffees from the market were measured and caffeine and pyroglutamate levels were compared. Those coffees with higher pyroglutamate with or without caffeine were preliminarily tested for sedative/stimulant properties and cognition enhancing effects in mice. The most relevant finding was a partial reversal of scopolamine-induced amnesia in the passive avoidance paradigm after oral administration of one coffee.

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.

Caffeine intake increases plasma ketones: an acute metabolic study in humans.

PubMed

Vandenberghe, Camille; St-Pierre, Valérie; Courchesne-Loyer, Alexandre; Hennebelle, Marie; Castellano, Christian-Alexandre; Cunnane, Stephen C

2017-04-01

Brain glucose uptake declines during aging and is significantly impaired in Alzheimer's disease. Ketones are the main alternative brain fuel to glucose so they represent a potential approach to compensate for the brain glucose reduction. Caffeine is of interest as a potential ketogenic agent owing to its actions on lipolysis and lipid oxidation but whether it is ketogenic in humans is unknown. This study aimed to evaluate the acute ketogenic effect of 2 doses of caffeine (2.5; 5.0 mg/kg) in 10 healthy adults. Caffeine given at breakfast significantly stimulated ketone production in a dose-dependent manner (+88%; +116%) and also raised plasma free fatty acids. Whether caffeine has long-term ketogenic effects or could enhance the ketogenic effect of medium chain triglycerides remains to be determined.

Biphasic effects of oxotremorine-M on turning behavior induced by caffeine in 6-OHDA-lesioned rats.

PubMed

Núñez-Taltavull, Juan Francisco; Prat, Gemma; Rubio, Antonia; Robledo, Patricia; Casas, Miguel

2004-12-03

This work studied the interactions between cholinergic and adenosine systems in the denervated striatum. For that purpose, we evaluated the effects of an intrastriatal administration of the muscarincic receptor agonist, oxotremorine-M on turning behavior induced by systemic caffeine in unilaterally 6-hydroxydopamine-lesioned rats. Low doses of oxotremorine-M (0.1 ng/microl) enhanced, whereas high doses (100 ng/microl) attenuated contralateral turning induced by caffeine. These results support a functional link between muscarinic and adenosinergic systems in the denervated striatum and suggest opposite actions of muscarinic M2 and M1 receptors on caffeine-induced turning behavior.

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

Acute caffeine administration effect on brain activation patterns in mild cognitive impairment.

PubMed

Haller, Sven; Montandon, Marie-Louise; Rodriguez, Cristelle; Moser, Dominik; Toma, Simona; Hofmeister, Jeremy; Sinanaj, Indrit; Lovblad, Karl-Olof; Giannakopoulos, Panteleimon

2014-01-01

Previous studies showed that acute caffeine administration enhances task-related brain activation in elderly individuals with preserved cognition. To explore the effects of this widely used agent on cognition and brain activation in early phases of cognitive decline, we performed a double-blinded, placebo-controlled functional magnetic resonance imaging (fMRI) study during an n-back working memory task in 17 individuals with mild cognitive impairment (MCI) compared to 17 age-matched healthy controls (HC). All individuals were regular caffeine consumers with an overnight abstinence and given 200 mg caffeine versus placebo tablets 30 minutes before testing. Analyses included assessment of task-related activation (general linear model), functional connectivity (tensorial-independent component analysis, TICA), baseline perfusion (arterial spin labeling, ASL), grey matter density (voxel-based morphometry, VBM), and white matter microstructure (tract-based spatial statistics, TBSS). Acute caffeine administration induced a focal activation of the prefrontal areas in HC with a more diffuse and posteromedial activation pattern in MCI individuals. In MCI, TICA documented a significant caffeine-related enhancement in the prefrontal cortex, supplementary motor area, ventral premotor and parietal cortex as well as the basal ganglia and cerebellum. The absence of significant group differences in baseline ASL perfusion patterns supports a neuronal rather than a purely vascular origin of these differences. The VBM and TBSS analyses excluded potentially confounding differences in grey matter density and white matter microstructure between MCI and HC. The present findings suggest a posterior displacement of working memory-related brain activation patterns after caffeine administration in MCI that may represent a compensatory mechanism to counterbalance a frontal lobe dysfunction.

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.

[Combined effect of cisplatin and caffeine on murine B16-BL6 melanoma cells].

PubMed

Yasutake, H; Tsuchiya, H; Sugihara, M; Tomita, K; Ueda, Y; Tanaka, M; Sasaki, T

1989-05-01

Combined effect of cisplatin and caffeine on murine B16-BL6 melanoma cells was studied. Synergistic inhibition of the cell growth was observed when caffeine (2 mM) was added continuously after one hour exposure of cisplatin. On the other hand, when caffeine was added before one hour exposure of cisplatin or one hour simultaneous exposure with cisplatin, synergistic effect was not shown. In the analysis of DNA histogram obtained from flow cytometry, S and G2/M accumulation was observed by the treatment of cisplatin and that accumulation was reduced by the combination of cisplatin and caffeine. From this findings, it was suggested that caffeine would inhibit DNA repair process. Furthermore, according to morphological studies with hematoxylin-eosin stain and Fontana-Masson stain, the addition of caffeine alone resulted in mild swelling of melanoma cells and the decrease of nuclear-cytoplasmic ratio. The combination of cisplatin and caffeine caused marked swelling of melanoma cells and remarkable increase of dendrite-like processes. Melanogenesis was also enhanced by the addition of these two drugs. Many matured melanosomes, increases of mitochondria, Golgi's apparatus and endoplasmic reticula were observed by the use of electron microscope. These findings implied that the combination of cisplatin and caffeine induced a differentiation of murine melanoma cells.

Effects of a single, oral 60 mg caffeine dose on attention in healthy adult subjects.

PubMed

Wilhelmus, Micha Mm; Hay, Justin L; Zuiker, Rob Gja; Okkerse, Pieter; Perdrieu, Christelle; Sauser, Julien; Beaumont, Maurice; Schmitt, Jeroen; van Gerven, Joop Ma; Silber, Beata Y

2017-02-01

Caffeine induces positive effects on sustained attention, although studies assessing the acute effects of low caffeine dose (<75 mg) on sustained attention are limited and use short-term tests. Therefore, we investigated the acute effects of a 60 mg dose of caffeine on sustained attention in tests lasting up to 45 minutes using 82 low or non-caffeine-consuming healthy male ( n=41) and female ( n=41) adults aged between 40 and 60 years. Vigilance was measured using Mackworth Clock test, Rapid Visual Information Processing Test, adaptive tracking test, saccadic eye movement and attention switch test. Effects on mood and fatigue were analysed using Bond and Lader and Caffeine Research visual analogue scales, and Samn-Perelli questionnaire. Saliva sampling was performed for both compliance and caffeine pharmacokinetic analysis. Administration of a 60 mg caffeine dose resulted in a significant improvement in sustained attention compared with the placebo. Also a significantly improved peak saccadic velocity and reaction time performance was found, and decreased error rate. Significantly increased feelings of alertness, contentment and overall mood after caffeine treatment compared with placebo were observed. This study demonstrated that in healthy adult subjects oral administration of a single 60 mg caffeine dose elicited a clear enhancement of sustained attention and alertness, measured both in multiple objective performances and in subjective scales.

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 Induces the Stress Response and Up-Regulates Heat Shock Proteins in Caenorhabditis elegans.

PubMed

Al-Amin, Mohammad; Kawasaki, Ichiro; Gong, Joomi; Shim, Yhong-Hee

2016-02-01

Caffeine has both positive and negative effects on physiological functions in a dose-dependent manner. C. elegans has been used as an animal model to investigate the effects of caffeine on development. Caffeine treatment at a high dose (30 mM) showed detrimental effects and caused early larval arrest. We performed a comparative proteomic analysis to investigate the mode of action of high-dose caffeine treatment in C. elegans and found that the stress response proteins, heat shock protein (HSP)-4 (endoplasmic reticulum [ER] chaperone), HSP-6 (mitochondrial chaperone), and HSP-16 (cytosolic chaperone), were induced and their expression was regulated at the transcriptional level. These findings suggest that high-dose caffeine intake causes a strong stress response and activates all three stress-response pathways in the worms, including the ER-, mitochondrial-, and cytosolic pathways. RNA interference of each hsp gene or in triple combination retarded growth. In addition, caffeine treatment stimulated a food-avoidance behavior (aversion phenotype), which was enhanced by RNAi depletion of the hsp-4 gene. Therefore, up-regulation of hsp genes after caffeine treatment appeared to be the major responses to alleviate stress and protect against developmental arrest.

Combined caffeine and carbohydrate ingestion: effects on nocturnal sleep and exercise performance in athletes.

PubMed

Miller, Ben; O'Connor, Helen; Orr, Rhonda; Ruell, Patricia; Cheng, Hoi Lun; Chow, Chin Moi

2014-12-01

In athletes, caffeine use is common although its effects on sleep have not been widely studied. This randomised, double-blind, placebo-controlled crossover trial investigated the effects of late-afternoon caffeine and carbohydrate-electrolyte (CEB) co-ingestion on cycling performance and nocturnal sleep. Six male cyclists/triathletes (age 27.5 ± 6.9 years) completed an afternoon training session (TS; cycling 80 min; 65% VO₂max) followed by a 5 kJ kg(-1) cycling time trial (TT). Caffeine (split dose 2 × 3 mg kg(-1)) or placebo was administered 1 h prior and 40 min into the TS. A 7.4% CEB (3 ml kg(-1) every 15 min) was administered during the TS, followed 30 min after by a standardised evening meal. Participants retired at their usual bedtime and indices of sleep duration and quality were monitored via polysomnography. mean ± SD. All participants performed better in the caffeine TT (caffeine 19.7 ± 3.3; placebo 20.5 ± 3.5 min; p = 0.006), while ratings of perceived exertion (caffeine 12.0 ± 0.6; placebo 12.9 ± 0.7; p = 0.004) and heart rate (caffeine 175 ± 6; placebo 167 ± 11 bpm; p = 0.085) were lower in the caffeine TS. Caffeine intake induced significant disruptions to a number of sleep indices including increased sleep onset latency (caffeine 51.1 ± 34.7; placebo 10.2 ± 4.2 min; p = 0.028) and decreased sleep efficiency (caffeine 76.1 ± 19.6; placebo 91.5 ± 4.2%; p = 0.028), rapid eye movement sleep (caffeine 62.1 ± 19.6; placebo 85.8 ± 24.7 min; p = 0.028) and total sleep time (caffeine 391 ± 97; placebo 464 ± 49 min; p = 0.028). This study supports a performance-enhancing effect of caffeine, although athletes (especially those using caffeine for late-afternoon/evening training and competition) should consider its deleterious effects on sleep.

Acute effects of theanine, caffeine and theanine-caffeine combination on attention.

PubMed

Kahathuduwa, Chanaka N; Dassanayake, Tharaka L; Amarakoon, A M Tissa; Weerasinghe, Vajira S

2017-07-01

l-theanine is a constituent of tea which is claimed to enhance cognitive functions. We aimed to determine whether theanine and theanine-caffeine combination have acute positive effects on cognitive and neurophysiological measures of attention, compared to caffeine (a positive control) and a placebo in healthy individuals. In a placebo-controlled, five-way crossover trial in 20 healthy male volunteers, we compared the effects of l-theanine (200 mg), caffeine (160 mg), their combination, black tea (one cup) and a placebo (distilled water) on cognitive (simple [SVRT] and recognition visual reaction time [RVRT]) and neurophysiological (event-related potentials [ERPs]) measures of attention. We also recorded visual (VEPs) and motor evoked potentials (MEPs) to examine any effects of treatments on peripheral visual and motor conduction, respectively. Mean RVRT was significantly improved by theanine (P = 0.019), caffeine (P = 0.043), and theanine-caffeine combination (P = 0.001), but not by tea (P = 0.429) or placebo (P = 0.822). VEP or MEP latencies or SVRT did not show significant inter-treatment differences. Theanine (P = 0.001) and caffeine (P = 0.001) elicited significantly larger mean peak-to-peak N2-P300 ERP amplitudes than the placebo, whereas theanine-caffeine combination elicited a significantly larger mean N2-P300 amplitude than placebo (P < 0.001), theanine (P = 0.029) or caffeine (P = 0.005). No significant theanine × caffeine interaction was observed for RVRT or N2-P300 amplitude. A dose of theanine equivalent of eight cups of back tea improves cognitive and neurophysiological measures of selective attention, to a degree that is comparable with that of caffeine. Theanine and caffeine seem to have additive effects on attention in high doses.

HR-TEM and FT-Raman dataset of the caffeine interacted Phe-Phe peptide nanotube for possible sensing applications.

PubMed

Narayanan, A Lakshmi; Dhamodaran, M; Solomon, J Samu; Karthikeyan, B; Govindhan, R

2018-02-01

Sensing ability of caffeine interaction with Phe-Phe annotates (PNTs), is presented (Govindhan et al., 2017; Karthikeyan et al., 2014; Tavagnacco et al., 2013; Kennedy et al., 2011; Wang et al., 2017) [1-5] in this data set. Investigation of synthesized caffeine carrying peptide nanotubes are carried out by FT-Raman spectral analysis and high resolution transmission electron microscopy (HR-TEM). Particle size of the caffeine loaded PNTs is < 40 nm. The FT-Raman spectrum signals are enhanced in the region of 400-1700 cm -1 . These data are ideal tool for the applications like biosensing and drug delivery research (DDS).

Assessment of the ergogenic effect of caffeine supplementation on mood, anticipation timing, and muscular strength in older adults

PubMed Central

Tallis, Jason; Duncan, Michael J; Wright, Sheila Leddington; Eyre, Emma L J; Bryant, Elizabeth; Langdon, Dominic; James, Rob S

2013-01-01

The effect of caffeine to promote improvements in mood, cognition, and exercise performance has been well established in young and athletic adults. However, little is known about whether such nutritional ergogenic aids are effective in enhancing psychological well-being, physiological or cognitive performance in older adults. This study assesses the ergogenic effect of caffeine on mood, perceptual-motor coupling, and muscular strength in an older human population. Following a familiarization session, 12 apparently healthy volunteers (nine females and three males; 69 ± 6 years) completed two laboratory visits. “Pre ingestion” trials of mood state Brunel Mood State Inventory (BRUMS) and coincidence anticipation performance (Bassin anticipation timer) at slow (3 mph) and fast (8 mph) stimulus speeds were completed on both visits. Using a randomized, double-blind, cross-over design, participants consumed either caffeine (3 mg/kg body mass) or a placebo. Sixty minutes postingestion participants repeated the trials before completing a set of 10 consecutive repetitions of maximal knee extension using isokinetic dynamometry. Rating of perceived exertion (RPE) was assessed following the fifth and final repetition. Caffeine ingestion significantly improved mood state scores for vigor by 17% (P = 0.009) and reduced absolute error by 35% (P = 0.045) during coincidence anticipation assessment at 8 mph compared to placebo. There were no other significant effects. Caffeine ingestion failed to augment maximal voluntary contraction of the knee extensors and RPE did not prove to be significantly different to from placebo (P > 0.33 in each case). Acute caffeine ingestion may not be an effective ergogenic aid for improving muscular strength in older adults but could possibly be used as a nutrition supplement for enhancing mood and improving cognitive performance in daily living tasks where interceptive timing skills are required. PMID:24303144

Enhanced mood and psychomotor performance by a caffeine-containing energy capsule in fatigued individuals.

PubMed

Childs, Emma; de Wit, Harriet

2008-02-01

Caffeine produces mild psychostimulant effects that may be particularly evident in individuals whose mood or performance is impaired by sleep restriction or caffeine withdrawal. Caffeinated energy drinks have been shown to improve energy and cognition but expectancy effects cannot be ruled out in these studies. Very few studies have examined the effects of caffeine-containing energy capsules upon behavioral and subjective measures. This study compared the effects of a caffeine-containing (200 mg) supplement (CAF) or placebo in capsule form after prolonged wakefulness, in participants who varied in their level of habitual caffeine use. Thirty-five healthy volunteers (16 male, 19 female) participated in two experimental sessions in which they remained awake between 5 p.m. and 5 a.m. At 3:30 a.m. they consumed CAF or placebo in random order under double-blind conditions. Participants completed subjective effects questionnaires and performed computerized attention tasks before and after consuming capsules. Heart rate and blood pressure were monitored at regular intervals. Compared to measures at 5 p.m., participants reported more tiredness and mood disturbance at 3 a.m., and exhibited longer reaction times and more attentional lapses. Heavier caffeine consumers exhibited the greatest decreases in Profile of Mood States (POMS) Vigor. CAF produced stimulant-like effects and significantly improved mood and reaction times upon the tasks. These effects did not vary with level of habitual caffeine consumption. These findings indicate that consumption of a caffeine-containing food supplement improves subjective state and cognitive performance in fatigued individuals that is likely a result of its caffeine content. 2008 APA

Effect of Caffeine on Oxidative Stress During Maximum Incremental Exercise

PubMed Central

Olcina, Guillermo J.; Muñoz, Diego; Timón, Rafael; Caballero, M. Jesús; Maynar, Juan I.; Córdova, Alfredo; Maynar, Marcos

2006-01-01

Caffeine (1,3,7-trimethylxanthine) is an habitual substance present in a wide variety of beverages and in chocolate-based foods and it is also used as adjuvant in some drugs. The antioxidant ability of caffeine has been reported in contrast with its pro- oxidant effects derived from its action mechanism such as the systemic release of catecholamines. The aim of this work was to evaluate the effect of caffeine on exercise oxidative stress, measuring plasma vitamins A, E, C and malonaldehyde (MDA) as markers of non enzymatic antioxidant status and lipid peroxidation respectively. Twenty young males participated in a double blind (caffeine 5mg·kg- 1 body weight or placebo) cycling test until exhaustion. In the exercise test, where caffeine was ingested prior to the test, exercise time to exhaustion, maximum heart rate, and oxygen uptake significantly increased, whereas respiratory exchange ratio (RER) decreased. Vitamins A and E decreased with exercise and vitamin C and MDA increased after both the caffeine and placebo tests but, regarding these particular variables, there were no significant differences between the two test conditions. The results obtained support the conclusion that this dose of caffeine enhances the ergospirometric response to cycling and has no effect on lipid peroxidation or on the antioxidant vitamins A, E and C. Key Points Caffeine ingestion may improve maximal aerobic performance in non trained men. Cellular oxidative damage is not altered by caffeine ingestion in maximal aerobic exercises. Antioxidant response to exercise, vitamins A, E and C, is not modified by caffeine action in maximal aerobic efforts. PMID:24357958

Caffeine dosing strategies to optimize alertness during sleep loss.

PubMed

Vital-Lopez, Francisco G; Ramakrishnan, Sridhar; Doty, Tracy J; Balkin, Thomas J; Reifman, Jaques

2018-05-28

Sleep loss, which affects about one-third of the US population, can severely impair physical and neurobehavioural performance. Although caffeine, the most widely used stimulant in the world, can mitigate these effects, currently there are no tools to guide the timing and amount of caffeine consumption to optimize its benefits. In this work, we provide an optimization algorithm, suited for mobile computing platforms, to determine when and how much caffeine to consume, so as to safely maximize neurobehavioural performance at the desired time of the day, under any sleep-loss condition. The algorithm is based on our previously validated Unified Model of Performance, which predicts the effect of caffeine consumption on a psychomotor vigilance task. We assessed the algorithm by comparing the caffeine-dosing strategies (timing and amount) it identified with the dosing strategies used in four experimental studies, involving total and partial sleep loss. Through computer simulations, we showed that the algorithm yielded caffeine-dosing strategies that enhanced performance of the predicted psychomotor vigilance task by up to 64% while using the same total amount of caffeine as in the original studies. In addition, the algorithm identified strategies that resulted in equivalent performance to that in the experimental studies while reducing caffeine consumption by up to 65%. Our work provides the first quantitative caffeine optimization tool for designing effective strategies to maximize neurobehavioural performance and to avoid excessive caffeine consumption during any arbitrary sleep-loss condition. © 2018 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.

The Effects of Preexercise Caffeinated Coffee Ingestion on Endurance Performance: An Evidence-Based Review.

PubMed

Higgins, Simon; Straight, Chad R; Lewis, Richard D

2016-06-01

Endurance athletes commonly ingest caffeine as a means to enhance training intensity and competitive performance. A widely-used source of caffeine is coffee, however conflicting evidence exists regarding the efficacy of coffee in improving endurance performance. In this context, the aims of this evidence-based review were threefold: 1) to evaluate the effects of preexercise coffee on endurance performance, 2) to evaluate the effects of coffee on perceived exertion during endurance performance, and 3) to translate the research into usable information for athletes to make an informed decision regarding the intake of caffeine via coffee as a potential ergogenic aid. Searches of three major databases were performed using terms caffeine and coffee, or coffee-caffeine, and endurance, or aerobic. Included studies (n = 9) evaluated the effects of caffeinated coffee on human subjects, provided the caffeine dose administered, administered caffeine ≥ 45 min before testing, and included a measure of endurance performance (e.g., time trial). Significant improvements in endurance performance were observed in five of nine studies, which were on average 24.2% over controls for time to exhaustion trials, and 3.1% for time to completion trials. Three of six studies found that coffee reduced perceived exertion during performance measures significantly more than control conditions (p < .05). Based on the reviewed studies there is moderate evidence supporting the use of coffee as an ergogenic aid to improve performance in endurance cycling and running. Coffee providing 3-8.1 mg/kg (1.36-3.68 mg/lb) of caffeine may be used as a safe alternative to anhydrous caffeine to improve endurance performance.

Chronic treatment with caffeine and its withdrawal modify the antidepressant-like activity of selective serotonin reuptake inhibitors in the forced swim and tail suspension tests in mice. Effects on Comt, Slc6a15 and Adora1 gene expression.

PubMed

Szopa, Aleksandra; Doboszewska, Urszula; Herbet, Mariola; Wośko, Sylwia; Wyska, Elżbieta; Świąder, Katarzyna; Serefko, Anna; Korga, Agnieszka; Wlaź, Aleksandra; Wróbel, Andrzej; Ostrowska, Marta; Terlecka, Joanna; Kanadys, Adam; Poleszak, Ewa; Dudka, Jarosław; Wlaź, Piotr

2017-12-15

Recent preclinical and clinical data suggest that low dose of caffeine enhances the effects of common antidepressants. Here we investigated the effects of chronic administration of caffeine (5mg/kg, twice daily for 14days) and its withdrawal on day 15th on the activity of per se ineffective doses of fluoxetine (5mg/kg) and escitalopram (2mg/kg) given on day 15th. We found decreased immobility time in the forced swim and tail suspension tests in mice in which caffeine was administered simultaneously with antidepressants on day 15th following a 14-day caffeine treatment and no alterations in the spontaneous locomotor activity. A decrease in the level of escitalopram and an increase in the level of caffeine in serum were observed after concomitant administration of these compounds, while the joint administration of caffeine and fluoxetine was not associated with changes in their levels in serum or brain. Caffeine withdrawal caused a decrease in Adora1 mRNA level in the cerebral cortex (Cx). Administration of escitalopram or fluoxetine followed by caffeine withdrawal caused an increase in this gene expression, whereas administration of escitalopram, but not fluoxetine, on day 15th together with caffeine caused a decrease in Adora1 mRNA level in the Cx. Furthermore, antidepressant-like activity observed after joint administration of the tested drugs with caffeine was associated with decreased Slc6a15 mRNA level in the Cx. The results show that withdrawal of caffeine after its chronic intake may change activity of antidepressants with concomitant alterations within monoamine, adenosine and glutamate systems. Copyright © 2017 Elsevier Inc. All rights reserved.

Caffeinated Energy Drinks -- A Growing Problem

PubMed Central

Reissig, Chad J.; Strain, Eric C.; Griffiths, Roland R.

2009-01-01

Since the introduction of Red Bull in Austria in 1987 and in the United States in 1997, the energy drink market has grown exponentially. Hundreds of different brands are now marketed, with caffeine content ranging from a modest 50 mg to an alarming 505 mg per can or bottle. Regulation of energy drinks, including content labeling and health warnings differs across countries, with some of the most lax regulatory requirements in the U.S. The absence of regulatory oversight has resulted in aggressive marketing of energy drinks, targeted primarily toward young males, for psychoactive, performance-enhancing and stimulant drug effects. There are increasing reports of caffeine intoxication from energy drinks, and it seems likely that problems with caffeine dependence and withdrawal will also increase. In children and adolescents who are not habitual caffeine users, vulnerability to caffeine intoxication may be markedly increased due to an absence of pharmacological tolerance. Genetic factors may also contribute to an individual’s vulnerability to caffeine related disorders including caffeine intoxication, dependence, and withdrawal. The combined use of caffeine and alcohol is increasing sharply, and studies suggest that such combined use may increase the rate of alcohol-related injury. Several studies suggest that energy drinks may serve as a gateway to other forms of drug dependence. Regulatory implications concerning labeling and advertising, and the clinical implications for children and adolescents are discussed. PMID:18809264

Caffeinated energy drinks--a growing problem.

PubMed

Reissig, Chad J; Strain, Eric C; Griffiths, Roland R

2009-01-01

Since the introduction of Red Bull in Austria in 1987 and in the United States in 1997, the energy drink market has grown exponentially. Hundreds of different brands are now marketed, with caffeine content ranging from a modest 50 mg to an alarming 505 mg per can or bottle. Regulation of energy drinks, including content labeling and health warnings differs across countries, with some of the most lax regulatory requirements in the U.S. The absence of regulatory oversight has resulted in aggressive marketing of energy drinks, targeted primarily toward young males, for psychoactive, performance-enhancing and stimulant drug effects. There are increasing reports of caffeine intoxication from energy drinks, and it seems likely that problems with caffeine dependence and withdrawal will also increase. In children and adolescents who are not habitual caffeine users, vulnerability to caffeine intoxication may be markedly increased due to an absence of pharmacological tolerance. Genetic factors may also contribute to an individual's vulnerability to caffeine-related disorders including caffeine intoxication, dependence, and withdrawal. The combined use of caffeine and alcohol is increasing sharply, and studies suggest that such combined use may increase the rate of alcohol-related injury. Several studies suggest that energy drinks may serve as a gateway to other forms of drug dependence. Regulatory implications concerning labeling and advertising, and the clinical implications for children and adolescents are discussed.

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.

What can isolated skeletal muscle experiments tell us about the effects of caffeine on exercise performance?

PubMed Central

Tallis, Jason; Duncan, Michael J; James, Rob S

2015-01-01

Caffeine is an increasingly popular nutritional supplement due to the legal, significant improvements in sporting performance that it has been documented to elicit, with minimal side effects. Therefore, the effects of caffeine on human performance continue to be a popular area of research as we strive to improve our understanding of this drug and make more precise recommendations for its use in sport. Although variations in exercise intensity seems to affect its ergogenic benefits, it is largely thought that caffeine can induce significant improvements in endurance, power and strength-based activities. There are a number of limitations to testing caffeine-induced effects on human performance that can be better controlled when investigating its effects on isolated muscles under in vitro conditions. The hydrophobic nature of caffeine results in a post-digestion distribution to all tissues of the body making it difficult to accurately quantify its key mechanism of action. This review considers the contribution of evidence from isolated muscle studies to our understating of the direct effects of caffeine on muscle during human performance. The body of in vitro evidence presented suggests that caffeine can directly potentiate skeletal muscle force, work and power, which may be important contributors to the performance-enhancing effects seen in humans. PMID:25988508

Comparing the benefits of caffeine, naps and placebo on verbal, motor and perceptual memory.

PubMed

Mednick, Sara C; Cai, Denise J; Kanady, Jennifer; Drummond, Sean P A

2008-11-03

Caffeine, the world's most common psychoactive substance, is used by approximately 90% of North Americans everyday. Little is known, however, about its benefits for memory. Napping has been shown to increase alertness and promote learning on some memory tasks. We directly compared caffeine (200mg) with napping (60-90min) and placebo on three distinct memory processes: declarative verbal memory, procedural motor skills, and perceptual learning. In the verbal task, recall and recognition for unassociated words were tested after a 7h retention period (with a between-session nap or drug intervention). A second, different, word list was administered post-intervention and memory was tested after a 20min retention period. The non-declarative tasks (finger tapping task (FTT) and texture discrimination task (TDT)) were trained before the intervention and then retested afterwards. Naps enhanced recall of words after a 7h and 20min retention interval relative to both caffeine and placebo. Caffeine significantly impaired motor learning compared to placebo and naps. Napping produced robust perceptual learning compared with placebo; however, naps and caffeine were not significantly different. These findings provide evidence of the limited benefits of caffeine for memory improvement compared with napping. We hypothesize that impairment from caffeine may be restricted to tasks that contain explicit information; whereas strictly implicit learning is less compromised.

(-)-Epigallocatechin-3-O-gallate (EGCG) attenuates the hemodynamics stimulated by caffeine through decrease of catecholamines release.

PubMed

Han, Jin-Yi; Moon, Yong-Jin; Han, Jong-Hyun; Kim, Jong-Hoon; Woo, Jae-Hoon; Yoo, Hwan-Soo; Hong, Jin Tae; Ahn, Hee-Yul; Hong, Jong-Myeon; Oh, Ki-Wan

2016-09-01

A human study of the effects on hemodynamics of caffeine and epigallocatechin-3-O-gallate (EGCG) was performed. Caffeine tablets (200 mg) were orally administered to healthy males aged between 25 and 35 years 30 min after oral administration of EGCG tablets (100 and 200 mg). The increase in BP induced by caffeine was inhibited when co-administrated with EGCG. We found that caffeine slightly decreased heart rate (HR) in the volunteers. Although EGCG enhanced HR reduction, the effect was not significant. In addition, caffeine increased blood catecholamine levels, but EGCG inhibited the increase in noradrenaline, adrenaline and dopamine levels induced by caffeine. Whether EGCG decreases the elevated HR and systolic perfusion pressure, and ventricular contractility induced by adrenergic agonists in the isolated rat heart was investigated. The modified Krebs-Henseleit solution was perfused through a Langendorff apparatus to the isolated hearts of rats. HR, systolic perfusion pressure, and developed maximal rates of contraction (+dP/dtmax) and relaxation (-dP/dtmax) were increased by epinephrine (EP) and isoproterenol (IP). In contrast, EGCG decreased the elevated HR, systolic perfusion pressure, and left ventricular ±dp/dtmax induced by EP and/or IP. In conclusion, EGCG could attenuate the hemodynamics stimulated by caffeine through decreasing catecholamine release.

Methylphenidate, modafinil, and caffeine for cognitive enhancement in chess: A double-blind, randomised controlled trial.

PubMed

Franke, Andreas G; Gränsmark, Patrik; Agricola, Alexandra; Schühle, Kai; Rommel, Thilo; Sebastian, Alexandra; Balló, Harald E; Gorbulev, Stanislav; Gerdes, Christer; Frank, Björn; Ruckes, Christian; Tüscher, Oliver; Lieb, Klaus

2017-03-01

Stimulants and caffeine have been proposed for cognitive enhancement by healthy subjects. This study investigated whether performance in chess - a competitive mind game requiring highly complex cognitive skills - can be enhanced by methylphenidate, modafinil or caffeine. In a phase IV, randomized, double-blind, placebo-controlled trial, 39 male chess players received 2×200mg modafinil, 2×20mg methylphenidate, and 2×200mg caffeine or placebo in a 4×4 crossover design. They played twenty 15-minute games during two sessions against a chess program (Fritz 12; adapted to players' strength) and completed several neuropsychological tests. Marked substance effects were observed since all three substances significantly increased average reflection time per game compared to placebo resulting in a significantly increased number of games lost on time with all three treatments. Treatment effects on chess performance were not seen if all games (n=3059) were analysed. Only when controlling for game duration as well as when excluding those games lost on time, both modafinil and methylphenidate enhanced chess performance as demonstrated by significantly higher scores in the remaining 2876 games compared to placebo. In conjunction with results from neuropsychological testing we conclude that modifying effects of stimulants on complex cognitive tasks may in particular result from more reflective decision making processes. When not under time pressure, such effects may result in enhanced performance. Yet, under time constraints more reflective decision making may not improve or even have detrimental effects on complex task performance. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

Effects of catechins and caffeine on the development of atherosclerosis in mice.

PubMed

Liu, Litong; Nagai, Izumi; Gao, Ying; Matsushima, Yoshibumi; Kawai, Yoshichika; Sayama, Kazutoshi

2017-10-01

Atherosclerosis is one of the diseases related to metabolic syndrome which is caused by obesity. Previous reports have shown that green tea and its components have anti-obesity effect. We examined whether catechins and caffeine can prevent the development of atherosclerosis by oral administration, singly or in combination to the atherosclerosis model mice. Results demonstrated that the number of atherosclerotic regions in the aorta was significantly reduced by the combined treatment, and the atherosclerotic area was also improved. Serum HDL-C increased by caffeine single treatment, but no effect on the TG and TC by any treatments. Moreover, ECG illuviated to atheromatous lesions in aorta and the illuviation was enhanced by caffeine. The mRNA expression levels of LOX-1 and TNF-α showed a tendency to suppress by the combined treatment. These results indicated that the combined administration of catechins and caffeine has the inhibitory effect on the development of atherosclerosis in mice.

Energy Drinks: Implications for the Breastfeeding Mother.

PubMed

Thorlton, Janet; Ahmed, Azza; Colby, David A

2016-01-01

Breastfeeding women may experience disrupted sleep schedules and be tempted to turn to popular energy drinks to reduce fatigue and enhance alertness, prompting the question: What are the maternal and child health implications for breastfeeding mothers consuming energy drinks? Caffeine and vitamin-rich energy drinks contain a variety of herbal ingredients and vitamins; however, ingredient amounts may not be clearly disclosed on product labels. Interactions between herbal ingredients and caffeine are understudied and not well defined in the literature. Some infants can be sensitive to caffeine and display increased irritability and sleep disturbances when exposed to caffeine from breastmilk. Breastfeeding women who consume energy drinks may be ingesting herbal ingredients that have not undergone scientific evaluation, and if taking prenatal vitamins, may unknowingly exceed the recommended daily intake. Caffeinated products are marketed in newer ways, fueling concerns about health consequences of caffeine exposure. We present implications associated with consumption of caffeine and vitamin-rich energy drinks among breastfeeding women. Product safety, labeling, common ingredients, potential interactions, and clinical implications are discussed. Healthcare providers should encourage breastfeeding women to read product labels for ingredients, carbohydrate content, serving size, and to discourage consumption of energy drinks when breastfeeding and/or taking prenatal vitamins, to avoid potential vitamin toxicity.

Coffee with co-workers: role of caffeine on evaluations of the self and others in group settings.

PubMed

Unnava, Vasu; Singh, Amit Surendra; Unnava, H Rao

2018-03-01

This research explores the effect of consuming a moderate amount of commercially available caffeinated coffee on an individual's self-evaluated participation in a group activity and subsequent evaluations of the experience. Across two studies, results show that consuming a moderate amount of caffeinated coffee prior to indulging in a group activity enhances an individual's task-relevant participation in the group activity. In addition, subjective evaluations of the participation of other group members and oneself are also positively influenced. Finally, the positive impact of consuming a moderate amount of caffeinated coffee on the evaluation of participation of other group members and oneself is moderated by a sense of an increased level of alertness.

Use of Taguchi methodology to enhance the yield of caffeine removal with growing cultures of Pseudomonas pseudoalcaligenes.

PubMed

Ashengroph, Morahem; Ababaf, Sajad

2014-12-01

Microbial caffeine removal is a green solution for treatment of caffeinated products and agro-industrial effluents. We directed this investigation to optimizing a bio-decaffeination process with growing cultures of Pseudomonas pseudoalcaligenes through Taguchi methodology which is a structured statistical approach that can be lowered variations in a process through Design of Experiments (DOE). Five parameters, i.e. initial fructose, tryptone, Zn(+2) ion and caffeine concentrations and also incubation time selected and an L16 orthogonal array was applied to design experiments with four 4-level factors and one 3-level factor (4(4) × 1(3)). Data analysis was performed using the statistical analysis of variance (ANOVA) method. Furthermore, the optimal conditions were determined by combining the optimal levels of the significant factors and verified by a confirming experiment. Measurement of residual caffeine concentration in the reaction mixture was performed using high-performance liquid chromatography (HPLC). Use of Taguchi methodology for optimization of design parameters resulted in about 86.14% reduction of caffeine in 48 h incubation when 5g/l fructose, 3 mM Zn(+2) ion and 4.5 g/l of caffeine are present in the designed media. Under the optimized conditions, the yield of degradation of caffeine (4.5 g/l) by the native strain of Pseudomonas pseudoalcaligenes TPS8 has been increased from 15.8% to 86.14% which is 5.4 fold higher than the normal yield. According to the experimental results, Taguchi methodology provides a powerful methodology for identifying the favorable parameters on caffeine removal using strain TPS8 which suggests that the approach also has potential application with similar strains to improve the yield of caffeine removal from caffeine containing solutions.

Maternal glucocorticoid elevation and associated blood metabonome changes might be involved in metabolic programming of intrauterine growth retardation in rats exposed to caffeine prenatally

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

Kou, Hao; Liu, Yansong; Liang, Gai

Our previous studies demonstrated that prenatal caffeine exposure causes intrauterine growth retardation (IUGR), fetuses are over-exposed to high levels of maternal glucocorticoids (GC), and intrauterine metabolic programming and associated metabonome alteration that may be GC-mediated. However, whether maternal metabonomes would be altered and relevant metabolite variations might mediate the development of IUGR remained unknown. In the present studies, we examined the dose- and time-effects of caffeine on maternal metabonome, and tried to clarify the potential roles of maternal GCs and metabonome changes in the metabolic programming of caffeine-induced IUGR. Pregnant rats were treated with caffeine (0, 20, 60 or 180more » mg/kg · d) from gestational days (GD) 11 to 20, or 180 mg/kg · d caffeine from GD9. Metabonomes of maternal plasma on GD20 in the dose–effect study and on GD11, 14 and 17 in the time–course study were analyzed by {sup 1}H nuclear magnetic resonance spectroscopy, respectively. Caffeine administration reduced maternal weight gains and elevated both maternal and fetal corticosterone (CORT) levels. A negative correlation between maternal/fetal CORT levels and fetal bodyweight was observed. The maternal metabonome alterations included attenuated metabolism of carbohydrates, enhanced lipolysis and protein breakdown, and amino acid accumulation, suggesting GC-associated metabolic effects. GC-associated metabolite variations (α/β-glucoses, high density lipoprotein-cholesterol, β-hydroxybutyrate) were observed early following caffeine administration. In conclusion, prenatal caffeine exposure induced maternal GC elevation and metabonome alteration, and maternal GC and relevant discriminatory metabolites might be involved in the metabolic programming of caffeine-induced IUGR. - Highlights: • Prenatal caffeine exposure elevated maternal blood glucocorticoid levels. • Prenatal caffeine exposure altered maternal blood metabonomes. • Maternal metabonome alterations were associated with glucocorticoid elevation. • Maternal metabonomes were altered at early stage after caffeine exposure. • Maternal glucocorticoid and associated metabolites may be involved in fetal programming.« less

Caffeine impairs the acquisition and retention, but not the consolidation of Pavlovian conditioned freezing in mice

PubMed Central

Dubroqua, Sylvain; Low, Samuel R.L.; Yee, Benjamin K.; Singer, Philipp

2014-01-01

Rationale The psychoactive substance, caffeine may improve cognitive performance, but its direct impact on learning and memory remains ill-defined. Conflicting reports suggest that caffeine may impair as well as enhance Pavlovian fear conditioning in animals, and its effect may vary across different phases of learning. Objectives To dissect the effect of a motor-stimulant dose of caffeine (30 mg/kg i.p.) on acquisition, retrieval or consolidation of conditioned fear in C57BL/6 mice. Methods Fear conditioning was evaluated in a conditioned freezing paradigm comprising 3 tone-shock pairings and a two-way active avoidance paradigm lasting two consecutive days with 80 conditioning trials per test session. Results Conditioning to both the discrete tone conditioned stimulus (CS) and the context was markedly impaired by caffeine. The deficits were similarly evident when caffeine was administered prior to acquisition or retrieval (48 and 72 h after conditioning); and the most severe impairment was seen in animals given caffeine before acquisition and before retrieval. A comparable deficit was observed in the conditioned active avoidance test. By contrast, caffeine administered immediately following acquisition neither affected the expression of tone freezing nor context freezing. Conclusions The present study challenges the previous report that caffeine primarily disrupts hippocampus-dependent conditioning to the context. At the relevant dose range, acute caffeine likely exerts more widespread impacts beyond the hippocampus, including amygdala and striatum that are anatomically connected to the hippocampus; and together they support the acquisition and retention of fear memories to discrete stimuli as well as diffused contextual cues. PMID:25172668

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.

Caffeine ingestion enhances perceptual responses during intermittent exercise in female team-game players.

PubMed

Ali, Ajmol; O'Donnell, Jemma; Von Hurst, Pamela; Foskett, Andrew; Holland, Sherina; Starck, Carlene; Rutherfurd-Markwick, Kay

2016-01-01

We examined the influence of caffeine supplementation on cognitive performance and perceptual responses in female team-game players taking low-dose monophasic oral contraceptives of the same hormonal composition. Ten females (24 ± 4 years; 59.7 ± 3.5 kg body mass; 2-6 training sessions per week) took part in a randomised, double-blind, placebo-controlled crossover-design trial. A 90-min intermittent treadmill-running protocol was completed 60 min following ingestion of a capsule containing either 6 mg • kg(-1) anhydrous caffeine or artificial sweetener (placebo). Perceptual responses (ratings of perceived exertion (RPE), feeling scale (FS), felt arousal scale (FAS)), mood (profile of mood states (POMS)) and cognitive performance (Stroop test, choice reaction time (CRT)) were completed before, during and after the exercise protocol, as well as after ~12 h post exercise. Caffeine ingestion significantly enhanced the ratings of pleasure (P = 0.008) and arousal (P = 0.002) during the exercise protocol, as well as increased vigour (POMS; P = 0.007), while there was a tendency for reduced fatigue (POMS; P = 0.068). Caffeine ingestion showed a tendency to decrease RPE (P = 0.068) and improve reaction times in the Stroop (P = 0.072) and CRT (P = 0.087) tests. Caffeine supplementation showed a positive effect on perceptual parameters by increasing vigour and a tendency to decrease fatigue during intermittent running activity in female games players taking low-dose monophasic oral contraceptive steroids (OCS).

Dose response effects of a caffeine-containing energy drink on muscle performance: a repeated measures design

PubMed Central

2012-01-01

Background Energy drinks have become the most used caffeine-containing beverages in the sport setting. The aim of this study was to determine the effects of two doses of a caffeine-containing energy drink on muscle performance during upper- and lower-body power-load tests. Methods In a randomized order, twelve active participants ingested 1 and 3 mg of caffeine per kg of body weight using a commercially available energy drink (Fure®, ProEnergetics) or the same drink without caffeine (placebo; 0 mg/kg). After sixty minutes, resting metabolic rate, heart rate and blood pressure were determined. Then, half-squat and bench-press power production with loads from 10 to 100% of 1 repetition maximum was determined using a rotator encoder. Results In comparison to the placebo, the ingestion of the caffeinated drink increased mean arterial pressure (82 ± 7 < 88 ± 8 ≈ 90 ± 6 mmHg for 0 mg/kg, 1 mg/kg, 3 mg/kg of caffeine, respectively; P < 0.05) and heart rate (57 ± 7 < 59 ± 8 < 62 ± 8 beats/min, respectively; P < 0.05) at rest in a dose response manner, though it did not affect resting metabolic rate. While the ingestion of 1 mg/kg of caffeine did not affect maximal power during the power-load tests with respect to the placebo, 3 mg/kg increased maximal power in the half-squat (2554 ± 167 ≈ 2549 ± 161 < 2726 ± 167 W, respectively; P < 0.05) and bench-press actions (349 ± 34 ≈ 358 ± 35 < 375 ± 33 W, respectively; P < 0.05). Conclusions A caffeine dose of at least 3 mg/kg in the form of an energy drink is necessary to significantly improve half-squat and bench-press maximal muscle power. PMID:22569090

Altered brain serotonergic neurotransmission following caffeine withdrawal produces behavioral deficits in rats.

PubMed

Khaliq, Saima; Haider, Saida; Naqvi, Faizan; Perveen, Tahira; Saleem, Sadia; Haleem, Darakhshan Jabeen

2012-01-01

Caffeine administration has been shown to enhance performance and memory in rodents and humans while its withdrawal on the other hand produces neurobehavioral deficits which are thought to be mediated by alterations in monoamines neurotransmission. A role of decreased brain 5-HT (5-hydroxytryptamine, serotonin) levels has been implicated in impaired cognitive performance and depression. Memory functions of rats were assessed by Water Maze (WM) and immobility time by Forced Swim Test (FST). The results of this study showed that repeated caffeine administration for 6 days at 30 mg/kg dose significantly increases brain 5-HT (p<0.05) and 5-HIAA (p<0.05) levels and its withdrawal significantly (p<0.05) decreased brain 5-HT levels. A significant decrease in latency time was exhibited by rats in the WM repeatedly injected with caffeine. Withdrawal of caffeine however produced memory deficits and significantly increases the immobility time of rats in FST. The results of this study are linked with caffeine induced alterations in serotonergic neurotransmission and its role in memory and depression.

(-)Ephedrine and caffeine mutually potentiate one another's amphetamine-like stimulus effects.

PubMed

Young, R; Gabryszuk, M; Glennon, R A

1998-10-01

Using rats trained to discriminate 1 mg/kg of (+)amphetamine (ED50 = 0.4 mg/kg) from saline vehicle in a two-lever drug discrimination procedure, it was shown that (-)ephedrine (ED50 = 4.5 mg/kg), but not (+)ephedrine, substitutes for the (+)AMPH stimulus. It was also shown that caffeine (ED50 = 12.9 mg/kg) can substitute for (+)amphetamine in a dose-related fashion. Doses of (-)ephedrine and caffeine, which produced < or = 1% drug-appropriate responding when administered alone, were able to enhance each other's stimulus effects when administered in combination such that there was a twofold leftward shift in their respective dose-response curves. Furthermore, stimulus generalization occurred when a dose of caffeine that produced saline-appropriate responding when administered alone was administered in combination with (+)ephedrine. It would appear that low doses of (-)ephedrine and caffeine may mutually potentiate one another's stimulus effects in (+)AMPH-trained rats, and that a combination of caffeine and (+)ephedrine result in altered stimulus character when compared to comparable doses of either agent administered alone.

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.

Effect of caffeine on motility and vitality of sperm and in vitro fertilization of outbreed mouse in T6 and M16 media.

PubMed

Nabavi, Narges; Todehdehghan, Fatemeh; Shiravi, Abdollhossein

2013-09-01

Caffeine increases the CAMP production that stimulates spermatozoa movement. Caffeine is also used for induction of in vitro acrosome reaction in mammalian spermatozoa, an important step in achieving fertilization. The aim of this study was to assess the effect of caffeine on sperm's motility, vitality and laboratory fertilization rates in mouse in two T6 and M16 media. Epididymal mouse sperms were collected and treated by caffine in T6 and M16 media and their motility and vitality rates were evaluated. The pretreated sperms were added to oocytes in T6 and M16 media with and without caffeine and fertilization rates were recorded after 24 hours incubation. Sperm's motility (81.7±1.67%) and vitality (88.7±1.33%) rates and percentage of fertilized oocytes (67.52±8.16%) in T6 medium plus caffeine compare to control group have increased and shown significant differences at p≤0.01. While the percentages of these parameters in M16 medium supplemented with caffeine were 68.3±6.01%, 78±6.11%, and 42.6±12.96 respectively and in comparison to control group (M16 without caffeine) have not shown significant differences. Addition of caffeine to T6 medium promotes the sperm's motility and vitality and enhances fertilization and early in vitro development of mouse embryos. This article extracted from M.Sc. thesis. (Narges Navabi).

Effects of hyperoxia and caffeine on the expression of fragile site at Xq27.3

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

Rafi, S.K.; Surana, R.B.; Christopher, K.L.

1996-02-02

To enhance the cytogenetic expression of the fragile X chromosome, we studied the effects of hyperoxia and caffeine on the induction of fragile Xq27.3. A lymphoblastoid cell line (GM 06912) derived from a fragile X male proband was cultured in RPMI 1640 containing 16% dialyzed fetal calf serum. The cells were synchronously subjected to one of 3 different atmospheric oxygen tensions (21%, 21.3 kPa, hyperoxic) during the last 24 hours of the 72 hour culture, immediately after the addition of 2{prime}-deoxy-5-fluorouridine (FUdR) at 25 ng/ml. To study the enhancing effect of caffeine, with or without hyperoxia, a second set ofmore » cultures was additionally subjected to caffeine (2.5 mM) during the last 6 hours of the culture. When the fragility of hyperoxic cells (38.1 kPa dissolved oxygen) was compared to that of normoxic control cells (13.3 kPa dissolved oxygen), the difference was significant (P < 0.05). These data suggest that there is a mean increase in the fragile Xq27.3 expressivity as the dissolved oxygen tension increases. Additionally, we observed that caffeine, with or without hyperoxia, significantly (P <0.05) suppressed the expression of the fragile X site in this lymphoblastoid cell line. 34 refs., 2 tabs.« less

The Tea Tree Genome Provides Insights into Tea Flavor and Independent Evolution of Caffeine Biosynthesis.

PubMed

Xia, En-Hua; Zhang, Hai-Bin; Sheng, Jun; Li, Kui; Zhang, Qun-Jie; Kim, Changhoon; Zhang, Yun; Liu, Yuan; Zhu, Ting; Li, Wei; Huang, Hui; Tong, Yan; Nan, Hong; Shi, Cong; Shi, Chao; Jiang, Jian-Jun; Mao, Shu-Yan; Jiao, Jun-Ying; Zhang, Dan; Zhao, Yuan; Zhao, You-Jie; Zhang, Li-Ping; Liu, Yun-Long; Liu, Ben-Ying; Yu, Yue; Shao, Sheng-Fu; Ni, De-Jiang; Eichler, Evan E; Gao, Li-Zhi

2017-06-05

Tea is the world's oldest and most popular caffeine-containing beverage with immense economic, medicinal, and cultural importance. Here, we present the first high-quality nucleotide sequence of the repeat-rich (80.9%), 3.02-Gb genome of the cultivated tea tree Camellia sinensis. We show that an extraordinarily large genome size of tea tree is resulted from the slow, steady, and long-term amplification of a few LTR retrotransposon families. In addition to a recent whole-genome duplication event, lineage-specific expansions of genes associated with flavonoid metabolic biosynthesis were discovered, which enhance catechin production, terpene enzyme activation, and stress tolerance, important features for tea flavor and adaptation. We demonstrate an independent and rapid evolution of the tea caffeine synthesis pathway relative to cacao and coffee. A comparative study among 25 Camellia species revealed that higher expression levels of most flavonoid- and caffeine- but not theanine-related genes contribute to the increased production of catechins and caffeine and thus enhance tea-processing suitability and tea quality. These novel findings pave the way for further metabolomic and functional genomic refinement of characteristic biosynthesis pathways and will help develop a more diversified set of tea flavors that would eventually satisfy and attract more tea drinkers worldwide. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Caffeine alters the behavioural and body temperature responses to mephedrone without causing long-term neurotoxicity in rats.

PubMed

Shortall, Sinead E; Green, A Richard; Fone, Kevin Cf; King, Madeleine V

2016-07-01

Administration of caffeine with 3,4-methylenedioxymethamphetamine (MDMA) alters the pharmacological properties of MDMA in rats. The current study examined whether caffeine alters the behavioural and neurochemical effects of mephedrone, which has similar psychoactive effects to MDMA. Rats received either saline, mephedrone (10 mg/kg), caffeine (10 mg/kg) or combined caffeine and mephedrone intraperitoneally twice weekly on consecutive days for three weeks. Locomotor activity (days 1 and 16), novel object discrimination (NOD, day 2), elevated plus maze (EPM) exploration (day 8), rectal temperature changes (day 9) and pre-pulse inhibition (PPI) of acoustic startle response (day 15) were assessed. Seven days after the final injection, brain regions were collected for the measurement of 5-hydroxytryptamine (5-HT), dopamine and their metabolites. Combined caffeine and mephedrone further enhanced the locomotor response observed following either drug administered alone, and converted mephedrone-induced hypothermia to hyperthermia. Co-administration also abolished mephedrone-induced anxiogenic response on the EPM, but had no effect on NOD or PPI. Importantly, no long-term neurotoxicity was detected following repeated mephedrone alone or when co-administered with caffeine. In conclusion, the study suggests a potentially dangerous effect of concomitant caffeine and mephedrone, and highlights the importance of taking polydrug use into consideration when investigating the acute adverse effect profile of popular recreational drugs. © The Author(s) 2016.

Comparing the benefits of Caffeine, Naps and Placebo on Verbal, Motor and Perceptual Memory

PubMed Central

Mednick, Sara C.; Cai, Denise J.; Kanady, Jennifer; Drummond, Sean P.A.

2008-01-01

Caffeine, the world’s most common psychoactive substance, is used by approximately 90% of North Americans everyday. Little is known, however, about its benefits for memory. Napping has been shown to increase alertness and promote learning on some memory tasks. We directly compared caffeine (200mg) with napping (60–90 minutes) and placebo on three distinct memory processes: declarative verbal memory, procedural motor skills, and perceptual learning. In the verbal task, recall and recognition for unassociated words were tested after a 7hr retention period (with a between-session nap or drug intervention). A second, different, word list was administered post-intervention and memory was tested after a 20min retention period. The non-declarative tasks (finger tapping task and texture discrimination task) were trained before the intervention and then retested afterwards. Naps enhanced recall of words after a 7hr and 20min retention interval relative to both caffeine and placebo. Caffeine significantly impaired motor learning compared to placebo and naps. Napping produced robust perceptual learning compared with placebo; however, naps and caffeine were not significantly different. These findings provide evidence of the limited benefits of caffeine for memory improvement compared with napping. We hypothesize that impairment from caffeine may be restricted to tasks that contain explicit information; whereas strictly implicit learning is less compromised. PMID:18554731

Effects of chronic administration of caffeine and stress on feeding behavior of rats.

PubMed

Pettenuzzo, Leticia Ferreira; Noschang, Cristie; von Pozzer Toigo, Eduardo; Fachin, Andrelisa; Vendite, Deusa; Dalmaz, Carla

2008-10-20

Anorectic effects of caffeine are controversial in the literature, while stress and obesity are growing problems in our society. Since many stressed people are coffee drinkers, the objective of the present study was to evaluate the effect of stress and chronic administration of caffeine on feeding behavior and body weight in male and female rats. Wistar rats (both males and females) were divided into 3 groups: control (receiving water), caffeine 0.3 g/L and caffeine 1.0 g/L (in the drinking water). These groups were subdivided into non-stressed and stressed (repeated-restraint stress for 40 days). During the entire treatment, chow consumption was monitored and rats were weighed monthly. Afterwards, feeding behavior was evaluated during 3-min trials in food-deprived and ad libitum fed animals and also in repeated exposures, using palatable food (Froot Loops and Cheetos). Chronic administration of caffeine did not affect rat chow consumption or body weight gain, but diminished the consumption of both salty (Cheetos) and sweet (Froot Loops) palatable food. In the repeated trial tests, stress diminished savory snack consumption in the later exposures [I.S. Racotta, J. Leblanc, D. Richard The effect of caffeine on food intake in rats: involvement of corticotropin-releasing factor and the sympatho-adrenal system. Pharmacol Biochem Behav. 1994, 48:887-892; S.D. Comer, M. Haney, R.W. Foltin, M.W. Fischman Effects of caffeine withdrawal on humans living in a residential laboratory. Exp Clin Psychopharmacol. 1997, 5:399-403; A. Jessen, B. Buemann, S. Toubro, I.M. Skovgaard, A. Astrup The appetite-suppressant effect of nicotine is enhanced by caffeine. Diab Ob Metab. 2005, 7:327-333; J.M. Carney Effects of caffeine, theophylline and theobromine on scheduled controlled responding in rats. Br J Pharmacol. 1982, 75:451-454] and caffeine diminished consumption of both palatable foods (savory and sweet) during the early and later exposures. Most responses to caffeine were stronger in females, and stress exposure influenced the effect. Neither chronic caffeine nor stress affected adrenal weight and plasma corticosterone levels of the rats. These observations suggest that chronic caffeine consumption may have sex-specific effects on palatable food ingestion.

A hypothalamic–pituitary–adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion

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

Xu, D.; Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071; Wu, Y.

Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic–pituitary–adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; themore » level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases. -- Highlights: ► Prenatal caffeine ingestion induced HPA axis dysfunction in IUGR offspring rats. ► Caffeine induced a neuroendocrine metabolic programmed alteration in offspring rats. ► Caffeine induced a functional injury of hippocampus in IUGR offspring rats.« less

Effects of blue light and caffeine on mood.

PubMed

Ekström, Johan G; Beaven, C Martyn

2014-09-01

Both short wavelength (blue) light and caffeine have been studied for their mood enhancing effects on humans. The ability of blue light to increase alertness, mood and cognitive function via non-image forming neuropathways has been suggested as a non-pharmacological countermeasure for depression across a range of occupational settings. This experimental study compared blue light and caffeine and aimed to test the effects of blue light/placebo (BLU), white light/240-mg caffeine (CAF), blue light/240-mg caffeine (BCAF) and white light/placebo (PLA), on mood. A randomised, controlled, crossover design study was used, in a convenience population of 20 healthy volunteers. The participants rated their mood on the Swedish Core Affect Scales (SCAS) prior to and after each experimental condition to assess the dimensions of valence and activation. There was a significant main effect of light (p = 0.009), and the combination of blue light and caffeine had clear positive effects on core effects (ES, ranging from 0.41 to 1.20) and global mood (ES, 0.61 ± 0.53). The benefits of the combination of blue light and caffeine should be further investigated across a range of applications due to the observed effects on the dimensions of arousal, valence and pleasant activation.

Coffee, caffeine, and sleep: A systematic review of epidemiological studies and randomized controlled trials.

PubMed

Clark, Ian; Landolt, Hans Peter

2017-02-01

Caffeine is the most widely consumed psychoactive substance in the world. It is readily available in coffee and other foods and beverages, and is used to mitigate sleepiness, enhance performance, and treat apnea in premature infants. This review systematically explores evidence from epidemiological studies and randomized controlled trials as to whether coffee and caffeine have deleterious effects on sleep. Caffeine typically prolonged sleep latency, reduced total sleep time and sleep efficiency, and worsened perceived sleep quality. Slow-wave sleep and electroencephalographic (EEG) slow-wave activity were typically reduced, whereas stage-1, wakefulness, and arousals were increased. Dose- and timing-response relationships were established. The sleep of older adults may be more sensitive to caffeine compared to younger adults. Pronounced individual differences are also present in young people, and genetic studies isolated functional polymorphisms of genes implicated in adenosine neurotransmission and metabolism contributing to individual sensitivity to sleep disruption by caffeine. Most studies were conducted in male adults of Western countries, which limits the generalizability of the findings. Given the importance of good sleep for general health and functioning, longitudinal investigations aimed at establishing possible causal relationships among coffee- and caffeine-induced changes in sleep quality and health development are warranted. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Antibacterial potential of rutin conjugated with thioglycolic acid capped cadmium telluride quantum dots (TGA-CdTe QDs)

NASA Astrophysics Data System (ADS)

Ananth, Devanesan Arul; Rameshkumar, Angappan; Jeyadevi, Ramachandran; Jagadeeswari, Sivanadanam; Nagarajan, Natarajan; Renganathan, Rajalingam; Sivasudha, Thilagar

2015-03-01

Quantum dots not only act as nanocarrier but also act as stable and resistant natural fluorescent bio markers used in various in vitro and in vivo photolabelling and biological applications. In this study, the antimicrobial potential of TGA-CdTe QDs and commercial phenolics (rutin and caffeine) were investigated against Escherichiacoli. UV absorbance and fluorescence quenching study of TGA-CdTe QDs with rutin and caffeine complex was measured by spectroscopic technique. QDs-rutin conjugate exhibited excellent quenching property due to the -OH groups present in the rutin structure. But the same time caffeine has not conjugated with QDs because of lacking of -OH group in its structure. Photolabelling of E. coli with QDs-rutin and QDs-caffeine complex was analyzed by fluorescent microscopic method. Microbe E. coli cell membrane damage was assessed by atomic force (AFM) and confocal microscopy. Based on the results obtained, it is suggested that QDs-rutin conjugate enhance the antimicrobial activity more than the treatment with QDs, rutin and caffeine alone.

Spectral investigations and DFT studies of 3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione (caffeine) interaction and recognition by single amino acid derived self-assembled nanostructures

NASA Astrophysics Data System (ADS)

Govindhan, R.; Karthikeyan, B.

2018-03-01

Recognition of xanthine alkaloid caffeine with 3,5-bis(trifluoromethyl)benzylamine derived peptide nanotubes (BTTPNTs) through chemical interaction have been achieved through the host-guest like interaction. DFT simulation is carried out for caffeine interacted with BTTPNTs system and also experimentally characterized by ultraviolet-visible (UV-vis) absorbance, confocal Raman spectra (CRS) with microscopic imaging (CRM), FT-Raman, surface enhanced Raman scattering (SERS), UV-diffuse reflectance spectra (UV-DRS), high resolution transmission electron microscopy (HR-TEM) and cyclic voltammetry (CV) studies. The results are used to examine the morphologies, size of the nanostructure and study of its interaction with the caffeine molecule. The results show that BTTPNTs is having potential for sensing the caffeine molecules through the binding occurred from the NH2 of tyrosine moiety of the BTTPNTs. This intermolecular association through face-to-face stacking of BTTPNTs is explained by detailed DFT calculations.

Acute effects of caffeine on several operant behaviors in rhesus monkeys.

PubMed

Buffalo, E A; Gillam, M P; Allen, R R; Paule, M G

1993-11-01

The acute effects of 1,3-trimethylxanthine (caffeine) were assessed using an operant test battery (OTB) of complex food-reinforced tasks that are thought to depend upon relatively specific brain functions, such as motivation to work for food (progressive ratio, PR), learning (incremental repeated acquisition, IRA), color and position discrimination (conditioned position responding, CPR), time estimation (temporal response differentiation, TRD), and short-term memory and attention (delayed matching-to-sample, DMTS). Endpoints included response rates (RR), accuracies (ACC), and percent task completed (PTC). Caffeine sulfate (0.175-20.0 mg/kg, IV), given 15 min pretesting, produced significant dose-dependent decreases in TRD percent task completed and accuracy at doses > or = 5.6 mg/kg. Caffeine produced no systematic effects on either DMTS or PR responding, but low doses tended to enhance performance in both IRA and CPR tasks. Thus, in monkeys, performance of an operant task designed to model time estimation is more sensitive to the disruptive effects of caffeine than is performance of the other tasks in the OTB.

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.

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.

A hypothalamic-pituitary-adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion.

PubMed

Xu, D; Wu, Y; Liu, F; Liu, Y S; Shen, L; Lei, Y Y; Liu, J; Ping, J; Qin, J; Zhang, C; Chen, L B; Magdalou, J; Wang, H

2012-11-01

Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic-pituitary-adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases. Copyright © 2012 Elsevier Inc. 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.

Effect of caffeine on motility and vitality of sperm and in vitro fertilization of outbreed mouse in T6 and M16 media

PubMed Central

Nabavi, Narges; Todehdehghan, Fatemeh; Shiravi, Abdollhossein

2013-01-01

Background: Caffeine increases the CAMP production that stimulates spermatozoa movement. Caffeine is also used for induction of in vitro acrosome reaction in mammalian spermatozoa, an important step in achieving fertilization. Objective: The aim of this study was to assess the effect of caffeine on sperm's motility, vitality and laboratory fertilization rates in mouse in two T6 and M16 media. Materials and Methods: Epididymal mouse sperms were collected and treated by caffine in T6 and M16 media and their motility and vitality rates were evaluated. The pretreated sperms were added to oocytes in T6 and M16 media with and without caffeine and fertilization rates were recorded after 24 hours incubation. Results: Sperm's motility (81.7±1.67%) and vitality (88.7±1.33%) rates and percentage of fertilized oocytes (67.52±8.16%) in T6 medium plus caffeine compare to control group have increased and shown significant differences at p≤0.01. While the percentages of these parameters in M16 medium supplemented with caffeine were 68.3±6.01%, 78±6.11%, and 42.6±12.96 respectively and in comparison to control group (M16 without caffeine) have not shown significant differences. Conclusion: Addition of caffeine to T6 medium promotes the sperm's motility and vitality and enhances fertilization and early in vitro development of mouse embryos. This article extracted from M.Sc. thesis. (Narges Navabi) PMID:24639814

Twelve weeks supplementation with an extended-release caffeine and ATP-enhancing supplement may improve body composition without affecting hematology in resistance-trained men.

PubMed

Joy, Jordan M; Vogel, Roxanne M; Moon, Jordan R; Falcone, Paul H; Mosman, Matt M; Kim, Michael P

2016-01-01

Increased ATP levels may enhance training-induced muscle accretion and fat loss, and caffeine is a known ergogenic aid. A novel supplement containing ancient peat and apple extracts has reported enhanced mitochondrial ATP production and it has been coupled with an extended-release caffeine. Therefore, the purpose of this investigation was to determine the effects of this supplement on body composition when used in conjunction with 12 weeks of resistance training. Twenty-one resistance-trained subjects (27.2 ± 5.6y; 173.5 ± 5.7 cm; 82.8 ± 12.0 kg) completed this study. Subjects supplemented daily with either 1 serving of the supplement (TRT), which consisted of 150 mg ancient peat and apple extracts, 180 mg blend of caffeine anhydrous and pterostilbene-bound caffeine, and 38 mg B vitamins, or an equal-volume, visually-identical placebo (PLA) 45 min prior to training or at the same time of day on rest days. Supervised resistance training consisted of 8 weeks of daily undulating periodized training followed by a 2-week overreach and a 2-week taper phase. Body composition was assessed using DEXA and ultrasound at weeks 0, 4, 8, 10, and 12. Vital signs and blood markers were assessed at weeks 0, 8, and 12. Significant group x time (p < 0.05) interactions were present for cross-sectional area of the rectus femoris, which increased in TRT (+1.07 cm(2)) versus PLA (-0.08 cm(2)), as well as muscle thickness (TRT: +0.49 cm; PLA: +0.04 cm). A significant group x time (p < 0.05) interaction existed for creatinine (TRT: +0.00 mg/dL; PLA: +0.15 mg/dL) and estimated glomerular filtration rate (TRT: -0.70 mL/min/1.73; PLA: -14.6 mL/min/1.73), which remained within clinical ranges, but no other significant observations were observed. Supplementation with a combination of extended-release caffeine and ancient peat and apple extracts may enhance resistance training-induced skeletal muscle hypertrophy without adversely affecting blood chemistry.

Multi-ingredient, caffeine-containing dietary supplements: history, safety, and efficacy.

PubMed

Gurley, Bill J; Steelman, Susan C; Thomas, Sheila L

2015-02-01

Our objective was to review the history, safety, and efficacy of caffeine-containing dietary supplements in the United States and Canada. PubMed and Web of Science databases (1980-2014) were searched for articles related to the pharmacology, toxicology, and efficacy of caffeine-containing dietary supplements with an emphasis on Ephedra-containing supplements, Ephedra-free supplements, and energy drinks or shots. Among the first and most successful dietary supplements to be marketed in the United States were those containing Ephedra—combinations of ephedrine alkaloids, caffeine, and other phytochemicals. A decade after their inception, serious tolerability concerns prompted removal of Ephedra supplements from the US and Canadian markets. Ephedra-free products, however, quickly filled this void. Ephedra-free supplements typically contain multiple caffeine sources in conjunction with other botanical extracts whose purposes can often be puzzling and their pharmacologic properties difficult to predict. Ingestion of these products in the form of tablets, capsules, or other solid dosage forms as weight loss aids, exercise performance enhancers, or energy boosters have once again brought their tolerability and efficacy into question. In addition to Ephedra-free solid dosage forms, caffeine-containing energy drinks have gained a foothold in the world market along with concerns about their tolerability. This review addresses some of the pharmacologic and pharmaceutical issues that distinguish caffeine-containing dietary supplement formulations from traditional caffeine-containing beverages. Such distinctions may account for the increasing tolerability concerns affiliated with these products. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Pathway-specific effect of caffeine on protection against UV irradiation-induced apoptosis in corneal epithelial cells.

PubMed

Wang, Ling; Lu, Luo

2007-02-01

To define the role of molecular interaction between the UV-induced JNK (c-Jun N-terminal kinase) cascade and corneal epithelial cell apoptosis and protection against apoptosis by caffeine. Rabbit and human corneal epithelial cells were cultured in DMEM/F12 medium containing 10% FBS and 5 microg/mL insulin at 37 degrees C in 5% CO(2). DNA fragmentation and ethidium bromide/acridine orange (EB/AO) nuclear staining were performed to detect cell death. Western blot, immunoprecipitation, and kinase assays were used to measure UV-induced mitogen-activated protein (MAP) kinase activity. UV irradiation-induced apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and MAKK4 (SEK1) upstream from JNK was caffeine sensitive. Caffeine (1,3,7-trimethylxanthine), an agent that is one of the most popular additions to food consumed in the world and a potential enhancer of chemotherapy, effectively protected corneal epithelial cells against apoptosis by its specific effect on the JNK cascade. Theophylline (1,3-dimethylxanthine) exhibited an effect similar to that of caffeine on prevention of UV irradiation-induced apoptosis. However, alterations of either intracellular cAMP or Ca(2+) levels did not alter the effect of caffeine on the JNK signaling pathway. In addition, the blockade of PI3K-like kinases by wortmannin had no impact on the protective effect of caffeine against UV irradiation-induced apoptosis, suggesting that the protective effect of caffeine acts through a specific mechanism involving UV irradiation-induced activation of ASK1 and SEK1. In contrast, caffeine had no effects on melphalan-, hyperosmotic stress-, or IL-1beta-induced activation of the JNK signaling pathway in these cells. UV irradiation stress-induced activation of the ASK1-SEK1-JNK signaling pathway leading to apoptosis is a caffeine-sensitive process, and caffeine, as a multifunctional agent in cells, can specifically interact with the pathway to protect against apoptosis.

Effects of caffeine on prolonged intermittent-sprint ability in team-sport athletes.

PubMed

Schneiker, Knut Thomas; Bishop, David; Dawson, Brian; Hackett, Laurence Peter

2006-03-01

Caffeine can be a powerful ergogenic aid for the performance of prolonged, submaximal exercise. Little evidence, however, supports an ergogenic effect of caffeine on intermittent-sprint performance. Hence, this study was conducted to examine the effects of acute caffeine ingestion on prolonged intermittent-sprint performance. Using a double-blind, placebo-controlled design, 10 male team-sport athletes (amateur level, VO2peak 56.5 +/- 8.0 mL x kg(-1) x min(-1)) completed two exercise trials, separated by 7 d, 60 min after ingestion of either 6 mg x kg(-1) caffeine or placebo. The exercise trial was performed on a front-access cycle ergometer and consisted of 2 x 36-min halves, each composed of 18 x 4-s sprints with 2-min active recovery at 35% VO2peak between each sprint. Urinary caffeine levels were measured after exercise. The total amount of sprint work performed during the caffeine trial was 8.5% greater than that performed during the placebo trial in the first half (75,165.4 +/- 3,902.9 vs 69,265.6 +/- 3,719.7 J, P < 0.05), and was 7.6% greater in the second half (73,978.7 +/- 4,092.6 vs 68,783.2 +/- 3,574.4 J, P < 0.05). Similarly, the mean peak power score achieved during sprints in the caffeine trial was 7.0% greater than that achieved during the placebo trial in the first half (1330.9 +/- 68.2 vs 1244.2 +/- 60.7 W, P < 0.05), and was 6.6% greater in the second half (1314.5 +/- 68.4 vs 1233.2 +/- 59.9 W, P < 0.05). Urinary caffeine levels following the caffeine trial ranged from 3.5 to 9.1 microg x mL(-1) (6.9 +/- 0.6 microg x mL(-1)). This study revealed that acute caffeine ingestion can significantly enhance performance of prolonged, intermittent-sprint ability in competitive, male, team-sport athletes.

Effects of oral administration of caffeine and D-ribose on mental fatigue.

PubMed

Ataka, Suzuka; Tanaka, Masaaki; Nozaki, Satoshi; Mizuma, Hiroshi; Mizuno, Kei; Tahara, Tsuyoshi; Sugino, Tomohiro; Shirai, Tomoko; Kajimoto, Yoshitaka; Kuratsune, Hirohiko; Kajimoto, Osami; Watanabe, Yasuyoshi

2008-03-01

We examined the effects of administering two different candidate antifatigue substances, caffeine and D-ribose, on mental fatigue. In a double-blinded, placebo-controlled, three-way crossover design, 17 healthy volunteers were randomized to oral caffeine (200 mg/d), D-ribose (2000 mg/d), or placebo for 8 d. As fatigue-inducing mental tasks, subjects performed a 30-min Uchida-Kraepelin psychodiagnostic test and a 30-min advanced trail-making test on four occasions. During the tasks, the task performance of the caffeine group was better than that of the placebo group. However, after the fatigue-inducing tasks, although subjective perception of fatigue, motivation, or sleepiness was not significantly different, plasma branched-chain amino acid levels in the caffeine group were lower than those of the placebo group. Administration of D-ribose had no effect. Because plasma branched-chain amino acid levels are decreased by mental fatigue, these results suggest that administration of caffeine improved task performance through the enhancement of central nervous system activity without increasing the sensation of fatigue. However, further decreases in branched-chain amino acid levels indicate that caffeine might promote deeper fatigue than placebo. Unfortunately, research subsequent to our study design has shown that D-ribose dosing higher than we used is needed to see a clinical effect and therefore no conclusions can be made from this study as to the efficacy of D-ribose.

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.

Guarana Provides Additional Stimulation over Caffeine Alone in the Planarian Model

PubMed Central

Moustakas, Dimitrios; Mezzio, Michael; Rodriguez, Branden R.; Constable, Mic Andre; Mulligan, Margaret E.; Voura, Evelyn B.

2015-01-01

The stimulant effect of energy drinks is primarily attributed to the caffeine they contain. Many energy drinks also contain other ingredients that might enhance the tonic effects of these caffeinated beverages. One of these additives is guarana. Guarana is a climbing plant native to the Amazon whose seeds contain approximately four times the amount of caffeine found in coffee beans. The mix of other natural chemicals contained in guarana seeds is thought to heighten the stimulant effects of guarana over caffeine alone. Yet, despite the growing use of guarana as an additive in energy drinks, and a burgeoning market for it as a nutritional supplement, the science examining guarana and how it affects other dietary ingredients is lacking. To appreciate the stimulant effects of guarana and other natural products, a straightforward model to investigate their physiological properties is needed. The planarian provides such a system. The locomotor activity and convulsive response of planarians with substance exposure has been shown to provide an excellent system to measure the effects of drug stimulation, addiction and withdrawal. To gauge the stimulant effects of guarana we studied how it altered the locomotor activity of the planarian species Dugesia tigrina. We report evidence that guarana seeds provide additional stimulation over caffeine alone, and document the changes to this stimulation in the context of both caffeine and glucose. PMID:25880065

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.

A Combination of Amino Acids and Caffeine Enhances Sprint Running Capacity in a Hot, Hypoxic Environment.

PubMed

Eaton, Tom R; Potter, Aaron; Billaut, François; Panchuk, Derek; Pyne, David B; Gore, Christopher J; Chen, Ting-Ting; McQuade, Leon; Stepto, Nigel K

2016-02-01

Heat and hypoxia exacerbate central nervous system (CNS) fatigue. We therefore investigated whether essential amino acid (EAA) and caffeine ingestion attenuates CNS fatigue in a simulated team sport-specific running protocol in a hot, hypoxic environment. Subelite male team sport athletes (n = 8) performed a repeat sprint running protocol on a nonmotorized treadmill in an extreme environment on 4 separate occasions. Participants ingested one of four supplements: a double placebo, 3 mg.kg-1 body mass of caffeine + placebo, 2 x 7 g EAA (Musashi Create)+placebo, or caffeine + EAA before each exercise session using a randomized, double-blind crossover design. Electromyography (EMG) activity and quadriceps evoked responses to magnetic stimulation were assessed from the dominant leg at preexercise, halftime, and postexercise. Central activation ratio (CAR) was used to quantify completeness of quadriceps activation. Oxygenation of the prefrontal cortex was measured via near-infrared spectroscopy. Mean sprint work was higher (M = 174 J, 95% CI [23, 324], p < .05, d = 0.30; effect size, likely beneficial) in the caffeine + EAA condition versus EAAs alone. The decline in EMG activity was less (M = 13%, 95% CI [0, 26]; p < .01, d = 0.58, likely beneficial) in caffeine + EAA versus EAA alone. Similarly, the pre- to postexercise decrement in CAR was significantly less (M = -2.7%, 95% CI [0.4, 5.4]; p < .05, d = 0.50, likely beneficial) when caffeine + EAA were ingested compared with placebo. Cerebral oxygenation was lower (M = -5.6%, 95% CI [1.0, 10.1]; p < .01, d = 0.60, very likely beneficial) in the caffeine + EAA condition compared with LNAA alone. Co-ingestion of caffeine and EAA appears to maintain muscle activation and central drive, with a small improvement in running performance.

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.

The effects of ginseng, ephedrine, and caffeine on cognitive performance, mood and energy.

PubMed

Lieberman, H R

2001-04-01

A variety of claims regarding the purported energy-enhancing properties of nutritional supplements and food constituents have recently been made. It appears that the supplements most frequently associated with such assertions are ginseng, ephedrine, and caffeine. Claims of increased energy are difficult to evaluate objectively because their meaning is not usually defined or specified. Often it is not clear whether the claims refer to physical or mental energy or both. Furthermore, an agreed upon scientific definition of either physical or mental energy enhancement does not exist. In spite of obvious differences in what the term physical energy, as opposed to mental energy implies, there is no clear scientific consensus on whether there is a difference between the two types of energy. Because the substances in question have been anecdotally associated with improvements in both physical and mental performance, their effects on both functions will be discussed, but with an emphasis placed on cognitive function and mood. Of the three substances discussed, caffeine's effects on cognitive and physical function, mood, and energy are best understood. It is clear that this food/drug enhances these functions when administered in moderate doses. Ephedrine may also enhance certain physical and mental functions related to "energy," but the evidence that ginseng has such properties is exceedingly weak.

The effect of self-regulated caffeine use on cognition in young adults.

PubMed

Harvanko, Arit M; Derbyshire, Katherine L; Schreiber, Liana R N; Grant, Jon E

2015-03-01

Based on previous observational studies that have suggested self-regulated caffeine use by older adults may enhance reaction time performance and vigilance on cognitive tasks, the current study sought to examine whether this effect held true for young adults as well. One hundred and four young adults from two major metropolitan areas, ages 18-29 years, not meeting the criteria for a current psychiatric disorder, completed several cognitive tasks related to decision-making (Cambridge Gamble Task), response inhibition and reaction time (stop-signal task), and vigilance and reaction time (Rapid Visual Information Processing). Caffeine usage was self-reported using a reliable quantity and frequency questionnaire. Self-reported caffeine usage was not significantly associated with any of the cognitive measures used in this study after controlling for age, gender, cigarette smoking, alcohol use, cannabis use, and gambling frequency. These data suggest that self-regulated caffeine usage may not have a significant impact on reaction time, vigilance, response inhibition, or decision-making in young adults, or that these effects are contingent upon other variables not accounted for in the current study. Copyright © 2015 John Wiley & Sons, Ltd.

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

Acute effects of bright light and caffeine on nighttime melatonin and temperature levels in women taking and not taking oral contraceptives

NASA Technical Reports Server (NTRS)

Wright, K. P. Jr; Myers, B. L.; Plenzler, S. C.; Drake, C. L.; Badia, P.; Czeisler, C. A. (Principal Investigator)

2000-01-01

Caffeine and bright light effects on nighttime melatonin and temperature levels in women were tested during the luteal phase of the menstrual cycle (n=30) or the pseudo luteal phase for oral contraceptive users (n=32). Participants were randomly assigned to receive either bright (5000 lux) or dim room light (<88 lux) between 20:00 and 08:00 h under a modified constant routine protocol. Half the subjects in each lighting condition were administered either caffeine (100 mg) or placebo in a double-blind manner at 20:00, 23:00, 02:00 and 05:00 h. Results showed that the combination of bright light and caffeine enhanced nighttime temperature levels to a greater extent than did either caffeine or bright light alone. Both of the latter groups had higher temperature levels relative to the dim light placebo condition and the two groups did not differ. Temperature levels in the bright light caffeine condition were maintained at near peak circadian levels the entire night in the luteal and pseudo luteal phase. Melatonin levels were reduced throughout the duration of bright light exposure for all women. Caffeine reduced the onset of melatonin levels for women in the luteal phase, but it had little effect on melatonin levels for oral contraceptive users. The results for women in the luteal phase of the menstrual cycle are consistent with our previous findings in men. The results also suggest that oral contraceptives may alter the effects of caffeine on nighttime melatonin levels.

Hyperalgesia, low-anxiety, and impairment of avoidance learning in neonatal caffeine-treated rats.

PubMed

Pan, Hong-Zhen; Chen, Hwei-Hsien

2007-03-01

The nonselective adenosine receptor antagonist caffeine is used clinically to treat apnea in preterm infants. The brain developmental stage of preterm infants is usually at a period of rapid brain growth, referred as brain growth spurt, which occurs during early postnatal life in rats and is highly sensitive to central nervous system (CNS) acting drugs. The aim of this work was to study whether caffeine treatment during brain growth spurt produces long-term effects on the adenosine receptor-regulated behaviors including nociception, anxiety, learning, and memory. Neonatal male and female Sprague-Dawley rats were administered either deionized water or caffeine (15-20 mg kg(-1) day(-1)) through gavage (0.05 ml/10 g) over postnatal days (PN) 2-6. The hot-plate test, elevated plus-maze, dark-light transition test, and step-through inhibitory avoidance learning task were examined in juvenile rats. Furthermore, the responses to adenosine A(1) receptor agonist N(6)-cyclopentyladenosine (CPA)-induced hypothermia and A(2A) receptor agonist CGS21680-induced locomotor depression were also compared. Caffeine-treated rats showed hyperalgesia in hot-plate test, less anxiety than controls in the elevated plus-maze and dark-light transition, and impairment in step-through avoidance learning test. Moreover, the responses to CPA-induced hypothermia and CGS21680-induced locomotor depression were enhanced in caffeine-treated rats. These results indicate that caffeine exposure during brain growth spurt alters the adenosine receptor-regulated behaviors and the responsiveness to adenosine agonists, suggesting the risk of adenosine receptor-related behavioral dysfunction may exist in preterm newborns treated for apnea with caffeine.

Reduction of facial redness with resveratrol added to topical product containing green tea polyphenols and caffeine.

PubMed

Ferzli, Georgina; Patel, Mital; Phrsai, Natasha; Brody, Neil

2013-07-01

Many topical formulations include antioxidants to improve the antioxidant capability of the skin. This study evaluated the ability of a unique combination of antioxidants including resveratrol, green tea polyphenols, and caffeine to reduce facial redness. Subjects (n=16) presenting with facial redness applied the resveratrol-enriched product twice daily to the entire face. Reduction in redness was evaluated by trained staff members and dermatology house staff officers. Evaluators compared clinical photographs and spectrally enhanced images taken before treatment and at 2-week intervals for up to 12 weeks. 16 of 16 clinical images showed improvement and 13 of 16 spectrally enhanced images were improved. Reduction in facial redness continued to evolve over the duration of the study period but was generally detectable by 6 weeks of treatment. Adverse effects were not observed in any subject. The skin product combination of resveratrol, green tea polyphenols, and caffeine safely reduces facial redness in most patients by 6 weeks of continuous treatment and may provide further improvement with additional treatment.

The metabolic and performance effects of caffeine compared to coffee during endurance exercise.

PubMed

Hodgson, Adrian B; Randell, Rebecca K; Jeukendrup, Asker E

2013-01-01

There is consistent evidence supporting the ergogenic effects of caffeine for endurance based exercise. However, whether caffeine ingested through coffee has the same effects is still subject to debate. The primary aim of the study was to investigate the performance enhancing effects of caffeine and coffee using a time trial performance test, while also investigating the metabolic effects of caffeine and coffee. In a single-blind, crossover, randomised counter-balanced study design, eight trained male cyclists/triathletes (Mean ± SD: Age 41 ± 7 y, Height 1.80 ± 0.04 m, Weight 78.9 ± 4.1 kg, VO2 max 58 ± 3 ml • kg(-1) • min(-1)) completed 30 min of steady-state (SS) cycling at approximately 55% VO2max followed by a 45 min energy based target time trial (TT). One hour prior to exercise each athlete consumed drinks consisting of caffeine (5 mg CAF/kg BW), instant coffee (5 mg CAF/kg BW), instant decaffeinated coffee or placebo. The set workloads produced similar relative exercise intensities during the SS for all drinks, with no observed difference in carbohydrate or fat oxidation. Performance times during the TT were significantly faster (~5.0%) for both caffeine and coffee when compared to placebo and decaf (38.35 ± 1.53, 38.27 ± 1.80, 40.23 ± 1.98, 40.31 ± 1.22 min respectively, p<0.05). The significantly faster performance times were similar for both caffeine and coffee. Average power for caffeine and coffee during the TT was significantly greater when compared to placebo and decaf (294 ± 21 W, 291 ± 22 W, 277 ± 14 W, 276 ± 23 W respectively, p<0.05). No significant differences were observed between placebo and decaf during the TT. The present study illustrates that both caffeine (5 mg/kg/BW) and coffee (5 mg/kg/BW) consumed 1 h prior to exercise can improve endurance exercise performance.

The Metabolic and Performance Effects of Caffeine Compared to Coffee during Endurance Exercise

PubMed Central

Hodgson, Adrian B.; Randell, Rebecca K.; Jeukendrup, Asker E.

2013-01-01

There is consistent evidence supporting the ergogenic effects of caffeine for endurance based exercise. However, whether caffeine ingested through coffee has the same effects is still subject to debate. The primary aim of the study was to investigate the performance enhancing effects of caffeine and coffee using a time trial performance test, while also investigating the metabolic effects of caffeine and coffee. In a single-blind, crossover, randomised counter-balanced study design, eight trained male cyclists/triathletes (Mean±SD: Age 41±7y, Height 1.80±0.04 m, Weight 78.9±4.1 kg, VO2 max 58±3 ml•kg−1•min−1) completed 30 min of steady-state (SS) cycling at approximately 55% VO2max followed by a 45 min energy based target time trial (TT). One hour prior to exercise each athlete consumed drinks consisting of caffeine (5 mg CAF/kg BW), instant coffee (5 mg CAF/kg BW), instant decaffeinated coffee or placebo. The set workloads produced similar relative exercise intensities during the SS for all drinks, with no observed difference in carbohydrate or fat oxidation. Performance times during the TT were significantly faster (∼5.0%) for both caffeine and coffee when compared to placebo and decaf (38.35±1.53, 38.27±1.80, 40.23±1.98, 40.31±1.22 min respectively, p<0.05). The significantly faster performance times were similar for both caffeine and coffee. Average power for caffeine and coffee during the TT was significantly greater when compared to placebo and decaf (294±21 W, 291±22 W, 277±14 W, 276±23 W respectively, p<0.05). No significant differences were observed between placebo and decaf during the TT. The present study illustrates that both caffeine (5 mg/kg/BW) and coffee (5 mg/kg/BW) consumed 1 h prior to exercise can improve endurance exercise performance. PMID:23573201

Inhibitory effects of HgCl2 on excitation-secretion coupling at the motor nerve terminal and excitation-contraction coupling in the muscle cell.

PubMed

Røed, A; Herlofson, B B

1994-12-01

1. Indirect and direct twitch (0.1-Hz) stimulation of the rat phrenic nerve-diaphragm disclosed that the inhibitory effect of HgCl2, 3.7 x 10(-5) M, on the neuromuscular transmission and in the muscle cell, was accelerated by 10-sec periods of 50-Hz tetanic stimulation every 10 min. This activity-dependent enhancement suggested an inhibitory mechanism of HgCl2 related to the development of fatigue, like membrane depolarization or decreased excitability, decreased availability of transmitter, or interference with the factors controlling excitation-secretion coupling of the nerve terminal, i.e. (Ca2+)0 or (Ca2+)i, and excitation-contraction coupling in the muscle cell, i.e., (Ca2+)i. 2. During both indirect and direct stimulation, HgCl2-induced inhibition was enhanced markedly by pretreatment with caffeine, which releases Ca2+ from endoplasmic and sarcoplasmic reticulum in the nerve terminal and muscle cell, respectively. This caffeine-induced enhancement was completely antagonized by dantrolene, which inhibits the caffeine-induced release. However, dantrolene alone did not antagonize the HgCl2-induced inhibition. 3. Since caffeine depletes the intracellular Ca2+ stores of the smooth endoplasmic reticulum, HgCl2 probably inhibits by binding to SH groups of transport proteins conveying the messenger function of (Ca2+)i. In the muscle cell this leads to inhibition of contraction. In the nerve terminal, an additional enhancement of the HgCl2-induced inhibition, by inhibiting reuptake of choline by TEA and tetanic stimulation, suggested that HgCl2 inhibited a (Ca2+)i signal necessary for this limiting factor in resynthesis of acetylcholine. 4. The (Ca2+)0 signal necessary for stimulus-induced release of acetylcholine was not affected by HgCl2. Hyperpolarization in K(+)-free solution antagonized the inhibitory effect of HgCl2 at indirect stimulation, and Ca(2+)-free solution enhanced the inhibitory effect at direct stimulation. K+ depolarization, membrane electric field increase with high Ca2+, membrane stabilization with lidocaine, and half-threshold stimulation, did not change the inhibitory effect of HgCl CH3HgCl. 1.85 x 10(-5) M, disclosed a synergistic interaction with caffeine during direct, but not during indirect, stimulation.

Using Caffeine Pills for Performance Enhancement. An Experimental Study on University Students' Willingness and Their Intention to Try Neuroenhancements.

PubMed

Brand, Ralf; Koch, Helen

2016-01-01

Recent research has indicated that university students sometimes use caffeine pills for neuroenhancement (NE; non-medical use of psychoactive substances or technology to produce a subjective enhancement in psychological functioning and experience), especially during exam preparation. In our factorial survey experiment, we manipulated the evidence participants were given about the prevalence of NE amongst peers and measured the resulting effects on the psychological predictors included in the Prototype-Willingness Model of risk behavior. Two hundred and thirty-one university students were randomized to a high prevalence condition (read faked research results overstating usage of caffeine pills amongst peers by a factor of 5; 50%), low prevalence condition (half the estimated prevalence; 5%) or control condition (no information about peer prevalence). Structural equation modeling confirmed that our participants' willingness and intention to use caffeine pills in the next exam period could be explained by their past use of neuroenhancers, attitude to NE and subjective norm about use of caffeine pills whilst image of the typical user was a much less important factor. Provision of inaccurate information about prevalence reduced the predictive power of attitude with respect to willingness by 40-45%. This may be because receiving information about peer prevalence which does not fit with their perception of the social norm causes people to question their attitude. Prevalence information might exert a deterrent effect on NE via the attitude-willingness association. We argue that research into NE and deterrence of associated risk behaviors should be informed by psychological theory.

Using Caffeine Pills for Performance Enhancement. An Experimental Study on University Students’ Willingness and Their Intention to Try Neuroenhancements

PubMed Central

Brand, Ralf; Koch, Helen

2016-01-01

Recent research has indicated that university students sometimes use caffeine pills for neuroenhancement (NE; non-medical use of psychoactive substances or technology to produce a subjective enhancement in psychological functioning and experience), especially during exam preparation. In our factorial survey experiment, we manipulated the evidence participants were given about the prevalence of NE amongst peers and measured the resulting effects on the psychological predictors included in the Prototype-Willingness Model of risk behavior. Two hundred and thirty-one university students were randomized to a high prevalence condition (read faked research results overstating usage of caffeine pills amongst peers by a factor of 5; 50%), low prevalence condition (half the estimated prevalence; 5%) or control condition (no information about peer prevalence). Structural equation modeling confirmed that our participants’ willingness and intention to use caffeine pills in the next exam period could be explained by their past use of neuroenhancers, attitude to NE and subjective norm about use of caffeine pills whilst image of the typical user was a much less important factor. Provision of inaccurate information about prevalence reduced the predictive power of attitude with respect to willingness by 40-45%. This may be because receiving information about peer prevalence which does not fit with their perception of the social norm causes people to question their attitude. Prevalence information might exert a deterrent effect on NE via the attitude-willingness association. We argue that research into NE and deterrence of associated risk behaviors should be informed by psychological theory. PMID:26903909

Efficacy of Slimming Cream Containing 3.5% Water-Soluble Caffeine and Xanthenes for the Treatment of Cellulite: Clinical Study and Literature Review

PubMed Central

Byun, Sang-Young; Kwon, Soon-Hyo; Heo, Su-Hak; Shim, Jae-Seong; Du, Mi-Hee

2015-01-01

Background Cellulite is a 'cottage cheese-like' cutaneous change caused by subcutaneous fat bulging into the dermis that usually leads to cosmetic problems. Slimming cream containing 3.5% water-soluble caffeine and xanthenes exhibits a lipolytic effect with penetration into the dermis. Objective To evaluate the efficacy and safety of slimming cream for the treatment of cellulite. Methods Fifteen subjects with cellulite applied slimming cream to the thighs and inner side of the upper arms twice daily for 6 weeks. Efficacy was assessed using a standard visual scale, changes in the circumferences of the thighs and upper arms, and patient satisfaction by a questionnaire at baseline, week 3, and week 6. Safety was assessed by inquiring about adverse events through questionnaires. Results The standard visual scale score improved significantly by 0.49 points (19.8%) at week 6. Thigh and upper-arm circumferences decreased by 0.7 cm (1.7%) and 0.8 cm (2.3%), respectively, at week 6. Slight itching and transient flushing were commonly reported, but no serious adverse event occurred. Conclusion The slimming cream tested appears to be effective for the treatment of cellulitis without serious adverse effects. However, additional large clinical trials are required to confirm the efficacy and safety of slimming cream for the treatment of cellulitis. PMID:26082579

Caffeine affects the biological responses of human hematopoietic cells of myeloid lineage via downregulation of the mTOR pathway and xanthine oxidase activity

PubMed Central

Abooali, Maryam; Yasinska, Inna M.; Casely-Hayford, Maxwell A.; Berger, Steffen M.; Fasler-Kan, Elizaveta; Sumbayev, Vadim V.

2015-01-01

Correction of human myeloid cell function is crucial for the prevention of inflammatory and allergic reactions as well as leukaemia progression. Caffeine, a naturally occurring food component, is known to display anti-inflammatory effects which have previously been ascribed largely to its inhibitory actions on phosphodiesterase. However, more recent studies suggest an additional role in affecting the activity of the mammalian target of rapamycin (mTOR), a master regulator of myeloid cell translational pathways, although detailed molecular events underlying its mode of action have not been elucidated. Here, we report the cellular uptake of caffeine, without metabolisation, by healthy and malignant hematopoietic myeloid cells including monocytes, basophils and primary acute myeloid leukaemia mononuclear blasts. Unmodified caffeine downregulated mTOR signalling, which affected glycolysis and the release of pro-inflammatory/pro-angiogenic cytokines as well as other inflammatory mediators. In monocytes, the effects of caffeine were potentiated by its ability to inhibit xanthine oxidase, an enzyme which plays a central role in human purine catabolism by generating uric acid. In basophils, caffeine also increased intracellular cyclic adenosine monophosphate (cAMP) levels which further enhanced its inhibitory action on mTOR. These results demonstrate an important mode of pharmacological action of caffeine with potentially wide-ranging therapeutic impact for treating non-infectious disorders of the human immune system, where it could be applied directly to inflammatory cells. PMID:26384306

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

Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS)-based metabolomics for comparison of caffeinated and decaffeinated coffee and its implications for Alzheimer's disease.

PubMed

Chang, Kai Lun; Ho, Paul C

2014-01-01

Findings from epidemiology, preclinical and clinical studies indicate that consumption of coffee could have beneficial effects against dementia and Alzheimer's disease (AD). The benefits appear to come from caffeinated coffee, but not decaffeinated coffee or pure caffeine itself. Therefore, the objective of this study was to use metabolomics approach to delineate the discriminant metabolites between caffeinated and decaffeinated coffee, which could have contributed to the observed therapeutic benefits. Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS)-based metabolomics approach was employed to characterize the metabolic differences between caffeinated and decaffeinated coffee. Orthogonal partial least squares discriminant analysis (OPLS-DA) showed distinct separation between the two types of coffee (cumulative Q(2) = 0.998). A total of 69 discriminant metabolites were identified based on the OPLS-DA model, with 37 and 32 metabolites detected to be higher in caffeinated and decaffeinated coffee, respectively. These metabolites include several benzoate and cinnamate-derived phenolic compounds, organic acids, sugar, fatty acids, and amino acids. Our study successfully established GC-TOF-MS based metabolomics approach as a highly robust tool in discriminant analysis between caffeinated and decaffeinated coffee samples. Discriminant metabolites identified in this study are biologically relevant and provide valuable insights into therapeutic research of coffee against AD. Our data also hint at possible involvement of gut microbial metabolism to enhance therapeutic potential of coffee components, which represents an interesting area for future research.

Length dependence of staircase potentiation: interactions with caffeine and dantrolene sodium.

PubMed

Rassier, D E; MacIntosh, B R

2000-04-01

In skeletal muscle, there is a length dependence of staircase potentiation for which the mechanism is unclear. In this study we tested the hypothesis that abolition of this length dependence by caffeine is effected by a mechanism independent of enhanced Ca2+ release. To test this hypothesis we have used caffeine, which abolishes length dependence of potentiation, and dantrolene sodium, which inhibits Ca2+ release. In situ isometric twitch contractions of rat gastrocnemius muscle before and after 20 s of repetitive stimulation at 5 Hz were analyzed at optimal length (Lo), Lo - 10%, and Lo + 10%. Potentiation was observed to be length dependent, with an increase in developed tension (DT) of 78 +/- 12, 51 +/- 5, and 34 +/- 9% (mean +/- SEM), at Lo - 10%, Lo, and Lo + 10%, respectively. Caffeine diminished the length dependence of activation and suppressed the length dependence of staircase potentiation, giving increases in DT of 65+/-13, 53 +/- 11, and 45 +/- 12% for Lo - 10%, Lo, and Lo + 10%, respectively. Dantrolene administered after caffeine did not reverse this effect. Dantrolene alone depressed the potentiation response, but did not affect the length dependence of staircase potentiation, with increases in DT of 58 +/- 17, 26 +/- 8, and 18 +/- 7%, respectively. This study confirms that there is a length dependence of staircase potentiation in mammalian skeletal muscle which is suppressed by caffeine. Since dantrolene did not alter this suppression of the length dependence of potentiation by caffeine, it is apparently not directly modulated by Ca2+ availability in the myoplasm.

Gas Chromatography Time-Of-Flight Mass Spectrometry (GC-TOF-MS)-Based Metabolomics for Comparison of Caffeinated and Decaffeinated Coffee and Its Implications for Alzheimer’s Disease

PubMed Central

Chang, Kai Lun; Ho, Paul C.

2014-01-01

Findings from epidemiology, preclinical and clinical studies indicate that consumption of coffee could have beneficial effects against dementia and Alzheimer’s disease (AD). The benefits appear to come from caffeinated coffee, but not decaffeinated coffee or pure caffeine itself. Therefore, the objective of this study was to use metabolomics approach to delineate the discriminant metabolites between caffeinated and decaffeinated coffee, which could have contributed to the observed therapeutic benefits. Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS)-based metabolomics approach was employed to characterize the metabolic differences between caffeinated and decaffeinated coffee. Orthogonal partial least squares discriminant analysis (OPLS-DA) showed distinct separation between the two types of coffee (cumulative Q2 = 0.998). A total of 69 discriminant metabolites were identified based on the OPLS-DA model, with 37 and 32 metabolites detected to be higher in caffeinated and decaffeinated coffee, respectively. These metabolites include several benzoate and cinnamate-derived phenolic compounds, organic acids, sugar, fatty acids, and amino acids. Our study successfully established GC-TOF-MS based metabolomics approach as a highly robust tool in discriminant analysis between caffeinated and decaffeinated coffee samples. Discriminant metabolites identified in this study are biologically relevant and provide valuable insights into therapeutic research of coffee against AD. Our data also hint at possible involvement of gut microbial metabolism to enhance therapeutic potential of coffee components, which represents an interesting area for future research. PMID:25098597

Caffeine intake is associated with pupil dilation and enhanced accommodation

PubMed Central

Abokyi, S; Owusu-Mensah, J; Osei, K A

2017-01-01

Purpose It is purported that caffeine, an autonomic stimulant, affects visual performance. This study sought to assess whether caffeine intake was associated with changes in pupil size and/or amplitude of accommodation. Patients and methods A double-masked, crossover study was conducted in 50 healthy subjects of age range 19 to 25 years. Subjects were randomized to treatments such that subjects consumed either 250 mg caffeine drink or vehicle on separate days. Amplitude of accommodation was measured by the push-up technique, and pupil size using a millimeter ruler fixed to a slit lamp biomicroscope in dim illumination (5 lux). Amplitude of accommodation and pupil size were taken at baseline, and at 30, 60 and 90 min time points post treatment. Repeated measures one-way ANOVA and paired t-test were used in analyzing data. Results Amplitude of accommodation and pupil size after caffeine intake were significantly greater than vehicle (P<0.001) at each time point. Consumption of the caffeine beverage was associated with significant increases in amplitude of accommodation and pupil size with time (P<0.001). Amplitude of accommodation rose from 12.4 (±2.2 D) at baseline to 15.8(±2.6 D) at 90 min. Similarly, pupil size increased from 3.4 (±0.4 mm) at baseline to 4.5 (±0.72 mm) at 90 min. Consumption of vehicle was not associated with increase in amplitude of accommodation or pupil size with time. Conclusion Pupil size and accommodation are affected after ingestion of caffeine. This study suggests caffeine may have some influence on visual functions. PMID:27983733

Caffeine and diphenyl diselenide improve long-term memory impaired in middle-aged rats.

PubMed

Leite, Marlon R; Marcondes Sari, Marcel Henrique; de Freitas, Mayara L; Oliveira, Lia P; Dalmolin, Laíza; Brandão, Ricardo; Zeni, Gilson

2014-05-01

The aim of the present study was to evaluate the effects of diphenyl diselenide (PhSe)2 supplemented diet (10ppm) associated to the administration of caffeine (15mg/kg; i.g.) for 30days on the novel object recognition memory in middle-aged rats. The present findings showed that (PhSe)2-supplemented diet enhanced short-term memory, but not long-term memory, of middle-aged rats in the novel object recognition task. The (PhSe)2 supplemented diet associated with caffeine administration improved long-term memory, but did not alter short-term memory, impaired in middle-aged rats. Daily caffeine administration to middle-aged rats had no effect on the memory tasks. Diet supplemented with (PhSe)2 plus caffeine administration increased the number of crossings and rearings reduced in middle-aged rats. Caffeine administration plus (PhSe)2 diets were effective in increasing the number of rearings and crossings, respectively, in middle-aged rats, [(3)H] glutamate uptake was reduced in hippocampal slices of rats from (PhSe)2 and caffeine plus (PhSe)2 groups. In addition, animals supplemented with (PhSe)2 showed an increase in the pCREB/CREB ratio whereas pAkt/Akt ratio was not modified. These results suggest that the effects of (PhSe)2 on the short-term memory may be related to its ability to decrease the uptake of glutamate, influencing the increase of CREB phosphorylation. (PhSe)2-supplemented diet associated to the administration of caffeine improved long-term memory impaired in middle-aged rats, an effect independent of CREB and Akt phosphorylation. Copyright © 2014 Elsevier Inc. All rights reserved.

Alteration of carotid body chemoreflexes after neonatal intermittent hypoxia and caffeine treatment in rat pups.

PubMed

Julien, Cécile A; Joseph, Vincent; Bairam, Aida

2011-08-15

In human neonates, caffeine therapy for apnoea of prematurity, especially when associated with hypoxemia, is maintained for several weeks after birth. In the present study, we used newborn rats and whole-body plethysmography to test whether chronic exposure to neonatal caffeine treatment (NCT), alone or combined with neonatal intermittent hypoxia (n-IH) alters: (1) baseline ventilation and response to hypoxia (12% O(2), 20 min); and (2) response to acute i.p. injection of caffeine citrate (20 mg/kg) or domperidone, a peripheral dopamine D2 receptor antagonist (1 mg/kg). Four groups of rats were studied as follows: raised under normal conditions with daily gavage with water (NWT) or NCT, or exposed to n-IH (n-IH+NWT and n-IH+NCT) from postnatal days 3 to 12. In n-IH+NCT rats, baseline ventilation was higher than in the other groups. Caffeine or domperidone enhanced baseline ventilation only in NWT and n-IH+NWT rats, but neither caffeine nor domperidone affected the hypoxic ventilatory response in these groups. In n-IH+NWT rats, the response during the early phase of hypoxia (<10 min) was higher than in other groups. During the late response phase to hypoxia (20 min), ventilation was lower in n-IH+NWT and n-IH+NCT rats compared to NWT or NCT, and were not affected by caffeine or domperidone injection. NCT or caffeine injection decreased baseline apnoea frequency in all groups. These data suggest that chronic exposure to NCT alters both carotid body dopaminergic and adenosinergic systems and central regulation of breathing under baseline conditions and in response to hypoxia. Copyright © 2011 Elsevier B.V. All rights reserved.

l-Theanine and caffeine improve target-specific attention to visual stimuli by decreasing mind wandering: a human functional magnetic resonance imaging study.

PubMed

Kahathuduwa, Chanaka N; Dhanasekara, Chathurika S; Chin, Shao-Hua; Davis, Tyler; Weerasinghe, Vajira S; Dassanayake, Tharaka L; Binks, Martin

2018-01-01

Oral intake of l-theanine and caffeine supplements is known to be associated with faster stimulus discrimination, possibly via improving attention to stimuli. We hypothesized that l-theanine and caffeine may be bringing about this beneficial effect by increasing attention-related neural resource allocation to target stimuli and decreasing deviation of neural resources to distractors. We used functional magnetic resonance imaging (fMRI) to test this hypothesis. Solutions of 200mg of l-theanine, 160mg of caffeine, their combination, or the vehicle (distilled water; placebo) were administered in a randomized 4-way crossover design to 9 healthy adult men. Sixty minutes after administration, a 20-minute fMRI scan was performed while the subjects performed a visual color stimulus discrimination task. l-Theanine and l-theanine-caffeine combination resulted in faster responses to targets compared with placebo (∆=27.8milliseconds, P=.018 and ∆=26.7milliseconds, P=.037, respectively). l-Theanine was associated with decreased fMRI responses to distractor stimuli in brain regions that regulate visual attention, suggesting that l-theanine may be decreasing neural resource allocation to process distractors, thus allowing to attend to targets more efficiently. l-Theanine-caffeine combination was associated with decreased fMRI responses to target stimuli as compared with distractors in several brain regions that typically show increased activation during mind wandering. Factorial analysis suggested that l-theanine and caffeine seem to have a synergistic action in decreasing mind wandering. Therefore, our hypothesis is that l-theanine and caffeine may be decreasing deviation of attention to distractors (including mind wandering); thus, enhancing attention to target stimuli was confirmed. Copyright © 2017 Elsevier Inc. All rights reserved.

Does caffeine reduce postoperative bowel paralysis after elective laparoscopic colectomy? (CaCo trial): study protocol for a randomized controlled trial.

PubMed

Kruse, Christina; Müller, Sascha A; Warschkow, René; Lüthi, Cornelia; Brunner, Walter; Marti, Lukas; Sulz, Michael Christian; Schmied, Bruno M; Tarantino, Ignazio; Beutner, Ulrich

2016-04-04

Postoperative bowel paralysis is common after abdominal operations, including colectomy. As a result, hospitalization may be prolonged, thereby leading to increased cost. A recent randomized controlled trial showed that the consumption of regular black coffee after colectomy is associated with a significantly faster resumption of intestinal motility. The mechanism by which coffee stimulates intestinal motility is unknown, but caffeine seems to be the most likely stimulating agent. Thus, the effect of caffeine on postoperative bowel activity after colon surgery will be analyzed in this trial, herein referred to as CaCo. Patients scheduled for elective laparoscopic colectomy or upper rectum resection are eligible to participate in this double-blinded, placebo-controlled, randomized trial. Patients fulfilling all inclusion criteria will be allocated after the surgical procedure to one of three treatment arms: 100 mg caffeine, 200 mg caffeine, or placebo (corn starch). Patients will take the capsules containing the study medication three times daily with a meal. The primary endpoint of the study is the time to a solid bowel movement. The study treatment will be stopped after the patient produces a solid bowel movement or has taken ten capsules, whichever occurs first. To determine the colonic passage time, patients will take a capsule with radiopaque markers at breakfast for the first 3 days after surgery. On the fourth day, the location of the markers will be determined with an abdominal X-ray scan. Further secondary objectives are the postoperative morbidity and mortality, well-being, sleeping behavior, and length of hospital stay. The study size was calculated to be 180 patients with an interim analysis occurring after 60 patients. From a previous study investigating coffee, evidence exists that caffeine might have a positive influence on the postoperative bowel activity. This double-blinded, placebo-controlled, randomized trial tries to show that caffeine will shorten the postoperative bowel paralysis and, thus, will improve recovery and shorten the hospital stay after colon surgery. Clinicaltrials.gov NCT02510911 Swiss National Clinical Trials Portal SNCTP000001131.

In-vitro examination of the positive inotropic effect of caffeine and taurine, the two most frequent active ingredients of energy drinks.

PubMed

Chaban, R; Kornberger, A; Branski, N; Buschmann, K; Stumpf, N; Beiras-Fernandez, A; Vahl, C F

2017-08-10

Our study aimed to evaluate changes in the contractile behavior of human myocardium after exposure to caffeine and taurine, the main active ingredients of energy drinks (EDs), and to evaluate whether taurine exhibits any inotropic effect at all in the dosages commonly used in EDs. Myocardial tissue was removed from the right atrial appendages of patients undergoing cardiac surgery and prepared to obtain specimens measuring 4 mm in length. A total of 92 specimens were exposed to electrical impulses at a frequency of 75 bpm for at least 40 min to elicit their maximum contractile force before measuring the isometric contractile force (ICF) and duration of contraction (CD). Following this, each specimen was treated with either taurine (group 1, n = 29), or caffeine (group 2, n = 31) or both (group 3, n = 32). After exposure, ICF and CD measuring were repeated. Post-treatment values were compared with pre-treatments values and indicated as percentages. Exposure to taurine did not alter the contraction behavior of the specimens. Exposure to caffeine, in contrast, led to a significant increase in ICF (118 ± 03%, p < 0.01) und a marginal decrease in CD (95 ± 1.6%, p < 0.01). Exposure to a combination of caffeine and taurine also induced a statistically significant increase in ICF (124 ± 4%, p < 0.01) and a subtle reduction in CD (92 ± 1.4%, p < 0.01). The increase in ICF achieved by administration of caffeine was similar to that achieved by a combination of both caffeine and taurine (p = 0.2). The relative ICF levels achieved by administration of caffeine and a combination of taurine and caffeine, respectively, were both significantly higher (p < 0.01) than the ICF resulting from exposure to taurine only. While caffeine altered the contraction behavior of the specimen significantly in our in-vitro model, taurine did not exhibit a significant effect. Adding taurine to caffeine did not significantly enhance or reduce the effect of caffeine.

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.

Genetic tests in mice of caffeine alone and in combination with mutagens

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

Thayer, P.S.; Kensler, C.J.

1973-06-01

The possible mutagenicity of caffeine was studied in mice by the dominant-lethal method, in three experiments. Male mice were given caffeine in drinking water for 8 weeks at 3.6, 13.4, 49, and 122 mg/kg/day (comparable to human consumption of 2.8 to 95 cups of coffee per day). Subsequent mating of each of six males from each group to five females per week for 8 weeks showed no significant increase in dominant-lethal mutations (embryonic deaths) whether expressed as early deaths per pregnant female or as mutation index. Although males consuming the two higher levels of caffeine produced fewer pregnancies, litter sizesmore » of females giving birth were not reduced. Single ip injections of caffeine (15 mg/kg) were given to groups of male mice prior to, subsequent to, and immediately at the time of receiving x-rays (100 R). Each of five males from each group was mated to five females per week for 7 weeks. Embryonic deaths did not show any enhancing effect of caffeine on the mutagenicity produced by the irradiation. Three groups of male mice ingested caffeine in water for 16 weeks at levels of 0, 4, and 13 mg/kg/day. Subgroups of five from each group were given either: no further treatment, a single dose of triethylene melamine at 0.2 mg/kg, or 100 R of x ray, and mated for 7 weeks as above. Fertility and litter size were not affected by the caffeine pretreatment, nor did it modify the induction of dominant-lethal mutations by triethylene melamine or x rays. Litter sizes showed no significant preimplantation losses in any experiment. Thus, under the conditions described herein and at the doses employed (higher than human exposure), there was no evidence for the mutagenicity of caffeine or the inhibition of DNA repair mechanisms in these mammalian systems. (auth)« less

Fetal rat metabonome alteration by prenatal caffeine ingestion probably due to the increased circulatory glucocorticoid level and altered peripheral glucose and lipid metabolic pathways

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

Liu, Yansong; Xu, Dan; Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071

The aims of this study were to clarify the metabonome alteration in fetal rats after prenatal caffeine ingestion and to explore the underlying mechanism pertaining to the increased fetal circulatory glucocorticoid (GC). Pregnant Wistar rats were daily intragastrically administered with different doses of caffeine (0, 20, 60 and 180 mg/kg) from gestational days (GD) 11 to 20. Metabonome of fetal plasma and amniotic fluid on GD20 were analyzed by {sup 1}H nuclear magnetic resonance-based metabonomics. Gene and protein expressions involved in the GC metabolism, glucose and lipid metabolic pathways in fetal liver and gastrocnemius were measured by real-time RT-PCR andmore » immunohistochemistry. Fetal plasma metabonome were significantly altered by caffeine, which presents as the elevated α- and β‐glucose, reduced multiple lipid contents, varied apolipoprotein contents and increased levels of a number of amino acids. The metabonome of amniotic fluids showed a similar change as that in fetal plasma. Furthermore, the expressions of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD-2) were decreased, while the level of blood GC and the expressions of 11β-HSD-1 and glucocorticoid receptor (GR) were increased in fetal liver and gastrocnemius. Meanwhile, the expressions of insulin-like growth factor 1 (IGF-1), IGF-1 receptor and insulin receptor were decreased, while the expressions of adiponectin receptor 2, leptin receptors and AMP-activated protein kinase α2 were increased after caffeine treatment. Prenatal caffeine ingestion characteristically change the fetal metabonome, which is probably attributed to the alterations of glucose and lipid metabolic pathways induced by increased circulatory GC, activated GC metabolism and enhanced GR expression in peripheral metabolic tissues. -- Highlights: ► Prenatal caffeine ingestion altered the metabonome of IUGR fetal rats. ► Caffeine altered the glucose and lipid metabolic pathways of IUGR fetal rats. ► Prenatal caffeine ingestion induced GC metabolic activation in IUGR fetal rats.« less

[Risk assessment of synephrine in dietary supplements].

PubMed

Bakhyia, Nadiya; Dusemund, Birgit; Richter, Klaus; Lindtner, Oliver; Hirsch-Ernst, Karen Ildico; Schäfer, Bernd; Lampen, Alfonso

2017-03-01

Synephrine is a sympathomimetic phenylethylamine derivative that occurs naturally in citrus fruits. It is often added to dietary supplements intended for weight loss and enhancement of sports performance, typically in the form of Citrus aurantium extracts and in many cases in combination with caffeine. The health risks of synephrine were evaluated on the basis of the available toxicological data and in accordance to the EFSA guidance on the safety assessment of botanicals and botanical preparations intended for use in food supplements. In animal studies, orally applied synephrine induced adrenergic effects on the cardiovascular system (increase of blood pressure, ventricular arrhythmias), which were enhanced by the concomitant application of caffeine as well as physical activity. Some human intervention studies investigating the acute effects of synephrine on blood pressure and heart rate of healthy, normotensive test persons indicate that synephrine can induce cardiovascular effects in humans. A series of published case reports of adverse cardiovascular effects (hypertension, cardiac arrhythmia, myocardial infarction) were associated with consumption of synephrine- and caffeine-containing dietary supplements. In conclusion, consumption of high amounts of synephrine, especially in combination with caffeine and physical exercise, is associated with an increased risk of adverse effects on the cardiovascular system. According to the assessment by the BfR (Bundesinstitut für Risikobewertung), daily intake of synephrine through dietary supplements should not exceed the median intake from conventional foods.

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®.

Perturbation of cytosolic calcium by 2-aminoethoxydiphenyl borate and caffeine affects zebrafish myofibril alignment.

PubMed

Wu, Hsin-Ju; Fong, Tsorng-Harn; Chen, Shen-Liang; Wei, Jen-Cheng; Wang, I-Jong; Wen, Chi-Chung; Chang, Chao-Yuan; Chen, Xing-Guang; Chen, Wei-Yu; Chen, Hui-Min; Horng, Juin-Lin; Wang, Yun-Hsin; Chen, Yau-Hung

2015-03-01

The objective of the current study was to investigate the effects of Ca(2+) levels on myofibril alignment during zebrafish embryogenesis. To investigate how altered cytoplasmic Ca(2+) levels affect myofibril alignment, we exposed zebrafish embryos to 2-aminothoxyldiphenyl borate (2-APB; an inositol 1,4,5-trisphosphate receptor inhibitor that reduces cytosolic Ca(2+) levels) and caffeine (a ryanodine receptor activator that enhances cytosolic Ca(2+) levels). The results demonstrated that the most evident changes in zebrafish embryos treated with 2-APB were shorter body length, curved trunk and malformed somite boundary. In contrast, such malformed phenotypes were evident neither in untreated controls nor in caffeine-treated embryos. Subtle morphological changes, including changes in muscle fibers, F-actin and ultrastructures were easily observed by staining with specific monoclonal antibodies (F59 and α-laminin), fluorescent probes (phalloidin) and by transmission electron microscopy. Our data suggested that: (1) the exposure to 2-APB and/or caffeine led to myofibril misalignment; (2) 2-APB-treated embryos displayed split and short myofibril phenotypes, whereas muscle fibers from caffeine-treated embryos were twisted and wavy; and (3) zebrafish embryos co-exposed to 2-APB and caffeine resulted in normal myofibril alignment. In conclusion, we proposed that cytosolic Ca(2+) is important for myogenesis, particularly for myofibril alignment. Copyright © 2014 John Wiley & Sons, Ltd.

Subchronic intermittent caffeine administration to unilaterally 6-hydroxydopamine-lesioned rats sensitizes turning behaviour in response to dopamine D(1) but not D(2) receptor agonists.

PubMed

Cauli, Omar; Pinna, Annalisa; Morelli, Micaela

2005-12-01

The effects of caffeine, an antagonist of adenosine A(1) and A(2A) receptors, are significantly influenced by modifications in dopamine transmission. Administration of caffeine to unilaterally 6-hydroxydopamine-lesioned rats induces ipsilateral turning behaviour in rats never exposed to a dopamine receptor agonist, whereas contralateral turning is elicited if rats are repeatedly primed with a dopamine receptor agonist. In this study, rats unilaterally lesioned with 6-hydroxydopamine and subchronically treated with an intermittent administration of caffeine (15 mg/kg) or vehicle, were administered, 3 days after discontinuations of the treatment, with the dopamine D(1) receptor agonist 1-phenyl 1,2,3,4,5-tetrahydro(1H)-3-benzazepine-7,8-diolhydrochloride (SKF 38393), the D(2)/D(3) receptor agonist quinpirole, the D(2) receptor agonist R(-)-propylnorapomorphine or the dopamine precursor L-3,4-dihydroxyphenyl-alanine. Administration of SKF 38393 (1.5 mg/kg) or L-3,4-dihydroxyphenyl-alanine (6 mg/kg), but not quinpirole (0.15 mg/kg) or R(-)-propylnorapomorphine (0.01 mg/kg), induced a significantly higher contralateral turning behaviour in rats subchronically treated with caffeine than in vehicle-pretreated rats. The results show that repeated intermittent caffeine exposure enhances the motor stimulant effects elicited by dopamine agonists by a preferential sensitization of dopamine D(1) receptors.

Alcohol and caffeine consumption and decreased fertility.

PubMed

Hakim, R B; Gray, R H; Zacur, H

1998-10-01

To examine the effects of alcohol and caffeine on conception. Prospective observational study. Healthy volunteers in two manufacturing facilities. One hundred twenty-four women who provided daily urine samples for measurement of steroid hormones and hCG, and prospective information about alcohol and caffeine consumption. Probability of conception per 100 menstrual cycles. There was >50% reduction in the probability of conception during a menstrual cycle during which participants consumed alcohol. Caffeine consumption did not independently affect the probability of conception but may enhance alcohol's negative effect. Women who abstained from alcohol and consumed less than one cup of coffee or its equivalent per day conceived 26.9 pregnancies per 100 menstrual cycles compared with 10.5 per 100 menstrual cycles among those who consumed any alcohol and more than one cup of coffee per day. This study revealed an independent dose-related negative effect of alcohol consumption on the ability to conceive. Our results suggest that women who are attempting to conceive should abstain from consuming alcohol.

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

Nutraceuticals for body-weight management: The role of green tea catechins.

PubMed

Janssens, Pilou L H R; Hursel, Rick; Westerterp-Plantenga, Margriet S

2016-08-01

Green tea catechins mixed with caffeine have been proposed as adjuvants for maintaining or enhancing energy expenditure and for increasing fat oxidation, in the context of prevention and treatment of obesity. These catechins-caffeine mixtures seem to counteract the decrease in metabolic rate that occurs during weight loss. Their effects are of particular importance during weight maintenance after weight loss. Other metabolic targets may be fat absorption and the gut microbiota composition, but these effects still need further investigation in combination with weight loss. Limitations for the effects of green tea catechins are moderating factors such as genetic predisposition related to COMT-activity, habitual caffeine intake, and ingestion combined with dietary protein. In conclusion, a mixture of green tea catechins and caffeine has a beneficial effect on body-weight management, especially by sustained energy expenditure, fat oxidation, and preservation of fat free body-mass, after energy restriction induced body-weight loss, when taking the limitations into account. Copyright © 2016 Elsevier Inc. All rights reserved.

Biochemical evaluation of triploid progenies of diploid × tetraploid breeding populations of Camellia for genotypes rich in catechin and caffeine.

PubMed

Das, Sourabh Kumar; Sabhapondit, Santanu; Ahmed, Giasuddin; Das, Sudripta

2013-06-01

To verify the quality of triploid varieties of Camellia tea species at the secondary metabolite level, we tested caffeine and catechin profiles of 97 F(1) segregating progenies in two breeding populations with a common tetraploid parent and diploid parents of two geographic and varietal origins. Catechin and caffeine levels of the triploid progenies were quantified and compared against their diploid parent. Some of the progenies showed better performance than their diploid parent. Most of the progenies of the diploid C. sinensis × tetraploid cross showed heterosis for caffeine and EGCG. Progenies of the C. assamica subsp. lasiocalyx × tetraploid cross showed heterosis for +C, EC, EGC, and TC. The genomic contributions of the diploid parent seem to be the main factor in the variation between the two populations. Our studies showed quantitative enhancement of some of the quality-related parameters in tea, providing a platform to refocus on this classical breeding approach for developing quality cultivars in tea.

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.

The stimulatory effects of caffeine with oseltamivir (Tamiflu) on light-dark behavior and open-field behavior in mice.

PubMed

Uchiyama, Hidemori; Toda, Akihisa; Imoto, Masumi; Nishimura, Satoko; Kuroki, Hiroaki; Soeda, Shinji; Shimeno, Hiroshi; Watanabe, Shigenori; Eyanagi, Reiko

2010-01-22

Abnormal behaviors and death associated with the use of oseltamivir (Tamiflu) have emerged as a major issue in influenza patients taking the drug. Here, we investigated the mechanisms underlying the effects of oseltamivir on the behavior of mice using light-dark and open-field preference tests. Oseltamivir (75 and 150 mg/kg, intraperitoneally (i.p.)) alone affected neither time spent in the open area in the light-dark preference test nor ambulation in the open-field test at 2h post-injection. However, a non-selective adenosine A(1)/A(2) receptor antagonist, caffeine (10mg/kg, i.p.) in combination with oseltamivir (150 mg/kg, i.p.) increased time spent in the open area in the light-dark preference test. This enhancement was not inhibited by a benzodiazepine receptor antagonist, flumazenil (10-20mg/kg, subcutaneously (s.c.)). Enhancement of ambulation in the open-field test was also observed when caffeine (10mg/kg, i.p.) was combined with oseltamivir (150 mg/kg, i.p.). This enhancement was inhibited by a dopamine D(2) receptor antagonist, haloperidol (0.1mg/kg, s.c.). Furthermore, an adenosine A(2) receptor antagonist, SCH58261 (3mg/kg, i.p.) in combination with oseltamivir (150 mg/kg, i.p.) increased ambulation in the open-field test, while an adenosine A(1) receptor antagonist, DPCPX (1-3mg/kg, i.p.) did not. These findings suggest that the actions of oseltamivir may involve the dopamine and adenosine systems. Our findings suggest that due to the interaction between central blockade of adenosine A(2) receptors by caffeine, and oseltamivir-induced behavioral changes, patients being treated with oseltamivir should be closely monitored. (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Enhancement of HIV-1 VLP production using gene inhibition strategies.

PubMed

Fuenmayor, Javier; Cervera, Laura; Rigau, Cristina; Gòdia, Francesc

2018-05-01

Gag polyprotein from HIV-1 is able to generate virus-like particles (VLPs) when recombinantly expressed in animal cell platforms. HIV-1 VLP production in HEK293 cells can be improved by the use of different strategies for increasing product titers. One of them is the so-called extended gene expression (EGE), based on repeated medium exchanges and retransfections of the cell culture to prolong the production phase. Another approach is the media supplementation with gene expression enhancers such as valproic acid and caffeine, despite their detrimental effect on cell viability. Valproic acid is a histone deacetylase inhibitor while caffeine has a phosphodiesterase inhibition effect. Here, the combination of the EGE protocol with additive supplementation to maximize VLP production is first tested. As an alternative to the direct additive supplementation, the replacement of these chemical additives by iRNA for obtaining the same inhibition action is also tested. The combination of the EGE protocol with caffeine and valproic acid supplementation resulted in a 1.5-fold improvement in HIV-1 VLP production compared with the EGE protocol alone, representing an overall 18-fold improvement over conventional batch cultivation. shRNAs encoded in the expression vector were tested to substitute valproic acid and caffeine. This novel strategy enhanced VLP production by 2.3 fold without any detrimental effect on cell viability (91.7%) compared with the batch cultivation (92.0%). Finally, the combination of shRNA with EGE resulted in more than 15.6-fold improvement compared with the batch standard protocol traditionally used. The methodology developed enables the production of high titers of HIV-1 VLPs avoiding the toxic effects of additives.

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.

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.

Effect of melatonin and caffeine interaction on caffeine induced oxidative stress and sleep disorders.

PubMed

Obochi, G O; Amali, O O E; Ochalefu, D O

2010-11-24

Effect of interaction of melatonin and caffeine on caffeine induced oxidative stress and sleep disorders was studied. Fifteen wistar rats were randomly assigned into three study groups. The animals in group 1 (the control) received a placebo of 10.0 ml distilled water via gastric intubation. The hosts in groups 2 and 3 were treated with 100 mg caffeine/ kg, or melatonin/ kg, respectively, in a total volume of 10.0 ml vehicle. The experiment lasted for 30 days. One day after the final exposure, the animals were euthanized by inhalation of overdose of chloroform. Blood was collected by cardiac puncture. Serum was obtained by centrifugation (6000 Xg, 30 mins), and used for serum total protein and serum blood urea nitrogen levels. The brain of each rat was also harvested and processed into whole homogenate, frozen in liquid nitrogen (N2), and maintained at -80oC until used for total brain cholesterol and tryptophan levels. The results showed that interaction of melatonin and caffeine enhanced protein synthesis; stimulated gonadotrophin release,  and could be used as oral contraceptive for women, and may be beneficial in the treatment of impotence (androgen depression), leading to improved reproductive and sex life; stimulated tryptophan metabolism, which prevents vitamin B6 deficiency, anemia, negative nitrogen balance, tissue wasting and accumulation of xanthurenic acid, which promotes sleep; and could be beneficial in the treatment of hyper cholesterolemia, thereby preventing coronary heart disease, and post menopausal osteoporosis.

8-Aryl- and alkyloxycaffeine analogues as inhibitors of monoamine oxidase.

PubMed

Strydom, Belinda; Bergh, Jacobus J; Petzer, Jacobus P

2011-08-01

Recently it was reported that a series of 8-benzyloxycaffeine analogues are potent reversible inhibitors of human monoamine oxidase (MAO) A and B. In an attempt to discover additional C8 oxy substituents of caffeine that lead to potent MAO inhibition, a series of related 8-aryl- and alkyloxycaffeine analogues were synthesized and their MAO-A and -B inhibition potencies were compared to those of the 8-benzyloxycaffeines. The results document that while the 8-substituted-oxycaffeine analogues inhibited both human MAO isoforms, they displayed a high degree of selectivity for MAO-B. 8-(3-Phenylpropoxy)caffeine, 8-(2-phenoxyethoxy)caffeine and 8-[(5-methylhexyl)oxy]caffeine were found to be the especially potent MAO-B inhibitors with IC(50) values ranging from 0.38 to 0.62 μM. These inhibitors are therefore 2.5-4.6 fold more potent MAO-B inhibitors than is 8-benzyloxycaffeine (IC(50) = 1.77 μM). It is also demonstrated that, analogous to 8-benzyloxycaffeine, halogen substitution on the phenyl ring of the C8 substituent significantly enhances MAO binding affinity. For example, the most potent MAO-B inhibitor of the present series is 8-[2-(4-bromophenoxy)ethoxy]caffeine with an IC(50) value of 0.166 μM. This study also reports possible binding orientations of selected oxy caffeines within the active site cavities of MAO-A and MAO-B. Copyright © 2011 Elsevier Masson SAS. 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.

Current evidence for the use of coffee and caffeine to prevent age-related cognitive decline and Alzheimer's disease.

PubMed

Carman, A J; Dacks, P A; Lane, R F; Shineman, D W; Fillit, H M

2014-04-01

Although nothing has been proven conclusively to protect against cognitive aging, Alzheimer's disease or related dementias, decades of research suggest that specific approaches including the consumption of coffee may be effective. While coffee and caffeine are known to enhance short-term memory and cognition, some limited research also suggests that long-term use may protect against cognitive decline or dementia. In vitro and pre-clinical animal models have identified plausible neuroprotective mechanisms of action of both caffeine and other bioactive components of coffee, though epidemiology has produced mixed results. Some studies suggest a protective association while others report no benefit. To our knowledge, no evidence has been gathered from randomized controlled trials. Although moderate consumption of caffeinated coffee is generally safe for healthy people, it may not be for everyone, since comorbidities and personal genetics influence potential benefits and risks. Future studies could include short-term clinical trials with biomarker outcomes to validate findings from pre-clinical models and improved epidemiological studies that incorporate more standardized methods of data collection and analysis. Given the enormous economic and emotional toll threatened by the current epidemic of Alzheimer's disease and other dementias, it is critically important to validate potential prevention strategies such as coffee and caffeine.

Low-dose caffeine administered in chewing gum does not enhance cycling to exhaustion.

PubMed

Ryan, Edward J; Kim, Chul-Ho; Muller, Matthew D; Bellar, David M; Barkley, Jacob E; Bliss, Matthew V; Jankowski-Wilkinson, Andrea; Russell, Morgan; Otterstetter, Ronald; Macander, Daniela; Glickman, Ellen L; Kamimori, Gary H

2012-03-01

Low-dose caffeine administered in chewing gum does not enhance cycling to exhaustion. The purpose of the current investigation was to examine the effect of low-dose caffeine (CAF) administered in chewing gum at 3 different time points during submaximal cycling exercise to exhaustion. Eight college-aged (26 ± 4 years), physically active (45.5 ± 5.7 ml·kg(-1)·min(-1)) volunteers participated in 4 experimental trials. Two pieces of caffeinated chewing gum (100 mg per piece, total quantity of 200 mg) were administered in a double-blind manner at 1 of 3 time points (-35, -5, and +15 minutes) with placebo at the other 2 points and at all 3 points in the control trial. The participants cycled at 85% of maximal oxygen consumption until volitional fatigue and time to exhaustion (TTE) were recorded in minutes. Venous blood samples were obtained at -40, -10, and immediately postexercise and analyzed for serum-free fatty acid and plasma catecholamine concentrations. Oxygen consumption, respiratory exchange ratio, heart rate, glucose, lactate, ratings of perceived exertion, and perceived leg pain measures were obtained at baseline and every 10 minutes during cycling. The results showed that there were no significant differences between the trials for any of the parameters measured including TTE. These findings suggest that low-dose CAF administered in chewing gum has no effect on TTE during cycling in recreational athletes and is, therefore, not recommended.

Caffeine Increases Work Done above Critical Power, but Not Anaerobic Work.

PubMed

Silveira, Rodrigo; Andrade-Souza, Victor Amorim; Arcoverde, Lucyana; Tomazini, Fabiano; Sansonio, André; Bishop, David John; Bertuzzi, Romulo; Lima-Silva, Adriano Eduardo

2018-01-01

The assumption that the curvature constant (W') of the power-duration relationship represents anaerobic work capacity is a controversial, unresolved question. We investigated if caffeine ingestion could increase total work done above critical power (CP), and if this would be accompanied by greater anaerobic energy expenditure and by an enhanced maintenance of maximal oxidative metabolic rate. Nine men (26.6 ± 5.3 yr, V˙O2max 40.6 ± 5.8 mL·kg·min) cycled until exhaustion at different exercise intensities on different days to determine the CP and W'. On separated days, participants cycled until exhaustion in the severe-intensity domain (136% ± 7% of CP) after ingesting either caffeine (5 mg·kg body mass) or a placebo. Time to exhaustion was 34% longer with caffeine compared with placebo, and this was accompanied by a greater work done above CP (23.7 ± 5.7 vs 17.5 ± 3.6 kJ; 130% ± 30% vs 95% ± 14% of W', P < 0.01). Caffeine increased the aerobic energy expenditure (296.4 ± 91.0 vs 210.2 ± 71.9 kJ, P < 0.01), but not anaerobic lactic, anaerobic alactic, and total anaerobic (lactic + alactic) energy expenditure. The end values of heart rate and ventilation were higher with caffeine, but the V˙O2 end was similar between conditions and was not different from V˙O2max. Caffeine did not change time to reach V˙O2max but increased time maintained at V˙O2max (199.3 ± 105.9 vs 111.9 ± 87.1 s, P < 0.05). Caffeine increased total work done above CP, but this was not associated with greater anaerobic work. Rather, this was associated with a higher tolerance to maintain exercise at maximal oxidative metabolic rate.

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.

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.

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.

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.

Performance outcomes and unwanted side effects associated with energy drinks.

PubMed

Mora-Rodriguez, Ricardo; Pallarés, Jesús G

2014-10-01

Energy drinks are increasingly popular among athletes and others. Advertising for these products typically features images conjuring great muscle power and endurance; however, the scientific literature provides sparse evidence for an ergogenic role of energy drinks. Although the composition of energy drinks varies, most contain caffeine; carbohydrates, amino acids, herbs, and vitamins are other typical ingredients. This report analyzes the effects of energy drink ingredients on prolonged submaximal (endurance) exercise as well as on short-term strength and power (neuromuscular performance). It also analyzes the effects of energy drink ingredients on the fluid and electrolyte deficit during prolonged exercise. In several studies, energy drinks have been found to improve endurance performance, although the effects could be attributable to the caffeine and/or carbohydrate content. In contrast, fewer studies find an ergogenic effect of energy drinks on muscle strength and power. The existing data suggest that the caffeine dose given in studies of energy drinks is insufficient to enhance neuromuscular performance. Finally, it is unclear if energy drinks are the optimal vehicle to deliver caffeine when high doses are needed to improve neuromuscular performance. © 2014 International Life Sciences Institute.

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.

The ingestion of a caffeinated energy drink improves jump performance and activity patterns in elite badminton players.

PubMed

Abian, Pablo; Del Coso, Juan; Salinero, Juan José; Gallo-Salazar, Cesar; Areces, Francisco; Ruiz-Vicente, Diana; Lara, Beatriz; Soriano, Lidon; Muñoz, Victor; Abian-Vicen, Javier

2015-01-01

The aim of this study was to investigate the effectiveness of a caffeine-containing energy drink to enhance physical and match performance in elite badminton players. Sixteen male and elite badminton players (25.4 ± 7.3 year; 71.8 ± 7.9 kg) participated in a double-blind, placebo-controlled and randomised experiment. On two different sessions, badminton players ingested 3 mg of caffeine per kg of body mass in the form of an energy drink or the same drink without caffeine (placebo). After 60 min, participants performed the following tests: handgrip maximal force production, smash jump without and with shuttlecock, squat jump, countermovement jump and the agility T-test. Later, a 45-min simulated badminton match was played. Players' number of impacts and heart rate was measured during the match. The ingestion of the caffeinated energy drink increased squat jump height (34.5 ± 4.7 vs. 36.4 ± 4.3 cm; P < 0.05), squat jump peak power (P < 0.05), countermovement jump height (37.7 ± 4.5 vs. 39.5 ± 5.1 cm; P < 0.05) and countermovement jump peak power (P < 0.05). In addition, an increased number of total impacts was found during the badminton match (7395 ± 1594 vs. 7707 ± 2033 impacts; P < 0.05). In conclusion, the results show that the use of caffeine-containing energy drink may be an effective nutritional aid to increase jump performance and activity patterns during game in elite badminton players.

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.

Reduced Stress and Improved Sleep Quality Caused by Green Tea Are Associated with a Reduced Caffeine Content.

PubMed

Unno, Keiko; Noda, Shigenori; Kawasaki, Yohei; Yamada, Hiroshi; Morita, Akio; Iguchi, Kazuaki; Nakamura, Yoriyuki

2017-07-19

Caffeine, one of the main components in green tea, can interfere with sleep and block the effect of theanine. Since theanine, the main amino acid in tea leaves, has significant anti-stress effects in animals and humans, we examined the effects of green tea with lowered caffeine content, i.e., low-caffeine green tea (LCGT), on stress and quality of sleep of middle-aged individuals ( n = 20, mean age 51.3 ± 6.7 years) in a double-blind crossover design. Standard green tea (SGT) was used as the control. These teas (≥300 mL/day), which were eluted with room temperature water, were consumed over a period of seven days after a single washout term. The level of salivary α-amylase activity (sAA), a stress marker, was significantly lower in participants that consumed LCGT (64.7 U/mL) than in those that consumed SGT (73.9 U/mL). Sleep quality was higher in participants that consumed a larger quantity of LCGT. In addition, a self-diagnostic check for accumulated fatigue was significantly lower in those participants that consumed LCGT than SGT. These results indicate that LCGT intake can reduce stress in middle-aged individuals and improve their quality of sleep. The reduction in caffeine is suggested to be a valid reason for enhancing the anti-stress effect of green tea.

Reduced Stress and Improved Sleep Quality Caused by Green Tea Are Associated with a Reduced Caffeine Content

PubMed Central

Unno, Keiko; Noda, Shigenori; Kawasaki, Yohei; Yamada, Hiroshi; Morita, Akio; Iguchi, Kazuaki; Nakamura, Yoriyuki

2017-01-01

Caffeine, one of the main components in green tea, can interfere with sleep and block the effect of theanine. Since theanine, the main amino acid in tea leaves, has significant anti-stress effects in animals and humans, we examined the effects of green tea with lowered caffeine content, i.e., low-caffeine green tea (LCGT), on stress and quality of sleep of middle–aged individuals (n = 20, mean age 51.3 ± 6.7 years) in a double-blind crossover design. Standard green tea (SGT) was used as the control. These teas (≥300 mL/day), which were eluted with room temperature water, were consumed over a period of seven days after a single washout term. The level of salivary α-amylase activity (sAA), a stress marker, was significantly lower in participants that consumed LCGT (64.7 U/mL) than in those that consumed SGT (73.9 U/mL). Sleep quality was higher in participants that consumed a larger quantity of LCGT. In addition, a self-diagnostic check for accumulated fatigue was significantly lower in those participants that consumed LCGT than SGT. These results indicate that LCGT intake can reduce stress in middle-aged individuals and improve their quality of sleep. The reduction in caffeine is suggested to be a valid reason for enhancing the anti-stress effect of green tea. PMID:28753943

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

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)

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

Use pattern and predictors of use of highly caffeinated energy drinks among South Korean adolescents: a study using the Health Belief Model

PubMed Central

Ha, Dongmun; Song, Inmyung; Jang, Gyeongil; Lee, Eui-Kyung; Shin, Ju-Young

2017-01-01

Objectives Concerns about the use of highly caffeinated energy drinks among Korean adolescents remains. We compared adolescents’ perceptions regarding the use of drinks to their behaviours and factors. Design A structured questionnaire based on the Health Belief Model was administered to 850 freshmen and sophomores at three high schools in Bucheon, South Korea. Benefits were defined as beneficial effects from the use of highly caffeinated energy drinks (eg, awakening from sleepiness) and harms as adverse effects of the drinks (eg, cardiac palpitation). Likelihood of action represents the likelihood of taking actions that are perceived to be more beneficial after comparison of the benefits and harms of caffeine use. Descriptive analysis was used to quantify the relationship between their beliefs about highly caffeinated energy drinks and their use. We conducted hierarchical logistic regression to compute ORs and 95% CIs for: (1) demographic factors, (2) health threat, (3) likelihood of action and (4) cues to act. Results Altogether, 833 students responded to the questionnaire (effective response rate=98.0%). About 63.0% reported use of highly caffeinated energy drinks and 35.2% had used them as needed and habitually. The more susceptible the respondents perceived themselves to be to the risk of using these drinks, the less likely they were to use them (OR: 0.73, 95% CI 0.50 to 1.06). The more severe the perception of a health threat, the less that perception was associated with use (OR: 0.44, 95% CI 0.29 to 0.67). Likelihood of action was the strongest predictor of use, explaining 12.5% in use. Benefits and harms (OR: 4.43, 95% CI 2.77 to 7.09; OR: 1.86, 95% CI 1.16 to 2.99) also were significant predictors. Conclusions Enhancing adolescents’ perceptions of benefits and harms regarding using highly caffeinated energy drinks could be an effective way to influence the use of these drinks. PMID:28947455

Anti-correlated Networks, Global Signal Regression, and the Effects of Caffeine in Resting-State Functional MRI

PubMed Central

Wong, Chi Wah; Olafsson, Valur; Tal, Omer; Liu, Thomas T.

2012-01-01

Resting-state functional connectivity magnetic resonance imaging is proving to be an essential tool for the characterization of functional networks in the brain. Two of the major networks that have been identified are the default mode network (DMN) and the task positive network (TPN). Although prior work indicates that these two networks are anti-correlated, the findings are controversial because the anti-correlations are often found only after the application of a pre-processing step, known as global signal regression, that can produce artifactual anti-correlations. In this paper, we show that, for subjects studied in an eyes-closed rest state, caffeine can significantly enhance the detection of anti-correlations between the DMN and TPN without the need for global signal regression. In line with these findings, we find that caffeine also leads to widespread decreases in connectivity and global signal amplitude. Using a recently introduced geometric model of global signal effects, we demonstrate that these decreases are consistent with the removal of an additive global signal confound. In contrast to the effects observed in the eyes-closed rest state, caffeine did not lead to significant changes in global functional connectivity in the eyes-open rest state. PMID:22743194

Effects of coffee and caffeine anhydrous on strength and sprint performance

PubMed Central

TREXLER, ERIC T.; SMITH-RYAN, ABBIE E.; ROELOFS, ERICA J.; HIRSCH, KATIE R.; MOCK, MEREDITH G.

2015-01-01

Caffeine and coffee are widely used among active individuals to enhance performance. The purpose of the current study was to compare the effects of acute coffee (COF) and caffeine anhydrous (CAF) intake on strength and sprint performance. Fifty-four resistance-trained males completed strength testing, consisting of one-rep max (1RM) and repetitions to fatigue (RTF) at 80% of 1RM for leg press (LP) and bench press (BP). Participants then completed five, ten-second cycle ergometer sprints separated by one minute of rest. Peak power (PP) and total work (TW) were recorded for each sprint. At least 48 hours later, participants returned and ingested a beverage containing CAF (300 mg flat dose; yielding 3–5 mg/kg bodyweight), COF (8.9 g; 303 mg caffeine), or placebo (PLA; 3.8 g noncaloric flavoring) 30 minutes before testing. LP 1RM was improved more by COF than CAF (p=0.04), but not PLA (p=0.99). Significant interactions were not observed for BP 1RM, BP RTF, or LP RTF (p>0.05). There were no sprint × treatment interactions for PP or TW (p>0.05). 95% confidence intervals revealed a significant improvement in sprint 1 TW for CAF, but not COF or PLA. For PLA, significant reductions were observed in sprint 4 PP, sprint 2 TW, sprint 4 TW, and average TW; significant reductions were not observed with CAF or COF. Neither COF nor CAF improved strength outcomes more than PLA, while both groups attenuated sprint power reductions to a similar degree. Coffee and caffeine anhydrous may be considered suitable pre-exercise caffeine sources for high-intensity exercise. PMID:26394649

Effects of coffee and caffeine anhydrous on strength and sprint performance.

PubMed

Trexler, Eric T; Smith-Ryan, Abbie E; Roelofs, Erica J; Hirsch, Katie R; Mock, Meredith G

2016-09-01

Caffeine and coffee are widely used among active individuals to enhance performance. The purpose of the current study was to compare the effects of acute coffee (COF) and caffeine anhydrous (CAF) intake on strength and sprint performance. Fifty-four resistance-trained males completed strength testing, consisting of one-rep max (1RM) and repetitions to fatigue (RTF) at 80% of 1RM for leg press (LP) and bench press (BP). Participants then completed five, 10-second cycle ergometer sprints separated by one minute of rest. Peak power (PP) and total work (TW) were recorded for each sprint. At least 48 hours later, participants returned and ingested a beverage containing CAF (300 mg flat dose; yielding 3-5 mg/kg bodyweight), COF (8.9 g; 303 mg caffeine), or placebo (PLA; 3.8 g non-caloric flavouring) 30 minutes before testing. LP 1RM was improved more by COF than CAF (p = .04), but not PLA (p = .99). Significant interactions were not observed for BP 1RM, BP RTF, or LP RTF (p > .05). There were no sprint × treatment interactions for PP or TW (p > .05). 95% confidence intervals revealed a significant improvement in sprint 1 TW for CAF, but not COF or PLA. For PLA, significant reductions were observed in sprint 4 PP, sprint 2 TW, sprint 4 TW, and average TW; significant reductions were not observed with CAF or COF. Neither COF nor CAF improved strength outcomes more than PLA, while both groups attenuated sprint power reductions to a similar degree. Coffee and caffeine anhydrous may be considered suitable pre-exercise caffeine sources for high-intensity exercise.

Anti-aggressive effect elicited by coca-paste in isolation-induced aggression of male rats: influence of accumbal dopamine and cortical serotonin.

PubMed

Meikle, María Noel; Prieto, José Pedro; Urbanavicius, Jessika; López, Ximena; Abin-Carriquiry, Juan Andrés; Prunell, Giselle; Scorza, María Cecilia

2013-09-01

Coca-paste (CP), an illicit drug of abuse, has been frequently associated with aggressive and impulsive behaviors in humans. However, preclinical studies have not been carried out in order to characterize CP effects on aggression. The acute effect of CP, cocaine and caffeine (the main adulterant present in seized samples) on aggression was assessed using the isolation-induced aggression paradigm in male rats. The dopaminergic (DA) neurotransmission in the nucleus accumbens (NAcc) and serotonergic (5-HT) activity in the frontal cortex were explored. CP and cocaine induced a similar anti-aggressive effect on isolated rats although CP-treated animals showed a shorter latency to the first attack. Aggressive behavior was not increased per se by caffeine. Social investigation time was slightly reduced only by cocaine while exploratory activity and time spent walking were increased by the three drugs. Accumbal DA levels were significantly augmented by CP, cocaine and caffeine, although differences in DOPAC and HVA levels were evidenced. A decrease in DA turnover was only observed after CP and cocaine administration. Increased cortical 5-HT levels with a concomitant decrease in 5-HT turnover were observed after CP and cocaine whereas caffeine did not alter it. As cocaine but not caffeine reduced aggression, it seems like cocaine content was mainly responsible for CP anti-aggressive action; however, the presence of caffeine in CP may have a role in the shorter latency to attack compared to cocaine. Despite the increase in NAcc DA, the enhancement of cortical 5-HT levels can likely underlie the anti-aggression observed in CP-treated animals. © 2013 Elsevier Inc. All rights reserved.

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.

Commonly used stimulants: Sleep problems, dependence and psychological distress.

PubMed

Ogeil, Rowan P; Phillips, James G

2015-08-01

Caffeine and nicotine are commonly used stimulants that enhance alertness and mood. Discontinuation of both stimulants is associated with withdrawal symptoms including sleep and mood disturbances, which may differ in males and females. The present study examines changes in sleep quality, daytime sleepiness and psychological distress associated with use and dependence on caffeine and nicotine. An online survey comprising validated tools to assess sleep quality, excessive daytime sleepiness and psychological distress was completed by 166 participants (74 males, 96 females) with a mean age of 28 years. Participants completed the study in their own time, and were not offered any inducements to participate. Sleep quality was poorer in those dependent upon caffeine or nicotine, and there were also significant interaction effects with gender whereby females reported poorer sleep despite males reporting higher use of both stimulants. Caffeine dependence was associated with poorer sleep quality, increased daytime dysfunction, and increased levels of night time disturbance, while nicotine dependence was associated with poorer sleep quality and increased use of sleep medication and sleep disturbances. There were strong links between poor sleep and diminished affect, with psychological distress found to co-occur in the context of disturbed sleep. Stimulants are widely used to promote vigilance and mood; however, dependence on commonly used drugs including caffeine and nicotine is associated with decrements in sleep quality and increased psychological distress, which may be compounded in female dependent users. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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.

Investigating differences in the root to shoot transfer and xylem sap solubility of organic compounds between zucchini, squash and soybean using a pressure chamber method.

PubMed

Garvin, Naho; Doucette, William J; White, Jason C

2015-07-01

A pressure chamber method was used to examine differences in the root to shoot transfer and xylem sap solubility of caffeine (log Kow=-0.07), triclocarban (log Kow=3.5-4.2) and endosulfan (log Kow=3.8-4.8) for zucchini (cucurbita pepo ssp pepo), squash (cucurbita pepo ssp ovifera), and soybean (glycine max L.). Transpiration stream concentration factors (TSCF) for caffeine (TSCF=0.8) were statistically equivalent for all plant species. However, for the more hydrophobic endosulfan and triclocarban, the TSCF values for zucchini (TSCF=0.6 and 0.4, respectively) were 3 and 10 times greater than the soybean and squash (TSCF=0.2 and 0.05, respectively). The difference in TSCF values was examined by comparing the measured solubilities of caffeine, endosulfan and triclocarban in deionized water to those in soybean and zucchini xylem saps using a modified shake flask method. The measured solubility of organic contaminants in xylem sap has not previously been reported. Caffeine solubilities in the xylem saps of soybean and zucchini were statistically equal to deionized water (21500mgL(-1)) while endosulfan and triclocarban solubilities in the zucchini xylem sap were significantly greater (0.43 and 0.21mgL(-1), respectively) than that of the soybean xylem sap (0.31 and 0.11mgL(-1), respectively) and deionized water (0.34 and 0.11mgL(-1), respectively). This suggests that the enhanced root to shoot transfer of hydrophobic organics reported for zucchini is partly due to increased solubility in the xylem sap. Further xylem sap characterization is needed to determine the mechanism of solubility enhancement. Copyright © 2014 Elsevier Ltd. All rights reserved.

Acute impact of caffeinated alcoholic beverages on cognition: A systematic review.

PubMed

Lalanne, Laurence; Lutz, Pierre-Eric; Paille, François

2017-06-02

Energy drinks are popular beverages that are supposed to counteract sleepiness, increase energy, maintain alertness and reduce symptoms of hangover. Cognitive enhancing seems to be related to many compounds such as caffeine, taurine and vitamins. Currently, users mostly combine psychostimulant effects of energy drinks to counteract sedative effects of alcohol. However, recent literature suggests that this combination conducts to feel less intoxicated but still impaired. The goal of the present article is to review cognitive impact and subjective awareness in case of caffeinated alcoholic beverage (CAB) intoxication. PubMed (January 1960 to March 2016) database was searched using the following terms: cognitive impairments, alcohol, energy drinks; cognition, alcohol, caffeine. 99 papers were found but only 12 randomized controlled studies which explored cognitive disorders and subjective awareness associated with acute CAB or AED (alcohol associated with energy drinks) intoxication were included. The present literature review confirmed that energy drinks might counteract some cognitive deficits and adverse effects of alcohol i.e. dry mouth, fatigue, headache, weakness, and perception of intoxication due to alcohol alone. This effect depends on alcohol limb but disappears when the complexity of the task increases, when driving for example. Moreover, studies clearly showed that CAB/AEDs increase impulsivity which conducts to an overconsumption of alcohol and enhanced motivation to drink compared to alcohol alone, potentiating the risk of developing addictive behaviors. This is a huge problem in adolescents with high impulsivity and immature decision making processes. Although energy drinks counteract some cognitive deficits due to alcohol alone, their association promotes the risk of developing alcohol addiction. As a consequence, it is necessary to better understand the neurobiological mechanisms underlying these interactions in order to better prevent the development of alcohol dependence. Copyright © 2017 Elsevier Inc. All rights reserved.

A double-blind pilot study of the effect of Prokarin on fatigue in multiple sclerosis.

PubMed

Gillson, G; Richard, T L; Smith, R B; Wright, J V

2002-02-01

In this 12-week study with 29 subjects, the effect of Prokarin (n=22), a proprietary blend of histamine and caffeine, was compared to placebo group (n=7) for the following outcomes: 1) fatigue as measured by the Modified Fatigue Impact Scale (MFIS); 2) lower limb function as measured by timed walk test; 3) upper limb function as measured by the pegboard test; 4) cognitive function as measured by the Paced Auditory Serial Additions Test (PASAT); 5) serum caffeine level; 6) change in brain chemistry as measured by quantitative magnetic resonance spectroscopy assay of N-acetyl aspartate (NAA); and 7) safety as measured by routine blood chemistry, TSH and urinalysis. Data were acquired at baseline, 4, 8 and 12 weeks. The Prokarin group MFIS mean was significantly different rom the mean of the placebo group at 12 weeks (df=24, t=2.08, P=<0.02), with respective means of 37.40, SD=15.18, for the Prokarin group and 53.2, SD=11.39 for the controls. For the secondary endpoints (PASAT, 25 foot timed walk, peg test, and magnetic resonance spectroscopy [MRS]), there were no significant differences between the Prokarin-treated group and the placebo group. However, there were significant improvements within the Prokarin group for each of these measures for the pre- versus posttreatment comparison at 12 weeks. Serum caffeine data indicated that caffeine exerted no independent effect on performance. No laboratory abnormalities were seen, and the treatment was well tolerated. There was a modest-size statistical effect of Prokarin on fatigue in multiple sderosis (MS) compared with the placebo group. A larger trial is warranted, based on this pilot study.

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.

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.

The effects of combined caffeine and glucose drinks on attention in the human brain.

PubMed

Rao, Anling; Hu, Henglong; Nobre, Anna Christina

2005-06-01

The objective of this research was to measure the effects of energising drinks containing caffeine and glucose, upon mental activity during sustained selective attention. Non-invasive electrophysiological brain recordings were made during a behavioural study of selective attention in which participants received either energising or placebo drinks. We tested specifically whether energising drinks have significant effects upon behavioural measures of performance during a task requiring sustained visual selective attention, as well as on accompanying components of the event-related potential (ERPs) related to information processing in the brain. Forty healthy volunteers were blindly assigned to receive either the energising drink or a similar-tasting placebo drink. The behavioural task involved identifying predefined target stimulus among rapidly presented streams of peripheral visual stimuli, and making speeded motor responses to this stimulus. During task performance, accuracy, reaction times and ongoing brain activity were stored for analysis. The energising drink enhanced behavioural performance both in terms of accuracy and speed of reactions. The energising drink also had significant effects upon the event-related potentials. Effects started from the enhancement of the earliest components (Cl/P1), reflecting early visual cortical processing in the energising-drink group relative to the placebo group over the contralateral scalp. The later N1, N2 and P3 components related to decision-making and responses were also modulated by the energising drink. Energising drinks containing caffeine and glucose can enhance behavioural performance during demanding tasks requiring selective attention. The behavioural benefits are coupled to direct effects upon neural information processing.

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.

Physiological Responses to Cola Ingestion

ERIC Educational Resources Information Center

Van Handel, Peter J.; And Others

1977-01-01

Data from testing suggest that the ingestion of caffeine in the amount typically found in a single bottle of commercially available cola drink does not increase factors associated with coronary risk nor will it have an enhancing effect upon athletic performance. (MB)

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…

Induction of sister chromatid exchange in preimplantation mouse embryos in vitro by /sup 3/H-thymidine or ultraviolet light in combination with caffeine

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

Mueller, W.U.S.; Spindle, A.

1986-01-01

Preimplantation mouse embryos were exposed in vitro to /sup 3/H-thymidine (25, 100, or 250 Bq/ml) or ultraviolet (UV) light (1.35 or 4.05 J/m2), either alone or in combination with caffeine (1 mM with /sup 3/H-thymidine and 0.5 mM with UV light). Exposure to /sup 3/H-thymidine lasted for 2 days, from the two-cell stage to the late morula/early blastocyst stage, and UV radiation was applied acutely at the late morula/early blastocyst stage. The effects were quantified by the sister chromatid exchange (SCE) assay. All three agents induced SCEs when used singly. /sup 3/H-thymidine was effective in inducing SCEs only at 250more » Bq/ml, whereas UV light was effective at both fluences. Although caffeine did not induce SCEs when it was added before exposure to bromodeoxyuridine (BrdUrd), which is used to visualize SCEs, it did induce SCEs when present during the entire culture period (/sup 3/H-thymidine experiments) or during incubation in BrdUrd (UV experiments). Caffeine markedly enhanced the SCE-inducing effect of UV light but did not influence the effect of /sup 3/H-thymidine.« less

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

Anti-correlated networks, global signal regression, and the effects of caffeine in resting-state functional MRI.

PubMed

Wong, Chi Wah; Olafsson, Valur; Tal, Omer; Liu, Thomas T

2012-10-15

Resting-state functional connectivity magnetic resonance imaging is proving to be an essential tool for the characterization of functional networks in the brain. Two of the major networks that have been identified are the default mode network (DMN) and the task positive network (TPN). Although prior work indicates that these two networks are anti-correlated, the findings are controversial because the anti-correlations are often found only after the application of a pre-processing step, known as global signal regression, that can produce artifactual anti-correlations. In this paper, we show that, for subjects studied in an eyes-closed rest state, caffeine can significantly enhance the detection of anti-correlations between the DMN and TPN without the need for global signal regression. In line with these findings, we find that caffeine also leads to widespread decreases in connectivity and global signal amplitude. Using a recently introduced geometric model of global signal effects, we demonstrate that these decreases are consistent with the removal of an additive global signal confound. In contrast to the effects observed in the eyes-closed rest state, caffeine did not lead to significant changes in global functional connectivity in the eyes-open rest state. Copyright © 2012 Elsevier Inc. All rights reserved.

Sleep Deprivation and Caffeine Treatment Potentiate Photic Resetting of the Master Circadian Clock in a Diurnal Rodent.

PubMed

Jha, Pawan Kumar; Bouâouda, Hanan; Gourmelen, Sylviane; Dumont, Stephanie; Fuchs, Fanny; Goumon, Yannick; Bourgin, Patrice; Kalsbeek, Andries; Challet, Etienne

2017-04-19

Circadian rhythms in nocturnal and diurnal mammals are primarily synchronized to local time by the light/dark cycle. However, nonphotic factors, such as behavioral arousal and metabolic cues, can also phase shift the master clock in the suprachiasmatic nuclei (SCNs) and/or reduce the synchronizing effects of light in nocturnal rodents. In diurnal rodents, the role of arousal or insufficient sleep in these functions is still poorly understood. In the present study, diurnal Sudanian grass rats, Arvicanthis ansorgei , were aroused at night by sleep deprivation (gentle handling) or caffeine treatment that both prevented sleep. Phase shifts of locomotor activity were analyzed in grass rats transferred from a light/dark cycle to constant darkness and aroused in early night or late night. Early night, but not late night, sleep deprivation induced a significant phase shift. Caffeine on its own induced no phase shifts. Both sleep deprivation and caffeine treatment potentiated light-induced phase delays and phase advances in response to a 30 min light pulse, respectively. Sleep deprivation in early night, but not late night, potentiated light-induced c-Fos expression in the ventral SCN. Caffeine treatment in midnight triggered c-Fos expression in dorsal SCN. Both sleep deprivation and caffeine treatment potentiated light-induced c-Fos expression in calbindin-containing cells of the ventral SCN in early and late night. These findings indicate that, in contrast to nocturnal rodents, behavioral arousal induced either by sleep deprivation or caffeine during the sleeping period potentiates light resetting of the master circadian clock in diurnal rodents, and activation of calbindin-containing suprachiasmatic cells may be involved in this effect. SIGNIFICANCE STATEMENT Arousing stimuli have the ability to regulate circadian rhythms in mammals. Behavioral arousal in the sleeping period phase shifts the master clock in the suprachiasmatic nuclei and/or slows down the photic entrainment in nocturnal animals. How these stimuli act in diurnal species remains to be established. Our study in a diurnal rodent, the Grass rat, indicates that sleep deprivation in the early rest period induces phase delays of circadian locomotor activity rhythm. Contrary to nocturnal rodents, both sleep deprivation and caffeine-induced arousal potentiate the photic entrainment in a diurnal rodent. Such enhanced light-induced circadian responses could be relevant for developing chronotherapeutic strategies. Copyright © 2017 the authors 0270-6474/17/374343-16$15.00/0.

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.

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

The influence of stimulants, sedatives, and fatigue on tunnel vision: risk factors for driving and piloting.

PubMed

Mills, K C; Spruill, S E; Kanne, R W; Parkman, K M; Zhang, Y

2001-01-01

A computerized task was used in two studies to examine the influence of stimulants, sedatives, and fatigue on single-target and divided-attention responses in different parts of the visual field. The drug effects were evaluated over time with repeated behavioral and subjective measures against ascending and descending drug levels. In the first study, 18 fully rested participants received placebo, alprazolam (0.5 mg), and dextroamphetamine (10 mg). Alprazolam impairs performance, whereas dextroamphetamine induces enhancement and tunnel vision. Study 2 exposed 32 participants to fatigue and no fatigue with a repeated-measures crossover design. Four independent groups subsequently received placebo, dextroamphetamine (10 mg), caffeine (250 mg), or alcohol (.07%). Under fatigue, stimulants have no performance-enhancing effects, whereas impairment from alcohol is severe. Under no fatigue, alcohol has a modest effect, caffeine has no effect, and dextroamphetamine significantly enhances divided-attention performance coincident with tunnel vision. Participants rate all drug effects more stimulating and less sedating while fatigued. Implications for transportation safety are discussed. Actual or potential applications of this research include driver and pilot training.

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.

The aminoglycoside antibiotic kanamycin damages DNA bases in Escherichia coli: caffeine potentiates the DNA-damaging effects of kanamycin while suppressing cell killing by ciprofloxacin in Escherichia coli and Bacillus anthracis.

PubMed

Kang, Tina Manzhu; Yuan, Jessica; Nguyen, Angelyn; Becket, Elinne; Yang, Hanjing; Miller, Jeffrey H

2012-06-01

The distribution of mutants in the Keio collection of Escherichia coli gene knockout mutants that display increased sensitivity to the aminoglycosides kanamycin and neomycin indicates that damaged bases resulting from antibiotic action can lead to cell death. Strains lacking one of a number of glycosylases (e.g., AlkA, YzaB, Ogt, KsgA) or other specific repair proteins (AlkB, PhrB, SmbC) are more sensitive to these antibiotics. Mutants lacking AlkB display the strongest sensitivity among the glycosylase- or direct lesion removal-deficient strains. This perhaps suggests the involvement of ethenoadenine adducts, resulting from reactive oxygen species and lipid peroxidation, since AlkB removes this lesion. Other sensitivities displayed by mutants lacking UvrA, polymerase V (Pol V), or components of double-strand break repair indicate that kanamycin results in damaged base pairs that need to be removed or replicated past in order to avoid double-strand breaks that saturate the cellular repair capacity. Caffeine enhances the sensitivities of these repair-deficient strains to kanamycin and neomycin. The gene knockout mutants that display increased sensitivity to caffeine (dnaQ, holC, holD, and priA knockout mutants) indicate that caffeine blocks DNA replication, ultimately leading to double-strand breaks that require recombinational repair by functions encoded by recA, recB, and recC, among others. Additionally, caffeine partially protects cells of both Escherichia coli and Bacillus anthracis from killing by the widely used fluoroquinolone antibiotic ciprofloxacin.

Use pattern and predictors of use of highly caffeinated energy drinks among South Korean adolescents: a study using the Health Belief Model.

PubMed

Ha, Dongmun; Song, Inmyung; Jang, Gyeongil; Lee, Eui-Kyung; Shin, Ju-Young

2017-09-24

Concerns about the use of highly caffeinated energy drinks among Korean adolescents remains. We compared adolescents' perceptions regarding the use of drinks to their behaviours and factors. A structured questionnaire based on the Health Belief Model was administered to 850 freshmen and sophomores at three high schools in Bucheon, South Korea. Benefits were defined as beneficial effects from the use of highly caffeinated energy drinks (eg, awakening from sleepiness) and harms as adverse effects of the drinks (eg, cardiac palpitation). Likelihood of action represents the likelihood of taking actions that are perceived to be more beneficial after comparison of the benefits and harms of caffeine use. Descriptive analysis was used to quantify the relationship between their beliefs about highly caffeinated energy drinks and their use. We conducted hierarchical logistic regression to compute ORs and 95% CIs for: (1) demographic factors, (2) health threat, (3) likelihood of action and (4) cues to act. Altogether, 833 students responded to the questionnaire (effective response rate=98.0%). About 63.0% reported use of highly caffeinated energy drinks and 35.2% had used them as needed and habitually. The more susceptible the respondents perceived themselves to be to the risk of using these drinks, the less likely they were to use them (OR: 0.73, 95% CI 0.50 to 1.06). The more severe the perception of a health threat, the less that perception was associated with use (OR: 0.44, 95% CI 0.29 to 0.67). Likelihood of action was the strongest predictor of use, explaining 12.5% in use. Benefits and harms (OR: 4.43, 95% CI 2.77 to 7.09; OR: 1.86, 95% CI 1.16 to 2.99) also were significant predictors. Enhancing adolescents' perceptions of benefits and harms regarding using highly caffeinated energy drinks could be an effective way to influence the use of these drinks. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The role of nicotine, cotinine and caffeine on the electrochemical behavior and bacterial colonization to cp-Ti.

PubMed

Barão, Valentim A R; Ricomini-Filho, Antonio P; Faverani, Leonardo P; Del Bel Cury, Altair A; Sukotjo, Cortino; Monteiro, Douglas R; Yuan, Judy Chia-Chun; Mathew, Mathew T; do Amaral, Regiane C; Mesquita, Marcelo F; da Silva, Wander J; Assunção, Wirley G

2015-11-01

Although smoking promotes deleterious effect to bone healing, there is a lack of study investigating its role on the implant structure and biofilm growth. We hypothesized that nicotine, cotinine and caffeine would impair the corrosion resistance of commercially-pure titanium (cp-Ti) and would enhance Streptococcus sanguinis biofilm growth. Neither the smoking products nor the caffeine affected the corrosion tendency (P>.05) and the oxide layer resistance (P=.762) of cp-Ti. Lower capacitance values were noted in the presence of nicotine (P=.001) and cotinine (P=.0006). SEM showed no pitting corrosion, and the EDS spectra did not differ among groups. Nicotine (300μg/mL) induced higher surface roughness (P=.03) and greater surface change of cp-Ti. Nicotine at 3μg/mL, and cotinine at 0.3 and 3μg/mL increased the number of viable cells (P<.05). Biofilm exposed to nicotine (0.3, 3 and 30μg/mL) (P=.025, .030, .040, respectively) and cotinine (3 and 30μg/mL) (P=.027, .049, respectively) enhanced carbohydrate content. Biofilm biomass and protein content were similar among groups (P>.05). These findings suggest a greater biofilm accumulation in smokers, a risk factor that may lead to peri-implantitis. Copyright © 2015 Elsevier B.V. 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

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.

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.

(+)-(S)-alapyridaine--a general taste enhancer?

PubMed

Soldo, Tomislav; Blank, Imre; Hofmann, Thomas

2003-06-01

N-(1-Carboxyethyl)-6-hydroxymethyl-pyridinium-3-ol inner salt (alapyridaine), recently identified in heated sugar/amino acid mixtures as well as in beef bouillon, has been shown to exhibit general taste-enhancing activities, although tasteless on its own. Differing from other taste enhancers reported so far, racemic (R/S)-alapyridaine and, to an even greater extent (+)-(S)-alapyridaine, the physiologically active enantiomer, are able to enhance more than one basic taste quality. The threshold concentrations for the sweet taste of glucose and sucrose, for the umami taste of monosodium L-glutamate (MSG) and guanosine-5'-monophosphate (GMP), as well as the salty taste of NaCl, were significantly decreased when alapyridaine was present. In contrast, perception of the bitter tastes of caffeine and L-phenylalanine, as well as of sour-tasting citric acid, was unaffected. Furthermore, alapyridaine was shown to intensify known taste synergies such as, for example, the enhancing effect of L-arginine on the salty taste of NaCl, as well as that of GMP on the umami taste of MSG. The activity of (+)-(S)-alapyridaine could be observed not only in solutions of single taste compounds, but also in more complex tastant mixtures; for example, the umami, sweet and salty taste of a solution containing MSG, sucrose, NaCl and caffeine was significantly modulated, thus indicating that alapyridaine is a general taste enhancer.

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.

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.

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.

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.

Caffeine Reverts Memory But Not Mood Impairment in a Depression-Prone Mouse Strain with Up-Regulated Adenosine A2A Receptor in Hippocampal Glutamate Synapses.

PubMed

Machado, Nuno J; Simões, Ana Patrícia; Silva, Henrique B; Ardais, Ana Paula; Kaster, Manuella P; Garção, Pedro; Rodrigues, Diana I; Pochmann, Daniela; Santos, Ana Isabel; Araújo, Inês M; Porciúncula, Lisiane O; Tomé, Ângelo R; Köfalvi, Attila; Vaugeois, Jean-Marie; Agostinho, Paula; El Yacoubi, Malika; Cunha, Rodrigo A; Gomes, Catarina A

2017-03-01

Caffeine prophylactically prevents mood and memory impairments through adenosine A 2A receptor (A 2A R) antagonism. A 2A R antagonists also therapeutically revert mood and memory impairments, but it is not known if caffeine is also therapeutically or only prophylactically effective. Since depression is accompanied by mood and memory alterations, we now explored if chronic (4 weeks) caffeine consumption (0.3 g/L) reverts mood and memory impairment in helpless mice (HM, 12 weeks old), a bred-based model of depression. HM displayed higher immobility in the tail suspension and forced swimming tests, greater anxiety in the elevated plus maze, and poorer memory performance (modified Y-maze and object recognition). HM also had reduced density of synaptic (synaptophysin, SNAP-25), namely, glutamatergic (vGluT1; -22 ± 7 %) and GABAergic (vGAT; -23 ± 8 %) markers in the hippocampus. HM displayed higher A 2A R density (72 ± 6 %) in hippocampal synapses, an enhanced facilitation of hippocampal glutamate release by the A 2A R agonist, CGS21680 (30 nM), and a larger LTP amplitude (54 ± 8 % vs. 21 ± 5 % in controls) that was restored to control levels (30 ± 10 %) by the A 2A R antagonist, SCH58261 (50 nM). Notably, caffeine intake reverted memory deficits and reverted the loss of hippocampal synaptic markers but did not affect helpless or anxiety behavior. These results reinforce the validity of HM as an animal model of depression by showing that they also display reference memory deficits. Furthermore, caffeine intake selectively reverted memory but not mood deficits displayed by HM, which are associated with an increased density and functional impact of hippocampal A 2A R controlling synaptic glutamatergic function.

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.

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.

Clinical and Physiological Correlates of Caffeine and Caffeine Metabolites in Primary Insomnia

PubMed Central

Youngberg, Mark R.; Karpov, Irina O.; Begley, Amy; Pollock, Bruce G.; Buysse, Daniel J.

2011-01-01

Objectives: To explore the relationship between plasma concentrations of caffeine and subjective and polysomnographic measures of sleep in both good sleeper controls (GSC) and individuals with primary insomnia (PI), following the consumption of low-moderate quantities of caffeine in the home environment. Methods: 65 PI and 29 GSC, each consuming < 4 four coffee cup equivalents of caffeine daily, were recruited. Subjects completed a diary detailing sleep habits and caffeine consumption, one night of polysomnography, and a blood sample for measurement of plasma caffeine and its metabolites at bedtime. Plasma concentrations of caffeine, its primary metabolite, paraxanthine, and other metabolites were determined for each subject and correlated with self-report and polysomnographic measures. Results: No statistically significant differences were found between GSC and PI with respect to number of caffeinated beverages consumed (p = 0.91), estimated absolute caffeine ingestion (p = 0.48), time of caffeine consumption (p = 0.22), or plasma concentrations of caffeine (p = 0.92) or paraxanthine (p = 0.88). Significant correlations were found between plasma concentrations of caffeine/paraxanthine and endorsed caffeine intake (r = 0.58, p < 0.05) and estimated absolute caffeine ingestion (r = 0.57, p < 0.05). Plasma caffeine/paraxanthine was significantly correlated with percent stage 1 sleep (r = 0.32, p < 0.05). However, plasma concentrations of caffeine/paraxanthine were not significantly correlated with other subjective or polysomnographic measures of sleep disturbance in either GSC or PI. Conclusions: These data suggest that low-moderate amounts of caffeine consumed in the home environment, and mostly during morning hours, have little effect on subjective or polysomnographic measures of sleep in GSC or PI. Citation: Youngberg MR; Karpov IO; Begley A; Pollock BG; Buysse DJ. Clinical and physiological correlates of caffeine and caffeine metabolites in primary insomnia. J Clin Sleep Med 2011;7(2):196-203. PMID:21509336

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.

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.

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.

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.

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.

Safety and performance benefits of arginine supplements for military personnel: a systematic review.

PubMed

Brooks, James R; Oketch-Rabah, Hellen; Low Dog, Tieraona; Gorecki, Dennis K J; Barrett, Marilyn L; Cantilena, Louis; Chung, Mei; Costello, Rebecca B; Dwyer, Johanna; Hardy, Mary L; Jordan, Scott A; Maughan, Ronald J; Marles, Robin J; Osterberg, Robert E; Rodda, Bruce E; Wolfe, Robert R; Zuniga, Jorge M; Valerio, Luis G; Jones, Donnamaria; Deuster, Patricia; Giancaspro, Gabriel I; Sarma, Nandakumara D

2016-11-01

Dietary supplements are widely used by military personnel and civilians for promotion of health. The objective of this evidence-based review was to examine whether supplementation with l-arginine, in combination with caffeine and/or creatine, is safe and whether it enhances athletic performance or improves recovery from exhaustion for military personnel. Information from clinical trials and adverse event reports were collected from 17 databases and 5 adverse event report portals. Studies and reports were included if they evaluated the safety and the putative outcomes of enhanced performance or improved recovery from exhaustion associated with the intake of arginine alone or in combination with caffeine and/or creatine in healthy adults aged 19 to 50 years. Information related to population, intervention, comparator, and outcomes was abstracted. Of the 2687 articles screened, 62 articles meeting the inclusion criteria were analyzed. Strength of evidence was assessed in terms of risk of bias, consistency, directness, and precision. Most studies had few participants and suggested risk of bias that could negatively affect the results. l-Arginine supplementation provided little enhancement of athletic performance or improvements in recovery. Short-term supplementation with arginine may result in adverse gastrointestinal and cardiovascular effects. No information about the effects of arginine on the performance of military personnel was available. The available information does not support the use of l-arginine, either alone or in combination with caffeine, creatine, or both, to enhance athletic performance or improve recovery from exhaustion. Given the information gaps, an evidence-based review to assess the safety or effectiveness of multi-ingredient dietary supplements was not feasible, and therefore the development of a computational model-based approach to predict the safety of multi-ingredient dietary supplements is recommended. © The Author(s) 2016. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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.

The science and complexity of bitter taste.

PubMed

Drewnowski, A

2001-06-01

Food choices and eating habits are largely influenced by how foods taste. Without being the dominant taste sensation, bitter taste contributes to the complexity and enjoyment of beverages and foods. Compounds that are perceived as bitter do not share a similar chemical structure. In addition to peptides and salts, bitter compounds in foods may include plant-derived phenols and polyphenols, flavonoids, catechins, and caffeine. Recent studies have shown that humans possess a multitude of bitter taste receptors and that the transduction of bitter taste may differ between one compound and another. Studies of mixture interactions suggest further that bitter compounds suppress or enhance sweet and sour tastes and interact with volatile flavor molecules. Caffeine, a natural ingredient of tea, coffee, and chocolate, has a unique flavor profile. Used as a flavoring agent, it enhances the sensory appeal of beverages. Research developments on the genetics and perception of bitter taste add to our understanding of the role of bitterness in relation to food preference.

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.

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.

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

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

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.

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.

Canine Malignant Hyperthermia: Diagnosis of Susceptibility in a Breeding Colony

PubMed Central

O'Brien, P. J.; Cribb, P. H.; White, R. J.; Olfert, E. D.; Steiss, J. E.

1983-01-01

Fifteen related dogs were studied for susceptibility to malignant hyperthermia using halothane challenge and caffeine contracture tests. These dogs had hypertrophied muscles, were of a nervous temperament and had rectal temperatures at the upper limit of the normal range. Clinical pathology findings were mild elevations of serum aspartate transaminase and mean corpuscular hemoglobin. In vitro caffeine contracture tests were performed on muscle biopsies from five of these dogs. The concentration of caffeine required to increase resting tension by 1 g in biopsy specimens of these dogs was significantly lower than that required for control dogs: 7.6 ± 1.38 (x̄ ± SEM) versus 15.5 ± 2.52 mM (P < 0.025), and in the presence of 1% halothane, 3.6 ± 1.44 versus 10.6 ± 2.19 mM (P < 0.05). Internal nuclei, fiber caliber variation and fiber hypertrophy were found in histological studies of muscle biopsies. Two other dogs possibly died of a canine stress syndrome analagous to the porcine stress syndrome which occurs in malignant hyperthermia susceptible swine. Eight others of this family were anesthetized with halothane or methoxyflurane. Methoxyflurane did not trigger the syndrome. The first exposure to halothane caused death from malignant hyperthermia in two dogs and a third died on the second exposure to halothane. Postmortem findings were nonspecific. The other three dogs exposed to halothane recovered uneventfully. Inheritance of the defect conforms to a multifactorial pattern, with gradations of susceptibility. PMID:17422267

The effect of a caffeinated energy drink on various psychological measures during submaximal cycling.

PubMed

Duncan, Michael J; Hankey, Joanne

2013-05-27

Caffeine containing energy drinks is commonly consumed in the belief that it will enhance the quality of an exercise session and enhance mood. However, studies examining their efficacy are sparse. The aim of this study was to examine the effect of a caffeinated energy drink on leg pain perception, perceived exertion, mood state and readiness to invest effort pre, during and post 60 min cycling exercise. Fourteen active individuals (7 males, 7 females, mean age ± S.D.=23.5 ± 3.5 years), completed two 60 min cycling trials at an intensity of 60% VO2 max preceded by ingestion of solutions containing either a caffeinated energy drink or placebo using a double-blind, deceptive, crossover design. During exercise, RPE (6-20 scale), leg pain (0-10 scale), heart rate (HR) and blood lactate (Bla) were recorded. Participants also completed measures of mood state and readiness to invest physical effort (RTIPE) pre- and post-exercise. Repeated measures analysis of variance was used to assess differences in all variables and across time and treatments, with gender used as a between subjects variable. Results indicate that HR was significantly higher (P=.002) from 30 to 60 min and RPE (P=.0001) and pain perception (P=.0001) were significantly lower from 20 to 60 min in the energy drink condition compared to placebo. Bla was significantly higher (P=.021) in the last 15 min of the energy drink trial and RTIPE (P=.001) increased significantly more from pre-ingestion to pre-exercise post-ingestion in the energy drink condition compared to placebo. No gender differences were evident (P>.05). The data revealed positive effects of energy drink ingestion on perception of exertion, leg muscle pain perception and readiness to invest effort during submaximal cycling in active adults. Copyright © 2013 Elsevier Inc. All rights reserved.

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 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.

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.

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.

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.

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

Effects of prenatal caffeine exposure on glucose homeostasis of adult offspring rats

NASA Astrophysics Data System (ADS)

Kou, Hao; Wang, Gui-hua; Pei, Lin-guo; Zhang, Li; Shi, Chai; Guo, Yu; Wu, Dong-fang; Wang, Hui

2017-12-01

Epidemiological evidences show that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR). The IUGR offspring also present glucose intolerance and type 2 diabetes mellitus after maturity. We have previously demonstrated that PCE induced IUGR and increased susceptibility to adult metabolic syndrome in rats. This study aimed to further investigate the effects of PCE on glucose homeostasis in adult offspring rats. Pregnant rats were administered caffeine (120 mg/kg/day, intragastrically) from gestational days 11 to 20. PCE offspring presented partial catch-up growth pattern after birth, characterizing by the increased body weight gain rates. Meanwhile, PCE had no significant influences on the basal blood glucose and insulin phenotypes of adult offspring but increased the glucose tolerance, glucose-stimulated insulin section and β cell sensitivity to glucose in female progeny. The insulin sensitivity of both male and female PCE offspring were enhanced accompanied with reduced β cell fraction and mass. Western blotting results revealed that significant augmentation in protein expression of hepatic insulin signaling elements of PCE females, including insulin receptor (INSR), insulin receptor substrate 1 (IRS-1) and the phosphorylation of serine-threonine protein kinase (Akt), was also potentiated. In conclusion, we demonstrated that PCE reduced the pancreatic β mass but increased the glucose tolerance in adult offspring rats, especially for females. The adaptive compensatory enhancement of β cell responsiveness to glucose and elevated insulin sensitivity mainly mediated by upregulated hepatic insulin signaling might coordinately contribute to the increased glucose tolerance.

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.

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.

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.

Predicting the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol mixtures via molecular simulation.

PubMed

Paluch, Andrew S; Parameswaran, Sreeja; Liu, Shuai; Kolavennu, Anasuya; Mobley, David L

2015-01-28

We present a general framework to predict the excess solubility of small molecular solids (such as pharmaceutical solids) in binary solvents via molecular simulation free energy calculations at infinite dilution with conventional molecular models. The present study used molecular dynamics with the General AMBER Force Field to predict the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol solvents. The simulations are able to predict the existence of solubility enhancement and the results are in good agreement with available experimental data. The accuracy of the predictions in addition to the generality of the method suggests that molecular simulations may be a valuable design tool for solvent selection in drug development processes.

Predicting the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol mixtures via molecular simulation

NASA Astrophysics Data System (ADS)

Paluch, Andrew S.; Parameswaran, Sreeja; Liu, Shuai; Kolavennu, Anasuya; Mobley, David L.

2015-01-01

We present a general framework to predict the excess solubility of small molecular solids (such as pharmaceutical solids) in binary solvents via molecular simulation free energy calculations at infinite dilution with conventional molecular models. The present study used molecular dynamics with the General AMBER Force Field to predict the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol solvents. The simulations are able to predict the existence of solubility enhancement and the results are in good agreement with available experimental data. The accuracy of the predictions in addition to the generality of the method suggests that molecular simulations may be a valuable design tool for solvent selection in drug development processes.

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.

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

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.

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.

Physical Demands, Mental Performance and Food Components in Military Settings

DTIC Science & Technology

2005-08-01

2004). Recently, this task showed to be sensitive for the performance enhancing effects of modafinil and caffeine (Simons et al. 2004, in press). 4.2.2...Simons, Struyvenberg et al., 1997; Valk, Van Roon, Simons, Rikken, 2004). Recently, the MAT also showed performance enhancing effects of modafinil and... Choline , a part of the B-vitamins complex, can pass the blood-brain barrier. It has however not showed any effect on cognitive functioning yet

Temporal patterns of caffeine intake in the United States.

PubMed

Martyn, Danika; Lau, Annette; Richardson, Philip; Roberts, Ashley

2018-01-01

To investigate whether caffeine intake among adolescents and adults in the U.S. varies across the week or throughout the day, data from a 7-day online beverage consumption survey (2010-2011) were analyzed. Mean (206.8-213.0 mg/day) and 90th percentile (437.4-452.6 mg/day) daily caffeine intakes among consumers 13 years and older were relatively constant across the week with no marked difference among weekdays versus weekend days. Percent consumers of caffeinated beverages likewise remained stable across the week. Mean daily caffeine intake for coffee and energy drink consumers 13 years and older was higher than contributions for tea and carbonated soft drink consumers. Caffeinated beverage consumers (13 + yrs) consumed most of their caffeine in the morning (61% versus 21% and 18% in the afternoon and evening) which was driven by coffee. Caffeinated beverage consumption patterns among adolescents (13-17 yrs) - who typically consume less daily caffeine - were more evenly distributed throughout the day. These findings provide insight into U.S. temporal caffeine consumption patterns among specific caffeinated beverage consumers and different age brackets. These data suggest that while caffeine intakes do not vary from day-to-day, mornings generally drive the daily caffeine intake of adults and is predominantly attributed to coffee. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Caffeine Use Disorder: A Comprehensive Review and Research Agenda.

PubMed

Meredith, Steven E; Juliano, Laura M; Hughes, John R; Griffiths, Roland R

2013-09-01

Caffeine is the most commonly used drug in the world. Although consumption of low to moderate doses of caffeine is generally safe, an increasing number of clinical studies are showing that some caffeine users become dependent on the drug and are unable to reduce consumption despite knowledge of recurrent health problems associated with continued use. Thus, the World Health Organization and some health care professionals recognize caffeine dependence as a clinical disorder. In this comprehensive literature review, we summarize published research on the biological evidence for caffeine dependence; we provide a systematic review of the prevalence of caffeine dependence and rates of endorsement of clinically meaningful indicators of distress and functional impairment among habitual caffeine users; we discuss the diagnostic criteria for Caffeine Use Disorder-a condition for further study included in the Diagnostic and Statistical Manual of Mental Disorders ( 5 th ed .); and we outline a research agenda to help guide future clinical, epidemiological, and genetic investigations of caffeine dependence. Numerous controlled laboratory investigations reviewed in this article show that caffeine produces behavioral and physiological effects similar to other drugs of dependence. Moreover, several recent clinical studies indicate that caffeine dependence is a clinically meaningful disorder that affects a nontrivial proportion of caffeine users. Nevertheless, more research is needed to determine the reliability, validity, and prevalence of this clinically important health problem.

Caffeine Use Disorder: A Comprehensive Review and Research Agenda

PubMed Central

Meredith, Steven E.; Juliano, Laura M.; Hughes, John R.

2013-01-01

Caffeine is the most commonly used drug in the world. Although consumption of low to moderate doses of caffeine is generally safe, an increasing number of clinical studies are showing that some caffeine users become dependent on the drug and are unable to reduce consumption despite knowledge of recurrent health problems associated with continued use. Thus, the World Health Organization and some health care professionals recognize caffeine dependence as a clinical disorder. In this comprehensive literature review, we summarize published research on the biological evidence for caffeine dependence; we provide a systematic review of the prevalence of caffeine dependence and rates of endorsement of clinically meaningful indicators of distress and functional impairment among habitual caffeine users; we discuss the diagnostic criteria for Caffeine Use Disorder—a condition for further study included in the Diagnostic and Statistical Manual of Mental Disorders (5th ed.); and we outline a research agenda to help guide future clinical, epidemiological, and genetic investigations of caffeine dependence. Numerous controlled laboratory investigations reviewed in this article show that caffeine produces behavioral and physiological effects similar to other drugs of dependence. Moreover, several recent clinical studies indicate that caffeine dependence is a clinically meaningful disorder that affects a nontrivial proportion of caffeine users. Nevertheless, more research is needed to determine the reliability, validity, and prevalence of this clinically important health problem. PMID:24761279

Storm in a coffee cup: caffeine modifies brain activation to social signals of threat

PubMed Central

Lawrence, Andrew D.; Diukova, Ana; Wise, Richard G.; Rogers, Peter J.

2012-01-01

Caffeine, an adenosine A1 and A2A receptor antagonist, is the most popular psychostimulant drug in the world, but it is also anxiogenic. The neural correlates of caffeine-induced anxiety are currently unknown. This study investigated the effects of caffeine on brain regions implicated in social threat processing and anxiety. Participants were 14 healthy male non/infrequent caffeine consumers. In a double-blind placebo-controlled crossover design, they underwent blood oxygenation level-dependent functional magnetic resonance imaging (fMRI) while performing an emotional face processing task 1 h after receiving caffeine (250 mg) or placebo in two fMRI sessions (counterbalanced, 1-week washout). They rated anxiety and mental alertness, and their blood pressure was measured, before and 2 h after treatment. Results showed that caffeine induced threat-related (angry/fearful faces > happy faces) midbrain-periaqueductal gray activation and abolished threat-related medial prefrontal cortex wall activation. Effects of caffeine on extent of threat-related amygdala activation correlated negatively with level of dietary caffeine intake. In concurrence with these changes in threat-related brain activation, caffeine increased self-rated anxiety and diastolic blood pressure. Caffeine did not affect primary visual cortex activation. These results are the first to demonstrate potential neural correlates of the anxiogenic effect of caffeine, and they implicate the amygdala as a key site for caffeine tolerance. PMID:21972425

Maternal caffeine intake during pregnancy and orofacial clefts.

PubMed

Collier, Sarah A; Browne, Marilyn L; Rasmussen, Sonja A; Honein, Margaret A

2009-10-01

Moderate caffeine intake during pregnancy is common, but little is known about its potential association with birth defects. The National Birth Defects Prevention Study is a population-based, case-control study of major birth defects, excluding infants with single-gene disorders and chromosomal abnormalities. This analysis includes infants with cleft lip with or without cleft palate (CL/P) and cleft palate only (CPO), excluding infants whose cleft was secondary to holoprosencephaly or amniotic band sequence. Mothers reported dietary caffeine intake from coffee, tea, sodas, and chocolate in the year before pregnancy and reported intake of medications containing caffeine during pregnancy. We assessed the association between dietary caffeine intake, frequency of consuming each type of caffeinated beverage, medications containing caffeine, and CL/P or CPO among infants born from October 1997 through December 2004. This analysis included 1531 infants with CL/P, 813 infants with CPO, and 5711 infants with no major birth defects (controls). Examining dietary sources among control mothers, 11% reported consuming at least 300 mg of caffeine per day and 17% reported consuming less than 10 mg of caffeine per day; high consumption (>or=3 servings per day) was reported by 8% (coffee), 4% (tea), and 15% (sodas); medications containing at least 100 mg caffeine/dose were reported by less than 1%. Although some effect estimates were elevated for moderate caffeine intake from all beverages, estimates were closer to the null for high caffeine levels. Isolated CL/P was associated with use of medications containing at least 100 mg of caffeine per dose. Our data do not suggest an association between maternal dietary caffeine intake and orofacial clefts, but caffeine-containing medications merit further study.

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.

A Unified Model of Performance for Predicting the Effects of Sleep and Caffeine

PubMed Central

Ramakrishnan, Sridhar; Wesensten, Nancy J.; Kamimori, Gary H.; Moon, James E.; Balkin, Thomas J.; Reifman, Jaques

2016-01-01

Study Objectives: Existing mathematical models of neurobehavioral performance cannot predict the beneficial effects of caffeine across the spectrum of sleep loss conditions, limiting their practical utility. Here, we closed this research gap by integrating a model of caffeine effects with the recently validated unified model of performance (UMP) into a single, unified modeling framework. We then assessed the accuracy of this new UMP in predicting performance across multiple studies. Methods: We hypothesized that the pharmacodynamics of caffeine vary similarly during both wakefulness and sleep, and that caffeine has a multiplicative effect on performance. Accordingly, to represent the effects of caffeine in the UMP, we multiplied a dose-dependent caffeine factor (which accounts for the pharmacokinetics and pharmacodynamics of caffeine) to the performance estimated in the absence of caffeine. We assessed the UMP predictions in 14 distinct laboratory- and field-study conditions, including 7 different sleep-loss schedules (from 5 h of sleep per night to continuous sleep loss for 85 h) and 6 different caffeine doses (from placebo to repeated 200 mg doses to a single dose of 600 mg). Results: The UMP accurately predicted group-average psychomotor vigilance task performance data across the different sleep loss and caffeine conditions (6% < error < 27%), yielding greater accuracy for mild and moderate sleep loss conditions than for more severe cases. Overall, accounting for the effects of caffeine resulted in improved predictions (after caffeine consumption) by up to 70%. Conclusions: The UMP provides the first comprehensive tool for accurate selection of combinations of sleep schedules and caffeine countermeasure strategies to optimize neurobehavioral performance. Citation: Ramakrishnan S, Wesensten NJ, Kamimori GH, Moon JE, Balkin TJ, Reifman J. A unified model of performance for predicting the effects of sleep and caffeine. SLEEP 2016;39(10):1827–1841. PMID:27397562

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.

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

Pretreatment With Caffeine Citrate to Increase Seizure Duration During Electroconvulsive Therapy: A Case Series.

PubMed

Pinkhasov, Aaron; Biglow, Michael; Chandra, Subhash; Pica, Tiffany

2016-04-01

Due to the shortage of parenteral caffeine and sodium benzoate, patients were pretreated with caffeine citrate to increase therapeutic seizure duration during electroconvulsive therapy (ECT). To date, no data are available on the use of caffeine citrate during ECT. This retrospective case series was done to demonstrate utilization of caffeine citrate as a substitute for caffeine and sodium benzoate in optimizing ECT. Medical records were reviewed to identify patients who received ECT and caffeine citrate. Physician notes were reviewed to determine the parameters of the ECT procedure, the seizure length, and the dose of caffeine citrate. Each chart was thoroughly studied to find the relationship between seizure duration and dose of caffeine citrate. Of the 12 ECT treatments utilizing caffeine citrate, 9 achieved at least 1 session lasting >30 seconds with an average seizure duration of 35 seconds. Increase in seizure duration ranged from -41% to 276% with an average increase of 48%. Only 3 treatment sessions utilizing caffeine citrate showed no increase in seizure duration. Doses ranged from 120 to 600 mg of both oral and parenteral caffeine citrate. Although increase in seizure duration was achieved for the majority of the ECT sessions, no dose-response correlation could be made. No significant adverse reactions were noted with the use of caffeine citrate during ECT. It was determined that, much like caffeine and sodium benzoate, caffeine citrate does increase the seizure duration. However, this response did vary due to many reasons including small sample size, concomitant medications, duration of illness, and number of ECTs they received in the past and how long ago they received the last ECT. Further research is required to elucidate the effect of these variables on seizure duration. © The Author(s) 2014.

The acute physiological and mood effects of tea and coffee: the role of caffeine level.

PubMed

Quinlan, P T; Lane, J; Moore, K L; Aspen, J; Rycroft, J A; O'Brien, D C

2000-05-01

The objective of this study was to determine the effect of caffeine level in tea and coffee on acute physiological responses and mood. Randomised full crossover design in subjects after overnight caffeine abstention was studied. In study 1 (n = 17) the caffeine level was manipulated naturalistically by preparing tea and coffee at different strengths (1 or 2 cups equivalent). Caffeine levels were 37.5 and 75 mg in tea, 75 and 150 mg in coffee, with water and no-drink controls. In study 2 (n = 15) caffeine level alone was manipulated (water, decaffeinated tea, plus 0, 25, 50, 100, and 200 mg caffeine). Beverage volume and temperature (55 degrees C) were constant. SBP, DBP, heart rate, skin temperature, skin conductance, and mood were monitored over each 3-h study session. In study 1, tea and coffee produced mild autonomic stimulation and an elevation in mood. There were no effects of tea vs. coffee or caffeine dose, despite a fourfold variation in the latter. Increasing beverage strength was associated with greater increases in DBP and energetic arousal. In study 2, caffeinated beverages increased SBP, DBP, and skin conductance and lowered heart rate and skin temperature compared to water. Significant dose-response relationships to caffeine were seen only for SBP, heart rate, and skin temperature. There were significant effects of caffeine on energetic arousal but no consistent dose-response effects. Caffeinated beverages acutely stimulate the autonomic nervous system and increase alertness. Although caffeine can exert dose-dependent effects on a number of acute autonomic responses, caffeine level is not an important factor. Factors besides caffeine may contribute to these acute effects.

Caffeine delays oocyte aging and maintains the quality of aged oocytes safely in mouse.

PubMed

Zhang, Xia; Liu, Xiaoyan; Chen, Li; Wu, Dan-Ya; Nie, Zheng-Wen; Gao, Ying-Ying; Miao, Yi-Liang

2017-03-28

Caffeine, as an oocyte aging inhibitor, was used in many different species to control or delay oocyte aging. However, the safety of caffeine and developmental competence of aged oocytes inhibited by caffeine has not been studied systematically. So we detected the spindle morphology, distribution of cortical granules, zona pellucida hardening and pronucleus formation to assess oocyte quality of caffeine treated oocytes. We found that aged oocytes treated by caffeine maintained weak susceptibility to activating stimuli and regained normal competent after aged further 6 hr. Caffeine maintained the spindle morphology, changed cortical granules distribution of aged oocytes and could not prevent zona pellucida hardening. Furthermore, caffeine increased pronucleus formation of aged oocytes and decreased fragmentation after fertilization. These results suggested that caffeine could maintain the quality of aged oocytes safely in mouse.

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

Caffeine biosynthesis and degradation in tea [Camellia sinensis (L.) O. Kuntze] is under developmental and seasonal regulation.

PubMed

Mohanpuria, Prashant; Kumar, Vinay; Joshi, Robin; Gulati, Ashu; Ahuja, Paramvir Singh; Yadav, Sudesh Kumar

2009-10-01

To study caffeine biosynthesis and degradation, here we monitored caffeine synthase gene expression and caffeine and allantoin content in various tissues of four Camellia sinensis (L.) O. Kuntze cultivars during non-dormant (ND) and dormant (D) growth phases. Caffeine synthase expression as well as caffeine content was found to be higher in commercially utilized tissues like apical bud, 1st leaf, 2nd leaf, young stem, and was lower in old leaf during ND compared to D growth phase. Among fruit parts, fruit coats have higher caffeine synthase expression, caffeine content, and allantoin content. On contrary, allantoin content was found lower in the commercially utilized tissues and higher in old leaf. Results suggested that caffeine synthesis and degradation in tea appears to be under developmental and seasonal regulation.

A Preliminary Investigation of Caffeinated Alcohol Use During Spring Break.

PubMed

Linden-Carmichael, Ashley N; Lau-Barraco, Cathy

2016-06-06

Caffeinated alcoholic beverages (e.g., Red Bull and vodka) are popular but associated with negative consequences. CABs may be particularly popular during Spring Break, a potentially risky social event. We aimed to identify the prevalence of Spring Break caffeinated alcohol use, determine how caffeinated alcohol use Spring Break drinking habits differ from usual, and examine the association between Spring Break caffeinated alcohol use and alcohol-related problems. Data were collected from 95 college students during March of 2013 and 2014. Students completed questionnaires of their alcohol and caffeinated alcohol use before and during Spring Break and Spring Break alcohol-related problems. Approximately 54% of students used caffeinated alcohol during Spring Break. Spring Break caffeinated alcohol use was associated with more alcohol-related problems, even after controlling for other alcohol consumed and Spring Break vacation status. Caffeinated alcoholic beverages are commonly consumed during Spring Break and their use uniquely predicted harms. Prevention efforts placed on caffeinated alcoholic beverage users may be helpful in reducing Spring Break-related harms.

Caffeine in the milk prevents respiratory disorders caused by in utero caffeine exposure in rats.

PubMed

Bodineau, Laurence; Saadani-Makki, Fadoua; Jullien, Hugues; Frugière, Alain

2006-01-25

Consequences of postnatal caffeine exposure by the milk on ponto-medullary respiratory disturbances observed following an in utero caffeine exposure were analysed. Ponto-medullary-spinal cord preparations from newborn rats exposed to caffeine during gestation but not after the birth display an increase in respiratory frequency and an exaggeration of the hypoxic respiratory depression compared to not treated preparations. These data suggest that tachypneic and apneic episodes encountered in human newborns whose mother consumed caffeine during pregnancy are due in large part to central effect of caffeine at the ponto-medullary level. Both baseline respiratory frequency increase and emphasis of hypoxic respiratory depression are not encountered if rat dams consumed caffeine during nursing. Our hypothesis is that newborn rats exposed to caffeine during gestation but not after the birth would be in withdrawal situation whereas, when caffeine is present in drinking fluid of lactating dams, it goes down the milk and is able to prevent ponto-medullary respiratory disturbances.

"Coffee, tea and me": moderate doses of caffeine affect sexual behavior in female rats.

PubMed

Guarraci, Fay A; Benson, Anastasia

2005-11-01

The present study evaluated the effects of acute caffeine administration on paced mating behavior and partner preference in ovariectomized rats primed with estrogen and progesterone. In Experiment 1, female rats were tested for paced mating behavior following acute administration of caffeine (15 mg/kg). Caffeine shortened the latency to return to a male following an ejaculation. Although this dose of caffeine did not alter the likelihood of leaving a male after receiving sexual stimulation, locomotor activity did increase significantly. Experiment 2 evaluated the dose response characteristics of caffeine (7.5, 15, 30 mg/kg) administration on paced mating behavior. Replicating Experiment 1, caffeine at the lower doses shortened the latency to return to a male following an ejaculation. Finally, to determine whether the effects of caffeine (15 mg/kg) on contact-return latency reflect a change in sexual motivation or merely an inability to inhibit locomotion, rats were tested for partner preference (intact male vs. estrous female) following caffeine administration (Experiment 3). Although caffeine did not disrupt preference for a sexual partner, caffeine selectively increased visits to the male when physical contact was possible. Collectively, these results suggest that the effects of caffeine on female mating behavior may reflect an increase in both sexual motivation and locomotor activity.

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.

A Unified Model of Performance for Predicting the Effects of Sleep and Caffeine.

PubMed

Ramakrishnan, Sridhar; Wesensten, Nancy J; Kamimori, Gary H; Moon, James E; Balkin, Thomas J; Reifman, Jaques

2016-10-01

Existing mathematical models of neurobehavioral performance cannot predict the beneficial effects of caffeine across the spectrum of sleep loss conditions, limiting their practical utility. Here, we closed this research gap by integrating a model of caffeine effects with the recently validated unified model of performance (UMP) into a single, unified modeling framework. We then assessed the accuracy of this new UMP in predicting performance across multiple studies. We hypothesized that the pharmacodynamics of caffeine vary similarly during both wakefulness and sleep, and that caffeine has a multiplicative effect on performance. Accordingly, to represent the effects of caffeine in the UMP, we multiplied a dose-dependent caffeine factor (which accounts for the pharmacokinetics and pharmacodynamics of caffeine) to the performance estimated in the absence of caffeine. We assessed the UMP predictions in 14 distinct laboratory- and field-study conditions, including 7 different sleep-loss schedules (from 5 h of sleep per night to continuous sleep loss for 85 h) and 6 different caffeine doses (from placebo to repeated 200 mg doses to a single dose of 600 mg). The UMP accurately predicted group-average psychomotor vigilance task performance data across the different sleep loss and caffeine conditions (6% < error < 27%), yielding greater accuracy for mild and moderate sleep loss conditions than for more severe cases. Overall, accounting for the effects of caffeine resulted in improved predictions (after caffeine consumption) by up to 70%. The UMP provides the first comprehensive tool for accurate selection of combinations of sleep schedules and caffeine countermeasure strategies to optimize neurobehavioral performance. © 2016 Associated Professional Sleep Societies, LLC.

Interindividual Differences in Caffeine Metabolism and Factors Driving Caffeine Consumption.

PubMed

Nehlig, Astrid

2018-04-01

Most individuals adjust their caffeine intake according to the objective and subjective effects induced by the methylxanthine. However, to reach the desired effects, the quantity of caffeine consumed varies largely among individuals. It has been known for decades that the metabolism, clearance, and pharmacokinetics of caffeine is affected by many factors such as age, sex and hormones, liver disease, obesity, smoking, and diet. Caffeine also interacts with many medications. All these factors will be reviewed in the present document and discussed in light of the most recent data concerning the genetic variability affecting caffeine levels and effects at the pharmacokinetic and pharmacodynamic levels that both critically drive the level of caffeine consumption. The pharmacokinetics of caffeine are highly variable among individuals due to a polymorphism at the level of the CYP1A2 isoform of cytochrome P450, which metabolizes 95% of the caffeine ingested. Moreover there is a polymorphism at the level of another critical enzyme, N -acetyltransferase 2. At the pharmacodynamic level, there are several polymorphisms at the main brain target of caffeine, the adenosine A2A receptor or ADORA2. Genetic studies, including genome-wide association studies, identified several loci critically involved in caffeine consumption and its consequences on sleep, anxiety, and potentially in neurodegenerative and psychiatric diseases. We start reaching a better picture on how a multiplicity of biologic mechanisms seems to drive the levels of caffeine consumption, although much more knowledge is still required to understand caffeine consumption and effects on body functions. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Effects of caffeine on alcohol-related changes in behavioural control and perceived intoxication in light caffeine consumers.

PubMed

Attwood, Angela S; Rogers, Peter J; Ataya, Alia F; Adams, Sally; Munafò, Marcus R

2012-06-01

Caffeinated alcoholic beverages have been associated with increased risk of alcohol-related harms. However, few studies have examined these combined effects on behavioural control, which is believed to underlie many of the negative effects of alcohol consumption. In addition, studies have often omitted subjective measures, and none have directly assessed the role of caffeine consumer history. To examine the combined effects of alcohol and caffeine on measures of behavioural control and perceived intoxication in abstinent, light caffeine consumers. Participants (n = 28; 50% male) attended four sessions at which they consumed one of the following beverages in a randomised order: placebo, alcohol alone (0.6 g/kg), caffeine alone (2.0 mg/kg), and alcohol/caffeine. They completed measures of mood, intoxication, anxiety and alcohol craving before and after a task battery comprising measures of behavioural control and reaction time performance. Caffeine attenuated alcohol-related performance deficits on stop-signal accuracy, had no effect on go-no-go performance deficits, and worsened accuracy on the Stroop task. Caffeine did not influence absolute changes in perceived intoxication but there was suggestion that caffeine may have changed the nature of intoxication with increases in stimulation. Caffeine appears to have mixed effects on alcohol intoxication that are task-dependent. We found increased stimulation in the alcohol/caffeine condition, supporting the contention that caffeinated alcoholic beverages enable an individual to drink for longer. Future research should model real world drinking behaviour by examining how these effects change across multiple drink administrations.

Caffeine Withdrawal and Dependence: A Convenience Survey Among Addiction Professionals.

PubMed

Budney, Alan J; Brown, Pamela C; Griffiths, Roland R; Hughes, John R; Juliano, Laura M

2013-06-01

Caffeine withdrawal was included in the research appendix of the DSM-IV to encourage additional research to assist with determining its status for the next version of the manual. Caffeine dependence was not included because of a lack of empirical research at the time of publication. This study assessed the beliefs of addiction professionals about the clinical importance of caffeine withdrawal and dependence. A 6-item survey was developed and delivered electronically to the members of six professional organizations that focus on addiction. Open-ended comments were also solicited. Five hundred members responded. The majority (95%) thought that cessation of caffeine could produce a withdrawal syndrome, and that caffeine withdrawal can have clinical importance (73%); however, only half (48%) thought that caffeine withdrawal should be included in the Diagnostic and Statistical Manual of Mental Disorders (DSM). A majority (58%) believed that some people develop caffeine dependence; however, only 44% indicated that it should be in the DSM. Comments suggested that trepidation about inclusion of caffeine diagnoses was due to the concerns about the field of psychiatry being criticized for including common disorders with a relatively low clinical severity. Others, however, expressed an urgent need to take caffeine-related problems more seriously. The majority of addiction professionals believe that caffeine withdrawal and dependence disorders exist and are clinically important; however, these professionals are divided in whether caffeine withdrawal and dependence should be included in DSM. Wider dissemination of the extant literature on caffeine withdrawal and additional research on caffeine dependence will be needed to provide additional guidance to policymakers and healthcare workers.

Design, formulation and evaluation of caffeine chewing gum

PubMed Central

Aslani, Abolfazl; Jalilian, Fatemeh

2013-01-01

Background: 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. Materials and Methods: 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. Results: 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. Conclusion: 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. PMID:24223387

Sleep-Disordered Breathing and Caffeine Consumption

PubMed Central

Aurora, R. Nisha; Crainiceanu, Ciprian; Caffo, Brian

2012-01-01

Background: Sleepiness is one of the most burdensome symptoms of sleep-disordered breathing (SDB). While caffeine is frequently used to avert sleepiness, the association between SDB and caffeine use has not been thoroughly explored. The current study examined whether SDB is associated with caffeine consumption and if factors such as sex, age, and daytime sleepiness explain or modify the association. Methods: Data from the Sleep Heart Health Study, a community-based study on the consequences of SDB, were used to characterize the association between SDB and caffeine intake. SDB was assessed with full-montage polysomnography. Caffeine use was quantified as the number of cans of soda or the cups of coffee or tea consumed daily. The Epworth Sleepiness Scale was used to assess daytime sleepiness. Multivariable negative binomial regression models were used to characterize the independent association between SDB and caffeine use. Results: Caffeinated soda, but not tea or coffee, intake was independently associated with SDB severity. Compared with participants without SDB, the relative ratios for caffeinated soda consumption in women with mild, moderate, and severe SDB were 1.20 (CI, 1.03-1.41), 1.46 (CI, 1.14-1.87), and 1.73 (CI, 1.23-2.42), respectively. For men, an association was only noted with severe SDB and caffeinated soda use. Age did not modify the SDB-caffeine association, and sleepiness could not explain the observed associations. Conclusions: SDB is independently associated with caffeinated soda use in the general community. Identifying excessive caffeine used in SDB has potential significance given the cardiovascular effects of caffeine and untreated SDB. PMID:22459776

Caffeine for apnea of prematurity: Effects on the developing brain.

PubMed

Atik, Anzari; Harding, Richard; De Matteo, Robert; Kondos-Devcic, Delphi; Cheong, Jeanie; Doyle, Lex W; Tolcos, Mary

2017-01-01

Caffeine is a methylxanthine that is widely used to treat apnea of prematurity (AOP). In preterm infants, caffeine reduces the duration of respiratory support, improves survival rates and lowers the incidence of cerebral palsy and cognitive delay. There is, however, little evidence relating to the immediate and long-term effects of caffeine on brain development, especially at the cellular and molecular levels. Experimental data are conflicting, with studies showing that caffeine can have either adverse or benefical effects in the developing brain. The aim of this article is to review current understanding of how caffeine ameliorates AOP, the cellular and molecular mechanisms by which caffeine exerts its effects and the effects of caffeine on brain development. A better knowledge of the effects of caffeine on the developing brain at the cellular and/or molecular level is essential in order to understand the basis for the impact of caffeine on postnatal outcome. The studies reviewed here suggest that while caffeine has respiratory benefits for preterm infants, it may have adverse molecular and cellular effects on the developing brain; indeed a majority of experimental studies suggest that regardless of dose or duration of administration, caffeine leads to detrimental changes within the developing brain. Thus there is an urgent need to assess the impact of caffeine, at a range of doses, on the structure and function of the developing brain in preclinical studies, particularly using clinically relevant animal models. Future studies should focus on determining the maximal dose of caffeine that is safe for the preterm brain. Copyright © 2017 Elsevier B.V. All rights reserved.

Genetic polymorphism of the adenosine A2A receptor is associated with habitual caffeine consumption.

PubMed

Cornelis, Marilyn C; El-Sohemy, Ahmed; Campos, Hannia

2007-07-01

Caffeine is the most widely consumed stimulant in the world, and individual differences in response to its stimulating effects may explain some of the variability in caffeine consumption within a population. We examined whether genetic variability in caffeine metabolism [cytochrome P450 1A2 (CYP1A2) -163A-->C] or the main target of caffeine action in the nervous system [adenosine A(2A) receptor (ADORA2A) 1083C-->T] is associated with habitual caffeine consumption. Subjects (n=2735) were participants from a study of gene-diet interactions and risk of myocardial infarction who did not have a history of hypertension. Genotype frequencies were examined among persons who were categorized according to their self-reported daily caffeine intake, as assessed with a validated food-frequency questionnaire. The ADORA2A, but not the CYP1A2, genotype was associated with different amounts of caffeine intake. Compared with persons consuming <100 mg caffeine/d, the odds ratios for having the ADORA2A TT genotype were 0.74 (95% CI: 0.53, 1.03), 0.63 (95% CI: 0.48, 0.83), and 0.57 (95% CI: 0.42, 0.77) for those consuming 100-200, >200-400, and >400 mg caffeine/d, respectively. The association was more pronounced among current smokers than among nonsmokers (P for interaction = 0.07). Persons with the ADORA2A TT genotype also were significantly more likely to consume less caffeine (ie, <100 mg/d) than were carriers of the C allele [P=0.011 (nonsmokers), P=0.008 (smokers)]. Our findings show that the probability of having the ADORA2A 1083TT genotype decreases as habitual caffeine consumption increases. This observation provides a biologic basis for caffeine consumption behavior and suggests that persons with this genotype may be less vulnerable to caffeine dependence.

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 Ingestion Reverses the Circadian Rhythm Effects on Neuromuscular Performance in Highly Resistance-Trained Men

PubMed Central

Mora-Rodríguez, Ricardo; Pallarés, Jesús García; López-Samanes, Álvaro; Ortega, Juan Fernando; Fernández-Elías, Valentín E.

2012-01-01

Purpose To investigate whether caffeine ingestion counteracts the morning reduction in neuromuscular performance associated with the circadian rhythm pattern. Methods Twelve highly resistance-trained men underwent a battery of neuromuscular tests under three different conditions; i) morning (10:00 a.m.) with caffeine ingestion (i.e., 3 mg kg−1; AMCAFF trial); ii) morning (10:00 a.m.) with placebo ingestion (AMPLAC trial); and iii) afternoon (18:00 p.m.) with placebo ingestion (PMPLAC trial). A randomized, double-blind, crossover, placebo controlled experimental design was used, with all subjects serving as their own controls. The neuromuscular test battery consisted in the measurement of bar displacement velocity during free-weight full-squat (SQ) and bench press (BP) exercises against loads that elicit maximum strength (75% 1RM load) and muscle power adaptations (1 m s−1 load). Isometric maximum voluntary contraction (MVCLEG) and isometric electrically evoked strength of the right knee (EVOKLEG) were measured to identify caffeine's action mechanisms. Steroid hormone levels (serum testosterone, cortisol and growth hormone) were evaluated at the beginning of each trial (PRE). In addition, plasma norepinephrine (NE) and epinephrine were measured PRE and at the end of each trial following a standardized intense (85% 1RM) 6 repetitions bout of SQ (POST). Results In the PMPLAC trial, dynamic muscle strength and power output were significantly enhanced compared with AMPLAC treatment (3.0%–7.5%; p≤0.05). During AMCAFF trial, muscle strength and power output increased above AMPLAC levels (4.6%–5.7%; p≤0.05) except for BP velocity with 1 m s−1 load (p = 0.06). During AMCAFF, EVOKLEG and NE (a surrogate of maximal muscle sympathetic nerve activation) were increased above AMPLAC trial (14.6% and 96.8% respectively; p≤0.05). Conclusions These results indicate that caffeine ingestion reverses the morning neuromuscular declines in highly resistance-trained men, raising performance to the levels of the afternoon trial. Our electrical stimulation data, along with the NE values, suggest that caffeine increases neuromuscular performance having a direct effect in the muscle. PMID:22496767

The effects of catechin rich teas and caffeine on energy expenditure and fat oxidation: a meta-analysis

USDA-ARS?s Scientific Manuscript database

Different outcomes of the effect of catechin-caffeine mixtures and caffeine-only supplementation on energy expenditure and fat oxidation have been reported in short-term studies. Therefore, a meta-analysis was conducted to elucidate whether catechin-caffeine mixtures and caffeine-only supplementatio...

Dose-Dependent Model of Caffeine Effects on Human Vigilance during Total Sleep Deprivation

DTIC Science & Technology

2014-05-20

does not consider the absorption of caffeine . This is a reasonable approximation for caffeine when ingested via coffee , tea, energy drinks, and most...Dose-dependent model of caffeine effects on human vigilance during total sleep deprivation Sridhar Ramakrishnan a, Srinivas Laxminarayan a, Nancy J...We modeled the dose-dependent effects of caffeine on human vigilance. The model predicted the effects of both single and repeated caffeine doses

Energy drinks and the neurophysiological impact of caffeine.

PubMed

Persad, Leeana Aarthi Bagwath

2011-01-01

Caffeine is the most widely used psychoactive stimulant with prevalent use across all age groups. It is a naturally occurring substance found in the coffee bean, tea leaf, the kola nut, cocoa bean. Recently there has been an increase in energy drink consumption leading to caffeine abuse, with aggressive marketing and poor awareness on the consequences of high caffeine use. With caffeine consumption being so common, it is vital to know the impact caffeine has on the body, as its effects can influence cardio-respiratory, endocrine, and perhaps most importantly neurological systems. Detrimental effects have being described especially since an over consumption of caffeine has being noted. This review focuses on the neurophysiological impact of caffeine and its biochemical pathways in the human body.

Energy Drinks and the Neurophysiological Impact of Caffeine

PubMed Central

Persad, Leeana Aarthi Bagwath

2011-01-01

Caffeine is the most widely used psychoactive stimulant with prevalent use across all age groups. It is a naturally occurring substance found in the coffee bean, tea leaf, the kola nut, cocoa bean. Recently there has been an increase in energy drink consumption leading to caffeine abuse, with aggressive marketing and poor awareness on the consequences of high caffeine use. With caffeine consumption being so common, it is vital to know the impact caffeine has on the body, as its effects can influence cardio-respiratory, endocrine, and perhaps most importantly neurological systems. Detrimental effects have being described especially since an over consumption of caffeine has being noted. This review focuses on the neurophysiological impact of caffeine and its biochemical pathways in the human body. PMID:22025909

Altered expression of the caffeine synthase gene in a naturally caffeine-free mutant of Coffea arabica.

PubMed

Maluf, Mirian Perez; da Silva, Carla Cristina; de Oliveira, Michelle de Paula Abreu; Tavares, Aline Gomes; Silvarolla, Maria Bernadete; Guerreiro, Oliveiro

2009-10-01

In this work, we studied the biosynthesis of caffeine by examining the expression of genes involved in this biosynthetic pathway in coffee fruits containing normal or low levels of this substance. The amplification of gene-specific transcripts during fruit development revealed that low-caffeine fruits had a lower expression of the theobromine synthase and caffeine synthase genes and also contained an extra transcript of the caffeine synthase gene. This extra transcript contained only part of exon 1 and all of exon 3. The sequence of the mutant caffeine synthase gene revealed the substitution of isoleucine for valine in the enzyme active site that probably interfered with enzymatic activity. These findings indicate that the absence of caffeine in these mutants probably resulted from a combination of transcriptional regulation and the presence of mutations in the caffeine synthase amino acid sequence.

Altered expression of the caffeine synthase gene in a naturally caffeine-free mutant of Coffea arabica

PubMed Central

2009-01-01

In this work, we studied the biosynthesis of caffeine by examining the expression of genes involved in this biosynthetic pathway in coffee fruits containing normal or low levels of this substance. The amplification of gene-specific transcripts during fruit development revealed that low-caffeine fruits had a lower expression of the theobromine synthase and caffeine synthase genes and also contained an extra transcript of the caffeine synthase gene. This extra transcript contained only part of exon 1 and all of exon 3. The sequence of the mutant caffeine synthase gene revealed the substitution of isoleucine for valine in the enzyme active site that probably interfered with enzymatic activity. These findings indicate that the absence of caffeine in these mutants probably resulted from a combination of transcriptional regulation and the presence of mutations in the caffeine synthase amino acid sequence. PMID:21637458

Caffeine and the dopaminergic system.

PubMed

Cauli, O; Morelli, M

2005-03-01

Caffeine is the most widely consumed psychostimulant substance, being self-administered throughout a wide range of conditions and present in numerous dietary products. Due to its widespread use and low abuse potential, caffeine is considered an atypical drug of abuse. The main mechanism of action of caffeine occurs via the blockade of adenosine A1 and A2A receptors. Adenosine is a modulator of CNS neurotransmission and its modulation of dopamine transmission through A2A receptors has been implicated in the effects of caffeine. This review provides an updated summary of the results reported in the literature concerning the behavioural pharmacology of caffeine and the neurochemical mechanisms underlying the psychostimulant effects elicited by caffeine. The review focuses on the effects of caffeine mediated by adenosine A2A receptors and on the influence that pre-exposure to caffeine may exert on the effects of classical drugs of abuse.

The neuroprotective effects of caffeine in neurodegenerative diseases.

PubMed

Kolahdouzan, Mahshad; Hamadeh, Mazen J

2017-04-01

Caffeine is the most widely used psychostimulant in Western countries, with antioxidant, anti-inflammatory and anti-apoptotic properties. In Alzheimer's disease (AD), caffeine is beneficial in both men and women, in humans and animals. Similar effects of caffeine were observed in men with Parkinson's disease (PD); however, the effect of caffeine in female PD patients is controversial due to caffeine's competition with estrogen for the estrogen-metabolizing enzyme, CYP1A2. Studies conducted in animal models of amyotrophic lateral sclerosis (ALS) showed protective effects of A 2 A R antagonism. A study found caffeine to be associated with earlier age of onset of Huntington's disease (HD) at intakes >190 mg/d, but studies in animal models have found equivocal results. Caffeine is protective in AD and PD at dosages equivalent to 3-5 mg/kg. However, further research is needed to investigate the effects of caffeine on PD in women. As well, the effects of caffeine in ALS, HD and Machado-Joseph disease need to be further investigated. Caffeine's most salient mechanisms of action relevant to neurodegenerative diseases need to be further explored. © 2017 John Wiley & Sons Ltd.

The drink remains the same: implicit positive associations in high but not moderate or non-caffeine users.

PubMed

Stafford, Lorenzo D; Wright, Claire; Yeomans, Martin R

2010-06-01

Research has demonstrated that high, but not low caffeine users exhibit an attentional bias to caffeine related stimuli. Separately, the Implicit Association Test (IAT; Greenwald, McGhee, & Schwartz, 1998) has been used to investigate the valence of implicit cognitions to drugs with some contradictory findings, though no work has addressed this issue with respect to caffeine. Here, we examined whether attentional bias would be found in high and moderate caffeine users using a pictorial version of the dot-probe task. A second aim was to explore differences in implicit cognitions between users and non-users. Fifteen high, moderate and non-caffeine users completed a picture dot-probe, IAT, and mood questionnaire following overnight caffeine deprivation. In the IAT, results demonstrated positive associations to caffeine related words for high but not moderate or non-users. Lower ratings for calmness were evident in both groups of caffeine compared to non-users. Dot-probe findings revealed an attentional bias among moderate caffeine users and non-users but not heavy users. The observed positive implicit associations to caffeine suggest that drug acceptability is the key in such perceptions. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

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.

Effects of Smoking Cues on Caffeine Urges in Heavy Smokers and Caffeine Consumers with and without Schizophrenia

PubMed Central

Adolfo, Amy B.; AhnAllen, Christopher G.; Tidey, Jennifer W.

2009-01-01

Cigarette smoking and caffeine use are established and problematic drug-use behaviors in people with schizophrenia. Associative links between drugs of abuse may occur but the relationship between caffeine use and cigarette smoking has received little attention in schizophrenia. In this cross-cue reactivity laboratory study, we examined the effects of neutral and smoking cues on craving for caffeinated beverages in participants with schizophrenia or schizoaffective disorder (SS; n = 15) and non-psychiatric controls (CS; n = 18) all of whom were heavy smokers and daily caffeine users. Participants were tested under non-abstinent and 5-hour abstinent conditions. SS tended to report greater daily levels of caffeine use than CS. Although this difference was not significant, that may be due to the small sample sizes as the size of this effect was large. Daily caffeine intake was significantly correlated with daily smoking rate in SS but not CS. A significant interaction between group and cue type after controlling for caffeine intake indicated that exposure to smoking cues increased urge for caffeinated beverages in SS but not CS. These results indicate support for associative connections between cigarette smoking cues and craving for caffeine in smokers with schizophrenia. PMID:19006656

Behavioural effects of compounds co-consumed in dietary forms of caffeinated plants.

PubMed

Haskell, C F; Dodd, F L; Wightman, E L; Kennedy, D O

2013-06-01

Research into the cognitive and mood effects of caffeine in human subjects has highlighted some fairly robust and well-accepted effects. However, the majority of these studies have focused on caffeine in isolation; whilst caffeine is normally consumed in the form of plant-derived products and extracts that invariably contain other potentially bioactive phytochemicals. The aim of the present review is to consider the possible mechanisms of action of co-occurring phytochemicals, and any epidemiological evidence suggesting that they contribute to potential health benefits ascribed to caffeine. Intervention studies to date that have been conducted to explore the effects on brain function of the non-caffeine components in caffeine-bearing plants (coffee, tea, cocoa, guaraná), either alone or in combination with caffeine, will also be summarised. Research is beginning to accumulate showing independent effects for several of the phytochemicals that co-occur with caffeine, and/or a modulation of the effects of caffeine when it is co-consumed with these naturally concomitant phytochemicals. The present review highlights that more research aimed at understanding the effects of these compounds is needed and, more importantly, the synergistic relationship that they may have with caffeine.

Exploring maternal patterns of dietary caffeine consumption before conception and during pregnancy.

PubMed

Chen, Lei; Bell, Erin M; Browne, Marilyn L; Druschel, Charlotte M; Romitti, Paul A

2014-12-01

We describe patterns of dietary caffeine consumption before and after pregnancy recognition in a cohort of women who recently gave birth. This study included 8,347 mothers of non-malformed liveborn control infants who participated in the National Birth Defects Prevention Study during 1997-2007. Maternal self-reported consumption of beverages (caffeinated coffee, tea, and soda) and chocolate the year before pregnancy was used to estimate caffeine intake. The proportions of prepregnancy caffeine consumption stratified by maternal characteristics are reported. In addition, patterns of reported change in consumption before and after pregnancy were examined by maternal and pregnancy characteristics. Adjusted prevalence ratios were estimated to assess factors most associated with change in consumption. About 97 % of mothers reported any caffeine consumption (average intake of 129.9 mg/day the year before pregnancy) and soda was the primary source of caffeine. The proportion of mothers reporting dietary caffeine intake of more than 300 mg/day was significantly increased among those who smoked cigarettes or drank alcohol. Most mothers stopped or decreased their caffeinated beverage consumption during pregnancy. Young maternal age and unintended pregnancy were associated with increases in consumption during pregnancy. Dietary caffeine consumption during pregnancy is still common in the US. A high level of caffeine intake was associated with known risk factors for adverse reproductive outcomes. Future studies may improve the maternal caffeine exposure assessment by acquiring additional information regarding the timing and amount of change in caffeine consumption after pregnancy recognition.

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.

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.

Exploring Maternal Patterns of Dietary Caffeine Consumption Before Conception and During Pregnancy

PubMed Central

Chen, Lei; Bell, Erin M.; Browne, Marilyn L.; Druschel, Charlotte M.; Romitti, Paul A.

2018-01-01

We describe patterns of dietary caffeine consumption before and after pregnancy recognition in a cohort of women who recently gave birth. This study included 8,347 mothers of non-malformed liveborn control infants who participated in the National Birth Defects Prevention Study during 1997–2007. Maternal self-reported consumption of beverages (caffeinated coffee, tea, and soda) and chocolate the year before pregnancy was used to estimate caffeine intake. The proportions of prepregnancy caffeine consumption stratified by maternal characteristics are reported. In addition, patterns of reported change in consumption before and after pregnancy were examined by maternal and pregnancy characteristics. Adjusted prevalence ratios were estimated to assess factors most associated with change in consumption. About 97 % of mothers reported any caffeine consumption (average intake of 129.9 mg/day the year before pregnancy) and soda was the primary source of caffeine. The proportion of mothers reporting dietary caffeine intake of more than 300 mg/day was significantly increased among those who smoked cigarettes or drank alcohol. Most mothers stopped or decreased their caffeinated beverage consumption during pregnancy. Young maternal age and unintended pregnancy were associated with increases in consumption during pregnancy. Dietary caffeine consumption during pregnancy is still common in the US. A high level of caffeine intake was associated with known risk factors for adverse reproductive outcomes. Future studies may improve the maternal caffeine exposure assessment by acquiring additional information regarding the timing and amount of change in caffeine consumption after pregnancy recognition. PMID:24791972

Obesity and thermogenesis related to the consumption of caffeine, ephedrine, capsaicin, and green tea.

PubMed

Diepvens, Kristel; Westerterp, Klaas R; Westerterp-Plantenga, Margriet S

2007-01-01

The global prevalence of obesity has increased considerably in the last decade. Tools for obesity management, including caffeine, ephedrine, capsaicin, and green tea have been proposed as strategies for weight loss and weight maintenance, since they may increase energy expenditure and have been proposed to counteract the decrease in metabolic rate that is present during weight loss. A combination of caffeine and ephedrine has shown to be effective in long-term weight management, likely due to different mechanisms that may operate synergistically, e.g., respectively inhibiting the phosphodiesterase-induced degradation of cAMP and enhancing the sympathetic release of catecholamines. However, adverse effects of ephedrine prevent the feasibility of this approach. Capsaicin has been shown to be effective, yet when it is used clinically it requires a strong compliance to a certain dosage, that has not been shown to be feasible yet. Also positive effects on body-weight management have been shown using green tea mixtures. Green tea, by containing both tea catechins and caffeine, may act through inhibition of catechol O-methyl-transferase, and inhibition of phosphodiesterase. Here, the mechanisms may also operate synergistically. In addition, tea catechins have antiangiogenic properties that may prevent development of overweight and obesity. Furthermore, the sympathetic nervous system is involved in the regulation of lipolysis, and the sympathetic innervation of white adipose tissue may play an important role in the regulation of total body fat in general.

The Relationship Between Caffeine, Sleep, and Behavior in Children.

PubMed

Watson, Emily J; Banks, Siobhan; Coates, Alison M; Kohler, Mark J

2017-04-15

To examine caffeine consumption from various dietary sources in a cohort of Australian children and the relationship between caffeine consumption, sleep, and daytime behavior. Children aged 8 to 12 years and their parents/guardians completed a battery of questionnaires. Children completed a caffeine questionnaire while parents completed questionnaires regarding demographics, sleep, and behavior. The final sample consisted of 309 children (mean ± standard deviation [SD] age 10.6 ± 1.3 years, male = 48%) and corresponding parent reports. On average a mean ± SD 10.2 ± 17.4 mg/day of caffeine was consumed with a range of zero to 151 mg/day. Of the children who consumed caffeine (87% of the sample), the largest contributor was coffee and tea; making up 41% of total caffeine intake, and sodas (soft drinks) contributed to 40% of caffeine intake. Total caffeine consumption was significantly associated with sleep routine ( r = 0.152); morning tiredness ( r = 0.129); restless sleep ( r = 0.113); and internalizing behavioral problems ( r = 0.128). Using path analysis, caffeine consumption was positively associated with morning tiredness (β = 0.111, P = .050) which was positively associated with internalizing behaviors (β = 0.432, P < .001). The addition of sleep routine and restless sleep to the model led to a complete mediation of caffeine consumption on morning tiredness, as well as a partial mediation of the association between morning tiredness and internal behaviors. In 8- to 12-year-olds the primary sources of caffeine are coffee/tea and sodas. Overall mean caffeine consumption is small by adult standards but has an effect on behavior and sleep in children. The effect on behavior is mediated by disrupted sleep, indicating that caffeine is a contributor to sleep problems and related behavior in children. © 2017 American Academy of Sleep Medicine

The perspective of caffeine and caffeine derived compounds in therapy.

PubMed

Pohanka, M

2015-01-01

Caffeine (1,3,7-trimethylxanthine) is a plant secondary metabolite with a significant impact on multiple processes and regulatory pathways in the body. Though major part of the population meets caffeine via coffee, tea or chocolate, it has also an important role in pharmacology and it is used as a supplementary substance in medicaments. Currently, the ability of caffeine to ameliorate some neurodegenerative disorders is proved in some studies. This review describes basic data about caffeine including toxicity, pharmacokinetics, biological mechanism of the action, and metabolism. Beside this, promising applications of caffeine, new medicaments and derivatives are discussed. Relevant papers and inventions are depicted in the manuscript. Caffeine is a pharmacologically promising substance that deserves big consideration in the current research and development. The compound has several reasons to be an object of scientific interest and to be used for pharmacology purposes. Despite an extensive research for a long time, no significantly negative effects on human health were proved hence caffeine can be considered as a completely safe compound. The recent data about amelioration of neurodegenerative and other disorders are promising and deserving more work on the issue. ARTICLE HIGHLIGHTS: Caffeine is a purine alkaloid from plants and it has a broad use in current pharmacology. Caffeine is a competitive antagonist of neurotransmitter adenosine on adenosine receptors. The substance is added as a supplementary to drugs and food.Besides interfering on adenosine receptors, caffeine interacts with acetylcholinesterase, monoamine oxidase, phosphodiesterase, ryanodine receptors and others.Current research is devoted to the role of caffeine in neurodegenerative diseases and immunity alteration. New chemical compounds based on caffeine moiety are prepared (Tab. 4, Fig. 6, Ref. 149).

Caffeine inhibits glucose transport by binding at the GLUT1 nucleotide-binding site

PubMed Central

Sage, Jay M.; Cura, Anthony J.; Lloyd, Kenneth P.

2015-01-01

Glucose transporter 1 (GLUT1) is the primary glucose transport protein of the cardiovascular system and astroglia. A recent study proposes that caffeine uncompetitive inhibition of GLUT1 results from interactions at an exofacial GLUT1 site. Intracellular ATP is also an uncompetitive GLUT1 inhibitor and shares structural similarities with caffeine, suggesting that caffeine acts at the previously characterized endofacial GLUT1 nucleotide-binding site. We tested this by confirming that caffeine uncompetitively inhibits GLUT1-mediated 3-O-methylglucose uptake in human erythrocytes [Vmax and Km for transport are reduced fourfold; Ki(app) = 3.5 mM caffeine]. ATP and AMP antagonize caffeine inhibition of 3-O-methylglucose uptake in erythrocyte ghosts by increasing Ki(app) for caffeine inhibition of transport from 0.9 ± 0.3 mM in the absence of intracellular nucleotides to 2.6 ± 0.6 and 2.4 ± 0.5 mM in the presence of 5 mM intracellular ATP or AMP, respectively. Extracellular ATP has no effect on sugar uptake or its inhibition by caffeine. Caffeine and ATP displace the fluorescent ATP derivative, trinitrophenyl-ATP, from the GLUT1 nucleotide-binding site, but d-glucose and the transport inhibitor cytochalasin B do not. Caffeine, but not ATP, inhibits cytochalasin B binding to GLUT1. Like ATP, caffeine renders the GLUT1 carboxy-terminus less accessible to peptide-directed antibodies, but cytochalasin B and d-glucose do not. These results suggest that the caffeine-binding site bridges two nonoverlapping GLUT1 endofacial sites—the regulatory, nucleotide-binding site and the cytochalasin B-binding site. Caffeine binding to GLUT1 mimics the action of ATP but not cytochalasin B on sugar transport. Molecular docking studies support this hypothesis. PMID:25715702

Withdrawal syndrome after the double-blind cessation of caffeine consumption.

PubMed

Silverman, K; Evans, S M; Strain, E C; Griffiths, R R

1992-10-15

People who stop consuming caffeine may have symptoms, but the incidence and severity of caffeine withdrawal are not known. This study was performed to determine the effects in the general population of ending one's dietary intake of caffeine. We studied 62 normal adults whose intake of caffeine was low to moderate (mean amount, 235 mg--the equivalent of 2.5 cups of coffee--per day). They completed questionnaires about symptoms and tests of their mood and performance when consuming their normal diets (base-line period) and at the end of each of two two-day periods during which they consumed caffeine-free diets and under double-blind conditions received capsules containing placebo (placebo period) or caffeine (caffeine period) in amounts equal to their daily caffeine consumption. More subjects had abnormally high Beck Depression Inventory scores (11 percent), high scores on the trait scale of the State-Trait Anxiety Inventory (8 percent), low vigor scores (11 percent) and high fatigue scores (8 percent) on the Profile of Mood States, and moderate or severe headache (52 percent) during the placebo period than during either the base-line period (2, 0, 0, 0, and 2 percent, respectively; P less than 0.05) or the caffeine period (3, 2, 2, 0, and 6 percent; P less than 0.05). More subjects reported unauthorized use of medications during the placebo period (13 percent) than during the caffeine period (2 percent, P = 0.017). Performance of a tapping task was slower during the placebo period than during the base-line and caffeine periods (P less than 0.01). Persons who consume low or moderate amounts of caffeine may have a withdrawal syndrome after their daily consumption of caffeine ceases.

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.

Caffeine can decrease subjective energy depending on the vehicle with which it is consumed and when it is measured.

PubMed

Young, H A; Benton, D

2013-07-01

Energy drinks contain glucose and caffeine, although in the longer term both adversely influence blood glucose homeostasis, with the unconsidered potential to have adverse consequences for cognition and mood. The objective of this study was to consider the influence on interstitial glucose levels, mood and cognition of drinks differing in their caffeine content and glycaemic load. Ninety minutes after a standard breakfast, a yoghurt-, glucose- or water-based drink, with or without 80 mg of caffeine, was consumed. The consumption of caffeine negatively influenced glucose homeostasis: that is, irrespective of the vehicle, caffeine consumption resulted in elevated levels of blood glucose throughout the study. Thirty minutes after consuming caffeine and water, rather than water alone, greater subjective energy was reported. However, after 90 and 150 min, caffeine administered in water increased tiredness, hostility and confusion. In contrast, combining caffeine with a yoghurt-based drink increased energy, agreeableness and clearheadedness later in the morning. There were no effects of caffeine on ratings of mood when it was taken with glucose. Caffeine, irrespective of vehicle, resulted in better memory, quicker reaction times in the choice reaction time test and the working memory task, and better and quicker responses with the vigilance task. Further research should consider how caffeine interacts with macronutrients and the timescale over which such effects occur.

Role of state-dependent learning in the cognitive effects of caffeine in mice.

PubMed

Sanday, Leandro; Zanin, Karina A; Patti, Camilla L; Fernandes-Santos, Luciano; Oliveira, Larissa C; Longo, Beatriz M; Andersen, Monica L; Tufik, Sergio; Frussa-Filho, Roberto

2013-08-01

Caffeine is the most widely used psychoactive substance in the world and it is generally believed that it promotes beneficial effects on cognitive performance. However, there is also evidence suggesting that caffeine has inhibitory effects on learning and memory. Considering that caffeine may have anxiogenic effects, thus changing the emotional state of the subjects, state-dependent learning may play a role in caffeine-induced cognitive alterations. Mice were administered 20 mg/kg caffeine before training and/or before testing both in the plus-maze discriminative avoidance task (an animal model that concomitantly evaluates learning, memory, anxiety-like behaviour and general activity) and in the inhibitory avoidance task, a classic paradigm for evaluating memory in rodents. Pre-training caffeine administration did not modify learning, but produced an anxiogenic effect and impaired memory retention. While pre-test administration of caffeine did not modify retrieval on its own, the pre-test administration counteracted the memory deficit induced by the pre-training caffeine injection in both the plus-maze discriminative and inhibitory avoidance tasks. Our data demonstrate that caffeine-induced memory deficits are critically related to state-dependent learning, reinforcing the importance of considering the participation of state-dependency on the interpretation of the cognitive effects of caffeine. The possible participation of caffeine-induced anxiety alterations in state-dependent memory deficits is discussed.

24h withdrawal following repeated administration of caffeine attenuates brain serotonin but not tryptophan in rat brain: implications for caffeine-induced depression.

PubMed

Haleem, D J; Yasmeen, A; Haleem, M A; Zafar, A

1995-01-01

Caffeine injected at doses of 20, 40 and 80 mg/kg increased brain levels of tryptophan, 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) in rat brain. In view of a possible role of 5-HT in caffeine-induced depression the effects of repeated administration of high doses of caffeine on brain 5-HT metabolism are investigated in rats. Caffeine was injected at doses of 80 mg/kg daily for five days. Control animals were injected with saline daily for five days. On the 6th day caffeine (80 mg/kg) injected to 5 day saline injected rats increased brain levels of tryptophan, 5-HT and 5-HIAA. Plasma total tryptophan levels were not affected and free tryptophan increased. Brain levels of 5-HT and 5-HIAA but not tryptophan decreased in 5 day caffeine injected rats injected with saline on the 6th day. Plasma total and free tryptophan were not altered in these rats. Caffeine-induced increases of brain tryptophan but not 5-HT and 5-HIAA were greater in 5 day caffeine than 5 day saline injected rats. The findings are discussed as repeated caffeine administration producing adaptive changes in the serotonergic neurons to decrease the conversion of tryptophan to 5-HT and this may precipitate depression particularly in conditions of caffeine withdrawal.

Behavioral Management of Excessive Caffeine Consumption: Three Case Studies.

ERIC Educational Resources Information Center

Johnson-Greene, Douglas; And Others

Although caffeine is seemingly harmless in ordinary daily intake, there has been increasing concern about the possible side effects of habitual caffeine ingestion. The excessive daily ingestion of caffeine in the form of coffee, soda pop, tea, and various medications may lead to a chronic disorder known as caffeinism. This study tested the…

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.

Caffeine intake and its sources: A review of national representative studies.

PubMed

Verster, Joris C; Koenig, Juergen

2018-05-24

Aim of this review is to summarize current daily caffeine intake of children, adolescents, and adults, and trends in caffeine intake over the past decade. A literature search was conducted (1997-2015) which yielded 18 reports on nationally representative studies, describing caffeine consumption of over 275,000 children, adolescents and adults. The data revealed that mean total daily caffeine intake in children, adolescents, and adults is below caffeine intake recommendations such as those stated by Health Canada (2.5 mg/kg bw/day for children and adolescents, and 400 mg/day for adults) and the European Food Safety Authority, EFSA (3 mg/kg bw/day for children and adolescents, and 400 mg/day for adults). Total daily caffeine intake has remained stable in the last 10-15 years, and coffee, tea and soft drinks are the most important caffeine sources. Across all age groups, energy drinks contribute little to total caffeine intake. The highest potential for reducing daily caffeine intake is by limiting coffee consumption, and in some countries and age groups, by reducing tea and soft drink consumption.

Validation of caffeine dehydrogenase from Pseudomonas sp. strain CBB1 as a suitable enzyme for a rapid caffeine detection and potential diagnostic test.

PubMed

Mohanty, Sujit K; Yu, Chi Li; Gopishetty, Sridhar; Subramanian, Mani

2014-08-06

Excess consumption of caffeine (>400 mg/day/adult) can lead to adverse health effects. Recent introduction of caffeinated products (gums, jelly beans, energy drinks) might lead to excessive consumption, especially among children and nursing mothers, hence attracting the Food and Drug Administration's attention and product withdrawals. An "in-home" test will aid vigilant consumers in detecting caffeine in beverages and milk easily and quickly, thereby restricting its consumption. Known diagnostic methods lack speed and sensitivity. We report a caffeine dehydrogenase (Cdh)-based test which is highly sensitive (1-5 ppm) and detects caffeine in beverages and mother's milk in 1 min. Other components in these complex test samples do not interfere with the detection. Caffeine-dependent reduction of the dye iodonitrotetrazolium chloride results in shades of pink proportional to the levels in test samples. This test also estimates caffeine levels in pharmaceuticals, comparable to high-performance liquid chromatography. The Cdh-based test is the first with the desired attributes of a rapid and robust caffeine diagnostic kit.

A genetic variation in the adenosine A2A receptor gene (ADORA2A) contributes to individual sensitivity to caffeine effects on sleep.

PubMed

Rétey, J V; Adam, M; Khatami, R; Luhmann, U F O; Jung, H H; Berger, W; Landolt, H-P

2007-05-01

Caffeine is the most widely used stimulant in Western countries. Some people voluntarily reduce caffeine consumption because it impairs the quality of their sleep. Studies in mice revealed that the disruption of sleep after caffeine is mediated by blockade of adenosine A2A receptors. Here we show in humans that (1) habitual caffeine consumption is associated with reduced sleep quality in self-rated caffeine-sensitive individuals, but not in caffeine-insensitive individuals; (2) the distribution of distinct c.1083T>C genotypes of the adenosine A2A receptor gene (ADORA2A) differs between caffeine-sensitive and -insensitive adults; and (3) the ADORA2A c.1083T>C genotype determines how closely the caffeine-induced changes in brain electrical activity during sleep resemble the alterations observed in patients with insomnia. These data demonstrate a role of adenosine A2A receptors for sleep in humans, and suggest that a common variation in ADORA2A contributes to subjective and objective responses to caffeine on sleep.

[Caffeine: a nutrient, a drug or a drug of abuse].

PubMed

Pardo Lozano, Ricardo; Alvarez García, Yolanda; Barral Tafalla, Diego; Farré Albaladejo, Magí

2007-01-01

Coffee, tea, chocolate and caffeinated drinks are the main sources of caffeine, which is consumed in almost all ages and socioeconomic levels. Caffeine acts as a non-selective adenosine receptor antagonist in the central nervous system. Its main effects are as psychostimulant, acting in addition on the respiratory, muscular and cardiovascular systems. Basically, caffeine is metabolized by the hepatic cytochrome P-450 1A2 enzymes (CYP1A2). Several drugs can interact with its metabolism. The observed interindividual differences of its effects can be explained by variations in its metabolism. The main therapeutic use of caffeine is bronchodilator in respiratory diseases. Other possible uses are under investigation. Acute or chronic consumption of caffeine can induce several adverse effects, including intoxication that can be lethal. Finally, caffeine can be considered a drug of abuse. It has positive reinforcing actions, produces tolerance, and a withdrawal syndrome after stopping its consumption. Caffeine can cause different mental disorders such as dependence, which is not included in the DSM-IV-R, withdrawal syndrome and intoxication. Depending on its use, caffeine can be considered a nutrient, a drug or a drug of abuse.

The Relationship Between Caffeine, Sleep, and Behavior in Children

PubMed Central

Watson, Emily J.; Banks, Siobhan; Coates, Alison M.; Kohler, Mark J.

2017-01-01

Study Objectives: To examine caffeine consumption from various dietary sources in a cohort of Australian children and the relationship between caffeine consumption, sleep, and daytime behavior. Methods: Children aged 8 to 12 years and their parents/guardians completed a battery of questionnaires. Children completed a caffeine questionnaire while parents completed questionnaires regarding demographics, sleep, and behavior. Results: The final sample consisted of 309 children (mean ± standard deviation [SD] age 10.6 ± 1.3 years, male = 48%) and corresponding parent reports. On average a mean ± SD 10.2 ± 17.4 mg/day of caffeine was consumed with a range of zero to 151 mg/day. Of the children who consumed caffeine (87% of the sample), the largest contributor was coffee and tea; making up 41% of total caffeine intake, and sodas (soft drinks) contributed to 40% of caffeine intake. Total caffeine consumption was significantly associated with sleep routine (r = 0.152); morning tiredness (r = 0.129); restless sleep (r = 0.113); and internalizing behavioral problems (r = 0.128). Using path analysis, caffeine consumption was positively associated with morning tiredness (β = 0.111, P = .050) which was positively associated with internalizing behaviors (β = 0.432, P < .001). The addition of sleep routine and restless sleep to the model led to a complete mediation of caffeine consumption on morning tiredness, as well as a partial mediation of the association between morning tiredness and internal behaviors. Conclusions: In 8- to 12-year-olds the primary sources of caffeine are coffee/tea and sodas. Overall mean caffeine consumption is small by adult standards but has an effect on behavior and sleep in children. The effect on behavior is mediated by disrupted sleep, indicating that caffeine is a contributor to sleep problems and related behavior in children. Citation: Watson EJ, Banks S, Coates AM, Kohler MJ. The relationship between caffeine, sleep and behavior in children. J Clin Sleep Med. 2017;13(4):533–543. PMID:28162144

[Caffeine dependence].

PubMed

Ogawa, Naoshi; Ueki, Hirofumi

2010-08-01

Caffeine is the most widely consumed psychoactive substance in the world and is a legal stimulant that is readily available to children. The potential for dependence on caffeine has been debated. Presently, due to a paucity of clinical evidence on caffeine dependence, no such diagnosis is included in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR). Although in recent studies, a subset of the general population was found to demonstrate caffeine dependence. It is valuable for psychiatrists and primary care physicians to recognize caffeine dependence as a clinical syndrome, since some people are distressed by their caffeine use and feel they can not control or stop their problematic use.

Caffeine's Influence on Nicotine's Effects in Nonsmokers

PubMed Central

Blank, Melissa D.; Kleykamp, Bethea A.; Jennings, Janine M.; Eissenberg, Thomas

2011-01-01

Objective To determine if nicotine's effects are influenced by caffeine in nonsmoking, moderate-caffeine consuming individuals (N=20). Methods The first 3 sessions included one of 3 randomly ordered, double-blind caffeine doses (0, 75, or 150 mg, oral [po]) and 2 single-blind nicotine gum doses (2 and 4 mg) in ascending order. The fourth session (single blind) repeated the 0 mg caffeine condition. Results Nicotine increased heart rate and subjective ratings indicative of aversive effects, and decreased reaction times. These effects were independent of caffeine dose and reliable across sessions. Conclusions In nonsmokers, nicotine effects are not influenced by moderate caffeine doses. PMID:17555378

The effects of caffeine on the cholinergic system.

PubMed

Pohanka, Miroslav

2014-01-01

Caffeine is a secondary metabolite of tea and coffee plants. It is the active psychostimulant ingredient of widely consumed beverages, chocolate and some drugs as well. The major pathways for caffeine including interaction with adenosine receptors have been identified but caffeine has several minor pathways as well that remain poorly understood including the cholinergic system. Given the role of caffeine in the cholinergic system, some molecular targets have been tracked and a mechanism of its action has been proposed in research studies. However, the biological effect of caffeine on the cholinergic system is not completely understood. The present review focuses on the role of caffeine in the cholinergic system.

Adolescent habitual caffeine consumption and hemodynamic reactivity during rest, psychosocial stress, and recovery.

PubMed

James, Jack E; Baldursdottir, Birna; Johannsdottir, Kamilla R; Valdimarsdottir, Heiddis B; Sigfusdottir, Inga Dora

2018-07-01

Most adolescents regularly consume caffeine. Whereas observational studies have suggested that coffee may be cardio-protective, pharmacological experimentation with adults shows that caffeine at dietary doses increases blood pressure, thereby implicating regular caffeine consumption as a potential source of harm for cardiovascular health. The present study was in response to the dearth of caffeine research among younger consumers. It was hypothesised that compared to the consumption of little or no caffeine, adolescents who habitually consume caffeine have overall higher blood pressure and increased vascular resistance. Using a quasi-experimental design, continuous measurements of blood pressure, cardiac output, and total peripheral resistance were taken non-invasively from adolescents (n = 333) aged 14-15 years and 18-19 years who reported "low", "moderate", or "high" levels of caffeine intake. Measurements were conducted when participants generally had negligible or low systematic caffeine levels while at rest, during stress, and during recovery from stress. Whereas habitual caffeine consumption did not predict blood pressure level, higher caffeine intake was associated with modestly increased vascular resistance during all phases of the experiment (i.e., at rest, during stress, and during recovery from stress). Present findings are important because they suggest that early exposure to caffeine may lead to persistent increases in vascular resistance, which in turn is an acknowledged risk factor for the development of hypertension. These results highlight the need for further studies of adolescents to determine the robustness of any persistent caffeine-related hemodynamic effects, and the implications such effects could have for long-term cardiovascular health. Copyright © 2018 Elsevier Inc. All rights reserved.

Maternal caffeine intake and risk of selected birth defects in the National Birth Defects Prevention Study.

PubMed

Browne, Marilyn L; Hoyt, Adrienne T; Feldkamp, Marcia L; Rasmussen, Sonja A; Marshall, Elizabeth G; Druschel, Charlotte M; Romitti, Paul A

2011-02-01

Caffeine intake is common during pregnancy, yet few epidemiologic studies have examined the association between maternal caffeine consumption and birth defects. Using data from the National Birth Defects Prevention Study (NBDPS), we examined the association between maternal caffeine consumption and anotia/microtia, esophageal atresia, small intestinal atresia, craniosynostosis, diaphragmatic hernia, omphalocele, and gastroschisis. The NBDPS is a multi-site population-based case-control study. The present analysis included 3,346 case infants and 6,642 control infants born from October 1997 through December 2005. Maternal telephone interview reports of demographic characteristics and conditions and exposures before and during pregnancy were collected. Odds ratios and 95% confidence intervals, adjusted for relevant covariates, were calculated to estimate the associations between maternal dietary caffeine intake (coffee, tea, soda, and chocolate) and maternal use of caffeine-containing medications and each defect. We observed small, statistically significant elevations in adjusted odds ratios ranging from 1.3 to 1.8 for total maternal dietary caffeine intake or specific types of caffeinated beverages and anotia/microtia, esophageal atresia, small intestinal atresia, and craniosynostosis; however, dose-response patterns were absent. Periconceptional use of caffeine-containing medications was infrequent and estimates were imprecise. We did not find convincing evidence of an association between maternal caffeine intake and the birth defects included in this study. The increasing popularity of caffeine-containing energy drinks and other caffeinated products may result in higher caffeine intake among women of childbearing age. Future studies should consider more detailed evaluation of such products. Copyright © 2010 Wiley-Liss, Inc.

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.

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.

Mechanisms of the psychostimulant effects of caffeine: Implications for substance use disorders

PubMed Central

Ferré, Sergi

2016-01-01

Background The psychostimulant properties of caffeine are reviewed and compared with those of prototypical psychostimulants, able to cause substance use disorders (SUD). Caffeine produces psychomotor activating, reinforcing and arousing effects, which depend on its ability to disinhibit the brake that endogenous adenosine imposes on the ascending dopamine and arousal systems. Objectives A model that considers the striatal adenosine A2A-dopamine D2 receptor heteromer as a key modulator of dopamine-dependent striatal functions (reward-oriented behavior and learning of stimulus-reward and reward-response associations) is introduced, which should explain most of the psychomotor and reinforcing effects of caffeine. Highlights The model can explain the caffeine-induced rotational behavior in rats with unilateral striatal dopamine denervation and the ability of caffeine to reverse the adipsic-aphagic syndrome in dopamine-deficient rodents. The model can also explain the weaker reinforcing effects and low abuse liability of caffeine, compared with prototypical psychostimulants. Finally the model can explain the actual major societal dangers of caffeine: the ability of caffeine to potentiate the addictive and toxic effects of drugs of abuse, with the particularly alarming associations of caffeine (as adulterant) with cocaine, amphetamine derivatives and synthetic cathinones and energy drinks with alcohol; and the higher sensitivity of children and adolescents to the psychostimulants effects of caffeine and its possible increase in the vulnerability to develop SUD. Conclusions The striatal A2A-D2 receptor heteromer constitutes an unequivocal main pharmacological target of caffeine and provides the main mechanisms by which caffeine potentiates the acute and long-term effects of prototypical psychostimulants. PMID:26786412

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

Tea component, epigallocatechin gallate, potentiates anticataleptic and locomotor-sensitizing effects of caffeine in mice.

PubMed

Kasture, Sanjay B; Gaikar, Mayur; Kasture, Veena; Arote, Sanjay; Salve, Balu; Rosas, Michela; Cotti, Elisabetta; Acquas, Elio

2015-02-01

Tea is the most popular beverage worldwide. Caffeine, the psychoactive principle of tea, pharmacologically interacts with several drugs and bioactive molecules. Epigallocatechin gallate (EGCG) is a major component of tea and its known interactions with caffeine make it worthwhile to further study them by investigating the influence of EGCG on the anticataleptic and locomotor-sensitizing effects of caffeine. In the present investigation, we observed that (a) administration of caffeine or EGCG alone inhibited haloperidol-induced catalepsy, a widely used animal model to study parkinsonism, and (b) a combination of caffeine and EGCG produced greater inhibition of haloperidol-induced catalepsy. Furthermore, after repeated administration of caffeine and EGCG, either alone or in combination, we observed that (c) caffeine and EGCG contrasted the sensitization of catalepsy observed after repeated haloperidol administration by significantly reducing the duration of catalepsy. Furthermore, as haloperidol-induced catalepsy was also associated with increased lipid peroxidation, we observed that (d) EGCG administration reduced striatal lipid peroxide levels in a dose-dependent manner and that (e) the combination of caffeine with EGCG was most effective in reducing haloperidol-increased striatal lipid peroxide. Finally, we observed that (f) chronic caffeine and EGCG significantly elicited locomotor sensitization and that (g) their combination resulted in significantly greater effects. In conclusion, EGCG potentiated the effects of caffeine on haloperidol-induced catalepsy and of caffeine-elicited locomotor sensitization. Overall, these observations indicate critical interactions between caffeine and EGCG in an animal model of parkinsonism and locomotor activity and suggest that tea consumption might reduce antipsychotic-induced side effects.

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.

Effects of acute and chronic caffeine on risk-taking behavior in children and adolescents.

PubMed

Temple, Jennifer L; Ziegler, Amanda M; Graczyk, Adam M; Crandall, Amanda

2017-05-01

Consumption of caffeinated beverages is associated with increased risk-taking behavior. The purpose of this study was to determine if acute caffeine administration influences risk-taking behavior in a dose-dependent manner. Participants were pre- (ages 8-9) and post-pubertal (ages 15-17) children who visited the laboratory three times and consumed a beverage containing 0, 1, or 2 mg/kg of caffeine. Thirty minutes later, participants completed the balloon analogue risk task (BART), the Iowa gambling task (IGT), and a delay discounting task. The number of balloons exploded on the BART task was significantly increased after 2 mg/kg of caffeine in moderate caffeine consumers, but was decreased after 2 mg/kg of caffeine in high caffeine consumers. There were no main effects of caffeine dose on the delay discounting task or on the IGT. Post-pubertal participants showed reduced delay discounting compared with pre-pubertal participants. Finally, average daily caffeine use was significantly, positively correlated with scores on a risk-taking questionnaire. These data suggest that caffeine dose-dependently influences decision making and risk taking. More research is needed to determine the mechanism of this difference as well as the extent to which sex and pubertal phase influence these relationships.

Caffeine tolerance: behavioral, electrophysiological and neurochemical evidence

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

Chou, D.T.; Khan, S.; Forde, J.

The development of tolerance to the stimulatory action of caffeine upon mesencephalic reticular neurons and upon spontaneous locomotor activity was evaluated in rats after two weeks of chronic exposure to low doses of caffeine (5-10 mg/kg/day via their drinking water). These doses are achievable through dietary intake of caffeine-containing beverages in man. Concomitant measurement of (/sup 3/H)-CHA binding in the mesencephalic reticular formation was also carried out in order to explore the neurochemical basis of the development of tolerance. Caffeine, 2.5 mg/kg i.v., markedly increased the firing rate of reticular neurons in caffeine naive rats but failed to modify themore » neuronal activity in a group exposed chronically to low doses of caffeine. In addition, in spontaneous locomotor activity studies, the data show a distinct shift to the right of the caffeine dose-response curve in caffeine pretreated rats. These results clearly indicate that tolerance develops to the stimulatory action of caffeine upon the reticular formation at the single neuronal activity level as well as upon spontaneous locomotor activity. Furthermore, in chronically caffeine exposed rats, an increase in the number of binding sites for (/sup 3/H)-CHA was observed in reticular formation membranes without any change in receptor affinity. 28 references, 4 figures.« less

Caffeine intake antagonizes salt sensitive hypertension through improvement of renal sodium handling

PubMed Central

Yu, Hao; Yang, Tao; Gao, Peng; Wei, Xing; Zhang, Hexuan; Xiong, Shiqiang; Lu, Zongshi; Li, Li; Wei, Xiao; Chen, Jing; Zhao, Yu; Arendshorst, William J.; Shang, Qianhui; Liu, Daoyan; Zhu, Zhiming

2016-01-01

High salt intake is a major risk factor for hypertension. Although acute caffeine intake produces moderate diuresis and natriuresis, caffeine increases the blood pressure (BP) through activating sympathetic activity. However, the long-term effects of caffeine on urinary sodium excretion and blood pressure are rarely investigated. Here, we investigated whether chronic caffeine administration antagonizes salt sensitive hypertension by promoting urinary sodium excretion. Dahl salt-sensitive (Dahl-S) rats were fed with high salt diet with or without 0.1% caffeine in drinking water for 15 days. The BP, heart rate and locomotor activity of rats was analyzed and urinary sodium excretion was determined. The renal epithelial Na+ channel (ENaC) expression and function were measured by in vivo and in vitro experiments. Chronic consumption of caffeine attenuates hypertension induced by high salt without affecting sympathetic nerve activity in Dahl-S rats. The renal α-ENaC expression and ENaC activity of rats decreased after chronic caffeine administration. Caffeine increased phosphorylation of AMPK and decrease α-ENaC expression in cortical collecting duct cells. Inhibiting AMPK abolished the effect of caffeine on α-ENaC. Chronic caffeine intake prevented the development of salt-sensitive hypertension through promoting urinary sodium excretion, which was associated with activation of renal AMPK and inhibition of renal tubular ENaC. PMID:27173481

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.

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.

Effects of Long-Term Caffeine Consumption on the Adenosine A1 Receptor in the Rat Brain: an In Vivo PET Study with [18F]CPFPX.

PubMed

Nabbi-Schroeter, Danje; Elmenhorst, David; Oskamp, Angela; Laskowski, Stefanie; Bauer, Andreas; Kroll, Tina

2018-04-01

Caffeine, a nonselective antagonist of adenosine receptors, is the most popular psychostimulant worldwide. Recently, a protective role of moderate chronic caffeine consumption against neurodegenerative diseases such as Alzheimer's and Parkinson's disease has been discussed. Thus, aim of the present study was an in vivo investigation of effects of long-term caffeine consumption on the adenosine A 1 receptor (A 1 AR) in the rat brain. Sixteen adult, male rats underwent five positron emission tomography (PET) scans with the highly selective A 1 AR radioligand [ 18 F]CPFPX in order to determine A 1 AR availability. After the first baseline PET scan, the animals were assigned to two groups: Caffeine treatment and control group. The caffeine-treated animals received caffeinated tap water (30 mg/kg bodyweight/day, corresponding to 4-5 cups of coffee per day in humans) for 12 weeks. Subsequently, caffeine was withdrawn and repeated PET measurements were performed on day 1, 2, 4, and 7 of caffeine withdrawal. The control animals were measured according to the same time schedule. At day 1, after 4.4 h of caffeine withdrawal, a significant decrease (- 34.5%, p < 0.001) of whole brain A 1 AR availability was observed. Unlike all other investigated brain regions in caffeine-treated rats, the hypothalamus and nucleus accumbens showed no significant intraindividual differences between baseline and first withdrawal PET scan. After approximately 27 h of caffeine withdrawal, the region- and group-specific effects disappeared and A 1 AR availability settled around baseline. The present study provides evidence that chronic caffeine consumption does not lead to persistent changes in functional availability of cerebral A 1 ARs which have previously been associated with neuroprotective effects of caffeine. The acute and region-specific decrease in cerebral A 1 AR availability directly after caffeine withdrawal is most likely caused by residual amounts of caffeine metabolites disguising an unchanged A 1 AR expression at this early time-point.

Prior sleep with zolpidem enhances the effect of caffeine or modafinil during 18 hours continuous work.

PubMed

Batéjat, Denise; Coste, Olivier; Van Beers, Pascal; Lagarde, Didier; Piérard, Christophe; Beaumont, Maurice

2006-05-01

Continuous military operations may disrupt sleep-wakefulness cycles, resulting in impaired performance and fatigue. We assessed the treatment efficacy of a hypnotic-psychostimulant combination to maintain sleep quality, performance, and alertness during a 42-h simulated military operation. A 6-h prophylactic sleep period with zolpidem (ZOL) followed by a 18-h continuous work period with administration at midway of 300 mg of slow release caffeine (CAF) or 200 mg of modafinil (MOD) was performed by eight healthy male subjects. Performance level was assessed with a reaction time test, a memory search test, a dual task, an attention test, and a computerized Stroop test. Cortical activation level was evaluated by the Critical Flicker Frequency test. Subjective sleepiness was evaluated using a visual analog scale and questionnaires. Effects of drugs on prophylactic and recovery sleep were also quantified from EEG recordings. CAF and MOD maintained performance and alertness throughout the 18-h work period. As shown by EEG recordings, ZOL improved prophylactic sleep without any deleterious effect on performance immediately after waking. As a result of its positive effects on prophylactic sleep, a lower pressure for slow wave sleep during recovery sleep was observed; nevertheless, zolpidem did not enhance the effects of either psychostimulant on performance. MOD and CAF may be of value in promoting performance and wakefulness during shiftwork or military operations while zolpidem improves prophylactic sleep quality without any deleterious effect after waking. We concluded that a zolpidem/ caffeine or modafinil combination could be useful in a context of environmental conditions not conducive to sleep.

Clinical Inquiry: Does caffeine intake during pregnancy affect birth weight?

PubMed

Adams, Taralee; Kelsberg, Gary; Safranek, Sarah

2016-03-01

No. Reducing caffeinated coffee consumption by 180 mg of caffeine (the equivalent of 2 cups) per day after 16 weeks' gestation doesn't affect birth weight. Consuming more than 300 mg of caffeine per day is associated with a clinically trivial, and statistically insignificant (less than 1 ounce), reduction in birth weight, compared with consuming no caffeine.

The Effects of Caffeine on Athletic Performance

ERIC Educational Resources Information Center

McDaniel, Larry W.; McIntire, Kyle; Streitz, Carmyn; Jackson, Allen; Gaudet, Laura

2010-01-01

Athletes who use caffeine before exercising or competition may be upgrading themselves more than they realize. Caffeine is classified as a stimulant and is the most commonly used drug in the world. Caffeine has the same affects that amphetamines and cocaine have, just to a lesser degree. Caffeine crosses the membranes of all the body's tissues. It…

Understanding Adolescent Caffeine Use: Connecting Use Patterns with Expectancies, Reasons, and Sleep

ERIC Educational Resources Information Center

Ludden, Alison Bryant; Wolfson, Amy R.

2010-01-01

Little is known about adolescents' caffeine use, yet caffeinated soda, and more recently coffee and energy drinks, are part of youth culture. This study examines adolescents' caffeine use and, using cluster analysis, identifies three groups of caffeine users who differed in their reasons for use, expectancies, and sleep behaviors. In this high…

Predicting the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol mixtures via molecular simulation

PubMed Central

Paluch, Andrew S.; Parameswaran, Sreeja; Liu, Shuai; Kolavennu, Anasuya; Mobley, David L.

2015-01-01

We present a general framework to predict the excess solubility of small molecular solids (such as pharmaceutical solids) in binary solvents via molecular simulation free energy calculations at infinite dilution with conventional molecular models. The present study used molecular dynamics with the General AMBER Force Field to predict the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol solvents. The simulations are able to predict the existence of solubility enhancement and the results are in good agreement with available experimental data. The accuracy of the predictions in addition to the generality of the method suggests that molecular simulations may be a valuable design tool for solvent selection in drug development processes. PMID:25637996

Estimation of caffeine intake from analysis of caffeine metabolites in wastewater.

PubMed

Gracia-Lor, Emma; Rousis, Nikolaos I; Zuccato, Ettore; Bade, Richard; Baz-Lomba, Jose Antonio; Castrignanò, Erika; Causanilles, Ana; Hernández, Félix; Kasprzyk-Hordern, Barbara; Kinyua, Juliet; McCall, Ann-Kathrin; van Nuijs, Alexander L N; Plósz, Benedek G; Ramin, Pedram; Ryu, Yeonsuk; Santos, Miguel M; Thomas, Kevin; de Voogt, Pim; Yang, Zhugen; Castiglioni, Sara

2017-12-31

Caffeine metabolites in wastewater were investigated as potential biomarkers for assessing caffeine intake in a population. The main human urinary metabolites of caffeine were measured in the urban wastewater of ten European cities and the metabolic profiles in wastewater were compared with the human urinary excretion profile. A good match was found for 1,7-dimethyluric acid, an exclusive caffeine metabolite, suggesting that might be a suitable biomarker in wastewater for assessing population-level caffeine consumption. A correction factor was developed considering the percentage of excretion of this metabolite in humans, according to published pharmacokinetic studies. Daily caffeine intake estimated from wastewater analysis was compared with the average daily intake calculated from the average amount of coffee consumed by country per capita. Good agreement was found in some cities but further information is needed to standardize this approach. Wastewater analysis proved useful to providing additional local information on caffeine use. Copyright © 2017 Elsevier B.V. All rights reserved.

The effect of acute caffeine intake on insulin sensitivity and glycemic control in people with diabetes.

PubMed

Dewar, Lisa; Heuberger, Roschelle

2017-12-01

The prevalence of diabetes is growing globally, and with no current cure for the disease, management is focused on optimizing blood glucose control to limit complications. The purpose of this review was to examine the effect of caffeine intake on blood glucose levels in people with diabetes. Electronic searches were completed using Pub Med, CINAHL, and Web of Science using the search terms "coffee and insulin," "caffeine and insulin," "caffeine and diabetes," "caffeine and type 1 diabetes," "caffeine and type 2 diabetes," and "caffeine and glycemia." Seven trials were found to meet the search criteria. Five of the 7 studies suggest caffeine intake increases blood glucose levels, and prolongs the period of high blood glucose levels. Future research should focus on larger clinical trials to confirm the relationship and mechanism of action related to caffeine intake and glycemic control in individuals with diabetes. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Towards generating caffeine-free tea by metabolic engineering.

PubMed

Yadav, Sudesh Kumar; Ahuja, Paramvir Singh

2007-12-01

Tea is a rich source of antioxidants which are contributing substantially to the promotion of health and the prevention of various chronic diseases. Despite the fact that tea has various important compounds, it also contains a purine alkaloid, caffeine. High intake of tea leads to an increase in level of caffeine in addition to its important antioxidant constituents. Increased level of caffeine causes several health related problems. Therefore, tea can become a most useful source of beneficial compounds, if only its caffeine level is either decreased or eliminated all together from the plant itself. This could be achieved through either of the techniques; overexpressing caffeine degradative pathway genes or silencing caffeine biosynthesis pathway gene. The identification and cloning of caffeine biosynthesis in tea and degradative genes in microorganisms opens up the possibility of using genetic engineering to produce naturally decaffeinated tea. Here we review these different strategies which can be employed to make caffeine-free tea, a human health beneficial drink.

Nutritional Strategies for Women Participating in Competitive/Recreational Sports.

ERIC Educational Resources Information Center

Fort, Inza L.; Di Brezzo, Ro

The preponderance of articles and research on nutrition can be confusing. The active woman over 30 can enhance performance and health with a high-quality diet. Specific nutritional concerns for women after the college years, such as nutrient content, iron, calcium, vitamin supplementation, and caffeine are discussed. Evidence that processed foods…

The caffeine contents of non-alcoholic beverages.

PubMed

Galasko, G T; Furman, K I; Alberts, E

1989-01-01

The caffeine content of a number of non-alcoholic beverages was determined using HPLC. It was found that Diet Coke had a greater caffeine content than Coke (4.15 compared with 3.13 mg/fl oz), Tab is virtually caffeine free, and Lucozade, sold as a tonic, contains more caffeine than any of the other carbonated beverages tested (5.17 mg/fl oz). The pure instant coffee tested contained much more caffeine than the coffee/chicory mixtures (12.61 compared with 3.18 mg/fl oz). The caffeine content of Ceylon tea blends increases with the time the tea is allowed to draw (from about 8 mg/fl oz after 1 min to about 12 mg/fl oz after 20 min). Tea that has been allowed to draw for 20 min has a caffeine content similar to that of pure coffee.

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.

A Brief Manualized Treatment for Problematic Caffeine Use: A Randomized Control Trial

PubMed Central

Evatt, Daniel P.; Juliano, Laura M.; Griffiths, Roland R.

2015-01-01

Objective The goal of the present investigation was to develop and test a brief therapist-guided manualized treatment for problematic caffeine use including cognitive-behavioral strategies and 5-weeks of progressively decreased consumption. Methods Individuals seeking treatment for problematic caffeine use (mean daily caffeine consumption of 666.0 mg at baseline) were randomized using a waitlist-control design to receive immediate (N = 33) treatment or delayed (N = 34) treatment (∼6 weeks later). A one-hour long treatment session designed to help individuals quit or reduce caffeine consumption was provided by a trained counselor along with a take-home booklet. After the treatment session, participants completed daily diaries of caffeine consumption for 5 weeks. They returned for follow-up assessments at 6, 12, and 26 weeks and had a telephone interview at 52-weeks post-treatment. Results Treatment resulted in a significant reduction in self reported caffeine use and salivary caffeine levels. No significant post-treatment increases in caffeine use were observed for up to one year follow-up. Comparisons to the waitlist control condition revealed that reductions in caffeine consumption were due to treatment and not the passing of time, with a treatment effect size of R2 = .35 for the model. Conclusions A brief one-session manualized intervention with follow-up was efficacious at reducing caffeine consumption. Future research should replicate and extend these findings, as well as consider factors affecting dissemination of treatment for problematic caffeine use to those in need. PMID:26501499

Are energy Drinks Scapegoats? Decomposing Teenagers' Caffeine intake from Energy Drinks and Soda Beverages.

PubMed

Turel, Ofir

2018-02-22

Energy drinks have been repeatedly blamed for contributing to caffeine intake among teenagers. This study aimed to estimate and compare the caffeine intake of US teenagers from soda drinks versus energy drinks and shots. Data were taken from a 2015 nationally representative survey (Monitoring the Future) of 8th and 10th graders in the US (47.2% 8th grade; 51.1% female). Participants reported their numbers of consumed sodas, diet sodas, energy drinks, and energy shots per day. These were converted into mg caffeine/day and were contrasted with common guidelines for healthy caffeine intake, stratified by age group and sex. Error-bar charts, ANOVA and ROC curves were used for contrasting caffeine intake from soda drinks and energy drinks, as well as their contribution to exceeding recommended caffeine intake cutoffs. First, in both sexes and grades the intake from soda drinks was significantly higher than the intake from energy drinks. The soda and energy drink intake for males was higher than the intake for females; intake for 8th graders was higher than this of 10th graders. Second, caffeine intake from soda drinks was significantly higher even in those who exceeded the recommended maximum caffeine intake. Third, caffeine intakes from soda and energy drinks were efficacious in explaining the exceeding of the recommended threshold for daily caffeine intake, but the explanatory power of soda drinks was larger. From a caffeine consumption standpoint, health professionals should emphasize reduction in both soda and energy drinks.

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

Dose-dependent model of caffeine effects on human vigilance during total sleep deprivation.

PubMed

Ramakrishnan, Sridhar; Laxminarayan, Srinivas; Wesensten, Nancy J; Kamimori, Gary H; Balkin, Thomas J; Reifman, Jaques

2014-10-07

Caffeine is the most widely consumed stimulant to counter sleep-loss effects. While the pharmacokinetics of caffeine in the body is well-understood, its alertness-restoring effects are still not well characterized. In fact, mathematical models capable of predicting the effects of varying doses of caffeine on objective measures of vigilance are not available. In this paper, we describe a phenomenological model of the dose-dependent effects of caffeine on psychomotor vigilance task (PVT) performance of sleep-deprived subjects. We used the two-process model of sleep regulation to quantify performance during sleep loss in the absence of caffeine and a dose-dependent multiplier factor derived from the Hill equation to model the effects of single and repeated caffeine doses. We developed and validated the model fits and predictions on PVT lapse (number of reaction times exceeding 500 ms) data from two separate laboratory studies. At the population-average level, the model captured the effects of a range of caffeine doses (50-300 mg), yielding up to a 90% improvement over the two-process model. Individual-specific caffeine models, on average, predicted the effects up to 23% better than population-average caffeine models. The proposed model serves as a useful tool for predicting the dose-dependent effects of caffeine on the PVT performance of sleep-deprived subjects and, therefore, can be used for determining caffeine doses that optimize the timing and duration of peak performance. Published by Elsevier Ltd.

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

Evaluating Dependence Criteria for Caffeine.

PubMed

Striley, Catherine L W; Griffiths, Roland R; Cottler, Linda B

2011-12-01

Background: Although caffeine is the most widely used mood-altering drug in the world, few studies have operationalized and characterized Diagnostic and Statistical Manual IV (DSM-IV) substance dependence criteria applied to caffeine. Methods: As a part of a nosological study of substance use disorders funded by the National Institute on Drug Abuse, we assessed caffeine use and dependence symptoms among high school and college students, drug treatment patients, and pain clinic patients who reported caffeine use in the last 7 days and also reported use of alcohol, nicotine, or illicit drugs within the past year ( n =167). Results: Thirty-five percent met the criteria for dependence when all seven of the adopted DSM dependence criteria were used. Rates of endorsement of several of the most applicable diagnostic criteria were as follows: 26% withdrawal, 23% desire to cut down or control use, and 44% continued use despite harm. In addition, 34% endorsed craving, 26% said they needed caffeine to function, and 10% indicated that they talked to a physician or counselor about problems experienced with caffeine. There was a trend towards increased caffeine dependence among those dependent on nicotine or alcohol. Within a subgroup that had used caffeine, alcohol, and nicotine in the past year, 28% fulfilled criteria for caffeine dependence compared to 50% for alcohol and 80% for nicotine. Conclusion: The present study adds to a growing literature suggesting the reliability, validity, and clinical utility of the caffeine dependence diagnosis. Recognition of caffeine dependence in the DSM-V may be clinically useful.

Chronic caffeine ingestion causes microglia activation, but not proliferation in the healthy brain

PubMed Central

Steger, Rob; Kamal, Arifa; Lutchman, Sara; Intrabartolo, Liliana; Sohail, Rabia; Brumberg, Joshua C.

2014-01-01

Caffeine is the most popular psychoactive drug in the world which contributes to behavioral and metabolic changes when ingested. Within the central nervous system (CNS), caffeine has a high affinity for A1 and A2a adenosine receptors. Serving as an antagonist, caffeine affects the ability for adenosine to bind to these receptors. Caffeine has been shown to alter neuronal functioning through increasing spontaneous firing. However, the effects of caffeine on non-neuronal cells in the CNS has been not been studied extensively. Microglia are one phenotype of non-neuronal glia within the CNS. Acting as phagocytes, they contribute to the immune defense system of the brain and express A1 and A2a adenosine receptors. Caffeine, therefore, may affect microglia. In order to test this hypothesis, CD-1 mice were randomly placed into one of three groups: control, low caffeine (0.3g/L water) and high caffeine (1.0g/L water) and were allowed to drink freely for 30 days. Following 30 days, brain sections were stained to reveal microglia. Morphological reconstructions and density measurements were examined in cortical and subcortical areas including the primary sensory cortex, primary motor cortex and striatum. Results indicate that microglial density throughout the brain is decreased in the caffeine groups as compared to the control. Caffeine also impacted microglia morphology shortening process length and decreasing branching. These results suggest that chronic caffeine ingestion has a systemic impact on microglia density and their activation. PMID:24881873

Solid-state characterization and solubility of a genistein-caffeine cocrystal

NASA Astrophysics Data System (ADS)

Sowa, Michał; Ślepokura, Katarzyna; Matczak-Jon, Ewa

2014-11-01

Combination of genistein and caffeine leads to a 1:1 cocrystalline phase, which was identified by means of a solvent-drop grinding experiment and isolated afterwards in a solution-evaporation approach. Obtained cocrystal was characterized by X-ray single-crystal and powder diffraction as well as investigated in terms of thermal stability and Hirshfeld surfaces. A scale-up procedure was provided by slurry technique, enabling solubility determination. Neutral forms of both compounds cocrystallize in a common P21/c space group of the monoclinic crystal system. Analysis of packing and interactions in the crystal lattice reveals formation of molecular layers, formed by O-H⋯O, O-H⋯N and C-H⋯O-type contacts between genistein and caffeine molecules, whereas stabilization of the three-dimensional crystal lattice is provided by π⋯π interactions. Dissolution studies in a 50:50 v/v ethanol-water medium revealed that the maximum solubility of the cocrystalline phase reached 0.861 mg/mL after 8 h, revealing some degree of enhancement as compared to parent genistein, maximum solubility of which was also reached after 8 h and equalled 0.588 mg/mL.

Caffeine and human cerebral blood flow: A positron emission tomography study

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

Cameron, O.G.; Modell, J.G.; Hariharan, M.

1990-01-01

Positron emission tomography (PET) was used to quantify the effect of caffeine on whole brain and regional cerebral blood flow (CBF) in humans. A mean dose of 250 mg of caffeine produced approximately a 30% decrease in whole brain CBF; regional differences in caffeine effect were not observed. Pre-caffeine CBF strongly influenced the magnitude of the caffeine-induced decrease. Caffeine decreased p{sub a}CO{sub 2} and increased systolic blood pressure significantly; the change in p{sub a}CO{sub 2} did not account for the change in CBF. Smaller increases in diastolic blood pressure, heart rate, plasma epinephrine and norepinephrine, and subjectively reported anxiety weremore » also observed.« less

Performance pressure and caffeine both affect cognitive performance, but likely through independent mechanisms.

PubMed

Boere, Julia J; Fellinger, Lizz; Huizinga, Duncan J H; Wong, Sebastiaan F; Bijleveld, Erik

2016-02-01

A prevalent combination in daily life, performance pressure and caffeine intake have both been shown to impact people's cognitive performance. Here, we examined the possibility that pressure and caffeine affect cognitive performance via a shared pathway. In an experiment, participants performed a modular arithmetic task. Performance pressure and caffeine intake were orthogonally manipulated. Findings indicated that pressure and caffeine both negatively impacted performance. However, (a) pressure vs. caffeine affected performance on different trial types, and (b) there was no hint of an interactive effect. So, though the evidence is indirect, findings suggest that pressure and caffeine shape performance via distinct mechanisms, rather than a shared one. Copyright © 2015 Elsevier Inc. All rights reserved.

Focus on Communications: Communicating the Message: Clarifying the Controversies About Caffeine.

PubMed

Hogan, Edith Howard; Hornick, Betsy A.; Bouchoux, Ann

2002-01-01

Today's "coffee culture" and the widespread availability of caffeine-containing foods and beverages fuel the ongoing study of caffeine and its subsequent coverage by the media. Although the media has become influential in communicating health and nutrition information to the public, coverage of emerging science, such as the study of caffeine, does not necessarily bring clarity or improved understanding for consumers. This article highlights the current knowledge of caffeine's effects on health, with emphasis on the most common areas of interest and confusion. To address persistent misperceptions about caffeine, this article also accentuates the need for nutrition professionals to help put the findings of caffeine research into perspective and suggests practical ways to do this.

Cardiovascular Effects of Caffeine

PubMed Central

Myers, Martin G.

1992-01-01

A review of the literature on the cardiovascular effects of caffeine indicates that moderate caffeine consumption does not cause cardiac arrhythmias, hypertension, or an increased incidence of coronary heart disease. Caffeine use is often associated with atherogenic behavior, such as cigarette smoking. Failure to take into account covariables for cardiovascular disease could be responsible for commonly held misconceptions about caffeine and heart disease. PMID:21221403

Determination of the caffeine contents of various food items within the Austrian market and validation of a caffeine assessment tool (CAT).

PubMed

Rudolph, E; Färbinger, A; König, J

2012-01-01

The caffeine content of 124 products, including coffee, coffee-based beverages, energy drinks, tea, colas, yoghurt and chocolate, were determined using RP-HPLC with UV detection after solid-phase extraction. Highest concentrations of caffeine were found for coffee prepared from pads (755 mg l⁻¹) and regular filtered coffee (659 mg l⁻¹). The total caffeine content of coffee and chocolate-based beverages was between 15 mg l⁻¹ in chocolate milk and 448 mg l⁻¹ in canned ice coffee. For energy drinks the caffeine content varied in a range from 266 to 340 mg l⁻¹. Caffeine concentrations in tea and ice teas were between 13 and 183 mg l⁻¹. Coffee-flavoured yoghurts ranged from 33 to 48 mg kg⁻¹. The caffeine concentration in chocolate and chocolate bars was between 17 mg kg⁻¹ in whole milk chocolate and 551 mg kg⁻¹ in a chocolate with coffee filling. A caffeine assessment tool was developed and validated by a 3-day dietary record (r²= 0.817, p < 0.01) using these analytical data and caffeine saliva concentrations (r²= 0.427, p < 0.01).

Caffeine alters emotion and emotional responses in low habitual caffeine consumers.

PubMed

Giles, Grace E; Spring, Alexander M; Urry, Heather L; Moran, Joseph M; Mahoney, Caroline R; Kanarek, Robin B

2018-02-01

Caffeine reliably increases emotional arousal, but it is unclear whether and how it influences other dimensions of emotion such as emotional valence. These experiments documented whether caffeine influences emotion and emotion regulation choice and success. Low to abstinent caffeine consumers (maximum 100 mg/day) completed measures of state anxiety, positive and negative emotion, and salivary cortisol before, 45 min after, and 75 min after consuming 400 mg caffeine or placebo. Participants also completed an emotion regulation choice task, in which they chose to employ cognitive reappraisal or distraction in response to high and low intensity negative pictures (Experiment 1), or a cognitive reappraisal task, in which they employed cognitive reappraisal or no emotion regulation strategy in response to negative and neutral pictures (Experiment 2). State anxiety, negative emotion, and salivary cortisol were heightened both 45 and 75 min after caffeine intake relative to placebo. In Experiment 1, caffeine did not influence the frequency with which participants chose reappraisal or distraction, but reduced negativity of the picture ratings. In Experiment 2, caffeine did not influence cognitive reappraisal success. Thus, caffeine mitigated emotional responses to negative situations, but not how participants chose to regulate such responses or the success with which they did so.

The interoceptive Pavlovian stimulus effects of caffeine

PubMed Central

Murray, Jennifer E.; Li, Chia; Palmatier, Matthew I.

2007-01-01

The present research sought to test whether caffeine functioned as a Pavlovian cue in two ways—as a positive drug feature or as a conditional stimulus (CS). As a positive feature (Experiment 1), brief light presentations were followed by sucrose only on sessions in which caffeine (10 mg/kg) was administered. On intermixed saline sessions, light presentations were not followed by sucrose. The light came to control robust goal-tracking (i.e., conditioned responding) only in caffeine sessions. Thus, caffeine disambiguates when the light was paired with sucrose. Decreasing the dose of caffeine decreased the conditioned responding evoked by the light (ED50=4.16 mg/kg). Neither nicotine nor amphetamine substituted for the caffeine feature. As a CS, caffeine (10 or 30 mg/kg, Experiments 2a and 2b, respectively) signaled intermittent access to sucrose—no light presentations. No sucrose or lights were presented on intermixed saline sessions. The caffeine CS, regardless of training dose, acquired the ability to evoke only a weak goal-tracking CR. The nature of this dissociation between caffeine as a drug feature versus a CS is discussed within the context of past research finding a similar dissociation with amphetamine and chlordiazepoxide, but not with nicotine. PMID:17477964

Role of adenosine receptors in caffeine tolerance

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

Holtzman, S.G.; Mante, S.; Minneman, K.P.

1991-01-01

Caffeine is a competitive antagonist at adenosine receptors. Receptor up-regulation during chronic drug treatment has been proposed to be the mechanism of tolerance to the behavioral stimulant effects of caffeine. This study reassessed the role of adenosine receptors in caffeine tolerance. Separate groups of rats were given scheduled access to drinking bottles containing plain tap water or a 0.1% solution of caffeine. Daily drug intake averaged 60-75 mg/kg and resulted in complete tolerance to caffeine-induced stimulation of locomotor activity, which could not be surmounted by increasing the dose of caffeine. 5'-N-ethylcarboxamidoadenosine (0.001-1.0 mg/kg) dose dependently decreased the locomotor activity ofmore » caffeine-tolerant rats and their water-treated controls but was 8-fold more potent in the latter group. Caffeine (1.0-10 mg/kg) injected concurrently with 5-N-ethylcarboxamidoadenosine antagonized the decreases in locomotor activity comparably in both groups. Apparent pA2 values for tolerant and control rats also were comparable: 5.05 and 5.11. Thus, the adenosine-antagonist activity of caffeine was undiminished in tolerant rats. The effects of chronic caffeine administration on parameters of adenosine receptor binding and function were measured in cerebral cortex. There were no differences between brain tissue from control and caffeine-treated rats in number and affinity of adenosine binding sites or in receptor-mediated increases (A2 adenosine receptor) and decreases (A1 adenosine receptor) in cAMP accumulation. These results are consistent with theoretical arguments that changes in receptor density should not affect the potency of a competitive antagonist. Experimental evidence and theoretical considerations indicate that up-regulation of adenosine receptors is not the mechanism of tolerance to caffeine-induced stimulation of locomotor activity.« less

Effects of caffeine on circadian phase, amplitude and period evaluated in cells in vitro and peripheral organs in vivo in PER2::LUCIFERASE mice

PubMed Central

Narishige, Seira; Kuwahara, Mari; Shinozaki, Ayako; Okada, Satoshi; Ikeda, Yuko; Kamagata, Mayo; Tahara, Yu; Shibata, Shigenobu

2014-01-01

Background and Purpose Caffeine is one of the most commonly used psychoactive substances. Circadian rhythms consist of the main suprachiasmatic nucleus (SCN) clocks and peripheral clocks. Although caffeine lengthens circadian rhythms and modifies phase changes in SCN-operated rhythms, the effects on caffeine on the phase, period and amplitude of peripheral organ clocks are not known. In addition, the role of cAMP/Ca2+ signalling in effects of caffeine on rhythm has not been fully elucidated. Experimental Approach We examined whether chronic or transient application of caffeine affects circadian period/amplitude and phase by evaluating bioluminescence rhythm in PER2::LUCIFERASE knock-in mice. Circadian rhythms were monitored in vitro using fibroblasts and ex vivo and in vivo for monitoring of peripheral clocks. Key Results Chronic application of caffeine (0.1–10 mM) increased period and amplitude in vitro. Transient application of caffeine (10 mM) near the bottom of the decreasing phase of bioluminescence rhythm caused phase advance in vitro. Caffeine (0.1%) intake caused a phase delay under light–dark or constant dark conditions, suggesting a period-lengthening effect in vivo. Caffeine (20 mg·kg−1) at daytime or at late night-time caused phase advance or delay in bioluminescence rhythm in the liver and kidney respectively. The complicated roles of cAMP/Ca2+ signalling may be involved in the caffeine-induced increase of period and amplitude in vitro. Conclusions and Implications Caffeine affects circadian rhythm in mice by lengthening the period and causing a phase shift of peripheral clocks. These results suggest that caffeine intake with food/drink may help with food-induced resetting of peripheral circadian clocks. PMID:25160990

Caffeine and central noradrenaline: effects on mood, cognitive performance, eye movements and cardiovascular function.

PubMed

Smith, Andrew; Brice, Carolyn; Nash, Jon; Rich, Neil; Nutt, David J

2003-09-01

There have been numerous studies on the effects of caffeine on behaviour and cardiovascular function. It is now important to clarify the mechanisms that underlie such effects, and the main objective of the present study was to investigate whether changes in central noradrenaline underlie some of the behavioural and cardiovascular effects of caffeine. This was examined using a clonidine challenge paradigm. Twenty-four healthy volunteers were assigned to one of four conditions: (i) clonidine/caffeine; (ii) clonidine/placebo; (iii) placebo/caffeine: (iv) placebo/placebo. Baseline measurements of mood, cognitive performance, saccadic eye movements and cardiovascular function were recorded. Subsequently, volunteers were given either clonidine (200 microg) or placebo and consumed coffee containing caffeine (1.5 mg/kg) or placebo. The test battery was then repeated 30 min, 150 min and 270 min later. A second cup of coffee (with the same amount of caffeine as the first) was consumed 120 min after the first cup. The results showed that clonidine reduced alertness, impaired many aspects of performance and slowed saccadic eye movements; caffeine removed many of these impairments. Both clonidine and caffeine influenced blood pressure (clonidine reduced it, caffeine raised it) but the effects appeared to be independent, suggesting that separate mechanisms were involved. In addition, there were some behavioural effects of caffeine that were independent of the clonidine effect (e.g. effects on speed of encoding of new information) and these may reflect other neurotransmitter systems (e.g cholinergic effects). Overall, the results suggest that caffeine counteracts reductions in the turnover of central noradrenaline. This mechanism may underlie the beneficial effects of caffeine seen in low alertness states.

Sources of Caffeine in Diets of US Children and Adults: Trends by Beverage Type and Purchase Location.

PubMed

Drewnowski, Adam; Rehm, Colin D

2016-03-10

New sources of caffeine, besides coffee and tea, have been introduced into the US food supply. Data on caffeine consumption age and purchase location can help guide public health policy. National Health and Nutrition Examination Surveys (NHANES) were used to estimate population-level caffeine intakes, using data from 24-h dietary recall. First, caffeine intakes by age-group and beverage type were estimated using the most recent 2011-2012 data (n = 7456). Second, fourteen years trends in caffeine consumption, overall and by beverage type, were evaluated for adults and children. Trend analyses were conducted by age groups. Last, trends in caffeine intakes by purchase location and beverage type were estimated. In 2011-2012, children aged four to eight years consumed the least caffeine (15 mg/day), and adults aged 51-70 years consumed the most (213 mg/day). The population mean (age ≥ four years) was 135 mg/day, driven largely by coffee (90 mg/day), tea (25 mg/day), and soda (21 mg/day). For the 14-19 years and 20-34 years age-groups, energy drinks contributed 6 mg/day (9.9%) and 5 mg/day (4.5%), respectively. The bulk of caffeine came from store-bought coffee and tea. Among both children and adults combined, caffeine intakes declined from 175 mg/day (1999-2000) to 142 mg/day (2011-2012), largely driven by a drop in caffeine from soda (41 mg/day to 21 mg/day). Store-bought coffee and tea remain principal drivers of caffeine intake in the US. Sodas and energy drinks make minor contributions to overall caffeine intakes.

Effects of acute caffeine on anxiety-related behavior in rats chronically exposed to the drug, with some evidence of possible withdrawal-reversal.

PubMed

Hughes, Robert N; Hancock, Nicola J

2017-03-15

For 20days male and female PVG/c hooded rats were provided with caffeinated (approximately 50mg/kg/day) or unadulterated drinking water, and then their anxiety-related behavior was observed in an open field and elevated plus maze. Their choices of a brightness change were also observed in a Y maze to assess any caffeine effects on spatial memory. 24h later, all rats were tested again following an intraperitoneal injection of 50mg/kg acute caffeine, or vehicle. Earlier chronic caffeine decreased ambulation, walking, rearing, center occupancy and increased immobility in the open field thereby suggesting increased anxiety. However, occupancy of the plus-maze open arms and the Y-maze novel arm were increased by caffeine for male rats, but decreased for females probably because of sex differences in control levels of the response rather than to drug effects on anxiety and memory respectively. Following caffeine withdrawal, acute caffeine had the opposite effect to chronic treatment namely, increased open-field ambulation, walking, center occupancy and decreased immobility and defecation for caffeine-naïve rats that were suggestive of decreased anxiety. Similar but more consistent effects (plus decreased emergence latencies from a darkened start box into the open field) also typified the caffeine-experienced rats which in this case may have been accentuated by caffeine withdrawal-reversal. There was no evidence of either chronic or acute caffeine affecting spatial memory measured in the Y maze. There were also examples of lower overall activity and higher anxiety in male rats, than in females, and some sex-dependent caffeine effects. Copyright © 2016 Elsevier B.V. All rights reserved.

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 and contraction synergistically stimulate 5′-AMP-activated protein kinase and insulin-independent glucose transport in rat skeletal muscle

PubMed Central

Tsuda, Satoshi; Egawa, Tatsuro; Kitani, Kazuto; Oshima, Rieko; Ma, Xiao; Hayashi, Tatsuya

2015-01-01

5′-Adenosine monophosphate-activated protein kinase (AMPK) has been identified as a key mediator of contraction-stimulated insulin-independent glucose transport in skeletal muscle. Caffeine acutely stimulates AMPK in resting skeletal muscle, but it is unknown whether caffeine affects AMPK in contracting muscle. Isolated rat epitrochlearis muscle was preincubated and then incubated in the absence or presence of 3 mmol/L caffeine for 30 or 120 min. Electrical stimulation (ES) was used to evoke tetanic contractions during the last 10 min of the incubation period. The combination of caffeine plus contraction had additive effects on AMPKα Thr172 phosphorylation, α-isoform-specific AMPK activity, and 3-O-methylglucose (3MG) transport. In contrast, caffeine inhibited basal and contraction-stimulated Akt Ser473 phosphorylation. Caffeine significantly delayed muscle fatigue during contraction, and the combination of caffeine and contraction additively decreased ATP and phosphocreatine contents. Caffeine did not affect resting tension. Next, rats were given an intraperitoneal injection of caffeine (60 mg/kg body weight) or saline, and the extensor digitorum longus muscle was dissected 15 min later. ES of the sciatic nerve was performed to evoke tetanic contractions for 5 min before dissection. Similar to the findings from isolated muscles incubated in vitro, the combination of caffeine plus contraction in vivo had additive effects on AMPK phosphorylation, AMPK activity, and 3MG transport. Caffeine also inhibited basal and contraction-stimulated Akt phosphorylation in vivo. These findings suggest that caffeine and contraction synergistically stimulate AMPK activity and insulin-independent glucose transport, at least in part by decreasing muscle fatigue and thereby promoting energy consumption during contraction. PMID:26471759

Effect of caffeine ingestion on anaerobic capacity quantified by different methods

PubMed Central

Arcoverde, Lucyana; Silveira, Rodrigo; Tomazini, Fabiano; Sansonio, André; Bertuzzi, Romulo; Andrade-Souza, Victor Amorim

2017-01-01

We investigated whether caffeine ingestion before submaximal exercise bouts would affect supramaximal oxygen demand and maximal accumulated oxygen deficit (MAOD), and if caffeine-induced improvement on the anaerobic capacity (AC) could be detected by different methods. Nine men took part in several submaximal and supramaximal exercise bouts one hour after ingesting caffeine (5 mg·kg-1) or placebo. The AC was estimated by MAOD, alternative MAOD, critical power, and gross efficiency methods. Caffeine had no effect on exercise endurance during the supramaximal bout (caffeine: 131.3 ± 21.9 and placebo: 130.8 ± 20.8 s, P = 0.80). Caffeine ingestion before submaximal trials did not affect supramaximal oxygen demand and MAOD compared to placebo (7.88 ± 1.56 L and 65.80 ± 16.06 kJ vs. 7.89 ± 1.30 L and 62.85 ± 13.67 kJ, P = 0.99). Additionally, MAOD was similar between caffeine and placebo when supramaximal oxygen demand was estimated without caffeine effects during submaximal bouts (67.02 ± 16.36 and 62.85 ± 13.67 kJ, P = 0.41) or when estimated by alternative MAOD (56.61 ± 8.49 and 56.87 ± 9.76 kJ, P = 0.91). The AC estimated by gross efficiency was also similar between caffeine and placebo (21.80 ± 3.09 and 20.94 ± 2.67 kJ, P = 0.15), but was lower in caffeine when estimated by critical power method (16.2 ± 2.6 vs. 19.3 ± 3.5 kJ, P = 0.03). In conclusion, caffeine ingestion before submaximal bouts did not affect supramaximal oxygen demand and consequently MAOD. Otherwise, caffeine seems to have no clear positive effect on AC. PMID:28617848

Sources of Caffeine in Diets of US Children and Adults: Trends by Beverage Type and Purchase Location

PubMed Central

Drewnowski, Adam; Rehm, Colin D.

2016-01-01

New sources of caffeine, besides coffee and tea, have been introduced into the US food supply. Data on caffeine consumption age and purchase location can help guide public health policy. National Health and Nutrition Examination Surveys (NHANES) were used to estimate population-level caffeine intakes, using data from 24-h dietary recall. First, caffeine intakes by age-group and beverage type were estimated using the most recent 2011–2012 data (n = 7456). Second, fourteen years trends in caffeine consumption, overall and by beverage type, were evaluated for adults and children. Trend analyses were conducted by age groups. Last, trends in caffeine intakes by purchase location and beverage type were estimated. In 2011–2012, children aged four to eight years consumed the least caffeine (15 mg/day), and adults aged 51–70 years consumed the most (213 mg/day). The population mean (age ≥ four years) was 135 mg/day, driven largely by coffee (90 mg/day), tea (25 mg/day), and soda (21 mg/day). For the 14–19 years and 20–34 years age-groups, energy drinks contributed 6 mg/day (9.9%) and 5 mg/day (4.5%), respectively. The bulk of caffeine came from store-bought coffee and tea. Among both children and adults combined, caffeine intakes declined from 175 mg/day (1999–2000) to 142 mg/day (2011–2012), largely driven by a drop in caffeine from soda (41 mg/day to 21 mg/day). Store-bought coffee and tea remain principal drivers of caffeine intake in the US. Sodas and energy drinks make minor contributions to overall caffeine intakes. PMID:26978391

Efficacy of different caffeine concentrations on growth and ochratoxin A production by Aspergillus species.

PubMed

Akbar, A; Medina, A; Magan, N

2016-07-01

The objective of this study was to evaluate the effect of different caffeine concentrations (0-4%) on (i) lag phase prior to growth, (ii) growth rates and (iii) ochratoxin A (OTA) production by strains from the Aspergillus section Circumdati and Aspergillus section Nigri groups, isolated from coffee, when grown on a conducive medium at 0·98 water activity and 30°C. The lag phases prior to growth increased with caffeine concentration. A strain of Aspergillus niger and Aspergillus carbonarius were the most sensitive to caffeine with growth being inhibited by <1% caffeine. For strains of Aspergillus westerdijkiae, Aspergillus ochraceus and Aspergillus steynii, although growth was inhibited significantly, some growth (10-15% of controls) occurred in 4% caffeine. OTA production was significantly inhibited by only 0·5% caffeine for strains of A. westerdijkiae, A. niger and A. carbonarius. For A. steynii at least 1·5% caffeine was required to inhibit OTA production. In contrast, for the strain of A. ochraceus there was a stimulation of OTA at 3% with a reduction at 4% caffeine. These results are discussed in the context of the different concentrations of caffeine found in Arabica and Robusta coffee and the development of minimization strategies. Arabic (0·6%) and Robusta coffee (4%) have significantly different amounts of endogenous caffeine. The growth of six ochratoxigenic fungi which contaminate coffee with ochratoxin A (OTA) had differential tolerance/sensitivity to concentrations of caffeine in vitro in this range. However, low concentrations of caffeine (<0·5%) was inhibitory to OTA production. These results are discussed in the context of the potential for using such information for the design of minimization strategies to control mycotoxin production in such products. © 2016 The Society for Applied Microbiology.

The effects of caffeine on wound healing.

PubMed

Ojeh, Nkemcho; Stojadinovic, Olivera; Pastar, Irena; Sawaya, Andrew; Yin, Natalie; Tomic-Canic, Marjana

2016-10-01

The purine alkaloid caffeine is a major component of many beverages such as coffee and tea. Caffeine and its metabolites theobromine and xanthine have been shown to have antioxidant properties. Caffeine can also act as adenosine-receptor antagonist. Although it has been shown that adenosine and antioxidants promote wound healing, the effect of caffeine on wound healing is currently unknown. To investigate the effects of caffeine on processes involved in epithelialisation, we used primary human keratinocytes, HaCaT cell line and ex vivo model of human skin. First, we tested the effects of caffeine on cell proliferation, differentiation, adhesion and migration, processes essential for normal wound epithelialisation and closure. We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) proliferation assay to test the effects of seven different caffeine doses ranging from 0·1 to 5 mM. We found that caffeine restricted cell proliferation of keratinocytes in a dose-dependent manner. Furthermore, scratch wound assays performed on keratinocyte monolayers indicated dose-dependent delays in cell migration. Interestingly, adhesion and differentiation remained unaffected in monolayer cultures treated with various doses of caffeine. Using a human ex vivo wound healing model, we tested topical application of caffeine and found that it impedes epithelialisation, confirming in vitro data. We conclude that caffeine, which is known to have antioxidant properties, impedes keratinocyte proliferation and migration, suggesting that it may have an inhibitory effect on wound healing and epithelialisation. Therefore, our findings are more in support of a role for caffeine as adenosine-receptor antagonist that would negate the effect of adenosine in promoting wound healing. © 2014 The Authors. International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

A double-blind, placebo-controlled study evaluating the effects of caffeine and L-theanine both alone and in combination on cerebral blood flow, cognition and mood.

PubMed

Dodd, F L; Kennedy, D O; Riby, L M; Haskell-Ramsay, C F

2015-07-01

Evidence suggests interactive effects of the tea components caffeine and L-theanine on behaviour, yet no data exists exploring the impact of the two on cerebral blood flow (CBF). The current placebo-controlled, double-blind, counterbalanced, crossover study examined the effects of caffeine and L-theanine on CBF and extended previous cognitive and mood findings by using lower doses than previous studies of a similar methodology, which more closely reflect the ratios present in tea. Twelve habitual consumers and 12 non-habitual consumers of caffeine each received 75 mg caffeine, 50 mg L-theanine, 75 mg caffeine plus 50 mg L-theanine, and placebo in a counterbalanced order across four separate visits. CBF was measured via near-infrared spectroscopy with cognition and mood assessed at baseline and 30 min post-dose. Salivary caffeine and peripheral haemodynamics were co-monitored. Caffeine reduced oxygenated haemoglobin (oxy-Hb), increased deoxygenated haemoglobin (deoxy-Hb), improved performance on attention tasks and increased overall mood ratings. Increases in deoxy-Hb following caffeine were more pronounced in non-consumers. Some evidence for increased deoxy-Hb remained when caffeine was combined with L-theanine, but this effect was attenuated and the effects of caffeine on oxy-Hb, cognition and mood were eradicated. Combining L-theanine with caffeine, at levels and ratios equivalent to one to two cups of tea, eliminated the vasoconstrictive effect and behavioural effects of caffeine. This supports previous findings of an interaction between these substances, despite a lack of effects of L-theanine in isolation. However, at the levels tested here, this did not lead to a positive impact on behaviour.

Impact of caffeine and coffee on our health.

PubMed

Gonzalez de Mejia, Elvira; Ramirez-Mares, Marco Vinicio

2014-10-01

Coffee is the most frequently consumed caffeine-containing beverage. The caffeine in coffee is a bioactive compound with stimulatory effects on the central nervous system and a positive effect on long-term memory. Although coffee consumption has been historically linked to adverse health effects, new research indicates that coffee consumption may be beneficial. Here we discuss the impact of coffee and caffeine on health and bring attention to the changing caffeine landscape that includes new caffeine-containing energy drinks and supplements, often targeting children and adolescents. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sensitivity of BN nano-cages to caffeine and nicotine molecules

NASA Astrophysics Data System (ADS)

Soltani, Alireza; Baei, Mohammad T.; Tazikeh Lemeski, E.; Shahini, Malihe

2014-12-01

Adsorption of caffeine and nicotine molecules over B12N12 and B16N16 nano-cages were investigated by using first-principles calculations to define whether BN nano-cages are applicable for filtering or sensing caffeine and nicotine molecules. The chemisorption energy of nicotine molecule on BN nano-cages is very stronger than caffeine molecule. Upon the adsorption of caffeine and nicotine molecules, the electronic properties of the BN nano-cages can be significantly changed, being too much sensitized on the caffeine and nicotine adsorptions.

Caffeine Intake from Food and Beverage Sources and Trends among Children and Adolescents in the United States: Review of National Quantitative Studies from 1999 to 201112345

PubMed Central

Ahluwalia, Namanjeet; Herrick, Kirsten

2015-01-01

There is increasing concern about potential adverse effects of caffeine in children. Our understanding of caffeine intake relies on studies dating to the late 1990s. This article synthesizes information from national studies since then to describe caffeine consumption, its association with sociodemographic factors, key dietary sources including caffeine-containing energy drinks (CCEDs), and trends in caffeine intake and sources among US children. Findings from the Kanter Worldpanel (KWP) Beverage Consumption Panel and the NHANES showed that caffeine consumption prevalence was generally consistent across studies and over time; more than one-half of 2- to 5-y-olds and ∼75% of older children (>5 y) consumed caffeine. The usual intakes of caffeine were 25 and 50 mg/d for children and adolescents aged 2–11 and 12–17 y, respectively (NHANES 2007–2010). Caffeine consumption correlated with age and was higher in non-Hispanic white children. The key sources of caffeine were soda and tea as well as flavored dairy (for children aged <12 y) and coffee (for those aged ≥12 y). The frequency of CCED use varied (2–30%) depending on study setting, methods, and demographic characteristics. A statistically significant but small decline in caffeine intake was noted in children overall during the 10- to 12-y period examined; intakes remained stable among older children (≥12 y). A significant increasing trend in CCED and coffee consumption and a decline in soda intake were noted (1999–2010). In 2009–2010, 10% of 12- to 19-y-olds and 10–25% of caffeine consumers (aged 12–19 y) had intakes exceeding Canadian maximal guidelines. Continued monitoring can help better understand changes in caffeine consumption patterns of youth. PMID:25593149

Acute Ingestion of Caffeinated Chewing Gum Improves Repeated Sprint Performance of Team Sport Athletes With Low Habitual Caffeine Consumption.

PubMed

Evans, Mark; Tierney, Peter; Gray, Nicola; Hawe, Greg; Macken, Maria; Egan, Brendan

2018-04-23

The effects of acute ingestion of caffeine on short-duration high-intensity performance are equivocal, while studies of novel modes of delivery and the efficacy of low doses of caffeine are warranted. The aims of the present study were to investigate the effect of acute ingestion of caffeinated chewing gum on repeated sprint performance (RSP) in team sport athletes, and whether habitual caffeine consumption alters the ergogenic effect, if any, on RSP. A total of 18 male team sport athletes undertook four RSP trials using a 40-m maximum shuttle run test, which incorporates 10 × 40-m sprints with 30 s between the start of each sprint. Each participant completed two familiarization sessions, followed by caffeine (CAF; caffeinated chewing gum; 200 mg caffeine) and placebo (PLA; noncaffeinated chewing gum) trials in a randomized, double-blind manner. RSP, assessed by sprint performance decrement (%), did not differ (p = .209; effect size = 0.16; N = 18) between CAF (5.00 ± 2.84%) and PLA (5.43 ± 2.68%). Secondary analysis revealed that low habitual caffeine consumers (<40 mg/day, n = 10) experienced an attenuation of sprint performance decrement during CAF relative to PLA (5.53 ± 3.12% vs. 6.53 ± 2.91%, respectively; p = .049; effect size = 0.33); an effect not observed in moderate/high habitual caffeine consumers (>130 mg/day, n = 6; 3.98 ± 2.57% vs. 3.80 ± 1.79%, respectively; p = .684; effect size = 0.08). The data suggest that a low dose of caffeine in the form of caffeinated chewing gum attenuates the sprint performance decrement during RSP by team sport athletes with low, but not moderate-to-high, habitual consumption of caffeine.

Increased DNA methylation of scavenger receptor class B type I contributes to inhibitory effects of prenatal caffeine ingestion on cholesterol uptake and steroidogenesis in fetal adrenals

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

Wu, Dong-Mei; He, Zheng; Ma, Liang-Peng

Steroid hormones synthesized from cholesterol in the fetal adrenal are crucial for fetal development. We have observed the inhibited fetal adrenal corticosterone synthesis and increased intrauterine growth retardation (IUGR) rate in rats under prenatal caffeine ingestion. The aim of this study is to evaluate the effects of prenatal caffeine ingestion on cholesterol supply in fetal adrenal steroidogenesis in rats and explore the underlying epigenetic mechanisms. Pregnant Wistar rats were treated with 60 mg/kg·d caffeine from gestational day (GD) 7 to GD17. Histological changes of fetal adrenals and increased IUGR rates were observed in the caffeine group. There were significantly decreasedmore » steroid hormone contents and cholesterol supply in caffeine-treated fetal adrenals. Data from the gene expression array suggested that prenatal caffeine ingestion caused increased expression of genes related to DNA methylation and decreased expression of genes related to cholesterol uptake. The following conjoint analysis of DNA methylation array with these differentially expressed genes suggested that scavenger receptor class B type I (SR-BI) may play an important role in caffeine-induced cholesterol supply deficiency. Moreover, real-time RT-PCR and immunohistochemical detection certified the inhibitory effects of caffeine on both mRNA expression and protein expression of SR-BI in the fetal adrenal. And the increased DNA methylation frequency in the proximal promoter of SR-BI was confirmed by bisulfite-sequencing PCR. In conclusion, prenatal caffeine ingestion can induce DNA hypermethylation of the SR-BI promoter in the rat fetal adrenal. These effects may lead to decreased SR-BI expression and cholesterol uptake, which inhibits steroidogenesis in the fetal adrenal. - Highlights: • Prenatal caffeine ingestion inhibits steroid hormone production in the fetal adrenal. • Prenatal caffeine ingestion inhibits cholesterol uptake in the fetal adrenal. • Prenatal caffeine ingestion inhibits the expression of SR-BI. • Prenatal caffeine ingestion induces increased DNA methylation of SR-BI promoter.« less

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.

Caffeine Consuming Children and Adolescents Show Altered Sleep Behavior and Deep Sleep

PubMed Central

Aepli, Andrina; Kurth, Salome; Tesler, Noemi; Jenni, Oskar G.; Huber, Reto

2015-01-01

Caffeine is the most commonly ingested psychoactive drug worldwide with increasing consumption rates among young individuals. While caffeine leads to decreased sleep quality in adults, studies investigating how caffeine consumption affects children’s and adolescents’ sleep remain scarce. We explored the effects of regular caffeine consumption on sleep behavior and the sleep electroencephalogram (EEG) in children and adolescents (10–16 years). While later habitual bedtimes (Caffeine 23:14 ± 11.4, Controls 22:17 ± 15.4) and less time in bed were found in caffeine consumers compared to the control group (Caffeine 08:10 ± 13.3, Controls 09:03 ± 16.1), morning tiredness was unaffected. Furthermore, caffeine consumers exhibited reduced sleep EEG slow-wave activity (SWA, 1–4.5 Hz) at the beginning of the night compared to controls (20% ± 9% average reduction across all electrodes and subjects). Comparable reductions were found for alpha activity (8.25–9.75 Hz). These effects, however, disappeared in the morning hours. Our findings suggest that caffeine consumption in adolescents may lead to later bedtimes and reduced SWA, a well-established marker of sleep depth. Because deep sleep is involved in recovery processes during sleep, further research is needed to understand whether a caffeine-induced loss of sleep depth interacts with neuronal network refinement processes that occur during the sensitive period of adolescent development. PMID:26501326

Differential concentration-specific effects of caffeine on cell viability, oxidative stress, and cell cycle in pulmonary oxygen toxicity in vitro

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

Tiwari, Kirti Kumar; Chu, Chun; Couroucli, Xanthi

Highlights: • Caffeine at 0.05 mM decreases oxidative stress in hyperoxia. • Caffeine at 1 mM decreases cell viability, increases oxidative stress in hyperoxia. • Caffeine at 1 but not 0.05 mM, abrogates hyperoxia-induced G2/M arrest. - Abstract: Caffeine is used to prevent bronchopulmonary dysplasia (BPD) in premature neonates. Hyperoxia contributes to the development of BPD, inhibits cell proliferation and decreases cell survival. The mechanisms responsible for the protective effect of caffeine in pulmonary oxygen toxicity remain largely unknown. A549 and MLE 12 pulmonary epithelial cells were exposed to hyperoxia or maintained in room air, in the presence of differentmore » concentrations (0, 0.05, 0.1 and 1 mM) of caffeine. Caffeine had a differential concentration-specific effect on cell cycle progression, oxidative stress and viability, with 1 mM concentration being deleterious and 0.05 mM being protective. Reactive oxygen species (ROS) generation during hyperoxia was modulated by caffeine in a similar concentration-specific manner. Caffeine at 1 mM, but not at the 0.05 mM concentration decreased the G2 arrest in these cells. Taken together this study shows the novel funding that caffeine has a concentration-specific effect on cell cycle regulation, ROS generation, and cell survival in hyperoxic conditions.« less

Caffeine prevents weight gain and cognitive impairment caused by a high-fat diet while elevating hippocampal BDNF.

PubMed

Moy, Gregory A; McNay, Ewan C

2013-01-17

Obesity, high-fat diets, and subsequent type 2 diabetes (T2DM) are associated with cognitive impairment. Moreover, T2DM increases the risk of Alzheimer's disease (AD) and leads to abnormal elevation of brain beta-amyloid levels, one of the hallmarks of AD. The psychoactive alkaloid caffeine has been shown to have therapeutic potential in AD but the central impact of caffeine has not been well-studied in the context of a high-fat diet. Here we investigated the impact of caffeine administration on metabolism and cognitive performance, both in control rats and in rats placed on a high-fat diet. The effects of caffeine were significant: caffeine both (i) prevented the weight-gain associated with the high-fat diet and (ii) prevented cognitive impairment. Caffeine did not alter hippocampal metabolism or insulin signaling, likely because the high-fat-fed animals did not develop full-blown diabetes; however, caffeine did prevent or reverse a decrease in hippocampal brain-derived neurotrophic factor (BDNF) seen in high-fat-fed animals. These data confirm that caffeine may serve as a neuroprotective agent against cognitive impairment caused by obesity and/or a high-fat diet. Increased hippocampal BDNF following caffeine administration could explain, at least in part, the effects of caffeine on cognition and metabolism. Copyright © 2012 Elsevier Inc. All rights reserved.

Maternal caffeine consumption and risk of cardiovascular malformations.

PubMed

Browne, Marilyn L; Bell, Erin M; Druschel, Charlotte M; Gensburg, Lenore J; Mitchell, Allen A; Lin, Angela E; Romitti, Paul A; Correa, Adolfo

2007-07-01

The physiologic effects and common use of caffeine during pregnancy call for examination of maternal caffeine consumption and risk of birth defects. Epidemiologic studies have yielded mixed results, but such studies have grouped etiologically different defects and have not evaluated effect modification. The large sample size and precise case classification of the National Birth Defects Prevention Study allowed us to examine caffeine consumption and specific cardiovascular malformation (CVM) case groups. We studied consumption of caffeinated coffee, tea, soda, and chocolate to estimate total caffeine intake and separately examined exposure to each caffeinated beverage. Smoking, alcohol, vasoactive medications, folic acid supplement use, and infant gender were evaluated for effect modification. Maternal interview reports for 4,196 CVM case infants overall and 3,957 control infants were analyzed. We did not identify any significant positive associations between maternal caffeine consumption and CVMs. For tetralogy of Fallot, nonsignificant elevations in risk were observed for moderate (but not high) caffeine intake overall and among nonsmokers (ORs of 1.3 to 1.5). Risk estimates for both smoking and consuming caffeine were less than the sum of the excess risks for each exposure. We observed an inverse trend between coffee intake and risk of atrial septal defect; however, this single significant pattern of association might have been a chance finding. Our study found no evidence for an appreciable teratogenic effect of caffeine with regard to CVMs. (c) 2007 Wiley-Liss, Inc.

Acute personalized habitual caffeine doses improve attention and have selective effects when considering the fractionation of executive functions.

PubMed

Lanini, Juliana; Galduróz, José Carlos Fernandes; Pompéia, Sabine

2016-01-01

Caffeine is widely used, often consumed with food, and improves simple and complex/executive attention under fasting conditions. We investigated whether these cognitive effects are observed when personalized habitual doses of caffeine are ingested by caffeine consumers, whether they are influenced by nutriments and if various executive domains are susceptible to improvement. This was a double-blind, placebo-controlled study including 60 young, healthy, rested males randomly assigned to one of four treatments: placebo fasting, caffeine fasting, placebo meal and caffeine meal. Caffeine doses were individualized for each participant based on their self-reported caffeine consumption at the time of testing (morning). The test battery included measures of simple and sustained attention, executive domains (inhibiting, updating, shifting, dual tasking, planning and accessing long-term memory), control measures of subjective alterations, glucose and insulin levels, skin conductance, heart rate and pupil dilation. Regardless of meal intake, acute habitual doses of caffeine decreased fatigue, and improved simple and sustained attention and executive updating. This executive effect was not secondary to the habitual weekly dose consumed, changes in simple and sustained attention, mood, meal ingestion and increases in cognitive effort. We conclude that the morning caffeine "fix" has positive attentional effects and selectively improved executive updating whether or not caffeine is consumed with food. Copyright © 2015 John Wiley & Sons, Ltd.

Dose-response study of caffeine effects on cerebral functional activity with a specific focus on dependence.

PubMed

Nehlig, A; Boyet, S

2000-03-06

Caffeine is a behavioral stimulant consumed on a worldwide basis. The question of whether caffeine is addictive has been debated for over a decade. Caffeine acts as a mild positive reinforcer but is not consistently self-administered in humans or animals. With [14C]2-deoxyglucose autoradiography, we studied the effects of increasing doses of caffeine on cerebral glucose utilization in rats. At 1 mg/kg, caffeine activated the caudate nucleus mediating locomotion, and the raphe nuclei and locus coeruleus involved with mood and sleep. After 2.5 and 5 mg/kg caffeine, metabolic activation spread to other components of the nigrostriatal dopaminergic system, the thalamus, ventral tegmental area and amygdala. The functional activation of the shell of the nucleus accumbens, an area involved in addiction and reward, was only induced by the highest dose of caffeine, 10 mg/kg. At this dose, the activation of the shell of the nucleus accumbens occurred together with that of the core of the nucleus accumbens and of most other brain regions. These data correlate well with the known sensitivity of locomotion, mood and sleep to low doses of caffeine. They also show that low doses of caffeine which reflect the usual human level of consumption fail to activate reward circuits in the brain and thus provide functional evidence of the very low addictive potential of caffeine.

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.

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.

Caffeine: Friend or Foe?

PubMed

Doepker, Candace; Lieberman, Harris R; Smith, Andrew Paul; Peck, Jennifer D; El-Sohemy, Ahmed; Welsh, Brian T

2016-01-01

The debate on the safety of and regulatory approaches for caffeine continues among various stakeholders and regulatory authorities. This decision-making process comes with significant challenges, particularly when considering the complexities of the available scientific data, making the formulation of clear science-based regulatory guidance more difficult. To allow for discussions of a number of key issues, the North American Branch of the International Life Sciences Institute (ILSI) convened a panel of subject matter experts for a caffeine-focused session entitled "Caffeine: Friend or Foe?," which was held during the 2015 ILSI Annual Meeting. The panelists' expertise covered topics ranging from the natural occurrence of caffeine in plants and interindividual metabolism of caffeine in humans to specific behavioral, reproductive, and cardiovascular effects related to caffeine consumption. Each presentation highlighted the potential risks, benefits, and challenges that inform whether caffeine exposure warrants concern. This paper aims to summarize the key topics discussed during the session.

Fatal caffeine overdose: a case report and review of literature.

PubMed

Jabbar, Seema B; Hanly, Mark G

2013-12-01

Caffeine is a central nervous system stimulant that is consumed by large numbers of people on a routine basis, usually in the form of coffee or tea. However, if consumed in high doses, this xanthine alkaloid is profoundly toxic and can result in death. Increasingly being sold as a dietary supplement, many people, particularly those in the health and fitness community, where it is touted as a fitness and muscle building aid, are consuming caffeine anhydrous on a daily basis. We report a case of fatal caffeine overdose in a 39-year-old man resulting from the self-administered ingestion of approximately 12 g of pure caffeine anhydrous. Autopsy blood caffeine levels were 350 mg/L. We recommend mandated labeling of pure caffeine anhydrous, highlighting the toxicity risk of ingesting this chemical; and we recommend ensuring that caffeine levels are included in the comprehensive forensic toxicology panel performed on all cases.

Co-occurrent use of cigarettes, alcohol, and caffeine in a retired military population.

PubMed

Talcott, G W; Poston, W S; Haddock, C K

1998-03-01

Previous studies have linked the use of caffeine, nicotine, and alcohol to health complications and have also found that the use of these substances significantly covary. Given the prevalence of health problems of older adults, it is surprising that no studies to date have examined the co-occurrent use of alcohol, caffeine, and nicotine in a senior population. This investigation evaluated the co-occurrent use of cigarettes, caffeine, and alcohol in a community sample of older Americans. Respondents (1,095 women and 1,371 men) completed a questionnaire examining their use of caffeine, nicotine, and alcohol. This study replicated earlier findings that tobacco, caffeine, and alcohol use co-occur and that there are consistent use patterns for these substances. The results suggest that health organizations could better target services by prescreening for smoking, alcohol, and caffeine use and possibly targeting smokers and ex-smokers for potentially problematic use patterns of caffeine and alcohol.

[Effect of caffeine on myocardial blood flow during pharmacological vasodilation].

PubMed

Wielepp, J P; Fricke, E; Horstkotte, D; Burchert, W

2005-02-01

Pharmacologic stress with adenosine is frequently used for noninvasive detection of coronary artery disease. Dietary intake of caffeinated food, beverages or medications might alter adenosine-induced hyperemic blood flow, thereby compromising the diagnostic sensitivity of adenosine stress testing. In this case we report on a male patient with CAD. Myocardial blood flow at rest and during adenosine-induced hyperemia 2 hours after consumption of decaffeinated coffee and again without caffeine intake were quantified by ammonia PET. After caffeine intake there was a clearly diminished increase of myocardial blood flow during adenosine. The average coronary flow reserve in the myocardium was 1.3 after caffeine. In the baseline study without caffeine the coronary flow reserve has been improved to 2.3. Caffeine intake alters the coronary vasodilatory capacity. These findings emphasize the importance of carefully screening patients for intake of caffeinated food prior to adenosine stress testing.

Caffeine consumption.

PubMed

Barone, J J; Roberts, H R

1996-01-01

Scientific literature cites a wide range of values for caffeine content in food products. The authors suggest the following standard values for the United States: coffee (5 oz) 85 mg for ground roasted coffee, 60 mg for instant and 3 mg for decaffeinated; tea (5 oz): 30 mg for leaf/bag and 20 mg for instant; colas: 18 mg/6 oz serving; cocoa/hot chocolate: 4 mg/5 oz; chocolate milk: 4 mg/6 oz; chocolate candy: 1.5-6.0 mg/oz. Some products from the United Kingdom and Denmark have higher caffeine content. Caffeine consumption survey data are limited. Based on product usage and available consumption data, the authors suggest a mean daily caffeine intake for US consumers of 4 mg/kg. Among children younger than 18 years of age who are consumers of caffeine-containing foods, the mean daily caffeine intake is about 1 mg/kg. Both adults and children in Denmark and UK have higher levels of caffeine intake.

Caffeine: implications of recent research for clinical practice.

PubMed

Wells, Susan J

1984-07-01

Caffeine is a central nervous system stimulant that has come under increasing scrutiny due to its effects on the health and mental health of those who consume it. This article summarizes the physiological effects of caffeine, reviews recent research on behavioral and mood changes associated with consumption, and discusses clinical implications for the mental health professional. Data on caffeine consumption and principal sources of caffeine are outlined.

Intake of Caffeinated Soft Drinks before and during Pregnancy, but Not Total Caffeine Intake, Is Associated with Increased Cerebral Palsy Risk in the Norwegian Mother and Child Cohort Study.

PubMed

Tollånes, Mette C; Strandberg-Larsen, Katrine; Eichelberger, Kacey Y; Moster, Dag; Lie, Rolv Terje; Brantsæter, Anne Lise; Meltzer, Helle Margrete; Stoltenberg, Camilla; Wilcox, Allen J

2016-09-01

Postnatal administration of caffeine may reduce the risk of cerebral palsy (CP) in vulnerable low-birth-weight neonates. The effect of antenatal caffeine exposure remains unknown. We investigated the association of intake of caffeine by pregnant women and risk of CP in their children. The study was based on The Norwegian Mother and Child Cohort Study, comprising >100,000 live-born children, of whom 222 were subsequently diagnosed with CP. Mothers reported their caffeine consumption in questionnaires completed around pregnancy week 17 (102,986 mother-child pairs), week 22 (87,987 mother-child pairs), and week 30 (94,372 mother-child pairs). At week 17, participants were asked about present and prepregnancy consumption. We used Cox regression models to estimate associations between exposure [daily servings (1 serving = 125 mL) of caffeinated coffee, tea, and soft drinks and total caffeine consumption] and CP in children, with nonconsumers as the reference group. Models included adjustment for maternal age and education, medically assisted reproduction, and smoking, and for each source of caffeine, adjustments were made for the other sources. Total daily caffeine intake before and during pregnancy was not associated with CP risk. High consumption (≥6 servings/d) of caffeinated soft drinks before pregnancy was associated with an increased CP risk (HR: 1.9; 95% CI: 1.2, 3.1), and children of women consuming 3-5 daily servings of caffeinated soft drinks during pregnancy weeks 13-30 also had an increased CP risk (HR: 1.7; 95% CI: 1.1, 2.8). A mean daily consumption of 51-100 mg caffeine from soft drinks during the first half of pregnancy was associated with a 1.9-fold increased risk of CP in children (HR: 1.9; 95% CI: 1.1, 3.6). Maternal total daily caffeine consumption before and during pregnancy was not associated with CP risk in children. The observed increased risk with caffeinated soft drinks warrants further investigation. © 2016 American Society for Nutrition.

Naturalistic Effects of Five Days of Bedtime Caffeine Use on Sleep, Next-Day Cognitive Performance, and Mood

PubMed Central

Tiplady, Brian; Priestley, Caroline M.; Rogers, Peter J.

2014-01-01

Background: Disruptive effects of caffeine on sleep have previously been reported, although measures of next-day mood and performance have rarely been included. The present study aims to evaluate the effects of caffeine on sleep and associated next-day effects in a naturalistic field setting. Methods: Nineteen participants (daily caffeine intake 0–141 mg), assessed as good sleepers, took part in a randomized, placebo-controlled, double-blind, 2-week crossover study to assess the effects of bedtime caffeine use (250 mg) on sleep and next-day cognitive performance and mood, which were assessed on a mobile phone in the morning and afternoon. Sleep was assessed objectively (actiwatch) and subjectively (sleep diary). Results: Caffeine's effects on sleep were largely restricted to the first day of administration, with actigraphically measured reduced sleep efficiency, increased activity score and fragmentation index, decreased self-rated sleep quality, and an increased occurrence of participants waking early; only decreased sleep efficiency remained over the week. Effects on next-day performance and mood were evident over the whole week, although despite disrupting sleep, accuracy on a working memory task was higher after caffeine than placebo administration. Conclusions: Caffeine disrupted sleep, although when assessing next-day performance, which may have been affected by the presence of residual caffeine, performance appeared better after caffeine compared to placebo, although this was most likely due to prevention of the effects of overnight withdrawal from caffeine rather than representing a net benefit. Furthermore, partial tolerance developed to the effects of caffeine on sleep. PMID:24868491

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.

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.