Wandersee, Nancy J; Maciaszek, Jamie L; Giger, Katie M; Hanson, Madelyn S; Zheng, Suilan; Guo, YiHe; Mickelson, Barbara; Hillery, Cheryl A; Lykotrafitis, George; Low, Philip S; Hogg, Neil
Humans and mice with sickle cell disease (SCD) have rigid red blood cells (RBCs). Omega-3 fatty acids, such as docosahexanoic acid (DHA), may influence RBC deformability via incorporation into the RBC membrane. In this study, sickle cell (SS) mice were fed natural ingredient rodent diets supplemented with 3% DHA (DHA diet) or a control diet matched in total fat (CTRL diet). After 8weeks of feeding, we examined the RBCs for: 1) stiffness, as measured by atomic force microscopy; 2) deformability, as measured by ektacytometry; and 3) percent irreversibly sickled RBCs on peripheral blood smears. Using atomic force microscopy, it is found that stiffness is increased and deformability decreased in RBCs from SS mice fed CTRL diet compared to wild-type mice. In contrast, RBCs from SS mice fed DHA diet had markedly decreased stiffness and increased deformability compared to RBCs from SS mice fed CTRL diet. Furthermore, examination of peripheral blood smears revealed less irreversibly sickled RBCs in SS mice fed DHA diet as compared to CTRL diet. In summary, our findings indicate that DHA supplementation improves RBC flexibility and reduces irreversibly sickled cells by 40% in SS mice. These results point to potential therapeutic benefits of dietary omega-3 fatty acids in SCD.
Hajjaji, Nawale; Schubnel, Valérie; Bougnoux, Philippe
Docosahexaenoic acid (DHA), upon incorporation into tumor tissue, has the potential to sensitize tumors to the effects of chemotherapy or radiation therapy. Although DHA has usually been supplied to tumor tissue in the diet, appropriate dietary conditions required to obtain optimal tumor levels have not been established. Hence, we studied mammary tumor tissue responses in rats fed various durations and doses of DHA. Rats fed a palm-oil enriched diet (diet 0) were switched to diets providing either 0.8 g DHA/d (diet 1) or 1.5 g DHA/d (diet 2). Tumor tissue fatty acid composition was analysed at baseline (diet 0), at weeks 1, 4 and 9 during diet 1 and at week 4 during diet 2. Dietary DHA supplementation differentially increased DHA within phospholipids (PL) and triacylglycerol (TAG) fractions in tumors. DHA level equilibrated between 2 and 4 weeks in PL while DHA increase was more progressive in TAG and did not reach a steady state. A higher dose of DHA further increased DHA content in tumor PL and TAG (P = 0.018 and P < 0.001 respectively). DHA concentration in plasma PL was positively correlated with DHA in tumor PL (r = 0.72; P = 0.0003) and TAG (r = 0.64; P = 0.003). We conclude that dietary DHA supplementation enhances tumor content of DHA in a time- and dose-dependent manner, and that DHA level in plasma PL could be used as a proxy for tumor DHA. These findings have implications for dietary DHA supplementations in cancer patients. PMID:21638063
Walker, Celia G; West, Annette L; Browning, Lucy M; Madden, Jackie; Gambell, Joanna M; Jebb, Susan A; Calder, Philip C
Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are increased in plasma lipids and blood cell membranes in response to supplementation. Whilst arachidonic acid (AA) is correspondingly decreased, the effect on other fatty acids (FA) is less well described and there may be site-specific differences. In response to 12 months EPA + DHA supplementation in doses equivalent to 0-4 portions of oily fish/week (1 portion: 3.27 g EPA+DHA) multinomial regression analysis was used to identify important FA changes for plasma phosphatidylcholine (PC), cholesteryl ester (CE) and triglyceride (TAG) and for blood mononuclear cells (MNC), red blood cells (RBC) and platelets (PLAT). Dose-dependent increases in EPA + DHA were matched by decreases in several n-6 polyunsaturated fatty acids (PUFA) in PC, CE, RBC and PLAT, but were predominantly compensated for by oleic acid in TAG. Changes were observed for all FA classes in MNC. Consequently the n-6:n-3 PUFA ratio was reduced in a dose-dependent manner in all pools after 12 months (37%-64% of placebo in the four portions group). We conclude that the profile of the FA decreased in exchange for the increase in EPA + DHA following supplementation differs by FA pool with implications for understanding the impact of n-3 PUFA on blood lipid and blood cell biology.
Rogers, Lynette K.; Valentine, Christina J.; Keim, Sarah A.
Dietary supplementation with (ω)-3 long chain fatty acids including docosahexaenoic acid (DHA) has increased in popularity in recent years and adequate DHA supplementation during pregnancy and early childhood is of clinical importance. Some evidence has been built for the neuro-cognitive benefits of supplementation with long chain polyunsaturated fatty acids (LCPUFA) such as DHA during pregnancy; however, recent data indicate that the anti-inflammatory properties may be of at least equal significance. Adequate DHA availability in the fetus/infant optimizes brain and retinal maturation in part by influencing neurotransmitter pathways. The anti-inflammatory properties of LCPUFA are largely mediated through modulation of signaling either directly through binding to receptors or through changes in lipid raft formation and receptor presentation. Our goal is to review the current findings on DHA supplementation, specifically in pregnancy and infant neurodevelopment, as a pharmacologic agent with both preventative and therapeutic value. Given the overall benefits of DHA, maternal and infant supplementation may improve neurological outcomes especially in vulernable populations. However, optimal composition of the supplement and dosing and treatment strategies still need to be determined to lend support for routine supplementation. PMID:23266567
Clayton, Edward H; Lamb, Tracy A; Refshauge, Gordon; Kerr, Matthew J; Bailes, Kristy L; Ponnampalam, Eric N; Friend, Michael A; Hopkins, David L
Algae high in docosahexaenoic acid (DHA) may provide a source of long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) for inclusion in the diet of lambs to improve the LCn-3PUFA status of meat. The effect of background LCn-3PUFA status on the metabolism of high DHA algae is, however, unknown. The aim of the current study was to determine whether the response to a high in DHA algae supplement fed to lambs for six weeks prior to slaughter was mediated by a maternal periconceptional diet. Forty Poll Dorset × Border Leicester × Merino weaner lambs were allocated to receive either a ration based on oat grain, lupin grain, and chopped lucerne (control) or the control ration with DHA-Gold™ algae included at 1.92 % DM (Algae) based on whether the dams of lambs had previously been fed a diet high in n-3 or n-6 around conception. LCn-3PUFA concentration was determined in plasma and red blood cells (RBC) prior to and following feeding. The concentrations of EPA and DHA in the plasma and RBC of lambs receiving the control ration were significantly (p < 0.001) lower when lambs received the ration for 14 days compared with pre-feeding concentrations. The concentrations of EPA and DHA were also significantly (p < 0.001) higher when lambs consumed the Algae ration compared with the control ration for 42 days. The increase in EPA and DHA was, however, significantly (p < 0.05) lower if lamb dams had previously been fed a diet high in n-6 at conception. Assessing the previous nutrition and n-3 status of lambs may allow producers to more accurately predict the likely response to supplements high in LCn-3PUFA, particularly, DHA.
Hoffman, Dennis; Ziegler, Ekhard; Mitmesser, Susan H; Harris, Cheryl L; Diersen-Schade, Deborah A
Healthy term infants (n = 244) were randomized to receive: (1) control, soy-based formula without supplementation or (2) docosahexaenoic acid-arachidonic acid (DHA + ARA), soy-based formula supplemented with at least 17 mg DHA/100 kcal (from algal oil) and 34 mg ARA/100 kcal (from fungal oil) in a double-blind, parallel group trial to evaluate safety, benefits, and growth from 14 to 120 days of age. Anthropometric measurements were taken at 14, 30, 60, 90, and 120 days of age and 24-h dietary and tolerance recall were recorded at 30, 60, 90, and 120 days of age. Adverse events were recorded throughout the study. Blood samples were drawn from subsets of 25 infants in each group. Capillary column gas chromatography was used to analyze the percentages of fatty acids in red blood cell (RBC) lipids and plasma phospholipids. Compared with the control group, percentages of fatty acids such as DHA and ARA in total RBC and plasma phospholipids were significantly higher in infants in the DHA + ARA group at 120 days of age (P < 0.001). Growth rates did not differ significantly between feeding groups at any assessed time point. Supplementation did not affect the tolerance of formula or the incidence of adverse events. Feeding healthy term infants soy-based formula supplemented with DHA and ARA from single cell oil sources at concentrations similar to human milk significantly increased circulating levels of DHA and ARA when compared with the control group. Both formulas supported normal growth and were well tolerated.
Our previous study with docosahexaenoic acid (DHA) supplementation to hypertriglyceridemic men showed that DHA reduced several risk factors for CVD, including the plasma concentration of inflammatory markers. To determine the effect of DHA supplementation on the global gene expression pattern, we pe...
Wu, Aiguo; Ying, Zhe; Gomez-Pinilla, Fernando
The pathology of traumatic brain injury (TBI) is characterized by the decreased capacity of neurons to metabolize energy and sustain synaptic function, likely resulting in cognitive and emotional disorders. Based on the broad nature of the pathology, we have assessed the potential of the omega-3 fatty acid docosahexaenoic acid (DHA) to counteract the effects of concussive injury on important aspects of neuronal function and cognition. Fluid percussion injury (FPI) or sham injury was performed, and rats were then maintained on a diet high in DHA (1.2% DHA) for 12 days. We found that DHA supplementation, which elevates brain DHA content, normalized levels of brain-derived neurotrophic factor (BDNF), synapsin I (Syn-1), cAMP-responsive element-binding protein (CREB), and calcium/calmodulin-dependent kinase II (CaMKII), and improved learning ability in FPI rats. It is known that BDNF facilitates synaptic transmission and learning ability by modulating Syn-I, CREB, and CaMKII signaling. The DHA diet also counteracted the FPI-reduced manganese superoxide dismutase (SOD) and Sir2 (a NAD+-dependent deacetylase). Given the involvement of SOD and Sir2 in promoting metabolic homeostasis, DHA may help the injured brain by providing resistance to oxidative stress. Furthermore, DHA normalized levels of calcium-independent phospholipase A2 (iPLA2) and syntaxin-3, which may help preserve membrane homeostasis and function after FPI. The overall results emphasize the potential of dietary DHA to counteract broad and fundamental aspects of TBI pathology that may translate into preserved cognitive capacity.
Querques, Giuseppe; Benlian, Pascale; Chanu, Bernard; Leveziel, Nicolas; Coscas, Gabriel; Soubrane, Gisele; Souied, Eric H
Background: We analyzed the effects of a docosahexaenoic acid (DHA) supplementation in patients affected with late onset Stargardt disease (STGD). Methods: DHA (840 mg/day) was given to 20 STGD patients for six months. A complete ophthalmologic examination, including best-corrected visual acuity (BCVA) and multifocal electroretinogram (mfERG), was performed at inclusion day 0 (D0) and at month 6 (M6). Results: Overall, no statistical differences have been observed at M6 vs D0 as regards BCVA and mfERG (P > 0.05). Mild Improvement of BCVA and improvement of mfERG was noted in seven/40 eyes of four/20 patients. In the first patient, the peak of the a wave increased from 66 nV/deg2 to 75.4 nV/deg2 in the right eye (RE) and 24.5 nV/deg2 to 49.1 nV/deg2 in the left eye (LE). The peak of the b wave improved from 122 nV/deg2 to 157 nV/deg2 in the RE, and 102 nV/deg2 to 149 nV/deg2 in the LE. In the second patient peaks of the a and b waves respectively increased from 11.8 nV/deg2 to 72.1 nV/deg2 and 53 nV/deg2 to 185 nV/deg2 in the RE. In the third patient the peak of the a wave increased from 37 nV/deg2 to 43 nV/deg2 in the RE, and from 31 nV/deg2 to 45 nV/deg2 in the LE; the peak of the b wave improved from 70 nV/deg2 to 89 nV/deg2 in the RE, and from 101 nV/deg2 to 108 nV/deg2 in the LE. In the fourth patient, the peak of the a wave increased from 39 nV/deg2 to 42 nV/deg2 in the RE, and from 40 nV/deg2 to 43 nV/deg2 in the LE; the peak of the b wave improved from 86 nV/deg2 to 94 nV/deg2 in the RE, and from 87 nV/deg2 to 107 nV/deg2 in the LE. Conclusion: DHA seems to influence some functional parameters in patients affected with STGD. However, no short-term benefit should be expected from DHA supplementation. PMID:20668719
Modern humans have evolved with a staple source of preformed docosahexaenoic acid (DHA) in the diet. An important turning point in human evolution was the discovery of high-quality, easily digested nutrients from coastal seafood and inland freshwater sources. Multi-generational exploitation of seafood by shore-based dwellers coincided with the rapid expansion of grey matter in the cerebral cortex, which characterizes the modern human brain. The DHA molecule has unique structural properties that appear to provide optimal conditions for a wide range of cell membrane functions. This has particular implications for grey matter, which is membrane-rich tissue. An important metabolic role for DHA has recently been identified as the precursor for resolvins and protectins. The rudimentary source of DHA is marine algae; therefore it is found concentrated in fish and marine oils. Unlike the photosynthetic cells in algae and higher plants, mammalian cells lack the specific enzymes required for the de novo synthesis of alpha-linolenic acid (ALA), the precursor for all omega-3 fatty acid syntheses. Endogenous synthesis of DHA from ALA in humans is much lower and more limited than previously assumed. The excessive consumption of omega-6 fatty acids in the modern Western diet further displaces DHA from membrane phospholipids. An emerging body of research is exploring a unique role for DHA in neurodevelopment and the prevention of neuropsychiatric and neurodegenerative disorders. DHA is increasingly being added back into the food supply as fish oil or algal oil supplementation. PMID:22254110
Lei, Yang; Mayo, Matthew S; Carlson, Susan E; Gajewski, Byron J
Personalized medicine aims to match patient subpopulation to the most beneficial treatment. The purpose of this study is to design a prospective clinical trial in which we hope to achieve the highest level of confirmation in identifying and making treatment recommendations for subgroups, when the risk levels in the control arm can be ordered. This study was motivated by our goal to identify subgroups in a DHA (docosahexaenoic acid) supplementation trial to reduce preterm birth (gestational age<37 weeks) rate. We performed a meta-analysis to obtain informative prior distributions and simulated operating characteristics to ensure that overall Type I error rate was close to 0.05 in designs with three different models: independent, hierarchical, and dynamic linear models. We performed simulations and sensitivity analysis to examine the subgroup power of models and compared results to a chi-square test. We performed simulations under two hypotheses: a large overall treatment effect and a small overall treatment effect. Within each hypothesis, we designed three different subgroup effects scenarios where resulting subgroup rates are linear, flat, or nonlinear. When the resulting subgroup rates are linear or flat, dynamic linear model appeared to be the most powerful method to identify the subgroups with a treatment effect. It also outperformed other methods when resulting subgroup rates are nonlinear and the overall treatment effect is big. When the resulting subgroup rates are nonlinear and the overall treatment effect is small, hierarchical model and chi-square test did better. Compared to independent and hierarchical models, dynamic linear model tends to be relatively robust and powerful when the control arm has ordinal risk subgroups.
Doughman, Scott D; Krupanidhi, Srirama; Sanjeevi, Carani B
Long-chain EPA/DHA omega-3 fatty acid supplementation can be co-preventative and co-therapeutic. Current research suggests increasing accumulated long chain omega-3s for health benefits and as natural medicine in several major diseases. But many believe plant omega-3 sources are nutritionally and therapeutically equivalent to the EPA/DHA omega-3 in fish oil. Although healthy, precursor ALA bio-conversion to EPA is inefficient and production of DHA is nearly absent, limiting the protective value of ALA supplementation from flax-oil, for example. Along with pollutants certain fish acquire high levels of EPA/DHA as predatory species. However, the origin of EPA/DHA in aquatic ecosystems is algae. Certain microalgae produce high levels of EPA or DHA. Now, organically produced DHA-rich microalgae oil is available. Clinical trials with DHA-rich oil indicate comparable efficacies to fish oil for protection from cardiovascular risk factors by lowering plasma triglycerides and oxidative stress. This review discusses 1) omega-3 fatty acids in nutrition and medicine; 2) omega-3s in physiology and gene regulation; 3) possible protective mechanisms of EPA/DHA in major diseases such as coronary heart disease, atherosclerosis, cancer and type 2 diabetes; 4) EPA and DHA requirements considering fish oil safety; and 5) microalgae EPA and DHA-rich oils and recent clinical results.
Kim, Junhwan; Yin, Tai; Shinozaki, Koichiro; Lampe, Joshua W.; Becker, Lance B.
Accumulating evidence illustrates the beneficial effects of dietary docosahexaenoic acid (DHA) on cardiovascular diseases. However, its effects on cardiac arrest (CA) remain controversial in epidemiological studies and have not been reported in controlled animal studies. Here, we examined whether dietary DHA can improve survival, the most important endpoint in CA. Male Sprague-Dawley rats were randomized into two groups and received either a control diet or a DHA-supplemented diet for 7–8 weeks. Rats were then subjected to 20 min asphyxia-induced cardiac arrest followed by 30 min cardiopulmonary bypass resuscitation. Rat survival was monitored for additional 3.5 h following resuscitation. In the control group, 1 of 9 rats survived for 4 h, whereas 6 of 9 rats survived in the DHA-treated group. Surviving rats in the DHA-treated group displayed moderately improved hemodynamics compared to rats in the control group 1 h after the start of resuscitation. Rats in the control group showed no sign of brain function whereas rats in the DHA-treated group had recurrent seizures and spontaneous respiration, suggesting dietary DHA also protects the brain. Overall, our study shows that dietary DHA significantly improves rat survival following 20 min of severe CA. PMID:27811958
de Luis, Daniel; Domingo, Joan Carles; Izaola, Olatz; Casanueva, Felipe F; Bellido, Diego; Sajoux, Ignacio
A VLCK diet supplemented with DHA, commercially available, was tested against an isocaloric VLCK diet without DHA. The main purpose of this study was to compare the effect of DHA supplementation in classic cardiovascular risk factors, adipokine levels, and inflammation-resolving eicosanoids. A total of obese patients were randomized into two groups: a group supplemented with DHA (n = 14) (PnK-DHA group) versus a group with an isocaloric diet free of supplementation (n = 15) (control group). The follow-up period was 6 months. The average weight loss after 6 months of treatment was 20.36 ± 5.02 kg in control group and 19.74 ± 5.10 kg in PnK-DHA group, without statistical differences between both groups. The VLCK diets induced a significant change in some of the biological parameters, such as insulin, HOMA-IR, triglycerides, LDL cholesterol, C-reactive protein, resistin, TNF alpha, and leptin. Following DHA supplementation, the DHA-derived oxylipins were significantly increased in the intervention group. The ratio of proresolution/proinflammatory lipid markers was increased in plasma of the intervention group over the entire study. Similarly, the mean ratios of AA/EPA and AA/DHA in erythrocyte membranes were dramatically reduced in the PnK-DHA group and the anti-inflammatory fatty acid index (AIFAI) was consistently increased after the DHA treatment (p < 0.05). The present study demonstrated that a very low-calorie ketogenic diet supplemented with DHA was significantly superior in the anti-inflammatory effect, without statistical differences in weight loss and metabolic improvement.
Righi, Valeria; Di Nunzio, Mattia; Danesi, Francesca; Schenetti, Luisa; Mucci, Adele; Boschetti, Elisa; Biagi, Pierluigi; Bonora, Sergio; Tugnoli, Vitaliano; Bordoni, Alessandra
It is well recognized that a high dietary intake of long-chain polyunsaturated fatty acids (LC-PUFA) has profound benefits on health and prevention of chronic diseases. In particular, in recent years there has been a dramatic surge of interest in the health effects of n-3 LC-PUFA derived from fish, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. Notwithstanding, the metabolic fate and the effects of these fatty acids once inside the cell has seldom been comprehensively investigated. Using cultured neonatal rat cardiomyocytes as model system we have investigated for the first time, by means of high-resolution magic-angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy in combination with gas chromatography (GC), the modification occurring in the cell lipid environment after EPA and DHA supplementation. The most important difference between control and n-3 LC-PUFA-supplemented cardiomyocytes highlighted by HR-MAS NMR spectroscopy is the increase of signals from mobile lipids, identified as triacylglycerols (TAG). The observed increase of mobile TAG is a metabolic response to n-3 LC-PUFA supplementation, which leads to an increased lipid storage. The sequestration of mobile lipids in lipid bodies provides a deposit of stored energy that can be accessed in a regulated fashion according to metabolic need. Interestingly, while n-3 LC-PUFA supplementation to neonatal rat cardiomyocytes causes a huge variation in the cell lipid environment, it does not induce detectable modifications in water-soluble metabolites, suggesting negligible interference with normal metabolic processes.
Background: DHA, a major component of the structural phospholipids of brain and retinal cell membranes, is thought by some to be an essential nutrient for infants. Indeed, some studies suggest that low dietary intake during infancy is associated with short-term adverse effects on visual and neural d...
Liu, Liang; Hu, Qinling; Wu, Huihui; Xue, Yihong; Cai, Liang; Fang, Min; Liu, Zhiguo; Yao, Ping; Wu, Yongning; Gong, Zhiyong
The effects of n3 polyunsaturated fatty acids (PUFA) on cardiovascular disease are controversial. We currently explored the effects of various ratios of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on high-fat-induced atherosclerosis. In model apoE(-/-) mice, high-fat diets (HFD) were partially replaced with fish and algal oils (DHA/EPA 2:1, 1:1 and 1:2) and/or plant oils enriched in linoleic and alpha-linolenic acids with an n6/n3 ratio of 4:1. PUFA supplementation significantly reduced the atherosclerotic plaque area, serum lipid profile, inflammatory response, aortic ROS production, proinflammatory factors and scavenger receptor expression as compared to those in the HFD group. However, plant oils did not have a significant effect on the following: serum HDL-C level; aortic ABCA1, ABCG1 and LAL mRNA expression; and CD36 and LOX-1 protein expression. Compared to the plant-oil-treated group, the DHA/EPA 1:1 group had a smaller atherosclerotic plaque area, higher serum HDL-C levels and lesser CD36 and MSR-1 mRNA expression; the DHA/EPA 2:1 group had lower serum TC, LDL-C and TNF-α levels and lower aortic ROS levels. Our study suggested that n3 PUFA from animals had more potent atheroprotective effects than that from plants. Supplementation involving higher DHA/EPA ratios and an n6/n3 ratio of 4:1 was beneficial for reducing serum "bad cholesterol" and a 1:1 DHA/EPA ratio with an n6/n3 ratio of 4:1 was beneficial for improving serum "good cholesterol" and inhibiting ox-LDL uptake. Our results suggest that achieving an n6/n3 ratio of 4:1 in the diet is also important in addition to having an optimal DHA/EPA ratio.
Domenichiello, Anthony F.; Chen, Chuck T.; Trepanier, Marc-Olivier; Stavro, P. Mark; Bazinet, Richard P.
Docosahexaenoic acid (DHA) is important for brain function, however, the exact amount required for the brain is not agreed upon. While it is believed that the synthesis rate of DHA from α-linolenic acid (ALA) is low, how this synthesis rate compares with the amount of DHA required to maintain brain DHA levels is unknown. The objective of this work was to assess whether DHA synthesis from ALA is sufficient for the brain. To test this, rats consumed a diet low in n-3 PUFAs, or a diet containing ALA or DHA for 15 weeks. Over the 15 weeks, whole body and brain DHA accretion was measured, while at the end of the study, whole body DHA synthesis rates, brain gene expression, and DHA uptake rates were measured. Despite large differences in body DHA accretion, there was no difference in brain DHA accretion between rats fed ALA and DHA. In rats fed ALA, DHA synthesis and accretion was 100-fold higher than brain DHA accretion of rats fed DHA. Also, ALA-fed rats synthesized approximately 3-fold more DHA than the DHA uptake rate into the brain. This work indicates that DHA synthesis from ALA may be sufficient to supply the brain. PMID:24212299
Amiri-Jami, Mitra; Lapointe, Gisele; Griffiths, Mansel W
Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to be of major importance in human health. Therefore, these essential polyunsaturated fatty acids have received considerable attention in both human and farm animal nutrition. Currently, fish and fish oils are the main dietary sources of EPA/DHA. To generate sustainable novel sources for EPA and DHA, the 35-kb EPA/DHA synthesis gene cluster was isolated from a marine bacterium, Shewanella baltica MAC1. To streamline the introduction of the genes into food-grade microorganisms such as lactic acid bacteria, unnecessary genes located upstream and downstream of the EPA/DHA gene cluster were deleted. Recombinant Escherichia coli harboring the 20-kb gene cluster produced 3.5- to 6.1-fold more EPA than those carrying the 35-kb DNA fragment coding for EPA/DHA synthesis. The 20-kb EPA/DHA gene cluster was cloned into a modified broad-host-range low copy number vector, pIL252m (4.7 kb, Ery) and expressed in Lactococcus lactis subsp. cremoris MG1363. Recombinant L. lactis produced DHA (1.35 ± 0.5 mg g(-1) cell dry weight) and EPA (0.12 ± 0.04 mg g(-1) cell dry weight). This is believed to be the first successful cloning and expression of EPA/DHA synthesis gene cluster in lactic acid bacteria. Our findings advance the future use of EPA/DHA-producing lactic acid bacteria in such applications as dairy starters, silage adjuncts, and animal feed supplements.
Bascoul-Colombo, Cécile; Guschina, Irina A.; Maskrey, Benjamin H.; Good, Mark; O'Donnell, Valerie B.; Harwood, John L.
Alzheimer's disease (AD) is of major concern in ageing populations and we have used the Tg2576 mouse model to understand connections between brain lipids and amyloid pathology. Because dietary docosahexaenoic acid (DHA) has been identified as beneficial, we compared mice fed with a DHA-supplemented diet to those on a nutritionally-sufficient diet. Major phospholipids from cortex, hippocampus and cerebellum were separated and analysed. Each phosphoglyceride had a characteristic fatty acid composition which was similar in cortex and hippocampus but different in the cerebellum. The biggest changes on DHA-supplementation were within ethanolamine phospholipids which, together with phosphatidylserine, had the highest proportions of DHA. Reciprocal alterations in DHA and arachidonate were found. The main diet-induced alterations were found in ethanolamine phospholipids, (and included their ether derivatives), as were the changes observed due to genotype. Tg mice appeared more sensitive to diet with generally lower DHA percentages when on the standard diet and higher relative proportions of DHA when the diet was supplemented. All four major phosphoglycerides analysed showed age-dependent decreases in polyunsaturated fatty acid contents. These data provide, for the first time, a detailed evaluation of phospholipids in different brain areas previously shown to be relevant to behaviour in the Tg2576 mouse model for AD. The lipid changes observed with genotype are consistent with the subtle alterations found in AD patients, especially for the ethanolamine phospholipid molecular species. They also emphasise the contrasting changes in fatty acid content induced by DHA supplementation within individual phospholipid classes. PMID:26968097
Kono, Keiko; Shimizu, Yoshiki; Takahashi, Satomi; Matsuoka, Sayuri; Yui, Kei
Objective The study aimed to verify that ingestion of multiple dietary supplement containing lutein, astaxanthin, cyanidin-3-glucoside and docosahexaenoic acid (DHA) would improve accommodative ability of aged and older subjects who were aware of eye strain on a daily basis. Methods A randomized double-blind placebo-controlled parallel group comparison study was conducted for 48 participants aged 45 to 64 years who complained of eye strain. The subjects took multiple dietary supplement containing 10 mg of lutein, 20 mg of bilberry extract and 26.5 mg of black soybean hull extract (a total of 2.3 mg of cyanidin-3-glucoside in both extracts), 4 mg of astaxanthin, and 50 mg of DHA (test supplement) or placebo for four consecutive weeks. Near-point accommodation (NPA) and subjective symptoms were evaluated both before and after four weeks’ intake. Results The variation of the NPA of both eyes from baseline to 4 weeks’ post-intake in the test supplement group was significantly higher than in the placebo group (1.321±0.394 diopter (D) in the test supplement group and 0.108±0.336 D in the placebo group, p=0.023). The multiple dietary supplement group showed improvement in the NPA. Regarding subjective symptoms, significant improvement of “stiff shoulders or neck” and “blurred vision” was also found in the test supplement group compared to the placebo group (p<0.05). There were no safety concerns in this study. Conclusion This study shows that multiple dietary supplement containing lutein, astaxanthin, cyanidin-3-glucoside, and DHA has effect to improve accommodative ability and subjective symptoms related to eye fatigue.
Diau, Guan-Yeu; Hsieh, Andrea T; Sarkadi-Nagy, Eszter A; Wijendran, Vasuki; Nathanielsz, Peter W; Brenna, J Thomas
Background Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are major components of the cerebral cortex and visual system, where they play a critical role in neural development. We quantitatively mapped fatty acids in 26 regions of the four-week-old breastfed baboon CNS, and studied the influence of dietary DHA and ARA supplementation and prematurity on CNS DHA and ARA concentrations. Methods Baboons were randomized into a breastfed (B) and four formula-fed groups: term, no DHA/ARA (T-); term, DHA/ARA supplemented (T+); preterm, no DHA/ARA (P-); preterm and DHA/ARA supplemented (P+). At four weeks adjusted age, brains were dissected and total fatty acids analyzed by gas chromatography and mass spectrometry. Results DHA and ARA are rich in many more structures than previously reported. They are most concentrated in structures local to the brain stem and diencephalon, particularly the basal ganglia, limbic regions, thalamus and midbrain, and comparatively lower in white matter. Dietary supplementation increased DHA in all structures but had little influence on ARA concentrations. Supplementation restored DHA concentrations to levels of breastfed neonates in all regions except the cerebral cortex and cerebellum. Prematurity per se did not exert a strong influence on DHA or ARA concentrations. Conclusion 1) DHA and ARA are found in high concentration throughout the primate CNS, particularly in gray matter such as basal ganglia; 2) DHA concentrations drop across most CNS structures in neonates consuming formulas with no DHA, but ARA levels are relatively immune to ARA in the diet; 3) supplementation of infant formula is effective at restoring DHA concentration in structures other than the cerebral cortex. These results will be useful as a guide to future investigations of CNS function in the absence of dietary DHA and ARA. PMID:15975147
Létondor, Anne; Buaud, Benjamin; Vaysse, Carole; Richard, Emmanuel; Layé, Sophie; Pallet, Véronique; Alfos, Serge
Studies suggest that eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and vitamin A are critical to delay aged-related cognitive decline. These nutrients regulate gene expression in the brain by binding to nuclear receptors such as the retinoid X receptors (RXRs) and the retinoic acid receptors (RARs). Moreover, EPA/DHA and retinoids activate notably kinase signaling pathways such as AKT or MAPK, which includes ERK1/2. This suggests that these nutrients may modulate brain function in a similar way. Therefore, we investigated in middle-aged rats the behavioral and molecular effects of supplementations with EPA/DHA and vitamin A alone or combined. 18-month-old rats exhibited reference and working memory deficits in the Morris water maze, associated with a decrease in serum vitamin A and hippocampal EPA/DHA contents. RARα, RXRβ, and RXRγ mRNA expression and CAMKII, AKT, ERK1/2 expression were decreased in the hippocampus of middle-aged rats. A combined EPA/DHA and vitamin A supplementation had a beneficial additive effect on reference memory but not in working memory in middle-aged rats, associated with an alleviation of the age-related decrease in RXRγ, CAMKII, AKT, and ERK1 expression in the hippocampus. This study provides a new combined nutritional strategy to delay brain aging.
Megur Ramakrishna Bhat, Kumar
Choline is an essential nutrient for humans which plays an important role in structural integrity and signaling functions. Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid, highly enriched in cell membranes of the brain. Dietary intake of choline or DHA alone by pregnant mothers directly affects fetal brain development and function. But no studies show the efficacy of combined supplementation of choline and DHA on fetal neurodevelopment. The aim of the present study was to analyze fetal neurodevelopment on combined supplementation of pregnant dams with choline and DHA. Pregnant dams were divided into five groups: normal control [NC], saline control [SC], choline [C], DHA, and C + DHA. Saline, choline, and DHA were given as supplements to appropriate groups of dams. NC dams were undisturbed during entire gestation. On postnatal day (PND) 40, brains were processed for Cresyl staining. Pups from choline or DHA supplemented group showed significant (p < 0.05) increase in number of neurons in hippocampus when compared to the same in NC and SC groups. Moreover, pups from C + DHA supplemented group showed significantly higher number of neurons (p < 0.001) in hippocampus when compared to the same in NC and SC groups. Thus combined supplementation of choline and DHA during normal pregnancy enhances fetal hippocampal neurodevelopment better than supplementation of choline or DHA alone. PMID:28210506
Molfino, Alessio; Amabile, Maria Ida; Monti, Massimo; Arcieri, Stefano; Rossi Fanelli, Filippo; Muscaritoli, Maurizio
Obesity represents a major under-recognized preventable risk factor for cancer development and recurrence, including breast cancer (BC). Healthy diet and correct lifestyle play crucial role for the treatment of obesity and for the prevention of BC. Obesity is significantly prevalent in western countries and it contributes to almost 50% of BC in older women. Mechanisms underlying obesity, such as inflammation and insulin resistance, are also involved in BC development. Fatty acids are among the most extensively studied dietary factors, whose changes appear to be closely related with BC risk. Alterations of specific ω-3 polyunsaturated fatty acids (PUFAs), particularly low basal docosahexaenoic acid (DHA) levels, appear to be important in increasing cancer risk and its relapse, influencing its progression and prognosis and affecting the response to treatments. On the other hand, DHA supplementation increases the response to anticancer therapies and reduces the undesired side effects of anticancer therapies. Experimental and clinical evidence shows that higher fish consumption or intake of DHA reduces BC cell growth and its relapse risk. Controversy exists on the potential anticancer effects of marine ω-3 PUFAs and especially DHA, and larger clinical trials appear mandatory to clarify these aspects. The present review article is aimed at exploring the capacity of DHA in controlling obesity-related inflammation and in reducing insulin resistance in BC development, progression, and response to therapies.
Sun, Mengjun; Zhou, Zichao; Dong, Jiachen; Zhang, Jichun; Xia, Yiru; Shu, Rong
Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are two major omega-3 polyunsaturated fatty acids (n-3 PUFAs) with antimicrobial properties. In this study, we evaluated the potential antibacterial and antibiofilm activities of DHA and EPA against two periodontal pathogens, Porphyromonas gingivalis (P. gingivalis) and Fusobacterium nucleatum (F. nucleatum). MTT assay showed that DHA and EPA still exhibited no cytotoxicity to human oral tissue cells when the concentration came to 100 μM and 200 μM, respectively. Against P. gingivalis, DHA and EPA showed the same minimum inhibitory concentration (MIC) of 12.5 μM, and a respective minimum bactericidal concentration (MBC) of 12.5 μM and 25 μM. However, the MIC and MBC values of DHA or EPA against F. nucleatum were both greater than 100 μM. For early-stage bacteria, DHA or EPA displayed complete inhibition on the planktonic growth and biofilm formation of P. gingivalis from the lowest concentration of 12.5 μM. And the planktonic growth of F. nucleatum was slightly but not completely inhibited by DHA or EPA even at the concentration of 100 μM, however, the biofilm formation of F. nucleatum at 24 h was significantly restrained by 100 μM EPA. For exponential-phase bacteria, 100 μM DHA or EPA completely killed P. gingivalis and significantly decreased the viable counts of F. nucleatum. Meanwhile, the morphology of P. gingivalis was apparently damaged, and the virulence factor gene expression of P. gingivalis and F. nucleatum was strongly downregulated. Besides, the viability and the thickness of mature P. gingivalis biofilm, together with the viability of mature F. nucleatum biofilm were both significantly decreased in the presence of 100 μM DHA or EPA. In conclusion, DHA and EPA possessed antibacterial activities against planktonic and biofilm forms of periodontal pathogens, which suggested that DHA and EPA might be potentially supplementary therapeutic agents for prevention
Zhang, Ke; Li, Huidong; Chen, Wuxi; Zhao, Minli; Cui, Haiyang; Min, Qingsong; Wang, Haijun; Chen, Shulin; Li, Demao
Docosapentaenoic acid/docosahexaenoic acid ratio (DPA/DHA ratio) in Schizochytrium was relatively stable. But ideally the ratio of DPA/DHA will vary according to the desired end use. This study reports several ways of modulating the DPA/DHA ratio. Incubation times changed the DPA/DHA ratio, and changes in this ratio were associated with the variations in the saturated fatty acid (SFAs) content. Propionic acid sharply increased the SFAs content in lipids, dramatically decreased the even-chain SFAs content, and reduced the DPA/DHA ratio. Pentanoic acid (C5:0) and heptanoic acid (C7:0) had similar effects as propionic acid, whereas butyric acid (C4:0), hexanoic acid (C6:0), and octanoic acid (C8:0) did not change the fatty acid profile and the DPA/DHA ratio. Transcription analyses show that β-oxidation might be responsible for this phenomenon. Iodoacetamide upregulated polyunsaturated fatty acid (PUFA) synthase genes, reduced the DHA content, and improved the DPA content, causing the DPA/DHA ratio to increase. These results present new insights into the regulation of the DPA/DHA ratio.
Jans, Linda A W; Giltay, Erik J; Van der Does, A J Willem
Depressive symptoms are common during pregnancy and the post-partum period. Although essential n-3 PUFA may have beneficial effects on depression, it remains unclear whether they are also effective for perinatal depression. The purpose of the present study was to assess the efficacy of n-3 supplementation for perinatal depression, by performing a meta-analysis on currently available data. After a thorough literature search, we included seven randomised controlled trials in the meta-analysis, all with EPA and/or DHA supplementation. Most studies were judged to be of low-to-moderate quality, mainly due to small sample sizes and failure to adhere to Consolidated Standards of Reporting Trials guidelines. Some studies were not primarily designed to address perinatal depression. A total of 309 women on n-3 fatty acid supplementation were compared with 303 women on placebo treatment. n-3 Supplementation was not found to be significantly more effective than placebo at post-treatment with a pooled effect size (Hedges's g) of - 0.03 (95 % CI - 0.18, 0.13; P = 0.76) using a fixed-effects model. Heterogeneity was low-to-moderate (I2 = 30 %). In a subgroup analysis of three small studies of pregnant women with major depression, there was some indication of effectiveness (effect size 0.17; 95 % CI - 0.21, 0.55). In conclusion, the question of whether EPA and DHA administration is effective in the prevention or treatment of perinatal depression cannot be answered yet. Future research should focus on women who are clinically depressed (or at risk). The quality of research in this area needs to improve.
Paschoal, V A; Vinolo, M A R; Crisma, A R; Magdalon, J; Curi, R
Fish oils are used as therapeutic agents in chronic inflammatory diseases. The omega-3 fatty acids (FA) found in these oils are mainly eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. The anti-inflammatory properties of fish oils are attributed to both omega-3 fatty acids. However, it is unknown whether such effects are due to either EPA or DHA. In this study, the effects of EPA and DHA on rat neutrophil function in vitro were compared. Both EPA and DHA increased the production of H₂O₂ when cells were stimulated or not with lipopolysaccharides (LPS). However, EPA was more potent than DHA in triggering an increase in superoxide release by cells in the basal condition or when stimulated with phorbol myristate acetate (PMA) or zymosan. Only DHA increased the phagocytic capacity and fungicidal activity of neutrophils. Both FA increased the release of tumor necrosis factor-α (TNF-α) in nonstimulated cells, but only EPA increased the production of cytokine-inducing neutrophil chemoattractant-2 (CINC-2) in the absence or presence of LPS, whereas production of interleukin-1 beta (IL-1β) was only increased by DHA in the presence of LPS. In addition, there was no alteration in the production of nitric oxide. In conclusion, we show herein that EPA and DHA can differently modulate aspects of the neutrophil response, which may be relevant for the development of therapies rich in one or other FA depending on the effect required.
Gruber, Florian; Ornelas, Cayo Mecking; Karner, Susanne; Narzt, Marie-Sophie; Nagelreiter, Ionela Mariana; Gschwandtner, Maria; Bochkov, Valery; Tschachler, Erwin
Fish oil rich in docosahexaenoic acid (DHA) has beneficial effects on human health. Omega-3 polyunsaturated fatty acids are precursors of eicosanoids and docosanoids, signaling molecules that control inflammation and immunity, and their dietary uptake improves a range of disorders including cardiovascular diseases, ulcerative colitis, rheumatoid arthritis, and psoriasis. The unsaturated nature of these fatty acids, however, makes them prone to oxidation, especially when they are incorporated into (membrane) phospholipids. The skin is an organ strongly exposed to oxidative stress, mainly due to solar ultraviolet radiation. Thus, increased levels of PUFA in combination with oxidative stress could cause increased local generation of oxidized lipids, whose action spectrum reaches from signaling molecules to reactive carbonyl compounds that can crosslink biomolecules. Here, we investigated whether PUFA supplements to fibroblasts are incorporated into membrane phospholipids and whether an increase of PUFA within phospholipids affects the responses of the cells to UV exposure. The redox-sensitive transcription factor Nrf2 is the major regulator of the fibroblast stress response to ultraviolet radiation or exposure to oxidized lipids. Here we addressed how Nrf2 signaling would be affected in PUFA-supplemented human dermal fibroblasts and mouse dermal fibroblasts from Nrf2-deficient and wild type mice. We found, using HPLC-tandem MS, that DHA supplements to culture media of human and murine fibroblasts were readily incorporated into phospholipids and that subsequent irradiation of the supplemented cells with UVA resulted in an increase in 1-palmitoyl-2-(epoxyisoprostane-E2)-sn-glycero-3-phosphorylcholine and Oxo-DHA esterified to phospholipid, both of which are Nrf2 agonists. Also, induction of Nrf2 target genes was enhanced in the DHA-supplemented fibroblasts after UVA irradiation. In Nrf2-deficient murine fibroblasts, the expression of the target genes was, as expected
Jackson, Philippa A.; Forster, Joanne S.; Bell, J. Gordon; Dick, James R.; Younger, Irene; Kennedy, David O.
A number of recent trials have demonstrated positive effects of dietary supplementation with the omega-3 polyunsaturated fatty acids (n-3 PUFAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on measures of cognitive function in healthy young and older adults. One potential mechanism by which EPA, and DHA in particular, may exert these effects is via modulation of cerebral hemodynamics. In order to investigate the effects of DHA alone or provided as one component of a multinutrient supplement (also including Gingko biloba, phosphatidylserine and vitamins B9 and B12) on measures of cerebral hemodynamics and cognitive function, 86 healthy older adults aged 50–70 years who reported subjective memory deficits were recruited to take part in a six month daily dietary supplementation trial. Relative changes in the concentration of oxygenated hemoglobin and deoxygenated hemoglobin were assessed using Near Infrared Spectroscopy (NIRS) during the performance of cognitive tasks prior to and following the intervention period. Performance on the cognitive tasks was also assessed. No effect of either active treatment was found for any of the NIRS measures or on the cognitive performance tasks, although the study was limited by a number of factors. Further work should continue to evaluate more holistic approaches to cognitive aging. PMID:26867200
Dasilva, Gabriel; Pazos, Manuel; García-Egido, Eduardo; Gallardo, Jose Manuel; Rodríguez, Isaac; Cela, Rafael; Medina, Isabel
Dietary intervention with ω-3 marine fatty acids may potentially modulate inflammation and oxidative stress markers related with CVD, metabolic syndrome and cancer. The aim of this study was to evaluate whether different proportions of ω-3 EPA and DHA intake provoke a modulation of the production of lipid mediators and then, an influence on different indexes of inflammation and oxidative stress in a controlled dietary animal experiment using Wistar rats. For such scope, a lipidomic SPE-LC-ESI-MS/MS approach previously developed was applied to determine lipid mediators profile in plasma samples. The effect of ω-3 fatty acids associated to different ratios EPA:DHA was compared with the effect exerted by ω-3 ALA supplementation from linseed oil and ω-6 LA from soybean oil. CRP showed a tendency to greater inflammatory status in all ω-3-fed animals. Interestingly, ratios 1:1 and 2:1 EPA:DHA evidenced a noteworthy healthy effect generating a less oxidative environment and modulating LOX and COX activities toward a decrease in the production of proinflammatory ARA eicosanoids and oxidative stress biomarkers from EPA and DHA. In addition, the ability of 1:1 and 2:1 fish oil diets to reduce lipid mediator levels was in concurrence with the protective effect exerted by decreasing inflammatory markers as ω-6/ω-3 ratio in plasma and membranes. It was also highlighted the effect of a higher DHA amount in the diet reducing the healthy benefits described in terms of inflammation and oxidative stress. Results support the antiinflammatory and antioxidative role of fish oils and, particularly, the effect of adequate proportions EPA:DHA.
van Goor, Saskia A; Dijck-Brouwer, D A Janneke; Erwich, Jan Jaap H M; Schaafsma, Anne; Hadders-Algra, Mijna
Docosahexaenoic acid (DHA) and arachidonic acid (AA) are important for neurodevelopment. The effects of DHA (220 mg/day, n=41), DHA+AA (220 mg/day, n=39) or placebo (n=34) during pregnancy and lactation on neurodevelopment at 18 months, and the relations between umbilical cord DHA, AA and Mead acid and neurodevelopment were studied. An age-specific, standardized neurological assessment for the evaluation of minor neurological dysfunction (MND), and the Bayley Scales of Infant Development (BSID) were used. The intervention did not influence any of the outcomes. Umbilical venous (UV) Mead acid was negatively and n-6 fatty acids were weakly positively associated to the BSID mental developmental index. Children with simple MND had lower UV DHA compared to normally classified children. We conclude that relatively short-term maternal DHA or DHA+AA supplementation does not influence neurodevelopment at toddler age, although some parameters of brain development are related to perinatal DHA and AA status.
Cazzola, Roberta; Rondanelli, Mariangela; Faliva, Milena; Cestaro, Benvenuto
A randomized, double-blind placebo-controlled clinical trial was carried out to assess the efficacy of a docosahexenoic acid (DHA)-phospholipids, melatonin and tryptophan supplemented diet in improving the erythrocyte oxidative stress, membrane fluidity and membrane-bound enzyme activities of elderly subjects suffering from mild cognitive impairment (MCI). These subjects were randomly assigned to the supplement group (11 subjects, 9F and 2M; age 85.3±5.3y) or placebo group (14-matched subjects, 11F and 3M; 86.1±6.5). The duration of the treatment was 12weeks. The placebo group showed no significant changes in erythrocyte membrane composition and function. The erythrocyte membranes of the supplement group showed a significant increase in eicosapentenoic acid, docosapentenoic acid and DHA concentrations and a significant decrease in arachidonic acid, malondialdehyde and lipofuscin levels. These changes in membrane composition resulted in an increase in the unsaturation index, membrane fluidity and acetylcholine esterase activity. Moreover, a significant increase in the ratio between reduced and oxidized glutathione was observed in the erythrocyte of the supplement group. Although this study is a preliminary investigation, we believe these findings to be of great speculative and interpretative interest to better understand the complex and multi-factorial mechanisms behind the possible links between diets, their functional components and possible molecular processes that contribute to increasing the risk of developing MCI and Alzheimer's.
Wu, A; Ying, Z; Gomez-Pinilla, F
Omega-3 fatty acids (i.e. docosahexaenoic acid; DHA), similar to exercise, improve cognitive function, promote neuroplasticity, and protect against neurological lesion. In this study, we investigated a possible synergistic action between DHA dietary supplementation and voluntary exercise on modulating synaptic plasticity and cognition. Rats received DHA dietary supplementation (1.25% DHA) with or without voluntary exercise for 12 days. We found that the DHA-enriched diet significantly increased spatial learning ability, and these effects were enhanced by exercise. The DHA-enriched diet increased levels of pro-brain-derived neurotrophic factor (BDNF) and mature BDNF, whereas the additional application of exercise boosted the levels of both. Furthermore, the levels of the activated forms of CREB and synapsin I were incremented by the DHA-enriched diet with greater elevation by the concurrent application of exercise. While the DHA diet reduced hippocampal oxidized protein levels, a combination of a DHA diet and exercise resulted in a greater reduction rate. The levels of activated forms of hippocampal Akt and CaMKII were increased by the DHA-enriched diet, and with even greater elevation by a combination of diet and exercise. Akt and CaMKII signaling are crucial step by which BDNF exerts its action on synaptic plasticity and learning and memory. These results indicate that the DHA diet enhanced the effects of exercise on cognition and BDNF-related synaptic plasticity, a capacity that may be used to promote mental health and reduce risk of neurological disorders.
Rogers, Lynette K; Valentine, Christina J; Pennell, Michael; Velten, Markus; Britt, Rodney D; Dingess, Kelly; Zhao, Xuilan; Welty, Stephen E; Tipple, Trent E
DHA is a long-chain fatty acid that has potent antiinflammatory properties. Whereas maternal DHA dietary supplementation has been shown to improve cognitive development in infants fed DHA-supplemented milk, the antiinflammatory effects of maternal DHA supplementation on the developing fetus and neonate have not been extensively explored. Pregnant C3H/HeN dams were fed purified control or DHA-supplemented diets (~0.25% of total fat) at embryonic d 16 and consumed these diets throughout the study. At birth, the nursing mouse pups were placed in room air (RA; 21% O(2)) or >95% O(2) (hyperoxia) for up to 7 d. These studies tested the hypothesis that maternal DHA supplementation would decrease inflammation and improve alveolarization in the lungs of newborn mouse pups exposed to hyperoxia. Survival, inflammatory responses, and lung growth were compared among control diet/RA, DHA/RA, control/O(2), and DHA/O(2) pups. There were fewer neutrophils and macrophages in lung tissues from pups nursed by DHA-supplemented dams than in those nursed by dams fed the control diet at 7 d of hyperoxia exposure (P < 0.015). Although differences due to hyperoxia exposure were observed, maternal diet did not affect keratinocyte-derived chemokine, macrophage inflammatory protein-2, IL-1β, or TNFα mRNA levels in pup tissues. Hyperoxia also induced NF-κB activity, but maternal diet did not affect NF-κB or PPARγ activities. In mice, DHA supplementation decreases leukocyte infiltration in the offspring exposed to hyperoxia, suggesting a potential role for DHA supplementation as a therapy to reduce inflammation in preterm infants.
Aasen, Inga Marie; Ertesvåg, Helga; Heggeset, Tonje Marita Bjerkan; Liu, Bin; Brautaset, Trygve; Vadstein, Olav; Ellingsen, Trond E
Thraustochytrids have been applied for industrial production of the omega-3 fatty acid docosahexaenoic (DHA) since the 1990s. During more than 20 years of research on this group of marine, heterotrophic microorganisms, considerable increases in DHA productivities have been obtained by process and medium optimization. Strains of thraustochytrids also produce high levels of squalene and carotenoids, two other commercially interesting compounds with a rapidly growing market potential, but where yet few studies on process optimization have been reported. Thraustochytrids use two pathways for fatty acid synthesis. The saturated fatty acids are produced by the standard fatty acid synthesis, while DHA is synthesized by a polyketide synthase. However, fundamental knowledge about the relationship between the two pathways is still lacking. In the present review, we extract main findings from the high number of reports on process optimization for DHA production and interpret these in the light of the current knowledge of DHA synthesis in thraustochytrids and lipid accumulation in oleaginous microorganisms in general. We also summarize published reports on squalene and carotenoid production and review the current status on strain improvement, which has been hampered by the yet very few published genome sequences and the lack of tools for gene transfer to the organisms. As more sequences now are becoming available, targets for strain improvement can be identified and open for a system-level metabolic engineering for improved productivities.
Iron and a mixture of DHA and EPA supplementation, alone and in combination, affect bioactive lipid signalling and morbidity of iron deficient South African school children in a two-by-two randomised controlled trial.
Malan, L; Baumgartner, J; Zandberg, L; Calder, P C; Smuts, C M
We recently reported that iron supplementation increased respiratory morbidity in iron deficient South African children. This increase, however, was attenuated when iron was provided in combination with a mixture of DHA/EPA. To explore potential underlying mechanisms, we examined the effects of iron and DHA/EPA, alone and in combination, on plasma lipid-derived immune modulator concentrations and related gene expression in peripheral blood mononuclear cells (PBMC). DHA/EPA decreased inflammatory 12-hydroxyeicosatetraenoic acid and tended to increase anti-inflammatory and pro-resolving 17-hydroxydocosahexaenoic acid (17-HDHA), while iron decreased 17-HDHA. However, in combination with iron, the anti-inflammatory effect of DHA/EPA was maintained. These biochemical changes may explain the prevention of iron-induced respiratory morbidity that we observed when iron was supplemented in combination with DHA/EPA during the 8.5 month randomised controlled trial and might lead to a safer approach of delivering iron supplementation. The study was registered at clinicaltrials.gov as NCT01092377.
Mozaffarian, Dariush; Wu, Jason H Y
Considerable research supports cardiovascular benefits of consuming omega-3 PUFA, also known as (n-3) PUFA, from fish or fish oil. Whether individual long-chain (n-3) PUFA have shared or complementary effects is not well established. We reviewed evidence for dietary and endogenous sources and cardiovascular effects on biologic pathways, physiologic risk factors, and clinical endpoints of EPA [20:5(n-3)], docosapentaenoic acid [DPA, 22:5(n-3)], and DHA [22:6(n-3)]. DHA requires direct dietary consumption, with little synthesis from or retroconversion to DPA or EPA. Whereas EPA is also largely derived from direct consumption, EPA can also be synthesized in small amounts from plant (n-3) precursors, especially stearidonic acid. In contrast, DPA appears principally derived from endogenous elongation from EPA, and DPA can also undergo retroconversion back to EPA. In experimental and animal models, both EPA and DHA modulate several relevant biologic pathways, with evidence for some differential benefits. In humans, both fatty acids lower TG levels and, based on more limited studies, favorably affect cardiac diastolic filling, arterial compliance, and some metrics of inflammation and oxidative stress. All three (n-3) PUFA reduce ex vivo platelet aggregation and DHA also modestly increases LDL and HDL particle size; the clinical relevance of such findings is uncertain. Combined EPA+DHA or DPA+DHA levels are associated with lower risk of fatal cardiac events and DHA with lower risk of atrial fibrillation, suggesting direct or indirect benefits of DHA for cardiac arrhythmias (although not excluding similar benefits of EPA or DPA). Conversely, EPA and DPA, but not DHA, are associated with lower risk of nonfatal cardiovascular endpoints in some studies, and purified EPA reduced risk of nonfatal coronary syndromes in one large clinical trial. Overall, for many cardiovascular pathways and outcomes, identified studies of individual (n-3) PUFA were relatively limited, especially
Bou, Marta; Østbye, Tone-Kari; Berge, Gerd M; Ruyter, Bente
The aim of the present study was to investigate how EPA, DHA, and lipoic acid (LA) influence the different metabolic steps in the n-3 fatty acid (FA) biosynthetic pathway in hepatocytes from Atlantic salmon fed four dietary levels (0, 0.5, 1.0 and 2.0%) of EPA, DHA or a 1:1 mixture of these FA. The hepatocytes were incubated with [1-(14)C] 18:3n-3 in the presence or absence of LA (0.2 mM). Increased endogenous levels of EPA and/or DHA and LA exposure both led to similar responses in cells with reduced desaturation and elongation of [1-(14)C] 18:3n-3 to 18:4n-3, 20:4n-3, and EPA, in agreement with reduced expression of the Δ6 desaturase gene involved in the first step of conversion. DHA production, on the other hand, was maintained even in groups with high endogenous levels of DHA, possibly due to a more complex regulation of this last step in the n-3 metabolic pathway. Inhibition of the Δ6 desaturase pathway led to increased direct elongation to 20:3n-3 by both DHA and LA. Possibly the route by 20:3n-3 and then Δ8 desaturation to 20:4n-3, bypassing the first Δ6 desaturase step, can partly explain the maintained or even increased levels of DHA production. LA increased DHA production in the phospholipid fraction of hepatocytes isolated from fish fed 0 and 0.5% EPA and/or DHA, indicating that LA has the potential to further increase the production of this health-beneficial FA in fish fed diets with low levels of EPA and/or DHA.
Sun, Grace Y; Simonyi, Agnes; Fritsche, Kevin L; Chuang, Dennis Y; Hannink, Mark; Gu, Zezong; Greenlief, C Michael; Yao, Jeffrey K; Lee, James C; Beversdorf, David Q
Docosahexaenoic acid (DHA), a polyunsaturated fatty acid (PUFA) enriched in phospholipids in the brain and retina, is known to play multi-functional roles in brain health and diseases. While arachidonic acid (AA) is released from membrane phospholipids by cytosolic phospholipase A2 (cPLA2), DHA is linked to action of the Ca(2+)-independent iPLA2. DHA undergoes enzymatic conversion by 15-lipoxygenase (Alox 15) to form oxylipins including resolvins and neuroprotectins, which are powerful lipid mediators. DHA can also undergo non-enzymatic conversion by reacting with oxygen free radicals (ROS), which cause the production of 4-hydoxyhexenal (4-HHE), an aldehyde derivative which can form adducts with DNA, proteins and lipids. In studies with both animal models and humans, there is evidence that inadequate intake of maternal n-3 PUFA may lead to aberrant development and function of the central nervous system (CNS). What is less certain is whether consumption of n-3 PUFA is important in maintaining brain health throughout one's life span. Evidence mostly from non-human studies suggests that DHA intake above normal nutritional requirements might modify the risk/course of a number of diseases of the brain. This concept has fueled much of the present interest in DHA research, in particular, in attempts to delineate mechanisms whereby DHA may serve as a nutraceutical and confer neuroprotective effects. Current studies have revealed ability for the oxylipins to regulation of cell redox homeostasis through the Nuclear factor (erythroid-derived 2)-like 2/Antioxidant response element (Nrf2/ARE) anti-oxidant pathway, and impact signaling pathways associated with neurotransmitters, and modulation of neuronal functions involving brain-derived neurotropic factor (BDNF). This review is aimed at describing recent studies elaborating these mechanisms with special regard to aging and Alzheimer's disease, autism spectrum disorder, schizophrenia, traumatic brain injury, and stroke.
Inflammation is an independent risk factor for the development of cardiovascular disease (CVD). N-3 polyunsaturated fatty acids (PUFA) reduce inflammation but the anti-inflammatory effect of docosahexenoic acid (DHA) in hypertriglyceridemic men has not been reported. We determined its effects on cir...
El-Mesery, ME; Al-Gayyar, MM; Salem, HA; Darweish, MM; El-Mowafy, AM
Background The fish oil-derived ω-3 fatty acids, like docosahexanoic (DHA), claim a plethora of health benefits. We currently evaluated the antitumor effects of DHA, alone or in combination with cisplatin (CP) in the EAC solid tumor mice model, and monitored concomitant changes in serum levels of C-reactive protein (CRP), lipid peroxidation (measured as malondialdehyde; MDA) and leukocytic count (LC). Further, we verified the capacity of DHA to ameliorate the lethal, CP-induced nephrotoxicity in rats and the molecular mechanisms involved therein. Results EAC-bearing mice exhibited markedly elevated LC (2-fold), CRP (11-fold) and MDA levels (2.7-fold). DHA (125, 250 mg/kg) elicited significant, dose-dependent reductions in tumor size (38%, 79%; respectively), as well as in LC, CRP and MDA levels. These effects for CP were appreciably lower than those of DHA (250 mg/kg). Interestingly, DHA (125 mg/kg) markedly enhanced the chemopreventive effects of CP and boosted its ability to reduce serum CRP and MDA levels. Correlation studies revealed a high degree of positive association between tumor growth and each of CRP (r = 0.85) and leukocytosis (r = 0.89), thus attesting to a diagnostic/prognostic role for CRP. On the other hand, a single CP dose (10 mg/kg) induced nephrotoxicity in rats that was evidenced by proteinuria, deterioration of glomerular filtration rate (GFR, -4-fold), a rise in serum creatinine/urea levels (2–5-fold) after 4 days, and globally-induced animal fatalities after 7 days. Kidney-homogenates from CP-treated rats displayed significantly elevated MDA- and TNF-α-, but reduced GSH-, levels. Rats treated with DHA (250 mg/kg, but not 125 mg/kg) survived the lethal effects of CP, and showed a significant recovery of GFR; while their homogenates had markedly-reduced MDA- and TNF-α-, but -increased GSH-levels. Significant association was detected between creatinine level and those of MDA (r = 0.81), TNF-α ) r = 0.92) and GSH (r = -0.82); implying
Hennebelle, Marie; Plourde, Mélanie; Chouinard-Watkins, Raphaël; Castellano, Christian-Alexandre; Barberger-Gateau, Pascale; Cunnane, Stephen C
Epidemiological studies fairly convincingly suggest that higher intakes of fatty fish and n-3 fatty acids are associated with reduced risk of Alzheimer's disease (AD). DHA in plasma is normally positively associated with DHA intake. However, despite being associated with lower fish and DHA intake, unexpectedly, plasma (or brain) DHA is frequently not lower in AD. This review will highlight some metabolic and physiological factors such as ageing and apoE polymorphism that influence DHA homeostasis. Compared with young adults, blood DHA is often slightly but significantly higher in older adults without any age-related cognitive decline. Higher plasma DHA in older adults could be a sign that their fish or DHA intake is higher. However, our supplementation and carbon-13 tracer studies also show that DHA metabolism, e.g. transit through the plasma, apparent retroconversion and β-oxidation, is altered in healthy older compared with healthy young adults. ApoE4 increases the risk of AD, possibly in part because it too changes DHA homeostasis. Therefore, independent of differences in fish intake, changing DHA homeostasis may tend to obscure the relationship between DHA intake and plasma DHA which, in turn, may contribute to making older adults more susceptible to cognitive decline despite older adults having similar or sometimes higher plasma DHA than in younger adults. In conclusion, recent development of new tools such as isotopically labelled DHA to study DHA metabolism in human subjects highlights some promising avenues to evaluate how and why DHA metabolism changes during ageing and AD.
Sinn, Natalie; Milte, Catherine M; Street, Steven J; Buckley, Jonathan D; Coates, Alison M; Petkov, John; Howe, Peter R C
Depressive symptoms may increase the risk of progressing from mild cognitive impairment (MCI) to dementia. Consumption of n-3 PUFA may alleviate both cognitive decline and depression. The aim of the present study was to investigate the benefits of supplementing a diet with n-3 PUFA, DHA and EPA, for depressive symptoms, quality of life (QOL) and cognition in elderly people with MCI. We conducted a 6-month double-blind, randomised controlled trial. A total of fifty people aged >65 years with MCI were allocated to receive a supplement rich in EPA (1·67 g EPA + 0·16 g DHA/d; n 17), DHA (1·55 g DHA + 0·40 g EPA/d; n 18) or the n-6 PUFA linoleic acid (LA; 2·2 g/d; n 15). Treatment allocation was by minimisation based on age, sex and depressive symptoms (Geriatric Depression Scale, GDS). Physiological and cognitive assessments, questionnaires and fatty acid composition of erythrocytes were obtained at baseline and 6 months (completers: n 40; EPA n 13, DHA n 16, LA n 11). Compared with the LA group, GDS scores improved in the EPA (P=0·04) and DHA (P=0·01) groups and verbal fluency (Initial Letter Fluency) in the DHA group (P=0·04). Improved GDS scores were correlated with increased DHA plus EPA (r 0·39, P=0·02). Improved self-reported physical health was associated with increased DHA. There were no treatment effects on other cognitive or QOL parameters. Increased intakes of DHA and EPA benefited mental health in older people with MCI. Increasing n-3 PUFA intakes may reduce depressive symptoms and the risk of progressing to dementia. This needs to be investigated in larger, depressed samples with MCI.
Mahanty, Arabinda; Sankar, T. V.; Anandan, R.; Paul, B. N.; Sarma, Debajit; Syama Dayal, J.; Venkateshwarlu, G.; Mathew, Suseela; Karunakaran, D.; Chanda, Soumen; Shahi, Neetu; Das, Puspita; Das, Partha; Akhtar, Md Shahbaz; Vijayagopal, P.; Sridhar, N.
Docosahexaenoic acid (DHA) is the principal constituent of a variety of cells especially the brain neurons and retinal cells and plays important role in fetal brain development, development of motor skills, and visual acuity in infants, lipid metabolism, and cognitive support and along with eicosapentaenoic acid (EPA) it plays important role in preventing atherosclerosis, dementia, rheumatoid arthritis, Alzheimer's disease, and so forth. Being an essential nutrient, it is to be obtained through diet and therefore searching for affordable sources of these ω-3 polyunsaturated fatty acids (PUFA) is important for consumer guidance and dietary counseling. Fish is an important source of PUFA and has unique advantage that there are many food fish species available and consumers have a wide choice owing to availability and affordability. The Indian subcontinent harbors a rich fish biodiversity which markedly varies in their nutrient composition. Here we report the DHA and EPA content and fatty acid profile of 39 important food fishes (including finfishes, shellfishes, and edible molluscs from both marine water and freshwater) from India. The study showed that fishes Tenualosa ilisha, Sardinella longiceps, Nemipterus japonicus, and Anabas testudineus are rich sources of DHA and EPA. Promotion of these species as DHA rich species would enhance their utility in public health nutrition. PMID:27579313
Mohanty, Bimal Prasanna; Ganguly, Satabdi; Mahanty, Arabinda; Sankar, T V; Anandan, R; Chakraborty, Kajal; Paul, B N; Sarma, Debajit; Syama Dayal, J; Venkateshwarlu, G; Mathew, Suseela; Asha, K K; Karunakaran, D; Mitra, Tandrima; Chanda, Soumen; Shahi, Neetu; Das, Puspita; Das, Partha; Akhtar, Md Shahbaz; Vijayagopal, P; Sridhar, N
Docosahexaenoic acid (DHA) is the principal constituent of a variety of cells especially the brain neurons and retinal cells and plays important role in fetal brain development, development of motor skills, and visual acuity in infants, lipid metabolism, and cognitive support and along with eicosapentaenoic acid (EPA) it plays important role in preventing atherosclerosis, dementia, rheumatoid arthritis, Alzheimer's disease, and so forth. Being an essential nutrient, it is to be obtained through diet and therefore searching for affordable sources of these ω-3 polyunsaturated fatty acids (PUFA) is important for consumer guidance and dietary counseling. Fish is an important source of PUFA and has unique advantage that there are many food fish species available and consumers have a wide choice owing to availability and affordability. The Indian subcontinent harbors a rich fish biodiversity which markedly varies in their nutrient composition. Here we report the DHA and EPA content and fatty acid profile of 39 important food fishes (including finfishes, shellfishes, and edible molluscs from both marine water and freshwater) from India. The study showed that fishes Tenualosa ilisha, Sardinella longiceps, Nemipterus japonicus, and Anabas testudineus are rich sources of DHA and EPA. Promotion of these species as DHA rich species would enhance their utility in public health nutrition.
Gladine, Cécile; Newman, John W.; Durand, Thierry; Pedersen, Theresa L.; Galano, Jean-Marie; Demougeot, Céline; Berdeaux, Olivier; Pujos-Guillot, Estelle; Mazur, Andrzej; Comte, Blandine
Abstract The anti-atherogenic effects of omega 3 fatty acids, namely eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) are well recognized but the impact of dietary intake on bioactive lipid mediator profiles remains unclear. Such a profiling effort may offer novel targets for future studies into the mechanism of action of omega 3 fatty acids. The present study aimed to determine the impact of DHA supplementation on the profiles of polyunsaturated fatty acids (PUFA) oxygenated metabolites and to investigate their contribution to atherosclerosis prevention. A special emphasis was given to the non-enzymatic metabolites knowing the high susceptibility of DHA to free radical-mediated peroxidation and the increased oxidative stress associated with plaque formation. Atherosclerosis prone mice (LDLR−/−) received increasing doses of DHA (0, 0.1, 1 or 2% of energy) during 20 weeks leading to a dose-dependent reduction of atherosclerosis (R2 = 0.97, p = 0.02), triglyceridemia (R2 = 0.97, p = 0.01) and cholesterolemia (R2 = 0.96, p<0.01). Targeted lipidomic analyses revealed that both the profiles of EPA and DHA and their corresponding oxygenated metabolites were substantially modulated in plasma and liver. Notably, the hepatic level of F4-neuroprostanes, a specific class of DHA peroxidized metabolites, was strongly correlated with the hepatic DHA level. Moreover, unbiased statistical analysis including correlation analyses, hierarchical cluster and projection to latent structure discriminate analysis revealed that the hepatic level of F4-neuroprostanes was the variable most negatively correlated with the plaque extent (p<0.001) and along with plasma EPA-derived diols was an important mathematical positive predictor of atherosclerosis prevention. Thus, oxygenated n-3 PUFAs, and F4-neuroprostanes in particular, are potential biomarkers of DHA-associated atherosclerosis prevention. While these may contribute to the anti-atherogenic effects of DHA
Muhlhausler, B S; Gibson, R A; Yelland, L N; Makrides, M
This paper aimed to identify the dietary and non-dietary determinants of docosahexaenoic acid (DHA) levels in umbilical cord blood at delivery. DHA was measured in cord blood plasma phospholipids of 1571 participants from the DOMInO (DHA to Optimize Mother Infant Outcome) randomized controlled trial. Socioeconomic, lifestyle and clinical data relating to the mother and current pregnancy were obtained from all women and their relationships with cord blood DHA assessed. DHA concentrations in the cord plasma phospholipids at delivery covered a 3-4 fold range in both control and DHA groups. The total number of DHA-rich intervention supplement capsules consumed over the course of pregnancy and gestational age at delivery individually explained 21% and 16% respectively of the variation in DHA abundance in the cord blood plasma phospholipids at delivery, but no other clinical or life-style factors explored in this study could account for >2% of the variation. Indeed, more than 65% of the variation remained unaccounted for even when all factors were included in the analysis. These data suggest that factors other than maternal DHA intake have an important role in determining cord blood DHA concentrations at delivery, and may at least partially explain the variation in the response of infants to maternal DHA supplementation reported in published trials.
Pyle, Denver J; Garcia, Rafael A; Wen, Zhiyou
Crude glycerol is the primary byproduct of the biodiesel industry. Producing docosahexaenoic acid (DHA, 22:6 n-3) through fermentation of the alga Schizochytrium limacinum on crude glycerol provides a unique opportunity to utilize a large quantity of this byproduct. The objective of this work is to investigate the effects of impurities contained in the crude glycerol on DHA production and algal biomass composition. Crude glycerol streams were obtained from different biodiesel refineries. All of the glycerol samples contained methanol, soaps, and various elements including calcium, phosphorus, potassium, silicon, sodium, and zinc. Both methanol and soap were found to negatively influence algal DHA production; these two impurities can be removed from culture medium by evaporation through autoclaving (for methanol) and by precipitation through pH adjustment (for soap). The glycerol-derived algal biomass contained 45-50% lipid, 14-20% protein, and 25% carbohydrate, with 8-13% ash content. Palmitic acid (C16:0) and DHA were the two major fatty acids in the algal lipid. The algal biomass was rich in lysine and cysteine, relative to many common feedstuffs. Elemental analysis by inductively coupled plasma showed that boron, calcium, copper, iron, magnesium, phosphorus, potassium, silicon, sodium, and sulfur were present in the biomass, whereas no heavy metals (such as mercury) were detected in the algal biomass. Overall, the results show that crude glycerol was a suitable carbon source for algal fermentation. The crude glycerol-derived algal biomass had a high level of DHA and a nutritional profile similar to that of commercial algal biomass, suggesting a great potential for using crude glycerol-derived algae in omega-3-fortified food or feed.
Molinar-Toribio, Eunice; Pérez-Jiménez, Jara; Ramos-Romero, Sara; Romeu, Marta; Giralt, Montserrat; Taltavull, Núria; Muñoz-Cortes, Mònica; Jáuregui, Olga; Méndez, Lucía; Medina, Isabel; Torres, Josep Lluís
The increasing incidence of the metabolic syndrome (MetS), a combination of risk factors before the onset of CVD and type 2 diabetes, encourages studies on the role of functional food components such as long-chain n-3 PUFA as preventive agents. In the present study, we explore the effect of EPA and DHA supplementation in different proportions on spontaneously hypertensive obese (SHROB) rats, a model for the MetS in a prediabetic state with mild oxidative stress. SHROB rats were randomised into four groups (n 7), each supplemented with EPA/DHA at ratios of 1:1, 2:1 and 1:2, or soyabean oil as the control for 13 weeks. The results showed that in all the proportions tested, EPA/DHA supplementation significantly lowered total and LDL-cholesterol concentrations, compared with those of the control group. EPA/DHA supplementation at the ratios of 1:1 and 2:1 significantly decreased inflammation (C-reactive protein levels) and lowered oxidative stress (decreased excretion of urinary isoprostanes), mainly at the ratio of 1:2. The activity of antioxidant enzymes increased in erythrocytes, abdominal fat and kidneys, with magnitudes depending on the EPA:DHA ratio. PUFA mixtures from fish affected different MetS markers of CVD risk factors in SHROB rats, depending on the ratios of EPA/DHA supplementation. The activation of endogenous defence systems may be related to the reduction of inflammation and oxidative stress.
Heaton, Alexandra E.; Meldrum, Suzanne J.; Foster, Jonathan K.; Prescott, Susan L.; Simmer, Karen
The proposal that dietary docosahexaenoic acid (DHA) enhances neurocognitive functioning in term infants is controversial. Theoretical evidence, laboratory research and human epidemiological studies have convincingly demonstrated that DHA deficiency can negatively impact neurocognitive development. However, the results from randomized controlled trials (RCTs) of DHA supplementation in human term-born infants have been inconsistent. This article will (i) discuss the role of DHA in the human diet, (ii) explore the physiological mechanisms by which DHA plausibly influences neurocognitive capacity, and (iii) seek to characterize the optimal intake of DHA during infancy for neurocognitive functioning, based on existing research that has been undertaken in developed countries (specifically, within Australia). The major observational studies and RCTs that have examined dietary DHA in human infants and animals are presented, and we consider suggestions that DHA requirements vary across individuals according to genetic profile. It is important that the current evidence concerning DHA supplementation is carefully evaluated so that appropriate recommendations can be made and future directions of research can be strategically planned. PMID:24312040
Sun, Mengjun; Dong, Jiachen; Xia, Yiru; Shu, Rong
The aim of this study was to evaluate the potential antibacterial activities of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) against planktonic and biofilm modes of Streptococcus mutans (S. mutans). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined. The effects on planktonic growth and biofilm metabolic activity were evaluated by growth curve determination and MTT assay, respectively. Then, colony forming unit (CFU) counting, scanning electron microscopy (SEM) and real-time PCR were performed to further investigate the actions of DHA and EPA on exponential phase-S. mutans. Confocal laser scanning microscopy (CLSM) was used to detect the influences on mature biofilms. The MICs of DHA and EPA against S. mutans were 100 μM and 50 μM, respectively; the MBC of both compounds was 100 μM. In the presence of 12.5 μM-100 μM DHA or EPA, the planktonic growth and biofilm metabolic activity were reduced in varying degrees. For exponential-phase S. mutans, the viable counts, the bacterial membranes and the biofilm-associated gene expression were damaged by 100 μM DHA or EPA treatment. For 1-day-old biofilms, the thickness was decreased and the proportion of membrane-damaged bacteria was increased in the presence of 100 μM DHA or EPA. These results indicated that, DHA and EPA possessed antibacterial activities against planktonic and biofilm growing S. mutans.
García-Calatayud, Salvador; Redondo, Carlos; Martín, Eva; Ruiz, José Ignacio; García-Fuentes, Miguel; Sanjurjo, Pablo
N-3 fatty acid deficiency has been related to decreased docosahexaenoic acid (DHA) and increased docosapentaenoic acid (DPA) levels in brain and to learning disadvantages. The influence of n-3 deficiency and supplementation on brain fatty acids and learning were investigated in young rats. Newborn Wistar rats were assigned to three groups of cross-foster mothers. The control group (C) was nursed by mothers that received essential fatty acids during pregnancy and lactation, and the deficient group (D) was nursed by mothers that did not receive those fatty acids. The supplemental group (S) had the same conditions as D, receiving an additional DHA and arachidonic acid supplement during lactation. Cerebral cortex and hippocampus fatty acid composition was examined using thin-layer and capillary column gas chromatography, and learning was measured by passive-avoidance procedure. D brains showed low DHA and high DPA levels, but S brain composition was similar to C. Learning in the S group was unaffected, but in the D group, it was poorer than C. Learning was directly correlated with DHA levels and inversely with DPA levels in brain. Low DHA and high DPA brain levels both were correlated with poor learning. DPA seems not to be a suitable brain functional analogue of DHA, and DHA supplementation reversed both biochemical and learning adverse effects observed in n-3 deficiency.
Arnoldussen, Ilse A. C.; Kiliaan, Amanda J.
Long chain polyunsaturated fatty acids (LC-PUFAs) are important mediators in improving and maintaining human health over the total lifespan. One topic we especially focus on in this review is omega-3 LC-PUFA docosahexaenoic acid (DHA). Adequate DHA levels are essential during neurodevelopment and, in addition, beneficial in cognitive processes throughout life. We review the impact of DHA on societal relevant metabolic diseases such as cardiovascular diseases, obesity, and diabetes mellitus type 2 (T2DM). All of these are risk factors for cognitive decline and dementia in later life. DHA supplementation is associated with a reduced incidence of both stroke and atherosclerosis, lower bodyweight and decreased T2DM prevalence. These findings are discussed in the light of different stages in the human life cycle: childhood, adolescence, adulthood and in later life. From this review, it can be concluded that DHA supplementation is able to inhibit pathologies like obesity and cardiovascular disease. DHA could be a dietary protector against these metabolic diseases during a person’s entire lifespan. However, supplementation of DHA in combination with other dietary factors is also effective. The efficacy of DHA depends on its dose as well as on the duration of supplementation, sex, and age. PMID:25528960
Pélerin, Hélène; Jouin, Mélanie; Lallemand, Marie-Sylvie; Alessandri, Jean-Marc; Cunnane, Stephen C; Langelier, Bénédicte; Guesnet, Philippe
Specific mechanisms for maintaining docosahexaenoic acid (DHA) concentration in brain cells but also transporting DHA from the blood across the blood-brain barrier (BBB) are not agreed upon. Our main objective was therefore to evaluate the level of gene expression of fatty acid transport and fatty acid binding proteins in the cerebral cortex and at the BBB level during the perinatal period of active brain DHA accretion, at weaning, and until the adult age. We measured by real time RT-PCR the mRNA expression of different isoforms of fatty acid transport proteins (FATPs), long-chain acyl-CoA synthetases (ACSLs), fatty acid binding proteins (FABPs) and the fatty acid transporter (FAT)/CD36 in cerebral cortex and isolated microvessels at embryonic day 18 (E18) and postnatal days 14, 21 and 60 (P14, P21 and P60, respectively) in rats receiving different n-3 PUFA dietary supplies (control, totally deficient or DHA-supplemented). In control rats, all the genes were expressed at the BBB level (P14 to P60), the mRNA levels of FABP5 and ACSL3 having the highest values. Age-dependent differences included a systematic decrease in the mRNA expressions between P14-P21 and P60 (2 to 3-fold), with FABP7 mRNA abundance being the most affected (10-fold). In the cerebral cortex, mRNA levels varied differently since FATP4, ACSL3 and ACSL6 and the three FABPs genes were highly expressed. There were no significant differences in the expression of the 10 genes studied in n-3 deficient or DHA-supplemented rats despite significant differences in their brain DHA content, suggesting that brain DHA uptake from the blood does not necessarily require specific transporters within cerebral endothelial cells and could, under these experimental conditions, be a simple passive diffusion process.
Davis, Paul F.; Ozias, Marlies K.; Carlson, Susan E.; Reed, Gregory A.; Winter, Michelle K.; McCarson, Kenneth E.; Levant, Beth
Decreased tissue levels of n-3 (omega-3) fatty acids, particularly docosahexaenoic acid (DHA), are implicated in the etiologies of non-puerperal and postpartum depression. This study examined the effects of a diet-induced loss of brain DHA content and concurrent reproductive status on dopaminergic parameters in adult female Long–Evans rats. An α-linolenic acid-deficient diet and breeding protocols were used to produce virgin and parous female rats with cortical phospholipid DHA levels 20–22% lower than those fed a control diet containing adequate α-linolenic acid. Decreased brain DHA produced a significant main effect of decreased density of ventral striatal D2-like receptors. Virgin females with decreased DHA also exhibited higher density of D1-like receptors in the caudate nucleus than virgin females with normal DHA. These receptor alterations are similar to those found in several rodent models of depression, and are consistent with the proposed hypodopaminergic basis for anhedonia and motivational deficits in depression. PMID:20670471
Li, Peng; Kim, Sung Woo; Li, Xilong; Datta, Sujay; Pond, Wilson G.
Cholesterol and docosahexaenoic acid (DHA) are important nutrients for neural development of infants. However, little is known about the effect of cholesterol or DHA on concentrations of amino acids (AA) in neonatal tissues. This study was conducted with the piglet (an established model for studying human infant nutrition) to test the hypothesis that dietary supplementation with the lipids may modulate AA availability in tissues. Sixteen newborn pigs were nursed by sows for 24 h and then assigned to one of four treatment groups, representing supplementation with 0.0% (control), 0.2% cholesterol, 0.2% DHA, or cholesterol plus DHA to the basal milk-formula. All piglets were euthanized at 49 days of age. In brain, cholesterol supplementation reduced (P < 0.05) concentrations of glutamate, serine, glutamine, threonine, β-alanine, alanine, methionine, isoleucine, leucine, and γ-aminobutyrate but increased (P < 0.05) concentrations of glycine and lysine, whereas DHA supplementation similarly affected (P < 0.05) concentrations of the same AA (except for isoleucine and lysine) and taurine. In addition, concentrations of most AA in liver, muscle and plasma were substantially altered by dietary supplementation of cholesterol and DHA in a tissue-dependent manner. Further, DHA reduced concentrations of carnosine in skeletal muscle, as well as ammonia in both plasma and brain. The results reveal that cholesterol and DHA can regulate AA metabolism and availability in various tissues of piglets. These novel findings have important implications for designing the next generation of infant formula to optimize neonatal growth and development. PMID:18972185
Dabkowski, Erinne R.; O’Connell, Kelly A.; Xu, Wenhong; Ribeiro, Rogerio F.; Hecker, Peter A.; Shekar, Kadambari Chandra; Stanley, William C.; Daneault, Caroline; Rosiers, Christine Des
Purpose Supplementation with the n3 polyunsaturated fatty acid docosahexaenoic acid (DHA) is beneficial in heart failure patients, however the mechanisms are unclear. DHA is incorporated into membrane phospholipids, which may prevent mitochondrial dysfunction. Thus we assessed the effects of DHA supplementation on cardiac mitochondria and the development of heart failure caused by aortic pressure overload. Methods Pathological cardiac hypertrophy was generated in rats by thoracic aortic constriction. Animals were fed either a standard diet or were supplemented with DHA (2.3 % of energy intake). Results After 14 weeks, heart failure was evident by left ventricular hypertrophy and chamber enlargement compared to shams. Left ventricle fractional shortening was unaffected by DHA treatment in sham animals (44.1±1.6 % vs. 43.5±2.2 % for standard diet and DHA, respectively), and decreased with heart failure in both treatment groups, but to a lesser extent in DHA treated animals (34.9±1.7 %) than with the standard diet (29.7±1.5 %, P <0.03). DHA supplementation increased DHA content in mitochondrial phospholipids and decreased membrane viscosity. Myocardial mitochondrial oxidative capacity was decreased by heart failure and unaffected by DHA. DHA treatment enhanced Ca2+ uptake by subsarcolemmal mitochondria in both sham and heart failure groups. Further, DHA lessened Ca2+-induced mitochondria swelling, an index of permeability transition, in heart failure animals. Heart failure increased hydrogen peroxide-induced mitochondrial permeability transition compared to sham, which was partially attenuated in interfibrillar mitochondria by treatment with DHA. Conclusions DHA decreased mitochondrial membrane viscosity and accelerated Ca2+ uptake, and attenuated susceptibility to mitochondrial permeability transition and development of left ventricular dysfunction. PMID:24013804
Block, Robert C; Abdolahi, Amir; Tu, Xin; Georas, Steve N; Brenna, J. Thomas; Phipps, Richard P; Lawrence, Peter; Mousa, Shaker A
Aspirin’s prevention of cardiovascular disease (CVD) events in individuals with type 2 diabetes mellitus is controversial. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and aspirin all affect the cyclooxygenase enzyme. The relationship between plasma EPA and DHA and aspirin’s effects has not been determined. Thirty adults with type 2 diabetes mellitus ingested aspirin (81 mg/day) for 7 days, then EPA+DHA (2.6 g/day) for 28 days, then both for another 7 days. Lysophosphatidic acid (LPA) species and more classic platelet function outcomes were determined. Plasma concentrations of total EPA+DHA were associated with 7-day aspirin reduction effects on these outcomes in a “V”-shaped manner for all 11 LPA species and ADP-induced platelet aggregation. This EPA+DHA concentration was quite consistent for each of the LPA species and ADP. These results support aspirin effects on lysolipid metabolism and platelet aggregation depending on plasma EPA+DHA concentrations in individuals with a disturbed lipid milieu. PMID:25555354
Block, Robert C; Abdolahi, Amir; Tu, Xin; Georas, Steve N; Brenna, J Thomas; Phipps, Richard P; Lawrence, Peter; Mousa, Shaker A
Aspirin's prevention of cardiovascular disease (CVD) events in individuals with type 2 diabetes mellitus is controversial. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and aspirin all affect the cyclooxygenase enzyme. The relationship between plasma EPA and DHA and aspirin's effects has not been determined. Thirty adults with type 2 diabetes mellitus ingested aspirin (81 mg/day) for 7 days, then EPA+DHA (2.6g/day) for 28 days, then both for another 7 days. Lysophosphatidic acid (LPA) species and more classic platelet function outcomes were determined. Plasma concentrations of total EPA+DHA were associated with 7-day aspirin reduction effects on these outcomes in a "V"-shaped manner for all 11 LPA species and ADP-induced platelet aggregation. This EPA+DHA concentration was quite consistent for each of the LPA species and ADP. These results support aspirin effects on lysolipid metabolism and platelet aggregation depending on plasma EPA+DHA concentrations in individuals with a disturbed lipid milieu.
Larson, Mark K; Tormoen, Garth W; Weaver, Lucinda J; Luepke, Kristen J; Patel, Ishan A; Hjelmen, Carl E; Ensz, Nicole M; McComas, Leah S; McCarty, Owen J T
Several studies have implicated the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in inhibition of normal platelet function, suggesting a role for platelets in EPA- and DHA-mediated cardioprotection. However, it is unclear whether the cardioprotective mechanisms arise from alterations to platelet-platelet, platelet-matrix, or platelet-coagulation factor interactions. Our previous results led us to hypothesize that EPA and DHA alter the ability of platelets to catalyze the generation of thrombin. We tested this hypothesis by exogenously modifying platelet membranes with EPA and DHA, which resulted in compositional changes analogous to increased dietary EPA and DHA intake. Platelets treated with EPA and DHA showed reductions in the rate of thrombin generation and exposure of platelet phosphatidylserine. In addition, treatment of platelets with EPA and DHA decreased thrombus formation and altered the processing of thrombin precursor proteins. Furthermore, treatment of whole blood with EPA and DHA resulted in increased occlusion time and a sharply reduced accumulation of fibrin under flow conditions. These results demonstrate that EPA and DHA inhibit, but do not eliminate, the ability of platelets to catalyze thrombin generation in vitro. The ability of EPA and DHA to reduce the procoagulant function of platelets provides a possible mechanism behind the cardioprotective phenotype in individuals consuming high levels of EPA and DHA.
Kwak, Suryang; Park, Yong-Cheol; Seo, Jin-Ho
3-Hydroxypropionic acid (3-HP) is a value-added chemical for polymer synthesis. For biosynthesis of 3-HP from glycerol, two dhaB and dhaR clusters encoding glycerol dehydratase and its reactivating factor, respectively, were cloned from Lactobacillus brevis KCTC33069 and expressed in Escherichia coli. Coexpression of dhaB and dhaR allowed the recombinant E. coli to convert glycerol to 3-hydroxypropionaldehyde, an intermediate of 3-HP biosynthesis. To produce 3-HP from glycerol, fed-batch fermentation with a two-step feeding strategy was designed to separate the cell growth from the 3-HP production stages. Finally, E. coli JHS00947 expressing L .brevis dhaB and dhaR, and E. coli aldH produced 14.3g/L 3-HP with 0.26 g/L-h productivity, which were 14.6 and 8.53 times higher than those of the batch culture. In conclusion, overexpression of L. brevis dhaB and dhaR clusters and E. coli aldH, and implementation of the two-step feeding strategy enabled recombinant E. coli to convert glycerol to 3-HP efficiently.
García-Layana, Alfredo; Recalde, Sergio; Alamán, Angel Salinas; Robredo, Patricia Fernández
We studied the macular pigment ocular density (MPOD) in patients with early age macular degeneration (AMD) before and 1 year after nutritional supplementation with lutein and docosahexaenoic acid (DHA). Forty-four patients with AMD were randomly divided into two groups that received placebo (n = 21) or a nutritional supplement (n = 23, 12 mg of lutein and 280 mg of DHA daily). Heterochromatic flicker photometry was used to determine the MPOD. At baseline, the MPOD in AMD patients with placebo was 0.286 ± 0.017 meanwhile in AMD patients with supplementation it was 0.291 ± 0.016. One year later, the mean MPOD had increased by 0.059 in the placebo group and by 0.162 in patients receiving lutein and DHA. This difference between groups was significant (p < 0.05). Lutein and DHA supplementation is effective in increasing the MPOD and may aid in prevention of age related macular degeneration.
Ali, Mehboob; Heyob, Kathryn; Rogers, Lynette K.
Persistent macrophages were observed in the lungs of murine offspring exposed to maternal LPS and neonatal hyperoxia. Maternal docosahexaenoic acid (DHA) supplementation prevented the accumulation of macrophages and improved lung development. We hypothesized that these macrophages are responsible for pathologies observed in this model and the effects of DHA supplementation. Primary macrophages were isolated from adult mice fed standard chow, control diets, or DHA supplemented diets. Macrophages were exposed to hyperoxia (O2) for 24 h and LPS for 6 h or 24 h. Our data demonstrate significant attenuation of Notch 1 and Jagged 1 protein levels in response to DHA supplementation in vivo but similar results were not evident in macrophages isolated from mice fed standard chow and supplemented with DHA in vitro. Co-culture of activated macrophages with MLE12 epithelial cells resulted in the release of high mobility group box 1 and leukotriene B4 from the epithelial cells and this release was attenuated by DHA supplementation. Collectively, our data indicate that long term supplementation with DHA as observed in vivo, resulted in deceased Notch 1/Jagged 1 protein expression however, DHA supplementation in vitro was sufficient to suppress release LTB4 and to protect epithelial cells in co-culture. PMID:26940787
Koppenol, A; Delezie, E; Wang, Y; Franssens, L; Willems, E; Ampe, B; Buyse, J; Everaert, N
Breeder age and nutrition are amongst the most important factors affecting progeny growth and development. The present experiment was carried out to evaluate the effects of n-3 fatty acid (FA), with special emphasis on the ratio of eicosapentaenoic (EPA, 20:5 n-3) and docosahexaenoic (DHA, 22:6 n-3) acid, provided to the diet of ageing broiler breeder hens at different ratios, on the incubation parameters and the performance of the offspring. Four hundred and eighty Ross-308 broiler breeder hens were fed one of four different diets (120/treatment), with an equal fat content. The control diet was a basal diet, rich in n-6 FAs (CON). Blends of fish oil were used to enrich the three other diets in n-3 FA and to obtain different EPA/DHA ratios of 1/1 (EPA=DHA), 1/2 (DHA) or 2/1 (EPA). Every 5 weeks, incubation parameters were assessed. Every 15 weeks, offspring was reared until slaughter age on a standard diet. Breeder age affected almost all incubation and post-hatch parameters, whereas n-3 FA treatment only lowered egg weight (p < 0.0001) and consequently hatched chick weight (p < 0.0001). Supplementation of EPA resulted in a higher proportional liver weight (p = 0.0219) at hatch, a lower body weight up to 28 days post-hatch (p = 0.0418), a lower daily weight gain (p = 0.0498) and a higher feed conversion ratio (p = 0.0395) during the starter period (p = 0.0498), resulting in a higher overall offspring feed conversion ratio (p = 0.0317) compared to the control diet. DHA supplementation, on the other hand, resulted in a lower residual yolk weight (p = 0.0220) and a higher overall offspring mortality (p = 0.0125). In conclusion, supplementation of n-3 FA could not counter the adverse effect of breeder flock age, but did not harm incubation or improve post-hatch performance, either. EPA and DHA affected offspring development differently during early post-hatch life.
Makrides, M; Neumann, M A; Simmer, K; Gibson, R A
The purpose of our study was to assess whether a supplement of fish oil (FO) and evening primrose oil (EPO) for formula-fed infants was capable of avoiding reductions in erythrocyte docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) associated with standard formula feeding. Healthy, term infants, whose mothers chose to formula feed, were randomized to either a placebo or supplemented formula for their first 30 wk of life. A reference group of beast-fed infants also was enrolled. Erythrocyte fatty acids were measured by capillary gas chromatography on day 5 and in weeks 6, 16, and 30. Supplementation of formula with 0.36% of total fatty acids as DHA resulted in erythrocyte DHA being maintained at or above breast-fed levels for the entire 30-wk study period, and breast feeding (0.21% DHA) resulted in a modest fall in erythrocyte DHA relative to baseline (day 5) values. The level of erythrocyte DHA in placebo formula-fed infants was halved by week 16. AA levels decreased in all infants in the first six weeks, but the levels in breast- and placebo formula-fed infants increased with age and returned to approximate baseline (day 5) values by 16 and 30 wk of age, respectively. Erythrocyte AA in FO+EPO-supplemented infants remained low and below breast- and placebo formula-fed levels. Our data suggest that dietary supplementation with DHA at 0.36% total fatty acids results in erythrocyte DHA levels above those found in breast-fed infants. EPO supplementation was not effective at maintaining erythrocyte AA when given with FO.
Manzi, Laura; Costantini, Lara; Molinari, Romina; Merendino, Nicolò
The omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are a class of lipids that has been shown to have beneficial effects on some chronic degenerative diseases such as cardiovascular diseases, rheumatoid arthritis, inflammatory disorders, diabetes, and cancer. Among ω-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA) has received particular attention for its antiproliferative, proapoptotic, antiangiogenetic, anti-invasion, and antimetastatic properties, even though the involved molecular mechanisms are not well understood. Recently, some in vitro studies showed that DHA promotes the inhibition of glycolytic enzymes and the Warburg phenotype. For example, it was shown that in breast cancer cell lines the modulation of bioenergetic functions is due to the capacity of DHA to activate the AMPK signalling and negatively regulate the HIF-1α functions. Taking into account these considerations, this review is focused on current knowledge concerning the role of DHA in interfering with cancer cell metabolism; this could be considered a further mechanism by which DHA inhibits cancer cell survival and progression. PMID:26339588
Manzi, Laura; Costantini, Lara; Molinari, Romina; Merendino, Nicolò
The omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are a class of lipids that has been shown to have beneficial effects on some chronic degenerative diseases such as cardiovascular diseases, rheumatoid arthritis, inflammatory disorders, diabetes, and cancer. Among ω-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA) has received particular attention for its antiproliferative, proapoptotic, antiangiogenetic, anti-invasion, and antimetastatic properties, even though the involved molecular mechanisms are not well understood. Recently, some in vitro studies showed that DHA promotes the inhibition of glycolytic enzymes and the Warburg phenotype. For example, it was shown that in breast cancer cell lines the modulation of bioenergetic functions is due to the capacity of DHA to activate the AMPK signalling and negatively regulate the HIF-1α functions. Taking into account these considerations, this review is focused on current knowledge concerning the role of DHA in interfering with cancer cell metabolism; this could be considered a further mechanism by which DHA inhibits cancer cell survival and progression.
Imhoff‐Kunsch, Beth; Stein, Aryeh D.; Villalpando, Salvador; Martorell, Reynaldo; Ramakrishnan, Usha
(n-3) PUFA, including DHA, are essential for neural development and accumulate extensively in the fetal and infant brain. (n-3) PUFA concentrations in breast milk, which are largely dependent on maternal diet and tissue stores, are correlated with infant PUFA status. We investigated the effect of prenatal DHA supplementation on PUFA concentrations in breast milk at 1 mo postpartum. In a double-blind, randomized, controlled trial conducted in Mexico, pregnant women were supplemented daily with 400 mg DHA or placebo from 18–22 wk gestation to parturition. Fatty acid concentrations in breast milk obtained from 174 women at 1 mo postpartum were determined using GLC and were expressed as % by weight of total detected fatty acids. Breast milk DHA concentrations in the DHA and placebo groups were (mean ± SD) 0.20 ± 0.06 and 0.17 ± 0.07 (P < 0.01), respectively, and those of α-linolenic acid (ALA) were 1.38 ± 0.47 and 1.24 ± 0.46 (P = 0.01), respectively. Concentrations of EPA and arachidonic acid did not differ between groups (P > 0.05). Maternal plasma DHA concentrations at 1 mo postpartum correlated positively with breast milk DHA at 1 mo postpartum in both the placebo and DHA groups (r = 0.4; P < 0.01 for both treatment groups). Prenatal DHA supplementation from 18–22 wk gestation to parturition increased concentrations of DHA and ALA in breast milk at 1 mo postpartum, providing a mechanism through which breast-fed infants could benefit. PMID:21178076
Gao, Mang; Song, Xiaojin; Feng, Yingang; Li, Wenli; Cui, Qiu
A heterotrophic microalga, strain SD116, with the ability to produce high concentrations of docosahexaenoic acid (DHA, C22:6n-3) was isolated from Shuidong Bay, Guangdong Province, China. Nucleotide sequence analysis of the 18S rDNA of SD116 showed that the strain has a close phylogenetic relationship to Aurantiochytrium species. The highest rates for growth and DHA accumulation for SD116 were obtained in 6.0% glucose, 2.0% yeast extract, and 50% artificial seawater (ASW) at a pH of 7 at 28°C. The maximum total lipid content reached 56.3% of the dry cell weight (DCW), and the maximum DHA content accounted for 50.9% of the total fatty acid (TFA) content. It was further found that urea may be a potential nitrogen source for industrial fermentation because of its cheap price and ability to induce a relatively high biomass and lipid production capacity. Using 5 L fermenters, the DCW, total lipid content, and DHA yield were found to be 70.43 g L(-1), 71.09% of the DCW, and 17.42 g L(-1) (34.79% of the TFA), respectively. The results show that Aurantiochytrium sp. SD116 is a promising candidate for commercial DHA production and could be useful for the synthesis of biomass-related products.
Capó, X; Martorell, M; Llompart, I; Sureda, A; Tur, J A; Pons, A
Exercise induces changes in circulating pro- and anti-inflammatory cytokines. The aim was to investigate the effect of docosahexaenoic acid (DHA) diet supplementation on the plasma cytokine levels and on the peripheral mononuclear (PBMCs) cells cytokine production after a training season or an acute bout of exercise. Fifteen male soccer players were randomly assigned to a placebo or an experimental group. The experimental group consumed an almond-based beverage enriched with DHA, whereas the placebo group consumed the same beverage without DHA. Three blood samples were taken: in basal conditions at the beginning of the nutritional intervention and after eight weeks of training season in basal and post-exercise conditions. The DHA content increased in erythrocytes after 8weeks of training and supplementation. Neither diet supplementation with DHA nor training season altered the basal plasma cytokines and growth factors. Only acute exercise significantly increased plasma IL6 in experimental and placebo groups. Lipopolysaccharide (LPS) activation induced the inflammatory response in PBMCs, with a significant production rate of TNFα, IL6 and IL8 mainly after acute exercise. DHA supplementation significantly reduced the rate of TNFα and IL6 production by stimulated PBMCs. Acute exercise increased the Toll-like receptor 4 (TLR4) protein levels in PBMCs, although the increase was only statistically significant in the placebo group. In conclusion, a training season does not induce significant changes in the circulating cytokine profile in well-trained soccer players. Exercise increases the PBMCs cell capabilities to produce cytokines after TLR4 stimulation with LPS and this rate of cytokine production is attenuated by diet DHA supplementation.
Villalpando, Diva M; Navarro, Rocío; Del Campo, Lara; Largo, Carlota; Muñoz, David; Tabernero, María; Baeza, Ramiro; Otero, Cristina; García, Hugo S; Ferrer, Mercedes
Over the past few decades, the cardiovascular benefits of a high dietary intake of long-chain polyunsaturated fatty acids (PUFAs), like docosahexaenoic acid (DHA), have been extensively studied. However, many of the molecular mechanisms and effects exerted by PUFAs have yet to be well explained. The lack of sex hormones alters vascular tone, and we have described that a DHA-supplemented diet to orchidectomized rats improve vascular function of the aorta. Based on these data and since the mesenteric artery importantly controls the systemic vascular resistance, the objective of this study was to analyze the effect of a DHA-supplemented diet on the mesenteric vascular function from orchidectomized rats. For this purpose mesenteric artery segments obtained from control, orchidectomized or orchidectomized plus DHA-supplemented diet were utilized to analyze: (1) the release of prostanoids, (2) formation of NO and ROS, (3) the vasodilator response to acetylcholine (ACh), as well as the involvement of prostanoids and NO in this response, and (4) the vasoconstrictor response to electrical field stimulation (EFS), analyzing also the effect of exogenous noradrenaline (NA), and the NO donor, sodium nitroprusside (SNP). The results demonstrate beneficial effects of DHA on the vascular function in orchidectomized rats, which include a decrease in the prostanoids release and superoxide formation that were previously augmented by orchidectomy. Additionally, there was an increase in endothelial NO formation and the response to ACh, in which NO involvement and the participation of vasodilator prostanoids were increased. DHA also reversed the decrease in EFS-induced response caused by orchidectomy. All of these findings suggest beneficial effects of DHA on vascular function by reversing the neurogenic response and the endothelial dysfunction caused by orchidectomy.
Villalpando, Diva M.; Navarro, Rocío; del Campo, Lara; Largo, Carlota; Muñoz, David; Tabernero, María; Baeza, Ramiro; Otero, Cristina; García, Hugo S.; Ferrer, Mercedes
Over the past few decades, the cardiovascular benefits of a high dietary intake of long-chain polyunsaturated fatty acids (PUFAs), like docosahexaenoic acid (DHA), have been extensively studied. However, many of the molecular mechanisms and effects exerted by PUFAs have yet to be well explained. The lack of sex hormones alters vascular tone, and we have described that a DHA-supplemented diet to orchidectomized rats improve vascular function of the aorta. Based on these data and since the mesenteric artery importantly controls the systemic vascular resistance, the objective of this study was to analyze the effect of a DHA-supplemented diet on the mesenteric vascular function from orchidectomized rats. For this purpose mesenteric artery segments obtained from control, orchidectomized or orchidectomized plus DHA-supplemented diet were utilized to analyze: (1) the release of prostanoids, (2) formation of NO and ROS, (3) the vasodilator response to acetylcholine (ACh), as well as the involvement of prostanoids and NO in this response, and (4) the vasoconstrictor response to electrical field stimulation (EFS), analyzing also the effect of exogenous noradrenaline (NA), and the NO donor, sodium nitroprusside (SNP). The results demonstrate beneficial effects of DHA on the vascular function in orchidectomized rats, which include a decrease in the prostanoids release and superoxide formation that were previously augmented by orchidectomy. Additionally, there was an increase in endothelial NO formation and the response to ACh, in which NO involvement and the participation of vasodilator prostanoids were increased. DHA also reversed the decrease in EFS-induced response caused by orchidectomy. All of these findings suggest beneficial effects of DHA on vascular function by reversing the neurogenic response and the endothelial dysfunction caused by orchidectomy. PMID:28068359
Preliminary Validation of a High Docosahexaenoic Acid (DHA) and -Linolenic Acid (ALA) Dietary Oil Blend: Tissue Fatty Acid Composition and Liver Proteome Response in Atlantic Salmon (Salmo salar) Smolts
Nuez-Ortín, Waldo G.; Carter, Chris G.; Wilson, Richard; Cooke, Ira; Nichols, Peter D.
Marine oils are important to human nutrition as the major source of docosahexaenoic acid (DHA), a key omega-3 long-chain (≥C20) polyunsaturated fatty acid (n-3 LC-PUFA) that is low or lacking in terrestrial plant or animal oils. The inclusion of fish oil as main source of n-3 LC-PUFA in aquafeeds is mostly limited by the increasing price and decreasing availability. Fish oil replacement with cheaper terrestrial plant and animal oils has considerably reduced the content of n-3 LC-PUFA in flesh of farmed Atlantic salmon. Novel DHA-enriched oils with high alpha-linolenic acid (ALA) content will be available from transgenic oilseeds plants in the near future as an alternative for dietary fish oil replacement in aquafeeds. As a preliminary validation, we formulated an oil blend (TOFX) with high DHA and ALA content using tuna oil (TO) high in DHA and the flaxseed oil (FX) high in ALA, and assessed its ability to achieve fish oil-like n-3 LC-PUFA tissue composition in Atlantic salmon smolts. We applied proteomics as an exploratory approach to understand the effects of nutritional changes on the fish liver. Comparisons were made between fish fed a fish oil-based diet (FO) and a commercial-like oil blend diet (fish oil + poultry oil, FOPO) over 89 days. Growth and feed efficiency ratio were lower on the TOFX diet. Fish muscle concentration of n-3 LC-PUFA was significantly higher for TOFX than for FOPO fish, but not higher than for FO fish, while retention efficiency of n-3 LC-PUFA was promoted by TOFX relative to FO. Proteomics analysis revealed an oxidative stress response indicative of the main adaptive physiological mechanism in TOFX fish. While specific dietary fatty acid concentrations and balances and antioxidant supplementation may need further attention, the use of an oil with a high content of DHA and ALA can enhance tissue deposition of n-3 LC-PUFA in relation to a commercially used oil blend. PMID:27556399
Sanjurjo, Pablo; Ruiz-Sanz, Jose I; Jimeno, Pilar; Aldámiz-Echevarría, Luis; Aquino, Lourdes; Matorras, Roberto; Esteban, Judit; Banqué, Montserrat
The nutritional significance of long-chain polyunsaturated fatty acids (LCPS) during the perinatal period is becoming increasingly important. There are currently very few studies on dietary intervention during gestation. The aim of the study was to analyze the effect of docosahexaenoic acid (DHA) supplementation during pregnancy on levels in both the newborn and the mother. A randomized placebo controlled study was carried out on 20 pregnant women in study group receiving 200 mg/day of docosahexaenoic acid-(DHA) during the last trimester of pregnancy. Results in both groups (A supplemented, B non-supplemented) highlighted a decrease in plasma arachidonic acid (5.99 +/- 0.91 vs. 4.51 +/- 0.71 p<0.001 for group A and 5.84 +/- 0.71 vs. 4.80 +/- 0.51 p<0.01 for group B) in the baseline-final intra-group comparison. The intergroup comparison revealed a significant difference in plasma DHA at delivery: it was found to be higher in the population of supplemented pregnant women (3.17 +/- 0.26 vs. 2.77 +/- 0.31). The neonate population displayed no significant differences between the two groups. The results show that LCPS are consumed during the final stages of pregnancy and that oral supplementation with 200 mg/day of DHA is reflected in an increase in the plasma level of this fatty acid in the mother. One could speculate that there would be a corresponding increase in DHA bioavailability for the fetus.
Walser, Buddy; Stebbins, Charles L
Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have beneficial effects on cardiovascular function. We tested the hypotheses that dietary supplementation with DHA (2 g/day) + EPA (3 g/day) enhances increases in stroke volume (SV) and cardiac output (CO) and decreases in systemic vascular resistance (SVR) during dynamic exercise. Healthy subjects received DHA + EPA (eight men, four women) or safflower oil (six men, three women) for 6 weeks. Both groups performed 20 min of bicycle exercise (10 min each at a low and moderate work intensity) before and after DHA + EPA or safflower oil treatment. Mean arterial pressure (MAP), heart rate (HR), SV, CO, and SVR were assessed before exercise and during both workloads. HR was unaffected by DHA + EPA and MAP was reduced, but only at rest (88 +/- 5 vs. 83 +/- 4 mm Hg). DHA + EPA augmented increases in SV (14.1 +/- 6.3 vs. 32.3 +/- 8.7 ml) and CO (8.5 +/- 1.0 vs. 10.3 +/- 1.2 L/min) and tended to attenuate decreases in SVR (-7.0 +/- 0.6 vs. -10.1 +/- 1.6 mm Hg L(-1) min(-1)) during the moderate workload. Safflower oil treatment had no effects on MAP, HR, SV, CO or SVR at rest or during exercise. DHA + EPA-induced increases in SV and CO imply that dietary supplementation with these fatty acids can increase oxygen delivery during exercise, which may have beneficial clinical implications for individuals with cardiovascular disease and reduced exercise tolerance.
Carvajal, Jorge A.
Uteroplacental ischemia may cause preterm birth, either due to preterm labor, preterm premature rupture of membranes, or medical indication (in the presence of preeclampsia or fetal growth restriction). Uteroplacental ischemia is the product of defective deep placentation, a failure of invasion, and transformation of the spiral arteries by the trophoblast. The failure of normal placentation generates a series of clinical abnormalities nowadays called “deep placentation disorders”; they include preeclampsia, fetal growth restriction, preterm labor, preterm premature rupture of membranes, in utero fetal death, and placental abruption. Early reports suggested that a LC-PUFAs (long chain polyunsaturated fatty acids) rich diet reduces the incidence of deep placentation disorders. Recent randomized controlled trials are inconsistent to show the benefit of docosahexaenoic acid (DHA) supplementation during pregnancy to prevent deep placentation disorders, but most of them showed that DHA supplementation was associated with lower risk of early preterm birth. We postulate that DHA supplementation, early in pregnancy, may reduce the incidence of deep placentation disorders. If our hypothesis is correct, DHA supplementation, early in pregnancy, will become a safe and effective strategy for primary prevention of highly relevant pregnancy diseases, such as preterm birth, preeclampsia, and fetal growth restriction. PMID:25019084
Ramakrishnan, Usha; Stinger, Amanda; DiGirolamo, Ann M.; Martorell, Reynaldo; Neufeld, Lynnette M.; Rivera, Juan A.; Schnaas, Lourdes; Stein, Aryeh D.; Wang, Meng
Objective We evaluated the effects of prenatal docosahexaenoic acid (DHA) supplementation on offspring development at 18 months of age. Design Randomized placebo double-blind controlled trial. Settings Cuernavaca, Mexico. Participants and Methods We followed up offspring (n = 730; 75% of the birth cohort) of women in Mexico who participated in a trial of DHA supplementation during the latter half of pregnancy. We assessed the effect of the intervention on child development and the potential modifying effects of gravidity, gender, SES, and quality of the home environment. Interventions or Main Exposures 400 mg/day of algal DHA. Outcome Measures Child development at 18 months of age measured using the Spanish version of the Bayley Scales of Infant Development-II. We calculated standardized psychomotor and mental development indices, and behavior rating scale scores. Results Intent-to-treat differences (DHA-control) were: Psychomotor Developmental Index -0.90 (95% CI: -2.35, 0.56), Mental Developmental Index -0.26 (95% CI: -1.63, 1.10) and Behavior Rating Scale -0.01 (95% CI: -0.95, 0.94). Prenatal DHA intake attenuated the positive association between home environment and psychomotor development index observed in the control group (p for interaction = 0.03) suggesting potential benefits for children living in home environments characterized by reduced caregiver interactions and opportunities for early childhood stimulation. Conclusions Prenatal DHA supplementation in a population with low intakes of DHA had no effects on offspring development at 18 months of age although there may be some benefit for infants from poor quality home environments. Trial Registration Clinicaltrials.gov NCT00646360 PMID:26262896
Wong, Bernice H; Chan, Jia Pei; Cazenave-Gassiot, Amaury; Poh, Rebecca W; Foo, Juat Chin; Galam, Dwight L A; Ghosh, Sujoy; Nguyen, Long N; Barathi, Veluchamy A; Yeo, Sia W; Luu, Chi D; Wenk, Markus R; Silver, David L
Eye photoreceptor membrane discs in outer rod segments are highly enriched in the visual pigment rhodopsin and the ω-3 fatty acid docosahexaenoic acid (DHA). The eye acquires DHA from blood, but transporters for DHA uptake across the blood-retinal barrier or retinal pigment epithelium have not been identified. Mfsd2a is a newly described sodium-dependent lysophosphatidylcholine (LPC) symporter expressed at the blood-brain barrier that transports LPCs containing DHA and other long-chain fatty acids. LPC transport via Mfsd2a has been shown to be necessary for human brain growth. Here we demonstrate that Mfsd2a is highly expressed in retinal pigment epithelium in embryonic eye, before the development of photoreceptors, and is the primary site of Mfsd2a expression in the eye. Eyes from whole body Mfsd2a-deficient (KO) mice, but not endothelium-specific Mfsd2a-deficient mice, were DHA-deficient and had significantly reduced LPC/DHA transport in vivo Fluorescein angiography indicated normal blood-retinal barrier function. Histological and electron microscopic analysis indicated that Mfsd2a KO mice exhibited a specific reduction in outer rod segment length, disorganized outer rod segment discs, and mislocalization of and reduction in rhodopsin early in postnatal development without loss of photoreceptors. Minor photoreceptor cell loss occurred in adult Mfsd2a KO mice, but electroretinography indicated visual function was normal. The developing eyes of Mfsd2a KO mice had activated microglia and up-regulation of lipogenic and cholesterogenic genes, likely adaptations to loss of LPC transport. These findings identify LPC transport via Mfsd2a as an important pathway for DHA uptake in eye and for development of photoreceptor membrane discs.
Lin, Yu Hong; Shah, Samit; Salem, Norman
To investigate the effect of docosahexaenoic acid (DHA) without other highly unsaturated fatty acids (HUFA) on n-3 and n-6 essential fatty acid (EFA) metabolism and fatty acid composition in mammals, a stable isotope tracer technique was used in adult rats fed diets with or without 1.3% of algal DHA in a base diet containing 15% of linoleic acid and 3% of alpha-linolenic acid over 8 weeks. The rats were administered orally a mixed oil containing 48 mg/kg body weight of deuterated linoleic and alpha-linolenic acids and euthanized at 4, 8, 24, 96, 168, 240, 360 and 600 h after administration of the isotopes. Fatty acid compositions and the concentrations of deuterated precursors and their respective metabolites were determined in rat liver, plasma, heart and brain as a function of time. DHA, docosapentaenoic acid and eicosapentaenoic acid in the n-3 EFA family were significantly increased in all organs tested in the DHA-fed group, ranging from 5% to 200% greater in comparison with the control group. The accumulation of the metabolites, deuterated-DHA and deuterated-docosapentaenoic acid n-6 was greatly decreased by 1.5- to 2.5-fold in the dietary DHA group. In summary, feeding preformed DHA led to a marked increase in n-3 HUFA content of rat organs at the expense of n-6 HUFA and also prevented the accumulation of newly synthesized deuterated end products. This is the first study which has isolated the effects of DHA on the de novo metabolism on both the n-6 and n-3 EFA pathways.
Eclov, Julie A; Qian, Qingwen; Redetzke, Rebecca; Chen, Quanhai; Wu, Steven C; Healy, Chastity L; Ortmeier, Steven B; Harmon, Erin; Shearer, Gregory C; O'Connell, Timothy D
Heart failure with preserved ejection fraction (HFpEF) is half of all HF, but standard HF therapies are ineffective. Diastolic dysfunction, often secondary to interstitial fibrosis, is common in HFpEF. Previously, we found that supra-physiologic levels of ω3-PUFAs produced by 12 weeks of ω3-dietary supplementation prevented fibrosis and contractile dysfunction following pressure overload [transverse aortic constriction (TAC)], a model that resembles aspects of remodeling in HFpEF. This raised several questions regarding ω3-concentration-dependent cardioprotection, the specific role of EPA and DHA, and the relationship between prevention of fibrosis and contractile dysfunction. To achieve more clinically relevant ω3-levels and test individual ω3-PUFAs, we shortened the ω3-diet regimen and used EPA- and DHA-specific diets to examine remodeling following TAC. The shorter diet regimen produced ω3-PUFA levels closer to Western clinics. Further, EPA, but not DHA, prevented fibrosis following TAC. However, neither ω3-PUFA prevented contractile dysfunction, perhaps due to reduced uptake of ω3-PUFA. Interestingly, EPA did not accumulate in cardiac fibroblasts. However, FFA receptor 4, a G protein-coupled receptor for ω3-PUFAs, was sufficient and required to block transforming growth factor β1-fibrotic signaling in cultured cardiac fibroblasts, suggesting a novel mechanism for EPA. In summary, EPA-mediated prevention of fibrosis could represent a novel therapy for HFpEF.
Jeckel, Kimberly M.; Veeramachaneni, D. N. Rao; Chicco, Adam J.; Chapman, Phillip L.; Mulligan, Christopher M.; Hegarty, Jennifer R.; Pagliassotti, Michael J.; Ferguson, Lindsay A.; Bouma, Gerrit J.; Frye, Melinda A.
Obesity increases risk for cardiomyopathy in the absence of hypertension, diabetes or ischemia. The fatty acid milieu, modulated by diet, may modify myocardial structure and function, lending partial explanation for the array of cardiomyopathic phenotypy. We sought to identify gross, cellular and ultrastructural myocardial changes associated with Western diet intake, and subsequent modification with docosahexaenoic acid (DHA) supplementation. Wistar and Sprague-Dawley (SD) rats received 1 of 3 diets: control (CON); Western (WES); Western + DHA (WES+DHA). After 12 weeks of treatment, echocardiography was performed and myocardial adiponectin, fatty acids, collagen, area occupied by lipid and myocytes, and ultrastructure were determined. Strain effects included higher serum adiponectin in Wistar rats, and differences in myocardial fatty acid composition. Diet effects were evident in that both WES and WES+DHA feeding were associated with similarly increased left ventricular (LV) diastolic cranial wall thickness (LVWcr/d) and decreased diastolic internal diameter (LVIDd), compared to CON. Unexpectedly, WES+DHA feeding was associated additionally with increased thickness of the LV cranial wall during systole (LVWcr/s) and the caudal wall during diastole (LVWca/d) compared to CON; this was observed concomitantly with increased serum and myocardial adiponectin. Diastolic dysfunction was present in WES+DHA rats compared to both WES and CON. Myocyte cross sectional area (CSA) was greater in WES compared to CON rats. In both fat-fed groups, transmission electron microscopy (TEM) revealed myofibril degeneration, disorganized mitochondrial cristae, lipid inclusions and vacuolation. In the absence of hypertension and whole body insulin resistance, WES+DHA intake was associated with more global LV thickening and with diastolic dysfunction, compared to WES feeding alone. Myocyte hypertrophy, possibly related to subcellular injury, is an early change that may contribute to gross
Abdi, J; Garssen, J; Faber, J; Redegeld, F A
The n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to enhance the effect of chemotherapeutic drugs in clinical studies in cancer patients and to induce apoptotic tumor cell death in vitro. Until now, EPA and DHA have never been investigated in multiple myeloma (MM). Human myeloma cells (L363, OPM-1, OPM-2 and U266) and normal peripheral blood mononuclear cells were exposed to EPA and DHA, and effects on mitochondrial function and apoptosis, caspase-3 activation, gene expression and drug toxicity were measured. Exposure to EPA and DHA induced apoptosis and increased sensitivity to bortezomib in MM cells. Importantly, they did not affect viability of normal human peripheral mononuclear cells. Messenger RNA expression arrays showed that EPA and DHA modulated genes involved in multiple signaling pathways including nuclear factor (NF) κB, Notch, Hedgehog, oxidative stress and Wnt. EPA and DHA inhibited NFκB activity and induced apoptosis through mitochondrial perturbation and caspase-3 activation. Our study suggests that EPA and DHA induce selective cytotoxic effects in MM and increase sensitivity to bortezomib and calls for further exploration into a potential application of these n-3 polyunsaturated fatty acids in the therapy of MM.
Stamey, J A; Shepherd, D M; de Veth, M J; Corl, B A
Fish oil is used as a ration additive to provide n-3 fatty acids to dairy cows. Fish do not synthesize n-3 fatty acids; they must consume microscopic algae or other algae-consuming fish. New technology allows for the production of algal biomass for use as a ration supplement for dairy cattle. Lipid encapsulation of the algal biomass protects n-3 fatty acids from biohydrogenation in the rumen and allows them to be available for absorption and utilization in the small intestine. Our objective was to examine the use of algal products as a source for n-3 fatty acids in milk. Four mid-lactation Holsteins were assigned to a 4×4 Latin square design. Their rations were supplemented with 1× or 0.5× rumen-protected (RP) algal biomass supplement, 1× RP algal oil supplement, or no supplement for 7 d. Supplements were lipid encapsulated (Balchem Corp., New Hampton, NY). The 1× supplements provided 29 g/d of docosahexaenoic acid (DHA), and 0.5× provided half of this amount. Treatments were analyzed by orthogonal contrasts. Supplementing dairy rations with rumen-protected algal products did not affect feed intake, milk yield, or milk component yield. Short- and medium-chain fatty acid yields in milk were not influenced by supplements. Both 0.5× and 1× RP algae supplements increased daily milk fat yield of DHA (0.5 and 0.6±0.10 g/d, respectively) compared with 1× RP oil (0.3±0.10 g/d), but all supplements resulted in milk fat yields greater than that of the control (0.1±0.10g/d). Yield of trans-18:1 fatty acids in milk fat was also increased by supplementation. Trans-11 18:1 yield (13, 20, 27, and 15±3.0 g/d for control, 0.5× RP algae, 1× RP algae, and 1× RP oil, respectively) was greater for supplements than for control. Concentration of DHA in the plasma lipid fraction on d 7 showed that the DHA concentration was greatest in plasma phospholipid. Rumen-protected algal biomass provided better DHA yield than algal oil. Feeding lipid-encapsulated algae supplements
Corder, Katherine E.; Newsham, Katherine R.; McDaniel, Jennifer L.; Ezekiel, Uthayashanker R.; Weiss, Edward P.
The omega-3 fatty acid docosahexaenoic acid (DHA) has anti-inflammatory and anti-nociceptive (pain inhibiting) effects. Because strenuous exercise often results in local inflammation and pain, we hypothesized that DHA supplementation attenuates the rise in markers of local muscle inflammation and delayed onset muscle soreness (DOMS) that occur after eccentric strength exercise. Twenty-seven, healthy women (33 ± 2 y, BMI 23.1±1.0 kg·m-2) were randomized to receive 9d of 3000 mg/d DHA or placebo in a double-blind fashion. On day 7 of the supplementation period, the participants performed 4 sets of maximal-effort eccentric biceps curl exercise. Before and 48h after the eccentric exercise, markers of inflammation were measured including measures of muscle soreness (10-point visual analog pain scale, VAS), swelling (arm circumference), muscle stiffness (active and passive elbow extension), skin temperature, and salivary C-reactive protein (CRP) concentrations. As expected, muscle soreness and arm circumference increased while active and passive elbow extension decreased. The increase in soreness was 23% less in the DHA group (48h increase in VAS soreness ratings: 4.380.4 vs. 5.600.5, p=0.02). Furthermore, the number of subjects who were able to achieve full active elbow extension 48h after eccentric exercise was greater in the DHA group (71% vs. 15%, p = 0.006), indicating significantly less muscle stiffness. No between-group differences were observed for passive elbow extension (p = 0.78) or arm swelling (p = 0.75). Skin temperature and salivary CRP concentrations did not change from baseline to 48h after exercise in either group. These findings indicate that short-term DHA supplementation reduces exercise-induced muscle soreness and stiffness. Therefore, in addition to other health benefits that n-3 fatty acids have been associated with, DHA supplementation could be beneficial for improving tolerance to new and/or strenuous exercise programs and thereby might
Corder, Katherine E; Newsham, Katherine R; McDaniel, Jennifer L; Ezekiel, Uthayashanker R; Weiss, Edward P
The omega-3 fatty acid docosahexaenoic acid (DHA) has anti-inflammatory and anti-nociceptive (pain inhibiting) effects. Because strenuous exercise often results in local inflammation and pain, we hypothesized that DHA supplementation attenuates the rise in markers of local muscle inflammation and delayed onset muscle soreness (DOMS) that occur after eccentric strength exercise. Twenty-seven, healthy women (33 ± 2 y, BMI 23.1±1.0 kg·m(-2)) were randomized to receive 9d of 3000 mg/d DHA or placebo in a double-blind fashion. On day 7 of the supplementation period, the participants performed 4 sets of maximal-effort eccentric biceps curl exercise. Before and 48h after the eccentric exercise, markers of inflammation were measured including measures of muscle soreness (10-point visual analog pain scale, VAS), swelling (arm circumference), muscle stiffness (active and passive elbow extension), skin temperature, and salivary C-reactive protein (CRP) concentrations. As expected, muscle soreness and arm circumference increased while active and passive elbow extension decreased. The increase in soreness was 23% less in the DHA group (48h increase in VAS soreness ratings: 4.380.4 vs. 5.600.5, p=0.02). Furthermore, the number of subjects who were able to achieve full active elbow extension 48h after eccentric exercise was greater in the DHA group (71% vs. 15%, p = 0.006), indicating significantly less muscle stiffness. No between-group differences were observed for passive elbow extension (p = 0.78) or arm swelling (p = 0.75). Skin temperature and salivary CRP concentrations did not change from baseline to 48h after exercise in either group. These findings indicate that short-term DHA supplementation reduces exercise-induced muscle soreness and stiffness. Therefore, in addition to other health benefits that n-3 fatty acids have been associated with, DHA supplementation could be beneficial for improving tolerance to new and/or strenuous exercise programs and thereby might
Keenan, Kate; Hipwell, Alison E.; Bortner, Jenna; Hoffmann, Amy; McAloon, Rose
Objective To test the association between docosahexaenoic acid (DHA)supplementation and perceived stress and cortisol response to a stressor during pregnancy in a sample of African American women living in low-income environments. Methods Sixty-four African American women were enrolled at 16–21 weeks of gestation. Power calculations were computed using published standard deviations for the Perceived Stress Scale and the Trier Social Stress Test. Participants were randomized to either 450 mg per day of DHA(n=43) or placebo (n=21).At baseline, 24, and 30 weeks of gestation, perceived stress was assessed by self-report. Cortisol response to a controlled stressor, the Trier Social Stress Test (TSST) was measured from saliva samples collected upon arrival to the laboratory and after the completion of the TSST. Results Women in the DHA supplementation group reported lower levels of perceived stress at 30 weeks of gestation, controlling for depression and negative life events (mean = 27.4 versus 29.5, (F [3, 47] = 5.06, p = .029, cohen’s d = .65). Women in the DHA supplementation had lower cortisol output in response to arriving to the laboratory and a more modulated response to the stressor (F [1.78, 83.85] = 6.24, p = .004, cohen’s d = .76). Conclusions Pregnant women living in urban low-income environments who received DHA reported reduced perceived stress and lower levels of stress hormones in the third trimester. DHA supplementation may be a method for attenuating the effects of maternal stress during late pregnancy and improving the uterine environment with regard to fetal exposure to glucocorticoids. PMID:25415158
Le Guen, Marie; Chaté, Valérie; Hininger-Favier, Isabelle; Laillet, Brigitte; Morio, Béatrice; Pieroni, Gérard; Schlattner, Uwe; Pison, Christophe; Dubouchaud, Hervé
Decline in skeletal muscle mass and function starts during adulthood. Among the causes, modifications of the mitochondrial function could be of major importance. Polyunsaturated fatty (ω-3) acids have been shown to play a role in intracellular functions. We hypothesize that docosahexaenoic acid (DHA) supplementation could improve muscle mitochondrial function that could contribute to limit the early consequences of aging on adult muscle. Twelve-month-old male Wistar rats were fed a low-polyunsaturated fat diet and were given DHA (DHA group) or placebo (control group) for 9 wk. Rats from the DHA group showed a higher endurance capacity (+56%, P < 0.05) compared with control animals. Permeabilized myofibers from soleus muscle showed higher O2 consumptions (P < 0.05) in the DHA group compared with the control group, with glutamate-malate as substrates, both in basal conditions (i.e., state 2) and under maximal conditions (i.e., state 3, using ADP), along with a higher apparent Km for ADP (P < 0.05). Calcium retention capacity of isolated mitochondria was lower in DHA group compared with the control group (P < 0.05). Phospho-AMPK/AMPK ratio and PPARδ mRNA content were higher in the DHA group compared with the control group (P < 0.05). Results showed that DHA enhanced endurance capacity in adult animals, a beneficial effect potentially resulting from improvement in mitochondrial function, as suggested by our results on permeabilized fibers. DHA supplementation could be of potential interest for the muscle function in adults and for fighting the decline in exercise tolerance with age that could imply energy-sensing pathway, as suggested by changes in phospho-AMPK/AMPK ratio.
Keithly, J I; Kott, R W; Berardinelli, J G; Moreaux, S; Hatfield, P G
Neonatal lamb mortality is a major factor affecting profitability in the sheep industry, and lamb thermogenesis is a key element in neonatal lamb survival. Increased lamb vigor has been reported when ewes were supplemented during late gestation with algae-derived docosahexaenoic acid (DHA); however, the effects of DHA on lamb thermogenesis and immunocompetence have not been investigated. Eighty twin-bearing Targhee ewes (ages 2 to 5 yr; 68.5 ± 3 kg) were assigned randomly to 1 of 2 supplement treatments to determine the effects of feeding DHA to ewes during late gestation and early lactation on lamb thermogenesis, serum metabolites and hormones, and lamb growth. Supplement treatments were 12 g·ewe(-1)·d(-1) of algae-derived DHA (DHA Gold Advanced Bionutrition Corp., Columbia, MD; algae-derived DHA); and no algae-derived DHA (control). Supplements were individually fed daily during the last 30 d (±7 d) of gestation and pen fed (6 pens/treatment with 6 or 7 ewes/pen) during the first 38 d (±7 d) of lactation. One hour after lambing and before nursing, twin-born lambs were weighed, blood sampled via jugular puncture, and placed in a dry cold chamber for 30 min (0°C), and rectal temperatures were recorded every minute for 30 min. Lambs were removed from the cold chamber, blood sampled, warmed for 15 min, and returned to their dam. Ewes were blood sampled, and colostrum samples were collected 1 h postpartum. Ewe and lamb sera were assayed for glucose, NEFA, cortisol, and leptin. Lamb rectal temperature, glucose, NEFA, cortisol, leptin, and birth weights did not differ between treatments. The BW at 38 d was greater (P = 0.03) for lambs born to control ewes than for lambs born to algae-derived DHA-supplemented ewes; however, the colostrum of algae-derived DHA-supplemented ewes had a greater specific gravity (P = 0.05) than for control ewes. Overall, despite a potentially positive effect on ewe colostral IgG concentrations, supplementation of algae-derived DHA during
Substitution of dietary saturated fat by oleic acid and/or polyunsaturated fatty acids (PUFA) has been described to reduce the cardiovascular risk by reducing blood lipids, mainly cholesterol. Additional benefits have been described for long chain omega-3 PUFA (eicosapentaenoic acid-EPA and docosahexaenoic acid-DHA) from fish oils. In recent years, food technology has been used to produce dairy drinks with a reduced content of saturated fat in favour of those fatty acids, most of them claiming cardiovascular benefits. This review summarises all the scientific evidence regarding the effects of milks enriched with long chain omega-3 PUFA (EPA+DHA) and/or oleic acid on cardiovascular health. Nine controlled intervention studies with enriched milks have reported effects on healthy volunteers, subjects with increased risk factors and cardiovascular patients. The main effects observed were reductions of blood lipids, mainly cholesterol, LDL-cholesterol and triglycerides.
Jackson, Philippa A; Deary, Michael E; Reay, Jonathon L; Scholey, Andrew B; Kennedy, David O
The n-3 PUFA are a unique class of fatty acids that cannot be manufactured by the body, and must be acquired via dietary sources. In the UK, as well as in other Western nations, these 'essential' fatty acids are consumed in quantities that fall below government guidelines. The present study explored the effects of 12 weeks' dietary supplementation with 1 g/d of two types of fish oil (FO; DHA-rich and EPA-rich) in 159 healthy young adults aged 18-35 years. An assessment of performance on a battery of computerised cognitive tasks and mood measures took place before and following the 12-week treatment regimen. Venous blood samples were also supplied by participants at both time points which were later analysed for serum fatty acid concentrations. Despite good adherence to the study protocol - as reflected in increased concentrations of n-3 serum fatty acids - compared with placebo, the observed effects of both active treatments were minimal. The only finding of note revealed that supplementation with EPA-rich FO may reduce subjective mental fatigue at times of high cognitive demand, although further investigation is required. These findings, taken together with other recent reports of null effects, suggest that dietary supplementation with n-3 PUFA in healthy, normally developing and impairment-free populations is unlikely to result in cognitive enhancement.
Effects of DHA Supplementation on Vascular Function, Telomerase Activity in PBMC, Expression of Inflammatory Cytokines, and PPARγ-LXRα-ABCA1 Pathway in Patients With Type 2 Diabetes Mellitus: Study Protocol for Randomized Controlled Clinical Trial.
Toupchian, Omid; Sotoudeh, Gity; Mansoori, Anahita; Djalali, Mahmoud; Keshavarz, Seyyed Ali; Nasli-Esfahani, Ensieh; Alvandi, Ehsan; Koohdani, Fariba
Docosahexaenoic acid (DHA), as an omega-3 fatty acid, in a natural ligand of peroxisome proliferator-activated receptors (PPARs). Regarding the combinative effects of Nutrigenomics and Nutrigenetics and due to the lack of in vivo studies conducted using natural ligands of PPARs, we aimed to evaluate the effects of DHA supplementation on vascular function, telomerase activity, and PPARγ-LXRα-ABCA1 pathway, in patients with type 2 diabetes mellitus (T2DM), based on the Pro12Ala polymorphism in PPARγ encoding gene. 72 T2DM patients (36 dominant and 36 recessive allele carriers), aged 30-70, with body mass index of 18.5 to 35 kg/m2, will be participated in this double blind randomized controlled trial. In each group, stratification will be performed based on sex and age and participants will be randomly assigned to receive 2.4 g/day DHA or placebo (paraffin) for 8 weeks. PPARγ genotyping will be carried out using PCR-RFLP method; Telomerase activity will be estimated by PCR-ELISA TRAP assay; mRNA expression levels of target genes will be assessed using real time PCR. Serum levels of ADMA, sCD163 and adiponectin, will be measured using ELISA commercial kits. The present study is designed in order to help T2DM patients to modify their health conditions based on their genetic backgrounds, and to recommend the proper food ingredients as the natural agonists for PPARs in order to prevent and treat metabolic abnormalities of the disease.
Gurzell, Eric A; Wiesinger, Jason A; Morkam, Christina; Hemmrich, Sophia; Harris, William S; Fenton, Jenifer I
Despite numerous studies investigating n-3 long chain polyunsaturated fatty acid (LCPUFA) supplementation and inflammatory bowel diseases (IBD), the extent to which dietary n-3 LCPUFAs incorporate in gastrointestinal (GI) tissues and correlate with red blood cell (RBC) n-3 LCPUFA content is unknown. In this study, mice were fed three diets with increasing percent of energy (%en) derived from eicosapentaenoic acid (EPA)+docosahexaenoic acid (DHA). Dietary levels reflected recommended intakes of fish/fish oil by the American Heart Association. We analyzed the FA composition of phospholipids extracted from RBCs, plasma, and GI tissues. We observed that the 0.1%en EPA+DHA diet was sufficient to significantly increase the omega-3 index (RBC EPA+DHA) after 5 week feeding. The baseline EPA levels were 0.2-0.6% across all tissues increasing to 1.6-4.3% in the highest EPA+DHA diet; these changes resulted in absolute increases of 1.4-3.9% EPA across tissues. The baseline DHA levels were 2.2-5.9% across all tissues increasing to 5.8-10.5% in the highest EPA+DHA diet; these changes resulted in absolute increases of 3.2-5.7% DHA across tissues. These increases in EPA and DHA across all tissues resulted in strong (r>0.91) and significant (P<0.001) linear correlations between the omega-3 index and plasma/GI tissue EPA+DHA content, suggesting that the omega-3 index reflects the relative amounts of EPA+DHA in GI tissues. These data demonstrate that the GI tissues are highly responsive to dietary LCPUFA supplementation and that the omega-3 index can serve as a valid biomarker for assessing dietary EPA+DHA incorporation into GI tissues.
Rousseau, D; Moreau, D; Raederstorff, D; Sergiel, J P; Rupp, H; Muggli, R; Grynberg, A
Epidemiological studies suggest that n-3 polyunsaturated fatty acids (PUFA) are involved in the prevention of cardiovascular disease. Stress is known to increase the incidence of CVD and the present study was realised to evaluate some physiological and biochemical effects of dietary docosahexaenoic acid (DHA) in male Wistar rats subjected to a psycho social stress. Rats were fed for 8 weeks a semi-purified diet containing 10% of either sunflower seed oil or the same oil supplemented with DHA. This food supply represented 50% of their daily requirement. The remaining 50% were supplied as 45 mg food pellets designed to induce stress in rats by an intermittent-feeding schedule process. The control group (n = 12) was fed the equivalent food ration as a single daily feeding. The physiological cardiovascular parameters were recorded by telemetry through a transmitter introduced in the abdomen. At the end of the experimentation, the heart and adrenals were withdrawn and the fatty acid composition and the catecholamine store were determined. Dietary DHA induced a pronounced alteration of the fatty acid profile of cardiac phospholipids (PL). The level of all the n-6 PUFAs was reduced while 22:6 n-3 was increased. The stress induced a significant increase in heart rate which was not observed in DHA-fed group. The time evolution of the systolic blood pressure was not affected by the stress and was roughly similar in the stressed rats of either dietary group. Conversely, the systolic blood pressure decreased in the unstressed rats fed DHA. Similar data were obtained for the diastolic blood pressure. The beneficial effect of DHA was also observed on cardiac contractility, since the dP/dt(max) increase was prevented in the DHA-fed rats. The stress-induced modifications were associated with an increase in cardiac noradrenaline level which was not observed in DHA-fed rats. The fatty acid composition of adrenals was significantly related to the fatty acid intake particularly the
Al Mamun, Abdullah; Hashimoto, Michio; Katakura, Masanori; Tanabe, Yoko; Tsuchikura, Satoru; Hossain, Shahdat; Shido, Osamu
The effects of cholesterol-lowering statins, which substantially benefit future cardiovascular events, on fatty acid metabolism have remained largely obscured. In this study, we investigated the effects of atorvastatin on fatty acid metabolism together with the effects of TAK-085 containing highly purified eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) ethyl ester on atorvastatin-induced n-3 polyunsaturated fatty acid lowering in SHR.Cg-Lepr(cp)/NDmcr (SHRcp) rats, as a metabolic syndrome model. Supplementation with 10mg/kg body weight/day of atorvastatin for 17 weeks significantly decreased plasma total cholesterol and very low density lipoprotein cholesterol. Atorvastatin alone caused a subtle change in fatty acid composition particularly of EPA and DHA in the plasma, liver or erythrocyte membranes. However, the TAK-085 consistently increased both the levels of EPA and DHA in the plasma, liver and erythrocyte membranes. After confirming the reduction of plasma total cholesterol, 300mg/kg body weight/day of TAK-085 was continuously administered for another 6 weeks. Supplementation with TAK-085 did not decrease plasma total cholesterol but significantly increased the EPA and DHA levels in both the plasma and liver compared with rats administered atorvastatin only. Supplementation with atorvastatin alone significantly decreased sterol regulatory element-binding protein-1c, Δ5- and Δ6-desaturases, elongase-5, and stearoyl-coenzyme A (CoA) desaturase-2 levels and increased 3-hydroxy-3-methylglutaryl-CoA reductase mRNA expression in the liver compared with control rats. TAK-085 supplementation significantly increased stearoyl-CoA desaturase-2 mRNA expression. These results suggest that long-term supplementation with atorvastatin decreases the EPA and DHA levels by inhibiting the desaturation and elongation of n-3 fatty acid metabolism, while TAK-085 supplementation effectively replenishes this effect in SHRcp rat liver.
Forsyth, Stewart; Gautier, Sheila; Salem, Norman
Although the literature on the contribution of DHA and arachidonic acid (ARA) to fundamental metabolic functions in brain, immune and cardiovascular systems is extensive, there is a lack of consensus on the need for explicit recommendations on dietary intake for both DHA and ARA during the early years of life. This review takes a public health perspective with the objective of ensuring that recommendations protect the most vulnerable children worldwide. Most studies on the effects of DHA and ARA in early life have been undertaken in high-income countries and this is reflected in policy recommendations. Although breast milk is considered the gold standard and always contains DHA and ARA, there are proposals that infant formulas, especially follow-on formulas, do not need to be supplemented with these fatty acids. Complementary foods frequently have low concentrations of ARA and DHA and this is most significant in low-income countries where availability is also limited. Recent evidence shows that in developing countries, intakes of DHA and ARA during the age period 6-36 months are low and this relates to low national income. It is concluded that a continuum of DHA and ARA intake needs to be maintained during early life, a critical period of infant growth and development. For both infant and follow-on formulas, DHA and ARA should be mandatory at levels that are equivalent to breast milk. An optional recommendation may be limited to countries that can demonstrate evidence of adequate intakes of DHA and ARA during early life.
Dyall, Simon C.
Omega-3 polyunsaturated fatty acids (PUFAs) exhibit neuroprotective properties and represent a potential treatment for a variety of neurodegenerative and neurological disorders. However, traditionally there has been a lack of discrimination between the different omega-3 PUFAs and effects have been broadly accredited to the series as a whole. Evidence for unique effects of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and more recently docosapentaenoic acid (DPA) is growing. For example, beneficial effects in mood disorders have more consistently been reported in clinical trials using EPA; whereas, with neurodegenerative conditions such as Alzheimer’s disease, the focus has been on DHA. DHA is quantitatively the most important omega-3 PUFA in the brain, and consequently the most studied, whereas the availability of high purity DPA preparations has been extremely limited until recently, limiting research into its effects. However, there is now a growing body of evidence indicating both independent and shared effects of EPA, DPA and DHA. The purpose of this review is to highlight how a detailed understanding of these effects is essential to improving understanding of their therapeutic potential. The review begins with an overview of omega-3 PUFA biochemistry and metabolism, with particular focus on the central nervous system (CNS), where DHA has unique and indispensable roles in neuronal membranes with levels preserved by multiple mechanisms. This is followed by a review of the different enzyme-derived anti-inflammatory mediators produced from EPA, DPA and DHA. Lastly, the relative protective effects of EPA, DPA and DHA in normal brain aging and the most common neurodegenerative disorders are discussed. With a greater understanding of the individual roles of EPA, DPA and DHA in brain health and repair it is hoped that appropriate dietary recommendations can be established and therapeutic interventions can be more targeted and refined. PMID:25954194
Dyall, Simon C
Omega-3 polyunsaturated fatty acids (PUFAs) exhibit neuroprotective properties and represent a potential treatment for a variety of neurodegenerative and neurological disorders. However, traditionally there has been a lack of discrimination between the different omega-3 PUFAs and effects have been broadly accredited to the series as a whole. Evidence for unique effects of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and more recently docosapentaenoic acid (DPA) is growing. For example, beneficial effects in mood disorders have more consistently been reported in clinical trials using EPA; whereas, with neurodegenerative conditions such as Alzheimer's disease, the focus has been on DHA. DHA is quantitatively the most important omega-3 PUFA in the brain, and consequently the most studied, whereas the availability of high purity DPA preparations has been extremely limited until recently, limiting research into its effects. However, there is now a growing body of evidence indicating both independent and shared effects of EPA, DPA and DHA. The purpose of this review is to highlight how a detailed understanding of these effects is essential to improving understanding of their therapeutic potential. The review begins with an overview of omega-3 PUFA biochemistry and metabolism, with particular focus on the central nervous system (CNS), where DHA has unique and indispensable roles in neuronal membranes with levels preserved by multiple mechanisms. This is followed by a review of the different enzyme-derived anti-inflammatory mediators produced from EPA, DPA and DHA. Lastly, the relative protective effects of EPA, DPA and DHA in normal brain aging and the most common neurodegenerative disorders are discussed. With a greater understanding of the individual roles of EPA, DPA and DHA in brain health and repair it is hoped that appropriate dietary recommendations can be established and therapeutic interventions can be more targeted and refined.
Li, You; Li, Hong-tian; Trasande, Leonardo; Ge, Hua; Yu, Li-xia; Xu, Gao-sheng; Bai, Man-xi; Liu, Jian-meng
Few studies have examined docosahexaenoic acid (DHA) in pregnant and lactating women in developing countries like China, where DHA-enriched supplements are increasingly popular. We aimed to assess the DHA status among Chinese pregnant and lactating women residing areas differing in the availability of aquatic products. In total, 1211 women in mid-pregnancy (17 ± 2 weeks), late pregnancy (39 ± 2 weeks), or lactation (42 ± 7 days) were enrolled from Weihai (coastland), Yueyang (lakeland), and Baotou (inland) city, with approximately 135 women in each participant group by region. DHA concentrations were measured using capillary gas chromatography, and are reported as weight percent of total fatty acids. Mean plasma DHA concentrations were higher in coastland (mid-pregnancy 3.19%, late pregnancy 2.54%, lactation 2.24%) and lakeland women (2.45%, 1.95%, 2.26%) than inland women (2.25%, 1.67%, 1.68%) (p values < 0.001). Similar differences were observed for erythrocyte DHA. We conclude that DHA concentrations of Chinese pregnant and lactating women are higher in coastland and lakeland regions than in inland areas. DHA status in the study population appears to be stronger than populations from other countries studied to date. PMID:26506380
Marangoni, Franca; Poli, Andrea
n-3 polyunsaturated fatty acids (n-3 PUFAs) are essential for mammalian cells that are not able to synthesise de novo their precursor, α-linolenic acid, and may only partially convert it to eicosapentaenoic acid (EPA) and to a very small extent to docosahexaenoic acid (DHA). For this reason, nutritional guidelines for cardiovascular prevention recommend regular fish consumption (approximately two portions per week) in order to increase the intake of the n-3 PUFAs EPA and DHA, mainly referring to fatty fish, living in cold waters, usually very rich in these fatty acids. However, the indication to consume fish regularly is unlikely to be sufficient to ensure that patients with documented coronary heart diseases receive the daily amount of EPA+DHA (ca. 1g) necessary for effective secondary prevention of the disease. This has prompted the development of pharmaceutical formulations both for dietary supplementation and for therapeutic administration, based on several dietary sources, containing greatly variable amounts of EPA and DHA, often with different availabilities. Critical knowledge of these characteristics allows the selection of the best approach in order to optimise the n-3 PUFA supply in various individuals.
Walker, Celia G; Jebb, Susan A; Calder, Philip C
There is substantial evidence to show that consumption and increased blood levels of the very long-chain (VLC) ω-3 polyunsaturated fatty acids (ω-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with health benefits. The consumption of oily fish is an effective way of increasing EPA and DHA intake and status, but intake in most Western countries remains below the levels recommended for optimal health. The reasons for this include not liking the taste, a concern about sustainability of fish supplies, or potential chemical and heavy metal contamination. Alternative dietary sources of ω-3 fatty acids to enhance EPA and DHA status in the body would therefore be beneficial. There are many non-fish food sources of the essential plant-derived ω-3 fatty acid α-linolenic acid, but conversion from this to longer-chain EPA and especially to DHA is poor. Stearidonic acid (SDA) is an intermediate fatty acid in the biosynthetic pathway from α-linolenic acid to VLC ω-3 PUFAs and the conversion from SDA is more efficient than from α-linolenic acid. However, there are few food sources rich in SDA. Oil crops naturally rich in SDA or enriched through genetic modification may offer an alternative supplemental oil to boost the population status of VLC ω-3 PUFAs. This review discusses the currently available evidence that increased SDA consumption can increase red blood cell EPA content, although this is less than the effect of supplementation directly with EPA. There is now a need for trials specifically designed to assess whether an increased SDA consumption would translate into improved human health outcomes.
Ghini, Veronica; Di Nunzio, Mattia; Tenori, Leonardo; Valli, Veronica; Danesi, Francesca; Capozzi, Francesco; Luchinat, Claudio; Bordoni, Alessandra
Cell supplementation with bioactive molecules often causes a perturbation in the whole intracellular environment. Omics techniques can be applied for the assessment of this perturbation. In this study, the overall effect of docosahexaenoic acid (DHA) supplementation on cultured human hepatocyte lipidome and metabolome has been investigated using nuclear magnetic resonance (NMR) in combination with traditional techniques. The effect of two additional bioactives sharing with DHA the lipid-lowering effect—propionic acid (PRO) and protocatechuic acid (PCA)—has also been evaluated in the context of possible synergism. NMR analysis of the cell lipid extracts showed that DHA supplementation, alone or in combination with PCA or PRO, strongly altered the cell lipid profile. The perfect discrimination between cells receiving DHA (alone or in combination) and the other cells reinforced the idea of a global rearrangement of the lipid environment induced by DHA. Notably, gas chromatography and fluorimetric analyses confirmed the strong discrimination obtained by NMR. The DHA signature was evidenced not only in the cell lipidome, but also in the metabolome. Results reported herein indicate that NMR, combined with other techniques, represents a fundamental approach to studying the effect of bioactive supplementation, particularly in the case of molecules with a broad spectrum of mechanisms of action. PMID:28208746
Emery, James A; Norambuena, Fernando; Trushenski, Jesse; Turchini, Giovanni M
Due to the scarcity of marine fish oil resources, the aquaculture industry is developing more efficient strategies for the utilization of dietary omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA). A better understanding of how fish utilize EPA and DHA, typically provided by fish oil, is needed. However, EPA and DHA have different physiological functions, may be metabolized and incorporated into tissues differently, and may vary in terms of their importance in meeting the fatty acid requirements of fish. To address these questions, Atlantic salmon were fed experimental diets containing, as the sole added dietary lipid source, fish oil (positive control), tallow (negative control), or tallow supplemented with EPA, DHA, or both fatty acids to ~50 or 100% of their respective levels in the positive control diet. Following 14 weeks of feeding, the negative control diet yielded optimum growth performance. Though surprising, these results support the notion that Atlantic salmon requirements for n-3 LC-PUFA are quite low. EPA was largely β-oxidized and inefficiently deposited in tissues, and increasing dietary levels were associated with potential negative effects on growth. Conversely, DHA was completely spared from catabolism and very efficiently deposited into flesh. EPA bioconversion to DHA was largely influenced by substrate availability, with the presence of preformed DHA having little inhibitory effect. These results clearly indicate EPA and DHA are metabolized differently by Atlantic salmon, and suggest that the n-3 LC-PUFA dietary requirements of Atlantic salmon may be lower than reported and different, if originating primarily from EPA or DHA.
Poudyal, Hemant; Panchal, Sunil K; Ward, Leigh C; Brown, Lindsay
We compared the cardiovascular, hepatic and metabolic responses to individual dietary n-3 fatty acids (α-linolenic acid, ALA; eicosapentaenoic acid, EPA; and docosahexaenoic acid, DHA) in a high-carbohydrate, high-fat diet-induced model of metabolic syndrome in rats. Additionally, we measured fatty acid composition of plasma, adipose tissue, liver, heart and skeletal muscle in these rats. The same dosages of ALA and EPA/DHA produced different physiological responses to decrease the risk factors for metabolic syndrome. ALA did not reduce total body fat but induced lipid redistribution away from the abdominal area and favorably improved glucose tolerance, insulin sensitivity, dyslipidemia, hypertension and left ventricular dimensions, contractility, volumes and stiffness. EPA and DHA increased sympathetic activation, reduced the abdominal adiposity and total body fat and attenuated insulin sensitivity, dyslipidemia, hypertension and left ventricular stiffness but not glucose tolerance. However, ALA, EPA and DHA all reduced inflammation in both the heart and the liver, cardiac fibrosis and hepatic steatosis. These effects were associated with complete suppression of stearoyl-CoA desaturase 1 activity. Since the physiological responses to EPA and DHA were similar, it is likely that the effects are mediated by DHA with EPA serving as a precursor. Also, ALA supplementation increased DHA concentrations but induced different physiological responses to EPA and DHA. This result strongly suggests that ALA has independent effects in metabolic syndrome, not relying on its metabolism to DHA.
Largo, Carlota; Muñoz, David; Tabernero, María; Baeza, Ramiro; Otero, Cristina; García, Hugo S.; Ferrer, Mercedes
Benefits of n-3 polyunsaturated fatty acids (PUFAs) against cardiovascular diseases have been reported. Vascular tone regulation is largely mediated by endothelial factors whose release is modulated by sex hormones. Since the incidence of cardiovascular pathologies has been correlated with decreased levels of sex hormones, the aim of this study was to analyze whether a diet supplemented with the specific PUFA docosahexaenoic acid (DHA) could prevent vascular changes induced by an impaired gonadal function. For this purpose, control and orchidectomized rats were fed with a standard diet supplemented with 5% (w/w) sunflower oil or with 3% (w/w) sunflower oil plus 2% (w/w) DHA. The lipid profile, the blood pressure, the production of prostanoids and nitric oxide (NO), and the redox status of biological samples from control and orchidectomized rats, fed control or DHA-supplemented diet, were analyzed. The vasodilator response and the contribution of NO, prostanoids and hyperpolarizing mechanisms were also studied. The results showed that orchidectomy negatively affected the lipid profile, increased the production of prostanoids and reactive oxygen species (ROS), and decreased NO production and the antioxidant capacity, as well as the participation of hyperpolarizing mechanisms in the vasodilator responses. The DHA-supplemented diet of the orchidectomized rats decreased the release of prostanoids and ROS, while increasing NO production and the antioxidant capacity, and it also improved the lipid profile. Additionally, it restored the participation of hyperpolarizing mechanisms by activating potassium. Since the modifications induced by the DHA-supplemented diet were observed in the orchidectomized, but not in the healthy group, DHA seems to exert cardioprotective effects in physiopathological situations in which vascular dysfunction exists. PMID:26540339
From a global health perspective, increased intake of omega-3 fatty acids (FAs), in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial for human health. However, the consumption of EPA- and DHA-rich foods such as fatty fish is low in the Western diet. Therefore, finding new ways to motivate people to increase their consumption of omega-3 FAs is essential. To find effective ways to motivate individuals, understanding people's awareness of omega-3 FAs and how they obtain their knowledge about nutrition and health is critical. Consequently, we developed an online survey to assess awareness and self-reported intake of omega-3 FAs and supplements in young adults. EPA and DHA are also produced endogenously to a limited extent through a pathway regulated by fatty acid desaturase 1 and 2 (FADS1 and FADS2) genes. Of relevance, single nucleotide polymorphisms (SNPs) in the FADS genes influence levels of omega-3 FAs, where minor allele carriers have lower levels compared with major allele carriers. Accordingly, we conducted a clinical trial to investigate FA levels in response to dietary EPA and DHA supplementation in young adults stratified by SNPs in FADS1 and FADS2. The level of reported awareness of omega-3 terminology varied depending on an individual's field of study and thus providing all participants with the same set of nutrition information could be an effective tool to increase knowledge and motivate behaviour change. Additionally, the variation in FA levels in accordance to SNPs in FADS1 and FADS2 could be used to create tailored nutritional recommendations which may improve lifestyle habits. The results discovered in the first 2 studies regarding awareness of omega-3 FAs and genetic variation were subsequently used to design a nutrigenetics intervention in young adults. Individuals who received their FADS1 genetic information were more aware of different omega-3 FAs and reported fewer barriers to their consumption by the end of
Lin, Lauren E.; Chen, Chuck T.; Hildebrand, Kayla D.; Liu, Zhen; Hopperton, Kathryn E.; Bazinet, Richard P.
To determine how the level of dietary n-6 PUFA affects the rate of loss of arachidonic acid (ARA) and DHA in brain phospholipids, male rats were fed either a deprived or adequate n-6 PUFA diet for 15 weeks postweaning, and then subjected to an intracerebroventricular infusion of 3H-ARA or 3H-DHA. Brains were collected at fixed times over 128 days to determine half-lives and the rates of loss from brain phospholipids (Jout). Compared with the adequate n-6 PUFA rats, the deprived n-6-PUFA rats had a 15% lower concentration of ARA and an 18% higher concentration of DHA in their brain total phospholipids. Loss half-lives of ARA in brain total phospholipids and fractions (except phosphatidylserine) were longer in the deprived n-6 PUFA rats, whereas the Jout was decreased. In the deprived versus adequate n-6 PUFA rats, the Jout of DHA was higher. In conclusion, chronic n-6 PUFA deprivation decreases the rate of loss of ARA and increases the rate of loss of DHA in brain phospholipids. Thus, a low n-6 PUFA diet can be used to target brain ARA and DHA metabolism. PMID:25477531
Objective. Consumption of long chain omega-3 polyunsaturated fatty acids is associated with reduced risks of cardiovascular disease but the role of their oxygenated metabolites remains unclear. We hypothesized that peroxidized metabolites of docosahexaenoic acid (DHA, 22:6 n-3) could play a role in ...
Jašarević, Eldin; Hecht, Patrick M; Fritsche, Kevin L; Beversdorf, David Q; Geary, David C
Chronic deficiency of dietary docosahexaenoic acid (DHA) during critical developmental windows results in severe deficits in spatial learning, anxiety and hippocampal neuroplasticity that parallel a variety of neuropsychiatric disorders. However, little is known regarding the influence of long-term, multigenerational exposure to dietary DHA enrichment on these same traits. To characterize the potential benefits of multigenerational DHA enrichment, mice were fed a purified 10:1 omega-6/omega-3 diet supplemented with either 0.1% preformed DHA/kg feed weight or 1.0% preformed DHA/kg feed weight through three generations. General locomotor activity, spatial learning, and anxiety-like behavior were assessed in adult male offspring of the third generation. Following behavioral assessments, ventral and dorsal hippocampus was collected for DHA and arachidonic acid (AA) analysis. Animals consuming the 0.1% and 1.0% DHA diet did not differ from control animals for locomotor activity or on performance during acquisition learning, but made fewer errors and showed more stable across-day performance during reversal learning on the spatial task and showed less anxiety-like behavior. Consumption of the DHA-enriched diets increased DHA content in the ventral and dorsal hippocampus in a region-specific manner. DHA content in the dorsal hippocampus predicted performance on the reversal training task. DHA content in the ventral hippocampus was correlated with anxiety-like behavior, but AA content in the dorsal hippocampus was a stronger predictor of this behavior. These results suggest that long-term, multigenerational DHA administration improves performance on some aspects of complex spatial learning, decreases anxiety-like behavior, and that modulation of DHA content in sub-regions of the hippocampus predicts which behaviors are likely to be affected.
Meyer, Barbara J; Grenyer, Brin F S; Crowe, Trevor; Owen, Alice J; Grigonis-Deane, Elizabeth M; Howe, Peter R C
The aim of this study was to determine if changes in omega-3 polyunsaturated fatty acid status following tuna oil supplementation correlated with changes in scores of depression. A total of 95 volunteers receiving treatment for major depression were randomised to consume 8 × 1 g capsules per day of HiDHA (2 g DHA, 0.6 g EPA and 10 mg Vitamin E) or olive oil (placebo) for 16 weeks, whilst undergoing weekly counseling sessions by trained clinical psychologists using a standard empirically validated psychotherapy. Depression status was assessed using the 17 item Hamilton rating scale for depression and the Beck Depression Inventory by a psychodiagnostician who was blind to the treatment. Blood was taken at baseline and 16 weeks (n = 48) for measurement of erythrocyte fatty acids. With HiDHA supplementation, erythrocyte DHA content rose from 4.1 ± 0.2 to 7.9 ± 0.4 % (mean ± SEM, p < 0.001) of total fatty acids but did not change (4.0 ± 0.2 to 4.1 ± 0.2 %) in the olive oil group. The mean changes in scores of depression did not differ significantly between the two groups (-12.2 ± 2.1 for tuna oil and -14.4 ± 2.3 for olive oil). However, analysis of covariance showed that in the fish oil group there was a significant correlation (r = -0.51) between the change in erythrocyte DHA and the change in scores of depression (p < 0.05). Further study of the relationship between DHA and depression is warranted.
Matsunaga, A.; Cottam, G.L.
A diet containing 0.45% DHA fed to NZB/W mice, a model of systemic lupus erythematosus, delays the time of onset, improves survival and decreases the formation of antibodies to ds-DNA. Essential fatty acid-deficient diets or inclusion of eicosapentaenoic acid have similar beneficial effects and led them to investigate arachidonic acid metabolism in response to feeding DHA. The arachidonic acid content of plasma cholesteryl ester decreased from 37.4 +/- 2.2 to 28.2 +/- 1.3 mg%. In total liver phospholipid the value decreased from 18.1 +/- 0.52 to 13.7 +/- 1.3 mg%, in total kidney phospholipid the value decreased from 24.10 +/- 0.87 to 20.7 +/- 0.32 mg% and in resident peritoneal macrophages the value decreased from 15.4 +/- 4.6 to 3.6 +/- 1.4 mg%. The metabolism of exogenous (1-/sup 14/C)arachidonic acid by resident peritoneal macrophages in response to Zymosan stimulation for 2 hr was examined by extraction of metabolites and separation by HPLC. Cells isolated from DHA-fed animals produced less PGE2 than controls, yet similar amounts of 6-keto PGF1..cap alpha.. were produced. Arachidonic acid metabolites have significant effects on the immune system and may be a mechanism involved in the benefits obtained by inclusion of DHA in the diet.
Falk, Michael C; Zheng, Xiaohui; Chen, Dieling; Jiang, Yue; Liu, Zeshen; Lewis, Kara D
The purpose of this study was to investigate the reproductive and developmental toxicity of dietary exposure to DHA-rich oil from Schizochytrium sp. and ARA-rich oil from Mortierella alpina. In a developmental toxicity study, pregnant Wistar rats were untreated (control) or administered corn oil (vehicle control), 1,000, 2,500, or 5000 mg/kg bw/day of DHA-rich oil or ARA-rich oil via gavage from gestation days 6 through day 20. In the reproductive toxicity study, male and female Wistar rats were administered vehicle control (corn oil), or 1,000, 2,500, or 5000 mg/kg bw/day of DHA- or ARA-rich oil via gavage throughout the mating period, pregnancy, and the nursing and lactation period. Differences in the number of fetuses, fetal skeletal malformations, and external and visceral anomalies in the developmental study and mortality, clinical signs, fertility indices, physical observations, gross necropsy findings, and gestation period length in the reproductive toxicity study were not dose-related or significantly different from control groups, and were not considered to be treatment related. The no observed adverse effect level (NOAEL) for maternal toxicity and embryo/fetal development and for paternal or maternal treatment-related reproductive toxicity for the DHA-rich oil and ARA-rich oil administered by gavage, was 5000 mg/kg bw/day.
Background The extent to which long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) from fish oil such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) exert their anti-inflammatory effects by down-regulating intestinal inflammation in humans is unknown. We investigated the impact of LCn-3PUFA supplementation on inflammatory gene expression in the duodenum of obese patients with type 2 diabetes. Findings This placebo-controlled randomized crossover study included 12 men with type 2 diabetes. After a 4-week run-in period, patients received in a random sequence 5 g/d of fish oil (providing 3 g of EPA + DHA) and a placebo (corn and soybean oil) for 8 weeks each. The two treatment phases were separated by a 12-week washout period. Gene expression was assessed by real-time polymerase chain reaction in duodenal biopsy samples obtained in the fasted state at the end of each treatment phase. Intestinal mRNA expression levels of interleukin (IL)-6 and tumor-necrosis factor (TNF)-α were hardly detectable after either treatment (<100 copies/105 copies of the reference gene ATP5o). Intestinal mRNA expression of IL-18 and of the transcription factor signal transducer and activator of transcription 3 (STAT3) was higher (>5000 copies/105 copies ATP5o) but still relatively low. EPA + DHA supplementation had no impact on any of these levels (all P ≥ 0.73). Conclusions These data suggest that duodenal cells gene expression of pro-inflammatory cytokines is low in patients with type 2 diabetes and not affected by EPA + DHA supplementation. Further studies are warranted to determine if inflammatory gene expression in other tissues surrounding the intestine is modulated by EPA + DHA supplementation. Trial registration ClinicalTrials.gov ID: NCT01449773 PMID:23855973
Neijat, M; Ojekudo, O; House, J D
The incorporation of omega-3 polyunsaturated fatty acids (PUFA) in the egg is dependent on both the transfer efficiency of preformed dietary omega-3 fatty acids to the eggs as well as endogenous PUFA metabolism and deposition. Employing an experimental design consisting of 70 Lohmann LSL-Classic hens (n=10/treatment) in a 6-week feeding trial, we examined the impact of graded levels of either flaxseed oil (alpha-linolenic acid, ALA) or algal DHA (preformed docosahexaenoic acid, DHA), each supplying 0.20%, 0.40% and 0.60% total omega-3s. The control diet was practically low in omega-3s. Study parameters included monitoring the changes of fatty acid contents in yolk, measures of hen performance, eggshell quality, total lipids and fatty acid contents of plasma. Data were analysed as a complete randomized design using Proc Mixed procedure of SAS. No significant differences were observed between treatments with respect to hen performance, eggshell quality and cholesterol content in plasma and egg yolk. Individual and total omega-3 PUFA in the yolk and plasma increased (P<0.0001) linearly as a function of total omega-3 PUFA intake. At the highest inclusion levels, DHA-fed hens incorporated 3-fold more DHA in eggs compared with ALA-fed hens (179±5.55 vs. 66.7±2.25mg/yolk, respectively). In both treatment groups, maximal enrichment of total n-3 PUFA was observed by week-2, declined by week-4 and leveled thereafter. In addition, accumulation of DHA in egg yolk showed linear (P<0.0001) and quadratic (P<0.05) effects for flaxseed oil (R(2)=0.89) and algal DHA (R(2)=0.95). The current data, based on defined level of total omega-3s in the background diet, provides evidence to suggest that exogenous as well as endogenous synthesis of DHA may be subject to a similar basis of regulation, and serve to highlight potential regulatory aspects explaining the limitations in the deposition of endogenously produced omega-3 LCPUFA.
Chhetry, Binod Thapa; Hezghia, Adrienne; Miller, Jeffrey M; Lee, Seonjoo; Rubin-Falcone, Harry; Cooper, Thomas B; Oquendo, Maria A; Mann, J John; Sublette, M Elizabeth
White matter abnormalities are implicated in major depressive disorder (MDD). As omega-3 polyunsaturated fatty acids (PUFAs) are low in MDD and affect myelination, we hypothesized that PUFA supplementation may alleviate depression through improving white matter integrity. Acutely depressed MDD patients (n = 16) and healthy volunteers (HV, n = 12) had 25-direction diffusion tensor imaging before and after 6 weeks of fish oil supplementation. Plasma phospholipid omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and omega-6 PUFA arachidonic acid (AA) levels were determined before and after supplementation using high-throughput extraction and gas chromatography and expressed as a percentage of total phospholipids (PUFA%). Fractional anisotropy (FA) was computed using a least-squares-fit diffusion tensor with non-linear optimization. Regression analyses were performed with changes in PUFA levels or Hamilton Depression Rating Scale scores as predictors, voxel-wise difference maps of FA as outcome, covariates age and sex, with family-wise correction for multiple comparisons. Increases in plasma phospholipid DHA% (but not EPA% or AA%) after fish oil predicted increases in FA in MDD but not HV, in a cluster including genu and body of the corpus callosum, and anterior corona radiata and cingulum (cluster-level p < 0.001, peak t-score = 8.10, p = 0.002). There was a trend for greater change in FA in MDD responders over nonresponders (t = -1.874, df = 13.56, p = 0.08). Decreased depression severity predicted increased FA in left corticospinal tract and superior longitudinal fasciculus (cluster-level p < 0.001, peak t-score = 5.04, p = 0.0001). Increased FA correlated with increased DHA% and decreased depression severity after fish oil supplementation suggests therapeutic effects of omega-3 PUFAs may be related to improvements in white matter integrity.
Patterson, Ashley C; Chalil, Alan; Aristizabal Henao, Juan J; Streit, Isaac T; Stark, Ken D
Blood levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been related to coronary heart disease risk. Understanding the response of EPA + DHA in blood to dietary intake of EPA + DHA would facilitate the use of blood measures as markers of adherence and enable the development of dietary recommendations. The objective of this study is examine the blood response to intakes of EPA + DHA ≤1 g/d with an intervention designed for dietary adherence. It was hypothesized this relationship would be linear and that intakes of EPA + DHA <1 g/d would result in blood levels below those associated with the highest level of protection for cardiovascular events. Background EPA + DHA intake of men and women (n = 20) was determined by food frequency questionnaire and adherence was monitored by weekly fingertip blood sampling for fatty acid determinations. Participants consumed nutraceuticals to achieve intakes of 0.25 g/d and 0.5 g/d EPA + DHA for successive four-week periods. A subgroup (n = 5) had intakes of 1.0 g/d EPA + DHA for an additional 4 weeks. Fatty acid composition of whole blood, erythrocytes, and plasma phospholipids were determined at each time point. Blood levels of EPA and DHA increased linearly in these pools. A comprehensive review of the literature was used to verify the blood-intake relationship. Blood levels of long chain omega-3 polyunsaturated fatty acids reached blood levels associated with the highest levels of primary cardiac arrest reduction and sudden cardiac death risk only with intakes of 1.0 g/d of EPA + DHA. The blood biomarker response to intakes of EPA + DHA ≤1 g/d is linear in a small but highly adherent study sample and this information can assist in determining adherence in clinical studies and help identify dietary intake targets from associations between blood and disease.
Lauritzen, Lotte; Brambilla, Paolo; Mazzocchi, Alessandra; Harsløf, Laurine B S; Ciappolino, Valentina; Agostoni, Carlo
Docosahexaenoic acid (DHA) is a structural constituent of membranes specifically in the central nervous system. Its accumulation in the fetal brain takes place mainly during the last trimester of pregnancy and continues at very high rates up to the end of the second year of life. Since the endogenous formation of DHA seems to be relatively low, DHA intake may contribute to optimal conditions for brain development. We performed a narrative review on research on the associations between DHA levels and brain development and function throughout the lifespan. Data from cell and animal studies justify the indication of DHA in relation to brain function for neuronal cell growth and differentiation as well as in relation to neuronal signaling. Most data from human studies concern the contribution of DHA to optimal visual acuity development. Accumulating data indicate that DHA may have effects on the brain in infancy, and recent studies indicate that the effect of DHA may depend on gender and genotype of genes involved in the endogenous synthesis of DHA. While DHA levels may affect early development, potential effects are also increasingly recognized during childhood and adult life, suggesting a role of DHA in cognitive decline and in relation to major psychiatric disorders.
Lauritzen, Lotte; Brambilla, Paolo; Mazzocchi, Alessandra; Harsløf, Laurine B. S.; Ciappolino, Valentina; Agostoni, Carlo
Docosahexaenoic acid (DHA) is a structural constituent of membranes specifically in the central nervous system. Its accumulation in the fetal brain takes place mainly during the last trimester of pregnancy and continues at very high rates up to the end of the second year of life. Since the endogenous formation of DHA seems to be relatively low, DHA intake may contribute to optimal conditions for brain development. We performed a narrative review on research on the associations between DHA levels and brain development and function throughout the lifespan. Data from cell and animal studies justify the indication of DHA in relation to brain function for neuronal cell growth and differentiation as well as in relation to neuronal signaling. Most data from human studies concern the contribution of DHA to optimal visual acuity development. Accumulating data indicate that DHA may have effects on the brain in infancy, and recent studies indicate that the effect of DHA may depend on gender and genotype of genes involved in the endogenous synthesis of DHA. While DHA levels may affect early development, potential effects are also increasingly recognized during childhood and adult life, suggesting a role of DHA in cognitive decline and in relation to major psychiatric disorders. PMID:26742060
Khaire, Amrita; Rathod, Richa; Randhir, Karuna; Kale, Anvita; Joshi, Sadhana
Our earlier studies indicate that micronutrients (vitamin B12, folic acid) and omega-3 fatty acids especially docosahexaenoic acid (DHA) are interlinked in one carbon cycle. The present study examines the effects of a sustained vitamin B12 deficiency/supplementation in the presence of omega-3 fatty acids across two generations on the pregnancy outcome and cardiometabolic profile [blood pressure, plasma lipid profile (cholesterol and triglycerides), plasma/liver fatty acid profile and hepatic lipid metabolism] in the second generation adult Wistar rat offspring. Two generations of animals were fed the following diets: control; vitamin B12 deficient; vitamin B12 supplemented; vitamin B12 deficient diet supplemented with omega-3 fatty acids; vitamin B12 and omega-3 fatty acid supplemented diets. Male offspring were sacrificed at 3 months of age. Vitamin B12 deficiency lowered the weight gain (p < 0.01) during pregnancy, increased systolic (p < 0.05) and diastolic (p < 0.01) blood pressure, and lowered the levels of plasma/liver DHA (p < 0.05 for both) but did not affect the lipid profile. Vitamin B12 supplementation showed weight gain, blood pressure and the fatty acid profile similar to the control. However, it increased (p < 0.05) the levels of plasma triglycerides. Omega-3 fatty acid supplementation to the vitamin B12 deficient group lowered the weight gain although the levels of cardiometabolic variables were comparable to the control. Omega-3 fatty acid supplementation in the presence of vitamin B12 improved the pregnancy outcome and all cardio-metabolic variables. Our study highlights the adverse effects of sustained vitamin B12 deficiency across two generations on the pregnancy outcome, fatty acid profile and blood pressure while a combined supplementation of vitamin B12 and omega-3 fatty acids is beneficial.
Sun, Dongzhe; Zhang, Zhao; Mao, Xuemei; Wu, Tao; Jiang, Yue; Liu, Jin; Chen, Feng
In the present study, light illumination was found to be efficient in elevating the total fatty acid content in a newly isolated heterotrophic microalga, Crypthecodinium sp. SUN. Under light illumination, the highest total fatty acid and DHA contents were achieved at 96h as 24.9% of dry weight and 82.8mgg(-1) dry weight, respectively, which were equivalent to 1.46-fold and 1.68-fold of those under the dark conditions. The elevation of total fatty acid content was mainly contributed by an increase of neutral lipids at the expense of starches. Moreover, light was found to alter the cell metabolism and led to a higher specific growth rate, higher glucose consumption rate and lower non-motile cell percentage. This is the first report that light can promote the total fatty acids accumulation in Crypthecodinium without growth inhibition.
Fernández-Iglesias, Anabel; Quesada, Helena; Díaz, Sabina; Pajuelo, David; Bladé, Cinta; Arola, Lluís; Josepa Salvadó, M; Mulero, Miquel
The excessive production of reactive oxygen species has been implicated in several pathologies, such as atherosclerosis, obesity, hypertension and insulin resistance. Docosahexaenoic acid (DHA) may protect against the above mentioned diseases, but paradoxically the main DHA treated pathologies are also associated with increased ROS levels. Therefore, the aim of this study was to explore if in vitro DHA supplementation may increase the sensitivity of cells to tert-BHP induced oxidative stress, and if the green tea polyphenol epigallocatechin-3-gallate (EGCG) is able to correct such detrimental effect. We found that DHA-enriched cells exacerbate ROS generation, decrease cell viability and increase Nrf2 nuclear translocation and HO-1 expression. Interestingly, cellular EGCG is able to counteract oxidative damage from either tert-BHP or DHA-enriched cells. In consequence, our results suggest that in a ROS enriched environment DHA could not always be beneficial for cells and can be considered a double-edged sword in terms of its benefits vs. risks. In this sense, our results propose that the supplementation with potent antioxidant molecules could be an appropriate strategy to reduce the risks related with the DHA supplementation in an oxidative stress-associated condition.
Xiao, Kang; Xu, Lin; Wang, Lian; Wan, Xia
The gene encoding phosphopantetheinyl transferase (PPTase), pfaE, a component of the polyketide synthase (PKS) pathway, is crucial for the production of docosahexaenoic acid (DHA, 22:6ω3), along with the other pfa cluster members pfaA, pfaB, pfaC and pfaD. DHA was produced in Escherichia coli by co-expressing pfaABCD from DHA-producing Colwellia psychrerythraea 34H with one of four pfaE genes from bacteria producing arachidonic acid (ARA, 20:4ω6), eicosapentaenoic acid (EPA, 20:5ω3) or DHA, respectively. Substitution of the pfaE gene from different strain source in E. coli did not influence the function of the PKS pathway producing DHA, although they led to different DHA yields and fatty acid profiles. This result suggested that the pfaE gene could be switchable between these strains for the production of DHA. The DHA production by expressing the reconstituted PKS pathway was also investigated in different E. coli strains, at different temperatures, or with the treatment of cerulenin. The highest DHA production, 2.2 mg of DHA per gram of dry cell weight or 4.1% of total fatty acids, was obtained by co-expressing pfaE(EPA) from the EPA-producing strain Shewanella baltica with pfaABCD in DH5α. Incubation at low temperature (10–15°C) resulted in higher accumulation of DHA compared to higher temperatures. The addition of cerulenin to the medium increased the proportion of DHA and saturated fatty acids, including C12:0, C14:0 and C16:0, at the expense of monounsaturated fatty acids, including C16:1 and C18:1. Supplementation with 1 mg/L cerulenin resulted in the highest DHA yield of 2.4 mg/L upon co-expression of pfaE(DHA) from C. psychrerythraea. PMID:27649078
Sauder, Katherine A.; Skulas-Ray, Ann C.; Campbell, Tavis S.; Johnson, Jillian A.; Kris-Etherton, Penny M.; West, Sheila G.
Objective This study examined the dose-dependent effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation on heart rate variability (HRV) at rest and during standard laboratory stress tasks. We also investigated whether EPA + DHA supplementation was associated with changes in mood state. Methods This placebo-controlled, double-blind, randomized, three-period crossover trial (8-week treatment, 6-week washout) compared two doses of EPA + DHA supplementation (0.85 and 3.4 g/d) in 26 adults with elevated triglycerides. After each treatment period, HRV was assessed during an acute stress protocol that included a resting baseline, standard laboratory stress tasks (speech task and cold pressor), and recovery periods. In addition, mood state was assessed. Results Root mean square of successive differences in interbeat interval and total power increased 9.9% and 20.6%, respectively, after the high dose relative to placebo (Tukey p = .016 and .012, respectively). The low dose was not significantly different from the high dose or placebo dose. There was a trend for a treatment effect on high-frequency HRV (p = .058), with 21.0% greater power observed after the high dose compared with placebo (Tukey p = .052). Mood did not differ between treatments, and there was no association between mood state and HRV. Conclusions In healthy adults with elevated triglycerides, supplementation of 3.4 g/d EPA + DHA resulted in greater HRV, whereas 0.85 g/d EPA + DHA had no effect. These results indicate that EPA + DHA supplementation may improve autonomic tone in adults at increased risk for cardiovascular disease within 8 weeks. Trial Registration NCT00504309 (ClinicalTrials.gov). PMID:23592752
West, Annette L; Burdge, Graham C; Calder, Philip C
Dietary supplementation is an effective means to improve EPA and DHA status. However, it is unclear whether lipid structure affects EPA+DHA bioavailability. We determined the effect of consuming different EPA and DHA lipid structures on their concentrations in blood during the postprandial period and during dietary supplementation compared with unmodified fish oil TAG (uTAG). In a postprandial cross-over study, healthy men (n 9) consumed in random order test meals containing 1·1 g EPA+0·37 g DHA as either uTAG, re-esterified TAG, free fatty acids (FFA) or ethyl esters (EE). In a parallel design supplementation study, healthy men and women (n 10/sex per supplement) consumed one supplement type for 12 weeks. Fatty acid composition was determined by GC. EPA incorporation over 6 h into TAG or phosphatidylcholine (PC) did not differ between lipid structures. EPA enrichment in NEFA was lower from EE than from uTAG (P=0·01). Plasma TAG, PC or NEFA DHA incorporation did not differ between lipid structures. Lipid structure did not affect TAG or NEFA EPA incorporation and PC or NEFA DHA incorporation following dietary supplementation. Plasma TAG peak DHA incorporation was greater (P=0·02) and time to peak shorter (P=0·02) from FFA than from uTAG in men. In both studies, the order of EPA and DHA incorporation was PC>TAG>NEFA. In conclusion, EPA and DHA lipid structure may not be an important consideration in dietary interventions.
Kaczmarski, Maciej; Sawicka-Żukowska, Małgorzata; Bobrus-Chociej, Anna
Some recent studies indicate that unsaturated fatty acids, components of cellular membranes and precursors of immunomodulators, play a significant role in the pathogenesis of some symptoms of atopic dermatitis. Since they cannot be synthesized by the human body, they must be provided with nutrition as the so called exogenous fatty acids: linoleic (a precursor of arachidonic acid) and α-linolenic acid (a precursor of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)). Their deficiency facilitates the development of some disorders, e.g. of the cardiovascular system or of the nervous system, or becomes the cause of intensification of ailments in their course e.g. pruritus and dryness in atopic dermatitis. Though clinical examinations to date confirm the efficacy of fatty acid supplementation in treatment of atopic dermatitis, their results are not explicit. PMID:24278056
Lapillonne, A; Picaud, J C; Chirouze, V; Goudable, J; Reygrobellet, B; Claris, O; Salle, B L
Because docosahexaenoic acid (DHA) may be an essential nutrient for the visual and early cognitive development of preterm infants, DHA enrichment of preterm formulas has been recommended. This randomized trial was designed to study the n-6 and n-3 fatty acid status of healthy preterm infants fed a formula enriched with a low eicosapentaenoic-fish oil until 4 mo corrected age compared with that of infants fed a standard formula. A reference group of breast-fed infants was studied concurrently. The fatty acid content of red blood cell (RBC) phospholipid was assessed at enrollment, hospital discharge, expected term, and 3 and 6 mo postterm. The DHA content of RBC phospholipid was higher in infants fed the enriched versus the standard formula at hospital discharge, expected term, and 3 and 6 mo postterm. However, compared with infants fed the standard formula, infants fed the enriched formula had also higher RBC phospholipid eicosapentaenoic content (0.69 +/- 0.15% versus 0.25 +/- 0.12%, p < 0.001), and lower RBC phospholipid arachidonic acid content (15.1 +/- 0.93% versus 18.8 +/- 0.89%; p < 0.001). We conclude that supplementing preterm infants with low-eicosapentaenoic fish oil is effective in improving DHA status, but results in worsening of n-6 fatty acid status. We speculate that preterm infants may require a dietary supply of arachidonic acid as well as DHA if the same fatty acid status as that of breast-fed infants is to be achieved.
Late life depression is often associated with a poor response to antidepressants; therefore an alternative strategy for therapy is required. Although several studies have reported that phosphatidylserine (PS) may be effective for late life depression and that omega-3 fatty acids DHA and EPA have also proven beneficial for many higher mental functions, including depression, no concrete conclusion has been reached. This study was performed to clarify the effect of PS and omega-3 fatty acid-containing supplement for late life depression by not only clinical evaluation but also salivary cortisol levels. Eighteen elderly subjects with major depression were selected for the study. In all, insufficient improvement had been obtained by antidepressant therapy for at least 6 months. The exclusion criteria from prior brain magnetic resonance images (MRI) included the presence of structural MRI findings compatible with stroke or other gross brain lesions or malformations, but not white matter hypersensitivities. They took a supplement containing PS 100 mg, DHA 119 mg and EPA 70 mg three times a day for 12 weeks. The effects of the supplement were assessed using the 17-item Hamilton depression scale (HAM-D17) and the basal levels and circadian rhythm of salivary cortisol. The study adopted them as indices because: salivary cortisol levels are high in patients with depression, their circadian rhythm related to salivary cortisol is often irregular, and these symptoms are alleviated as depression improves. The mean HAM-D17 in all subjects taking the supplement was significantly improved after 12 weeks of taking the supplement. These subjects were divided into 10 non-responders and 8 responders. The basal levels and circadian rhythm of salivary cortisol were normalized in the responders while not in non-responders. PS and omega-3 fatty acids, or other elements of the supplement, may be effective for late life depression, associated with the correction of basal levels and circadian
Jones, Peter JH; Senanayake, Vijitha K; Pu, Shuaihua; Jenkins, David JA; Connelly, Philip W; Lamarche, Benoît; Couture, Patrick; Charest, Amélie; Baril-Gravel, Lisa; West, Sheila G; Liu, Xiaoran; Fleming, Jennifer A; McCrea, Cindy E; Kris-Etherton, Penny M
Background: It is well recognized that amounts of trans and saturated fats should be minimized in Western diets; however, considerable debate remains regarding optimal amounts of dietary n−9, n−6, and n−3 fatty acids. Objective: The objective was to examine the effects of varying n−9, n−6, and longer-chain n−3 fatty acid composition on markers of coronary heart disease (CHD) risk. Design: A randomized, double-blind, 5-period, crossover design was used. Each 4-wk treatment period was separated by 4-wk washout intervals. Volunteers with abdominal obesity consumed each of 5 identical weight-maintaining, fixed-composition diets with one of the following treatment oils (60 g/3000 kcal) in beverages: 1) conventional canola oil (Canola; n−9 rich), 2) high–oleic acid canola oil with docosahexaenoic acid (CanolaDHA; n−9 and n−3 rich), 3) a blend of corn and safflower oil (25:75) (CornSaff; n−6 rich), 4) a blend of flax and safflower oils (60:40) (FlaxSaff; n−6 and short-chain n−3 rich), or 5) high–oleic acid canola oil (CanolaOleic; highest in n−9). Results: One hundred thirty individuals completed the trial. At endpoint, total cholesterol (TC) was lowest after the FlaxSaff phase (P < 0.05 compared with Canola and CanolaDHA) and highest after the CanolaDHA phase (P < 0.05 compared with CornSaff, FlaxSaff, and CanolaOleic). Low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol were highest, and triglycerides were lowest, after CanolaDHA (P < 0.05 compared with the other diets). All diets decreased TC and LDL cholesterol from baseline to treatment endpoint (P < 0.05). CanolaDHA was the only diet that increased HDL cholesterol from baseline (3.5 ± 1.8%; P < 0.05) and produced the greatest reduction in triglycerides (−20.7 ± 3.8%; P < 0.001) and in systolic blood pressure (−3.3 ± 0.8%; P < 0.001) compared with the other diets (P < 0.05). Percentage reductions in Framingham 10-y CHD risk scores (FRS) from
Lee, Ho-Sun; Barraza-Villarreal, Albino; Biessy, Carine; Duarte-Salles, Talita; Sly, Peter D.; Ramakrishnan, Usha; Rivera, Juan; Herceg, Zdenko
Epigenetic regulation of imprinted genes is regarded as a highly plausible explanation for linking dietary exposures in early life with the onset of diseases during childhood and adulthood. We sought to test whether prenatal dietary supplementation with docosahexaenoic acid (DHA) during pregnancy may modulate epigenetic states at birth. This study was based on a randomized intervention trial conducted in Mexican pregnant women supplemented daily with 400 mg of DHA or a placebo from gestation week 18–22 to parturition. We applied quantitative profiling of DNA methylation states at IGF2 promoter 3 (IGF2 P3), IGF2 differentially methylated region (DMR), and H19 DMR in cord blood mononuclear cells of the DHA-supplemented group (n = 131) and the control group (n = 130). In stratified analyses, DNA methylation levels in IGF2 P3 were significantly higher in the DHA group than the control group in preterm infants (P = 0.04). We also observed a positive association between DNA methylation levels and maternal body mass index; IGF2 DMR methylation was higher in the DHA group than the control group in infants of overweight mothers (P = 0.03). In addition, at H19 DMR, methylation levels were significantly lower in the DHA group than the control group in infants of normal weight mothers (P = 0.01). Finally, methylation levels at IGF2/H19 imprinted regions were associated with maternal BMI. These findings suggest that epigenetic mechanisms may be modulated by DHA, with potential impacts on child growth and development. PMID:25293351
Xiao, Shijun; Wang, Panpan; Dong, Linsong; Zhang, Yaguang; Han, Zhaofang; Wang, Qiurong
Whole-genome single-nucleotide polymorphism (SNP) markers are valuable genetic resources for the association and conservation studies. Genome-wide SNP development in many teleost species are still challenging because of the genome complexity and the cost of re-sequencing. Genotyping-By-Sequencing (GBS) provided an efficient reduced representative method to squeeze cost for SNP detection; however, most of recent GBS applications were reported on plant organisms. In this work, we used an EcoRI-NlaIII based GBS protocol to teleost large yellow croaker, an important commercial fish in China and East-Asia, and reported the first whole-genome SNP development for the species. 69,845 high quality SNP markers that evenly distributed along genome were detected in at least 80% of 500 individuals. Nearly 95% randomly selected genotypes were successfully validated by Sequenom MassARRAY assay. The association studies with the muscle eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content discovered 39 significant SNP markers, contributing as high up to ∼63% genetic variance that explained by all markers. Functional genes that involved in fat digestion and absorption pathway were identified, such as APOB, CRAT and OSBPL10. Notably, PPT2 Gene, previously identified in the association study of the plasma n-3 and n-6 polyunsaturated fatty acid level in human, was re-discovered in large yellow croaker. Our study verified that EcoRI-NlaIII based GBS could produce quality SNP markers in a cost-efficient manner in teleost genome. The developed SNP markers and the EPA and DHA associated SNP loci provided invaluable resources for the population structure, conservation genetics and genomic selection of large yellow croaker and other fish organisms. PMID:28028455
Bekhit, Michael Yemane; Grung, Bjørn; Mjøs, Svein Are
The potential of Fourier transform infrared (FT-IR), near-infrared (NIR), and Raman spectroscopic techniques combined with partial least squares (PLS) regression (PLSR) to predict concentrations of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and total omega-3 fatty acids (n-3 FAs) in fish oil supplements was investigated. FT-IR spectroscopy predicted EPA (coefficient of determination (R(2)) of 0.994, standard error of cross-validation (SECV) of 2.90%, and standard error of prediction (SEP) of 2.49%) and DHA (R(2) = 0.983, SECV = 2.89%, and SEP = 2.55%) with six to seven PLS factors, whereas a simpler PLS model with two factors was obtained for total n-3 FAs (R(2) = 0.985, SECV = 2.73%, and SEP = 2.75%). Selected regions in the NIR spectra gave models with good performances and predicted EPA (R(2) = 0.979, SECV = 2.43%, and SEP = 3.11%) and DHA (R(2) = 0.972, SECV = 2.34%, and SEP = 2.60%) with four to six PLS factors. Both the whole and selected NIR regions gave simple models (two PLS factors) with similar results (R(2) = 0.997, SECV = 2.18%, and SEP = 1.60%) for total n-3 FAs. The whole and selected regions of Raman spectra provided models with comparable results and predicted EPA (R(2) = 0.977, SECV = 3.18%, and SEP = 2.73%) and DHA (R(2) = 0.966, SECV = 3.31%, and SEP = 2.56%) with seven to eight PLS factors, whereas a simpler model (three PLS factors) with R(2) = 0.993, SECV = 2.82%, and SEP = 3.27% was obtained for total n-3 FAs. The results demonstrated that FT-IR, NIR, and Raman spectroscopy combined with PLSR can be used as simple, fast, and nondestructive methods for quantitative analysis of EPA, DHA, and total n-3 FAs. FT-IR and NIR spectroscopy, in particular, have the potential to be applied in process industries during production of fish oil supplements.
Decsi, Tamás; Boehm, Günther; Tjoonk, H M Ria; Molnár, Szilárd; Dijck-Brouwer, D A Janneke; Hadders-Algra, Mijna; Martini, Ingrid A; Muskiet, Frits A J; Boersma, E Rudy
Long-chain PUFA play an important role in early human neurodevelopment. Significant inverse correlations were reported between values of trans isomeric and long-chain PUFA in plasma lipids of preterm infants and children aged 1-15 yr as well as in venous cord blood lipids of full-term infants. Here we report FA compositional data of cord blood vessel wall lipids in 308 healthy, full-term infants (gestational age: 39.7 +/- 1.2 wk, birth weight: 3528 +/- 429 g, mean +/- SD). The median (interquartile range) of the sum of 18-carbon trans FA was 0.22 (0.13) % w/w in umbilical artery and 0.16 (0.10) % w/w in umbilical vein lipids. Nonparametric correlation analysis showed significant inverse correlations between the sum of 18-carbon trans FA and both arachidonic acid and DHA in artery (r = -0.38, P < 0.01, and r = -0.20, P < 0.01) and vein (r = -0.36, P < 0.01, and -0.17, P < 0.01) wall lipids. In addition, the sum of 18-carbon trans FA was significantly positively correlated to Mead acid, a general indicator of EFA deficiency, in both artery (r = +0.35, P < 0.01) and vein (r = +0.31, P< 0.01) wall lipids. The present results obtained in a large group of full-term infants suggest that maternal trans FA intake is inversely associated with long-chain PUFA status of the infant at birth.
Moallem, U; Zachut, M
The passage of long-chain fatty acids (FA) through the placenta in ruminants is limited. However, essential long-chain polyunsaturated FA, and especially n-3 FA, are crucial for normal development of the bovine fetus; therefore, uptake of these FA by the embryo must occur during pregnancy. The objectives of the present study were to examine the effects of enrichment of dam plasma with various n-3 FA during late gestation on newborn calf plasma FA composition. Twenty-seven multiparous cows at 256 d of pregnancy were divided into 3 groups and fed encapsulated fats as follows: 1) control: supplemented at 240 g/d per cow with saturated FA; 2) flaxseed oil (FLX): supplemented at 300 g/d per cow with fat that provided 56.1g/d per cow of α-linolenic acid (ALA) from flaxseed oil; and 3) fish oil (FO): supplemented at 300 g/d per cow with fat that provided 5.8 and 4.3g/d per cow eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil, respectively. Blood samples were taken from dams twice weekly and from calves immediately after calving before first colostrum. The FA composition in plasma was determined in dams at the last sample before parturition, on average 2d before calving. Feeding cows with FLX resulted in a 2.6-fold increase in the proportion of ALA in dam plasma as compared with the control. The proportion of EPA in cow plasma was not different between groups; however, the percentage of docosapentaenoic acid (DPA) was 1.4 and 2 times higher, respectively, in cows fed FLX and FO than in the controls. In addition, the plasma proportion of DHA was 15 times higher in FO cows than in controls. In calves, no differences between groups were observed in the plasma proportions of ALA and EPA; however, the proportion of DHA was 1.9 times higher in the FO calves than in controls. Across treatments, data showed no correlation between the proportions of ALA, EPA, and DPA in dam and calf plasma; however, positive correlation was demonstrated between dams and
Torok, Valeria A; Percy, Nigel J; Moate, Peter J; Ophel-Keller, Kathy
The rumen microbiota contributes to greenhouse gas emissions and has an impact on feed efficiency and ruminant product fatty acid composition. Dietary fat supplements have shown promise in reducing enteric methane production and in altering the fatty acid profiles of ruminant-derived products, yet in vivo studies on how these impact the rumen microbiota are limited. In this study, we investigated the rumen bacterial, archaeal, fungal, and ciliate protozoan communities of dairy cows fed diets supplemented with 4 levels of docosahexaenoic acid (DHA) (0, 25, 50, and 75 g·cow(-1)·day(-1)) and established linkages between microbial communities and production parameters. Supplementation with DHA significantly (P < 0.05) altered rumen bacterial and archaeal, including methanogenic archaeal, communities but had no significant (P > 0.05) effects on rumen fungal or ciliate protozoan communities. Rumen bacterial communities of cows receiving no DHA were correlated with increased saturated fatty acids (C18:0 and C11:0) in their milk. Furthermore, rumen bacterial communities of cows receiving a diet supplemented with 50 g DHA·cow(-1)·day(-1) were correlated with increases in monounsaturated fatty acids (C20:1n-9) and polyunsaturated fatty acids (C22:5n-3; C22:6n-3; C18:2 cis-9, trans-11; C22:3n-6; and C18:2n-6 trans) in their milk. The significant diet-associated changes in rumen archaeal communities observed did not result in altered enteric methane outputs in these cows.
Sidhu, Vishaldeep K; Huang, Bill X; Desai, Abhishek; Kevala, Karl; Kim, Hee-Yong
Aging has been related to diminished cognitive function, which could be a result of ineffective synaptic function. We have previously shown that synaptic plasma membrane proteins supporting synaptic integrity and neurotransmission were downregulated in docosahexaenoic acid (DHA)-deprived brains, suggesting an important role of DHA in synaptic function. In this study, we demonstrate aging-induced synaptic proteome changes and DHA-dependent mitigation of such changes using mass spectrometry-based protein quantitation combined with western blot or messenger RNA analysis. We found significant reduction of 15 synaptic plasma membrane proteins in aging brains including fodrin-α, synaptopodin, postsynaptic density protein 95, synaptic vesicle glycoprotein 2B, synaptosomal-associated protein 25, synaptosomal-associated protein-α, N-methyl-D-aspartate receptor subunit epsilon-2 precursor, AMPA2, AP2, VGluT1, munc18-1, dynamin-1, vesicle-associated membrane protein 2, rab3A, and EAAT1, most of which are involved in synaptic transmission. Notably, the first 9 proteins were further reduced when brain DHA was depleted by diet, indicating that DHA plays an important role in sustaining these synaptic proteins downregulated during aging. Reduction of 2 of these proteins was reversed by raising the brain DHA level by supplementing aged animals with an omega-3 fatty acid sufficient diet for 2 months. The recognition memory compromised in DHA-depleted animals was also improved. Our results suggest a potential role of DHA in alleviating aging-associated cognitive decline by offsetting the loss of neurotransmission-regulating synaptic proteins involved in synaptic function.
Kidd, Parris M
The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are orthomolecular, conditionally essential nutrients that enhance quality of life and lower the risk of premature death. They function exclusively via cell membranes, in which they are anchored by phospholipid molecules. DHA is proven essential to pre- and postnatal brain development, whereas EPA seems more influential on behavior and mood. Both DHA and EPA generate neuroprotective metabolites. In double-blind, randomized, controlled trials, DHA and EPA combinations have been shown to benefit attention deficit/hyperactivity disorder (AD/HD), autism, dyspraxia, dyslexia, and aggression. For the affective disorders, meta-analyses confirm benefits in major depressive disorder (MDD) and bipolar disorder, with promising results in schizophrenia and initial benefit for borderline personality disorder. Accelerated cognitive decline and mild cognitive impairment (MCI) correlate with lowered tissue levels of DHA/EPA, and supplementation has improved cognitive function. Huntington disease has responded to EPA. Omega-3 phospholipid supplements that combine DHA/EPA and phospholipids into the same molecule have shown marked promise in early clinical trials. Phosphatidylserine with DHA/EPA attached (Omega-3 PS) has been shown to alleviate AD/HD symptoms. Krill omega-3 phospholipids, containing mostly phosphatidylcholine (PC) with DHA/EPA attached, markedly outperformed conventional fish oil DHA/EPA triglycerides in double-blind trials for premenstrual syndrome/dysmenorrhea and for normalizing blood lipid profiles. Krill omega-3 phospholipids demonstrated anti-inflammatory activity, lowering C-reactive protein (CRP) levels in a double-blind trial. Utilizing DHA and EPA together with phospholipids and membrane antioxidants to achieve a triple cell membrane synergy may further diversify their currently wide range of clinical applications.
Cunnane, Stephen C; Chouinard-Watkins, Raphael; Castellano, Christian A; Barberger-Gateau, Pascale
A crossroads has been reached on research into docosahexaenoic acid (DHA) and Alzheimer's disease (AD). On the one hand, several prospective observational studies now clearly indicate a protective effect of higher fish and DHA intake against risk of AD. On the other hand, once AD is clinically evident, supplementation trials demonstrate essentially no benefit of DHA in AD. Despite apparently low DHA intake in AD, brain DHA levels are frequently the same as in controls, suggesting that low DHA intake results in low plasma DHA but does not necessarily reduce brain DHA in humans. Animal models involving dietary omega-3 fatty acid deficiency to deplete brain DHA may therefore not be appropriate in AD research. Studies in the healthy elderly suggest that DHA homeostasis changes during aging. Tracer methodology now permits estimation of DHA half-life in the human brain and whole body. Apolipoprotein E alleles have an important impact not only on AD but also on DHA homeostasis in humans. We therefore encourage further development of innovative approaches to the study of DHA metabolism and its role in human brain function. A better understanding of DHA metabolism in humans will hopefully help explain how higher habitual DHA intake protects against the risk of deteriorating cognition during aging and may eventually give rise to a breakthrough in the treatment of AD.
Fujita, Yukihiko; Okada, Tomoo; Abe, Yuriko; Kazama, Minako; Saito, Emiko; Kuromori, Yuki; Iwata, Fujihiko; Hara, Mitsuhiko; Ayusawa, Mamoru; Izumi, Hiroyuki; Kitamura, Yohei; Shimizu, Takashi
To investigate the effects of n-3 polyunsaturated fatty acids on stearoyl-CoA desaturase (SCD) activity, we treated 10 obese children (mean age: 12.9 years) with cod liver oil once daily for 12 weeks. The effects of cod liver oil supplementation on SCD activity, as estimated by the palmitoleate/palmitate ratio, depended on the docosahexaenoic acid (DHA) contents at baseline. Baseline DHA contents were negatively correlated with baseline SCD activity. After the treatment, baseline DHA contents were found to be significantly associated with the reduction of SCD activity. Cod liver oil supplementation may be a complementary treatment for obese children with low baseline contents of DHA.
Escamilla-Nuñez, María Consuelo; Barraza-Villarreal, Albino; Hernández-Cadena, Leticia; Navarro-Olivos, Efraín; Sly, Peter D.; Romieu, Isabelle
BACKGROUND: Prenatal consumption of omega-3 fatty acids can act as an adjuvant in the development of the immune system and affect the inflammatory response of neonates. METHODS: We conducted a double-blind, randomized, placebo-controlled trial in Cuernavaca, Mexico. We randomly assigned 1,094 pregnant women (18-35 years of age) to receive 400 mg/d of algal docosahexaenoic acid (DHA) or placebo from 18 to 22 weeks of gestation through delivery. Birth outcomes and respiratory symptoms information until 18 months were available for 869 mother-child pairs. Questionnaires were administered, and maternal blood samples were obtained at baseline. Maternal atopy was based on specific IgE levels. During follow-up, information on infants’ respiratory symptoms was collected through questionnaires administered at 1, 3, 6, 9, 12, and 18 months of age. Negative binomial regression models were used to evaluate the effect of supplementation on respiratory symptoms in infants. RESULTS: Among infants of atopic mothers, a statistically significant protective effect of DHA treatment was observed on phlegm with nasal discharge or nasal congestion (0.78; 95% CI, 0.60-1.02) and fever with phlegm and nasal discharge or nasal congestion (0.53; 95% CI, 0.29-0.99), adjusting for potential confounders. CONCLUSIONS: Our results support the hypothesis that DHA supplementation during pregnancy may decrease the incidence of respiratory symptoms in children with a history of maternal atopy. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00646360; URL: www.clinicaltrials.gov PMID:24626819
Beneficial effects of omega-3 fatty acids and vitamin B12 supplementation on brain docosahexaenoic acid, brain derived neurotrophic factor, and cognitive performance in the second-generation Wistar rats.
Rathod, Richa S; Khaire, Amrita A; Kale, Anvita A; Joshi, Sadhana R
In vegetarian population, vitamin B12 deficiency coexists with suboptimal levels of omega-3 fatty acids. Studies indicate a need for supplementation/fortification of vitamin B12 and omega-3 fatty acids to reduce the risk of brain disorders. We have described the effects of vitamin B12 and omega-3 fatty acid supplementation on brain development in F1 generation animals. The current study investigates the effects of vitamin B12 and omega-3 fatty acids supplementation on brain function and cognition. Pregnant Wistar rats were assigned the following groups: control, vitamin B12 deficient (BD), vitamin B12 deficient + omega-3 fatty acid (BDO), vitamin B12 supplemented (BS), vitamin B12 supplemented + omega-3 fatty acid (BSO). The same diets were continued for two generations. BDO group showed higher (P < 0.05) levels of BDNF (brain derived neurotrophic factor) and DHA (docosahexaenoic acid) in the cortex and hippocampus as compared with the BD group. The cognitive performance was also normalized in this group. BS showed comparable levels of DHA, BDNF (protein and mRNA), and CREB mRNA (cAMP response element-binding protein) to that of control group while Tropomyosin receptor kinase mRNA levels were higher. The combined vitamin B12 and omega-3 fatty acid supplementation further enhanced the levels of DHA (P < 0.05) and BDNF (P < 0.05) in the hippocampus and CREB mRNA (P < 0.01) in the cortex as compared with BS group. The cognitive performance of these animals was higher (P < 0.05) as compared with BS group. Our data indicates the beneficial effects of vitamin B12 and omega-3 fatty acid supplementation across two generations on brain development and function.
Lundebye, Anne-Katrine; Lock, Erik-Jan; Rasinger, Josef D; Nøstbakken, Ole Jakob; Hannisdal, Rita; Karlsbakk, Egil; Wennevik, Vidar; Madhun, Abdullah S; Madsen, Lise; Graff, Ingvild Eide; Ørnsrud, Robin
Contaminants and fatty acid levels in farmed- versus wild Atlantic salmon have been a hot topic of debate in terms of food safety. The present study determined dioxins (polychlorinated dibenzo-p-dioxin and dibenzofuran), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), organochlorine pesticides (OCPs), metals and fatty acids in wild and farmed Atlantic salmon. Contaminant levels of dioxins, PCBs, OCPs (DDT, dieldrin, lindane, chlordane, Mirex, and toxaphene), and mercury were higher in wild salmon than in farmed salmon, as were the concentrations of the essential elements selenium, copper, zinc and iron, and the marine omega-3 fatty acid docosahexaenoic acid (DHA). PBDE, endosulfan, pentachlorobenzene, hexachlorobenzene, cadmium and lead levels were low and comparable in both wild and farmed fish, and there was no significant difference in the marine omega-3 fatty acid eicosapentaenoic acid (EPA) concentration. The total fat content was significantly higher in farmed than wild salmon due to a higher content of both saturated and monounsaturated fatty acids, as well as a higher content of omega-6 fatty acids. The omega-3 to omega-6 fatty acid ratio was considerably lower in farmed than wild salmon due to the high level of omega-6 fatty acids. Contaminant concentrations in Atlantic salmon were well below maximum levels applicable in the European Union. Atlantic salmon, both farmed and wild, is a good source of EPA and DHA with a 200g portion per week contributing 3.2g or 2.8g respectively, being almost twice the intake considered adequate for adults by the European Food Safety Authority (i.e. 250mg/day or 1.75g/week).
Co-supplementation of healthy women with fish oil and evening primrose oil increases plasma docosahexaenoic acid, gamma-linolenic acid and dihomo-gamma-linolenic acid levels without reducing arachidonic acid concentrations.
Geppert, Julia; Demmelmair, Hans; Hornstra, Gerard; Koletzko, Berthold
Fish oil supplementation during pregnancy not only improves maternal and neonatal DHA status, but often reduces gamma-linolenic acid (GLA), dihomo-GLA (DGLA), and arachidonic acid (ARA) levels also, which may compromise foetal and infant development. The present study investigated the effects of a fish oil/evening primrose oil (FSO/EPO) blend (456 mg DHA/d and 353 mg GLA/d) compared to a placebo (mixture of habitual dietary fatty acids) on the plasma fatty acid (FA) composition in two groups of twenty non-pregnant women using a randomised, double-blind, placebo-controlled parallel design. FA were quantified in plasma total lipids, phospholipids, cholesterol esters, and TAG at weeks 0, 4, 6 and 8. After 8 weeks of intervention, percentage changes from baseline values of plasma total lipid FA were significantly different between FSO/EPO and placebo for GLA (+49.9 % v. +2.1 %, means), DGLA (+13.8 % v. +0.7 %) and DHA (+59.6 % v. +5.5 %), while there was no significant difference for ARA ( - 2.2 % v. - 5.9 %). FA changes were largely comparable between plasma lipid fractions. In both groups three subjects reported mild adverse effects. As compared with placebo, FSO/EPO supplementation did not result in any physiologically relevant changes of safety parameters (blood cell count, liver enzymes). In women of childbearing age the tested FSO/EPO blend was well tolerated and appears safe. It increases plasma GLA, DGLA, and DHA levels without impairing ARA status. These data provide a basis for testing this FSO/EPO blend in pregnant women for its effects on maternal and neonatal FA status and infant development.
Morse, Nancy L.
Scientific literature is increasingly reporting on dietary deficiencies in many populations of some nutrients critical for foetal and infant brain development and function. Purpose: To highlight the potential benefits of maternal supplementation with docosahexaenoic acid (DHA) and other important complimentary nutrients, including vitamin D, folic acid and iodine during pregnancy and/or breast feeding for foetal and/or infant brain development and/or function. Methods: English language systematic reviews, meta-analyses, randomised controlled trials, cohort studies, cross-sectional and case-control studies were obtained through searches on MEDLINE and the Cochrane Register of Controlled Trials from January 2000 through to February 2012 and reference lists of retrieved articles. Reports were selected if they included benefits and harms of maternal supplementation of DHA, vitamin D, folic acid or iodine supplementation during pregnancy and/or lactation. Results: Maternal DHA intake during pregnancy and/or lactation can prolong high risk pregnancies, increase birth weight, head circumference and birth length, and can enhance visual acuity, hand and eye co-ordination, attention, problem solving and information processing. Vitamin D helps maintain pregnancy and promotes normal skeletal and brain development. Folic acid is necessary for normal foetal spine, brain and skull development. Iodine is essential for thyroid hormone production necessary for normal brain and nervous system development during gestation that impacts childhood function. Conclusion: Maternal supplementation within recommended safe intakes in populations with dietary deficiencies may prevent many brain and central nervous system malfunctions and even enhance brain development and function in their offspring. PMID:22852064
Meale, S J; Chaves, A V; He, M L; McAllister, T A
Microalgae are the original source of docosahexaenoic acid (DHA; 22:6n-3) in the marine food chain, and its inclusion in animal feeds has been considered as a means of increasing the DHA level in foods of animal origin. As such, this study aimed to investigate the effects of supplementing an algal meal, high in DHA derived from Schizochytrium spp. (DHA-G), in the diet of Canadian Arcott lambs, on growth, carcass characteristics, wool production, and fatty acid (FA) profiles of subcutaneous adipose tissues (SAT), perirenal adipose tissues (PAT), and skirt muscle (SM). Forty-four lambs were randomly assigned to dietary treatments. Diets consisted of a pelleted, barley-based finishing diet with DHA-G supplemented at 0, 1, 2, or 3% DM as a replacement for flax oil and barley grain. Feed deliveries and orts were recorded daily. Lambs were weighed weekly and slaughtered once they reached ≥ 45 kg live weight. Carcass characteristics, ruminal pH, and liver weights were determined at slaughter. Wool yield was determined on mid-side patches of 100 cm(2) shorn at d 0 and on the day before slaughter (d 105 or 140). Dye bands were used to determine wool growth, fiber diameter, and staple length. Adipose tissues and SM samples were taken at slaughter and analyzed for FA profiles. Data were analyzed using mixed procedure in SAS with orthogonal contrasts testing for linear, quadratic, or cubic responses to increasing levels of DHA-G. Daily DMI, ADG, and G:F were similar as were wool quality and yield (P > 0.05). Carcass characteristics were generally unaffected (P > 0.05), except for body wall thickness (mm), which showed a quadratic response (P = 0.01) with increasing DHA-G. The concentration of eicosapentaenoic acid (EPA; 20:5n-6; mg/100 g fresh tissue) linearly increased (P < 0.001) with DHA-G in both adipose tissues and responded quadratically in SM (P = 0.05). Similarly, DHA (mg/100 g fresh tissue) increased linearly (P < 0.01) with DHA-G in all tissue types (P < 0
Mathews, Susan A; Oliver, William T; Phillips, Oulayvanh T; Odle, Jack; Diersen-Schade, Deborah A; Harrell, Robert J
Addition of arachidonic acid (AA) and docosahexaenoic acid (DHA) to infant formula promotes visual and neural development. This study was designed to determine whether the source of dietary long-chain polyunsaturated fatty acids (LCPUFA) affected overall animal health and safety. Piglets consumed ad libitum from 1 to 16 d of age a skim milk-based formula with different fat sources added to provide 50% of the metabolizable energy. Treatment groups were as follows: control (CNTL; no added LCPUFA), egg phospholipid (PL), algal/fungal triglyceride (TG) oils, TG plus PL (soy lecithin source) added to match phospholipid treatment (TG + PL) and essential fatty acid deficient (EFAD). Formulas with LCPUFA provided 0.6 and 0.3 g/100 g total fatty acids as AA and DHA, respectively. CNTL piglets had 40% longer ileal villi than PL piglets (P < 0.03), but the TG group was not different from the CNTL group. Gross liver histology did not differ among any of the formula-fed groups (P > 0.1). Apparent dry matter digestibility was 10% greater in CNTL, TG and TG + PL groups compared with PL piglets (P < 0.002). No differences in alanine aminotransferase were detected among treatments, but aspartate aminotransferase was elevated (P < 0.03) in PL piglets compared with TG + PL piglets. Total plasma AA concentration was greater in the TG group compared with CNTL piglets (P < 0.05). Total plasma DHA concentrations were greater in TG piglets compared with PL (P < 0.06) or CNTL (P < 0.02) piglets. These data demonstrate that the algal/fungal TG sources of DHA and AA may be a more appropriate supplement for infant formulas than the egg PL source based on piglet plasma fatty acid profiles and apparent dry matter digestibilities.
Boeckaert, C; Vlaeminck, B; Dijkstra, J; Issa-Zacharia, A; Van Nespen, T; Van Straalen, W; Fievez, V
Two experiments with rumen-fistulated dairy cows were conducted to evaluate the effects of feeding docosahexaenoic acid (DHA; C22:6 n-3)-enriched diets or diets provoking a decreased rumen pH on milk fatty acid composition. In the first experiment, dietary treatments were tested during 21-d experimental periods in a 4 x 4 Latin square design. Diets included a control diet, a starch-rich diet, a bicarbonate-buffered starch-rich diet, and a diet supplemented with DHA-enriched micro algae [Schizochytrium sp., 43.0 g/kg of dry matter intake (DMI)]. Algae were supplemented directly through the rumen fistula. The total mixed ration consisted of grass silage, corn silage, soybean meal, and a standard or glucogenic concentrate. The glucogenic and buffered glucogenic diet had no effect on rumen fermentation and milk fatty acid composition because, unexpectedly, no reduced rumen pH was detected. The algae diet had no effect on rumen pH but provoked decreased butyrate and increased isovalerate molar proportions in the rumen. In addition, algae supplementation affected rumen biohydrogenation of linoleic and linolenic acid as reflected in the modified milk fatty acid composition toward increased conjugated linoleic acid (CLA) cis-9 trans-11, CLA trans-9 cis-11, C18:1 trans-10, C18:1 trans-11, and C22:6 n-3 concentrations. Concomitantly, on average, a 45% decrease in DMI and milk yield was observed. Based on these drastic and impractical results, a second animal experiment was performed for 20 d in which 9.35 g/kg of total DMI of algae were incorporated in the concentrate and supplemented to 3 rumen-fistulated cows. Algae concentrate feeding increased rumen pH, which was associated with decreased rumen short-chain fatty acid concentrations. Moreover, a different shift in rumen short-chain fatty acid proportions was observed compared with the first experiment because molar proportions of butyrate, isobutyrate, and isovalerate increased, whereas acetate molar proportion decreased
Rapid measurement of a fatty acid supplement in poultry feed formulations was performed using near infrared (NIR) spectroscopy with chemometric analysis. A standard feed formulation was amended with up to 10 wt% fatty acid supplement containing docosahexaenoic acid (DHA) and scanned from 10,000 cm-1...
Sethi, Ankur; Bajaj, Anurag; Khosla, Sandeep; Arora, Rohit R
During last 2 decades, multiple studies have evaluated omega-3 polyunsaturated fatty acids (ω-3 PUFA) supplementation for cardiovascular prevention. The benefit found in previous studies was not demonstrated in more contemporary trials. We aimed to investigate effect of study characteristics, particularly concomitant statin therapy on results of randomized controlled trials. We systematically searched electronic databases for randomized controlled trials evaluating ω-3 PUFA supplementation and reporting clinical outcomes. A meta-analysis was performed using a random effect model, followed by a meta-regression of dose, docosahexaenoic acid/eicosapentaenoic acid (DHA/EPA) ratio, and duration of treatment and use of lipid-lowering/statin therapy in control group. Twenty-three studies with 77,776 patients (38,910 PUFA; 38,866 controls) were included. PUFA had no effect on total mortality [risk ratio (RR) = 0.96; 95% confidence interval (CI), 0.92-1.01] and myocardial infarction (RR = 0.87; 95% CI, 0.73-1.02), but marginally reduced cardiovascular mortality (RR = 0.93; 95% CI, 0.87-0.98). Lower control group statin use (b = 0.222, P = 0.027) and higher DHA/EPA (b = -0.105, P = 0.033) ratio was associated with higher reduction in total mortality. Duration and dose had no effect. None of the variables except duration had significant effect on reduction in cardiovascular mortality by PUFA supplementation. There was evidence of publication bias. Statin use may mitigate, and higher DHA/EPA ratio is associated with the beneficial effect of PUFA supplementation.
Objective: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have beneficial effects on inflammation and cardiovascular disease (CVD). Our aim was to assess the effect of a six-week supplementation with either olive oil, EPA, or DHA on gene expression in peripheral blood mononuclear cells (...
The omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have important nutrition and disease management properties. Presently fish oil (FO) supplementation relies on capsular triglyceride. Flavored emulsified lipid preparations may provide an improved approach to FO del...
Gustafson, K M; Carlson, S E; Colombo, J; Yeh, H-W; Shaddy, D J; Li, S; Kerling, E H
DHA (22:6n-3) supplementation during infancy has been associated with lower heart rate (HR) and improved neurobehavioral outcomes. We hypothesized that maternal DHA supplementation would improve fetal cardiac autonomic control and newborn neurobehavior. Pregnant women were randomized to 600 mg/day of DHA or placebo oil capsules at 14.4 (+/-4) weeks gestation. Fetal HR and HRV were calculated from magnetocardiograms (MCGs) at 24, 32 and 36 weeks gestational age (GA). Newborn neurobehavior was assessed using the Neonatal Behavioral Assessment Scale (NBAS). Post-partum maternal and infant red blood cell (RBC) DHA was significantly higher in the supplemented group as were metrics of fetal HRV and newborn neurobehavior in the autonomic and motor clusters. Higher HRV is associated with more responsive and flexible autonomic nervous system (ANS). Coupled with findings of improved autonomic and motor behavior, these data suggest that maternal DHA supplementation during pregnancy may impart an adaptive advantage to the fetus.
Gustafson, K.M.; Carlson, S.E.; Colombo, J.; Yeh, H.-W.; Shaddy, D.J.; Li, S.; Kerling, E.H.
DHA (22:6n-3) supplementation during infancy has been associated with lower heart rate (HR) and improved neurobehavioral outcomes. We hypothesized that maternal DHA supplementation would improve fetal cardiac autonomic control and newborn neurobehavior. Pregnant women were randomized to 600 mg/day of DHA or placebo oil capsules at 14.4 (+/−4) weeks gestation. Fetal HRand HRV were calculated from magnetocardiograms (MCGs) at 24, 32 and 36 weeks gestational age (GA). Newborn neurobehavior was assessed using the Neonatal Behavioral Assessment Scale (NBAS). Postpartum maternal and infant red blood cell (RBC) DHA was significantly higher in the supplemented group as were metrics of fetal HRV and newborn neurobehavior in the autonomic and motor clusters. Higher HRV is associated with more responsive and flexible autonomic nervous system (ANS). Coupled with findings of improved autonomic and motor behavior, these data suggest that maternal DHA supplementation during pregnancy may impart an adaptive advantage to the fetus. PMID:23433688
Nagakura, T; Matsuda, S; Shichijyo, K; Sugimoto, H; Hata, K
Omega-3 polyunsaturated fatty acids have anti-inflammatory effects in vitro, and high dietary levels are associated with a lower incidence of inflammatory diseases. However, only limited effects have been demonstrated in asthma. The effects of dietary supplementation with fish oil for 10 months in 29 children with bronchial asthma was investigated in a randomized controlled fashion. In order to minimize the effects of environmental inhaled allergens and diet, this study was performed in a long-term treatment hospital. Subjects received fish oil capsules containing 84 mg eicosapentaenoic acid (EPA) and 36 mg docosahexaenoic acid (DHA) or control capsules containing 300 mg olive oil. The daily dosages of EPA and DHA were 17.0-26.8 and 7.3-11.5 mg x kg body weight(-1), respectively. Asthma symptom scores decreased and responsiveness to acetylcholine decreased in the fish oil group but not in the control group. In addition, plasma EPA levels increased significantly only in the fish oil group (p<0.0088). No significant side-effects were observed. The present results suggest that dietary supplementation with fish oil rich in the omega-3 polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid is beneficial for children with bronchial asthma in a strictly controlled environment in terms of inhalant allergens and diet.
Broadhurst, C. Leigh; Schmidt, Walter F.; Kim, Moon S.; Nguyen, Julie K.; Qin, Jianwei; Chao, Kuanglin; Bauchan, Gary L.; Shelton, Daniel R.
The structural, cognitive and visual development of the human brain and retina strictly require long-chain polyunsaturated fatty acids (LC-PUFA). Excluding water, the mammalian brain is about 60% lipid. One of the great unanswered questions with respect to biological science in general is the absolute necessity of the LC-PUFA docosahexaenoic acid (DHA; 22:6n-3) in these fast signal processing tissues. A lipid of the same chain length with just one less diene group, docosapentaenoic acid (DPA; 22:5n-6) is fairly abundant in terrestrial food chains yet cannot substitute for DHA. Gradient Temperature Raman spectroscopy (GTRS) applies the temperature gradients utilized in differential scanning calorimetry to Raman spectroscopy, providing a straightforward technique to identify molecular rearrangements that occur near and at phase transitions. Herein we apply GTRS to DPA, and DHA from -100 to 20°C. 20 Mb three-dimensional data arrays with 1°C increments and first/second derivatives allows complete assignment of solid, liquid and transition state vibrational modes, including low intensity/frequency vibrations that cannot be readily analyzed with conventional Raman. DPA and DHA show significant spectral changes with premelting (-33 and -60°C, respectively) and melting (-27 and -44°C, respectively). The CH2-(HC=CH)-CH2 moieties are not identical in the second half of the DHA and DPA structures. The DHA molecule contains major CH2 twisting (1265 cm-1) with no noticeable CH2 bending, consistent with a flat helical structure with small pitch. Further modeling of neuronal membrane phospholipids must take into account this structure for DHA, which would be configured parallel to the hydrophilic head group line.
Li, Qingfei; Ai, Qinghui; Mai, Kangsen; Xu, Wei; Zheng, Yuefu
Comparative effects of different concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on immune responses of head-kidney macrophages isolated from large yellow croaker were studied in vitro. After exposing to serum-free medium for 1 day, cultured cells were incubated in medium supplemented with graded levels of EPA or DHA (0, 5, 25, 100, 200 and 1000 μM, respectively) in the form of fatty acid bovine serum albumin (FA-BSA) complex for 12 h, 24 h and 36 h, respectively. Control samples were incubated in the absence of EPA or DHA (2% bovine serum albumin, BSA). Following stimulation, cell viability, lipid peroxidation, secretary phopholipase A2 (sPLA2) and prostaglandin E2 (PGE2) production as well as some immune parameters including phagocytosis, respiratory burst activity and interleukin 1β (IL-1β) production were determined. Results showed that EPA and DHA affected cell viability in dose-dependent and time-dependent manners. In particular, cell viability was significantly decreased after 24 h and 36 h incubation with 1000 μM EPA or DHA (P < 0.05). Higher levels of EPA (200 and 1000 μM) caused a significant increase in the production of malondialdehyde (MDA) (P < 0.05), while DHA did not significantly affect the MDA production. EPA significantly increased the intracellular superoxide anion synthesis which, on the contrary, was significantly reduced by DHA. Phagocytosis percentage (PP) values were significantly higher in treatments with 5 μM DHA (P < 0.05), but significantly decreased by 200 and 1000 μM EPA and DHA compared to the control group (P < 0.05). Decreased PGE2 production was produced by cells treated with relatively low doses of EPA or DHA. When high levels of stimulants (1000 μM EPA or DHA) were used, PGE2 levels were elevated and reached a significant level (P < 0.05). Both EPA and DHA significantly inhibited the production of sPLA2, where DHA exerted the more potent inhibitory effects than EPA. No pronounced effect was
Figueroa, Johnny D.; Cordero, Kathia; llán, Miguel S.
Abstract Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) confer multiple health benefits and decrease the risk of neurological disorders. Studies are needed, however, to identify promising cellular targets and to assess their prophylactic value against neurodegeneration. The present study (1) examined the efficacy of a preventive diet enriched with ω-3 PUFAs to reduce dysfunction in a well-established spinal cord injury (SCI) animal model and (2) used a novel metabolomics data analysis to identify potential neurolipidomic targets. Rats were fed with either control chow or chow enriched with ω-3 PUFAs (750 mg/kg/day) for 8 weeks before being subjected to a sham or a contusion SCI operation. We report new evidence showing that rats subjected to SCI after being pre-treated with a diet enriched with ω-3 PUFAs exhibit significantly better functional outcomes. Pre-treated animals exhibited lower sensory deficits, autonomic bladder recovery, and early improvements in locomotion that persisted for at least 8 weeks after trauma. We found that SCI triggers a robust alteration in the cord PUFA neurolipidome, which was characterized by a marked docosahexaenoic acid (DHA) deficiency. This DHA deficiency was associated with dysfunction and corrected with the ω-3 PUFA-enriched diet. Multivariate data analyses revealed that the spinal cord of animals consuming the ω-3 PUFA-enriched diet had a fundamentally distinct neurolipidome, particularly increasing the levels of essential and long chain ω-3 fatty acids and lysolipids at the expense of ω-6 fatty acids and its metabolites. Altogether, dietary ω-3 PUFAs prophylaxis confers resiliency to SCI mediated, at least in part, by generating a neuroprotective and restorative neurolipidome. PMID:23294084
Liu, Shyh-Hwa; Chang, Chin-Dong; Chen, Pi-Hang; Su, Jheng-Ren; Chen, Chih-Cheng; Chaung, Hso-Chi
Epilepsy provoked by pentylenetetrazol (PTZ) is caused by an abnormal excitatory postsynaptic potential, which results in increased production of reactive oxygen species, and finally reducing cognitive functions. The objective of this study was to investigate the effects of dietary supplementation with DHA and PS, administered either alone or in combination, on oxidative stress and behavioral and cognitive spatial memory in neonatal rats with PTZ-induced epileptic seizure. In this study, rat pups received repetitive doses of PTZ for induction of epileptic seizure and docosahexaenoic acid (DHA, C22:6, n-3) and phosphatidylserine (PS) were orally administrated alone or together to the PTZ-induced epileptic animals daily for 36 d. The spatial memory, nitric mono-oxide (NO) production, and enzymatic activities of superoxide dismutase (SOD) and catalase in brain and liver tissues were determined. PTZ administration significantly reduced the cell numbers in the hippocampus, shortened the escape latency in the safe target region, decreased activities of SOD and catalase, but increased NO content in both brain and liver tissues, while DHA and PS significantly extended the escape latency, reversed the oxidative parameters observed in the brain, and enhanced SOD activity in the liver. Dietary supplementation with DHA and PS may protect brain tissue from the oxidative stress caused by epileptic seizures and could serve to improve learning and memory ability in vivo.
Shidfar, Farzad; Amani, Samira; Vafa, Mohammadreza; Shekarriz, Ramin; Hosseini, Sharieh; Shidfar, Shahrzad; Eshraghian, Mohammadreza; Mousavi, Seyedeh Neda
Numerous studies have demonstrated that tissue deposition of iron following prolonged high dose of oral supplementation for treatment of iron deficiency anemia (IDA) leads to body iron overload and oxidative stress, which starts the process of atherosclerosis. This study aimed to determine the effect of iron supplementation in combination with docosahexaenoic acid (DHA) on the cardiovascular disease risk based on paraoxonase-1 (PON-1), high-sensitivity C-reactive protein (hs-CRP), and ApoB/ApoA-I ratio in women with IDA. In this randomized controlled trial, 76 women with IDA, aged 15-45 years, were included. The patients were randomly assigned to receive 500 mg of DHA supplement or placebo with an iron tablet, once daily for 12 weeks. The participants were assessed by measurement of the serum iron, ferritin, PON-1, hs-CRP levels, and the ApoB/ApoA-I ratio at the beginning and end of study. Serum hs-CRP decreased in the DHA-supplemented group (p = 0.036), and ApoA-I decreased in the placebo group (p = 0.013). No significant difference was detected for the serum PON-1 concentration and the ApoB/ApoA-I ratio in two groups. Iron supplementation combined with DHA may have favorable effects on serum hs-CRP in women with IDA.
Popovic, Tamara; Ranic, Marija; Bulajic, Predrag; Milicevic, Miroslav; Arsic, Aleksandra; Vucic, Vesna; Glibetic, Marija
Nutritional and immunological status of patients with obstructive jaundice is usually severely altered, with high mortality rates. The n-3 polyunsaturate fatty acids (PUFA), particularly eicosapentaenoic acid (EPA, 20:5 n-3), posess potent immunomodulatory activities. Thus, our aim was to compare the plasma phospholipid fatty acid (FA) composition of these patients with healthy subjects, as well as before and after 7 days preoperative supplementation with high doses of EPA (0.9 g per day) and docosahexaenoic acid (DHA, 22:6 n-3, 0.6 g per day). We found impaired FA status in obstructive jaundice patients, especially EPA, DHA and PUFA, but significantly increased content of total n-3 FA, 22:5 n-3 FA and particularly EPA, which increased more than 3 fold, after 7 days supplementation. In addition, the n6/n3 ratio significantly decreased from 14.24 to 10.24, demonstrating severely improved plasma phospholipid profile in these patients after the intervention. PMID:19902030
Bou, Marta; Berge, Gerd M; Baeverfjord, Grete; Sigholt, Trygve; Østbye, Tone-Kari; Romarheim, Odd Helge; Hatlen, Bjarne; Leeuwis, Robin; Venegas, Claudia; Ruyter, Bente
Farmed salmon feeds have changed from purely marine-based diets with high levels of EPA and DHA in the 1990s to the current 70 % plant-based diets with low levels of these fatty acids (FA). The aim of this study was to establish the impacts of low dietary EPA and DHA levels on performance and tissue integrity of Atlantic salmon (Salmo salar). Atlantic salmon (50 g) in seawater were fed fourteen experimental diets, containing five levels (0, 0·5, 1·0, 1·5 and 2·0 %) of EPA, DHA or a 1:1 EPA+DHA plus control close to a commercial diet, to a final weight of 400 g. Lack of EPA and DHA did not influence mortality, but the n-3-deficient group exhibited moderately slower growth than those fed levels above 0·5 %. The heart and brain conserved EPA and DHA levels better than skeletal muscle, liver, skin and intestine. Decreased EPA and DHA favoured deposition of pro-inflammatory 20 : 4n-6 and 20 : 3n-6 FA in membrane phospholipids in all tissues. When DHA was excluded from diets, 18 : 3n-3 and EPA were to a large extent converted to DHA. Liver, skeletal and cardiac muscle morphology was normal in all groups, with the exception of cytoplasm packed with large or foamy vacuoles and sometimes swollen enterocytes of intestine in both deficient and EPA groups. DHA supplementation supported normal intestinal structure, and 2·0 % EPA+DHA alleviated deficiency symptoms. Thus, EPA and DHA dietary requirements cannot be based exclusively on growth; tissue integrity and fish health also need to be considered.
Docosahexaenoic acid prevents trans-10, cis-12 conjugated linoleic acid-induced non-alcoholic fatty liver disease in mice by altering expression of hepatic genes regulating fatty acid synthesis and oxidation
Background: Concomitant supplementation with docosahexaenoic acid (22:6 n-3; DHA) prevented t10, c12- conjugated linoleic acid (CLA)-induced non-alcoholic fatty liver disease (NAFLD) and insulin resistance. Effective dose of DHA and mechanisms involved are poorly understood. Methods: We examined abi...
Schnebelen-Berthier, Coralie; Acar, Niyazi; Pouillart, Philippe; Thabuis, Clementine; Rodriguez, Bertrand; Depeint, Flore; Clerc, Elise; Mathiaud, Adeline; Bourdillon, Anne; Baert, Blandine; Bretillon, Lionel; Lecerf, Jean-Michel
Lutein and docosahexaenoic acid (DHA) are associated with the prevention of age-related macular degeneration (AMD). Since microalgae are potent natural sources of these nutrients, their nutritional value should be evaluated based on the bioavailability of lutein and DHA for the retina via the plasmatic compartment. In this study, quail were fed for 5 months either with a diet supplemented or deprived with microalgae rich in lutein and DHA. In the microalgae-fed group, the retinal concentrations of lutein and zeaxanthin gradually increased whereas in plasma, these compounds started to increase from the first month of supplementation. We also observed a significant increase in retinal and plasmatic levels of DHA in the microalgae-fed group. In conclusion, the plasmatic and retinal contents of lutein and DHA were significantly increased in quail fed with lutein- and DHA-rich microalgae. Food fortification with microalgae may be an innovative way to increase lutein and DHA consumption in humans.
Maki, Kevin C; Reeves, Mathew S; Farmer, Mildred; Griinari, Mikko; Berge, Kjetil; Vik, Hogne; Hubacher, Rachel; Rains, Tia M
Antarctic krill, also known as Euphausia superba, is a marine crustacean rich in both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We tested the hypothesis that krill oil would increase plasma concentrations of EPA and DHA without adversely affecting indicators of safety, tolerability, or selected metabolic parameters. In this randomized, double-blind parallel arm trial, overweight and obese men and women (N = 76) were randomly assigned to receive double-blind capsules containing 2 g/d of krill oil, menhaden oil, or control (olive) oil for 4 weeks. Results showed that plasma EPA and DHA concentrations increased significantly more (P < .001) in the krill oil (178.4 +/- 38.7 and 90.2 +/- 40.3 micromol/L, respectively) and menhaden oil (131.8 +/- 28.0 and 149.9 +/- 30.4 micromol/L, respectively) groups than in the control group (2.9 +/- 13.8 and -1.1 +/- 32.4 micromol/L, respectively). Systolic blood pressure declined significantly more (P < .05) in the menhaden oil (-2.2 +/- 2.0 mm Hg) group than in the control group (3.3 +/- 1.5 mm Hg), and the response in the krill oil group (-0.8 +/- 1.4 mm Hg) did not differ from the other 2 treatments. Blood urea nitrogen declined in the krill oil group as compared with the menhaden oil group (P < .006). No significant differences for other safety variables were noted, including adverse events. In conclusion, 4 weeks of krill oil supplementation increased plasma EPA and DHA and was well tolerated, with no indication of adverse effects on safety parameters.
Prepartum maternal diets supplemented with oilseeds alter the fatty acid profile in bovine neonatal plasma possibly through reduced placental expression of fatty acid transporter protein 4 and fatty acid translocase.
Salehi, Reza; Ambrose, Divakar J
In the present study, we determined the effects of maternal dietary fat and the type of fat on plasma fatty acids and the expression of placental fatty acid transporter genes. In Experiment 1, Holstein cows in the last 35 days of gestation received diets containing sunflower seed (n=8; high in linoleic acid (LA)), canola seed (n=7; high in oleic acid (OLA)) or no oilseed (n=7; control). Fatty acids were quantified in dam and neonate plasma at calving. In Experiment 2, placental cotyledons were collected (LA: n=4; OLA: n=4; control: n=5) to quantify gene expression. Maternal long-chain polyunsaturated fatty acids, neonatal total n-3 fatty acids and eicosapentaenoic acid (EPA) declined, whereas docosahexaenoic acid (DHA) and total fat tended to decline following fat supplementation prepartum. Feeding of LA versus OLA prepartum tended to increase peroxisome proliferator-activated receptor α (PPARA) expression, whereas peroxisome proliferator-activated receptor δ (PPARD) and peroxisome proliferator-activated receptor γ (PPARG) expression tended to be higher in OLA- than LA-fed cows. Expression of fatty acid transporter protein 4 (FATP4) and fatty acid translocase (FAT/CD36) expression was lower in placental tissue of cows fed fat compared with control cows. Reduced total n-3 fatty acids, EPA and DHA in neonates born of dams fed fat prepartum is likely due to changes in PPARs and reduced expression of placental FATP4 and FAT/CD36.
Guzmán, José F.; Esteve, Hector; Pablos, Carlos; Pablos, Ana; Blasco, Cristina; Villegas, José A.
Omega-3 fatty acids (n-3) has shown to improve neuromotor function. This study examined the effects of docosahexaenoic acid (DHA) on complex reaction time, precision and efficiency, in female elite soccer players. 24 players from two Spanish female soccer Super League teams were randomly selected and assigned to two experimental groups, then administered, in a double-blind manner, 3.5 g·day-1 of either DHA-rich fish oil (FO =12) or olive oil (OO = 12) over 4 weeks of training. Two measurements (pre- and post-treatment) of complex reaction time and precision were taken. Participants had to press different buttons and pedals with left and right hands and feet, or stop responding, according to visual and auditory stimuli. Multivariate analysis of variance displayed an interaction between supplement administration (pre/post) and experimental group (FO/OO) on complex reaction time (FO pre = 0.713 ± 0.142 ms, FO post = 0.623 ± 0.109 ms, OO pre = 0.682 ± 1.132 ms, OO post = 0.715 ± 0.159 ms; p = 0.004) and efficiency (FO pre = 40.88 ± 17.41, FO post = 57.12 ± 11.05, OO pre = 49.52 ± 14.63, OO post = 49. 50 ± 11.01; p = 0.003). It was concluded that after 4 weeks of supplementation with FO, there was a significant improvement in the neuromotor function of female elite soccer players. Key points The results obtained from the study suggest that supplementation with DHA produced perceptual-motor benefits in female elite athletes. DHA could be a beneficial supplement in sports where decision making and reaction time efficiency are of importance. PMID:24149875
Tsiplakou, Eleni; Zervas, George
An effective strategy for enhancing the bioactive fatty acids (FA) in sheep milk could be dietary supplementation with a moderate level of a combination of soybean oil with fish oil (SFO) without negative effects on milk yield and its chemical composition. Thus, the objective of this study was to determine the effects of a moderate forage diet supplementation with SFO on milk chemical composition and FA profile, as well as on plasma FA. Twelve dairy sheep were assigned to two homogenous sub-groups. Treatments involved a control diet without added oil, and a diet supplemented with 23.6 g soybean oil and 4.7 g fish oil per kg dry matter (DM) of the total ration. The results showed that SFO diet had no effect on milk yield and chemical composition. In blood plasma the concentrations of trans-11 C(18:2) (VA), C(18:2n-6), C(20:5n-3) (EPA) and C(22:6n-3) (DHA) were significantly higher while those of C(14:0), C(16:0) and C(18:0) were lower in sheep fed with SFO diet compared with control. The SFO supplementation of sheep diet increased the concentrations of VA, cis-9, trans-11 C(18:2) CLA, trans-10, cis-12, C(18:2) CLA, EPA, DHA, monounsaturated FA (MUFA), polyusaturated fatty acids (PUFA) and n-3 FA and decreased those of short chain FA (SCFA), medium chain FA (MCFA), the saturated/unsaturated ratio and the atherogenicity index value in milk compared with the control. In conclussion, the SFO supplementation at the above levels in a sheep diet, with moderate forage to concentrate ratio, improved the milk FA profile from human health standpoint without negative effects on its chemical composition.
Lauritzen, Lotte; Fewtrell, Mary; Agostoni, Carlo
Arachidonic acid (AA) is supplied together with docosahexaenoic acid (DHA) in infant formulas, but we have limited knowledge about the effects of supplementation with either of these long-chain polyunsaturated fatty acids (LCPUFA) on growth and developmental outcomes. AA is present in similar levels in breast milk throughout the world, whereas the level of DHA is highly diet dependent. Autopsy studies show similar diet-dependent variation in brain DHA, whereas AA is little affected by intake. Early intake of DHA has been shown to affect visual development, but the effect of LCPUFA on neurodevelopment remains to be established. Few studies have found any functional difference between infants supplemented with DHA alone compared to DHA+AA, but some studies show neurodevelopmental advantages in breast-fed infants of mothers supplemented with n-3 LCPUFA alone. It also remains to be established whether the AA/DHA balance could affect allergic and inflammatory outcomes later in life. Disentangling effects of genetic variability and dietary intake on AA and DHA-status and on functional outcomes may be an important step in the process of determining whether AA-intake is of any physiological or clinical importance. However, based on the current evidence we hypothesize that dietary AA plays a minor role on growth and development relative to the impact of dietary DHA.
It takes more than 20 years before the human brain obtains its complex, adult configuration. Most dramatic developmental changes occur prenatally and early postnatally. During development, long-chain polyunsaturated fatty acids (LCPUFA) such as doxosahexaenoic acid (DHA) and arachidonic acid (AA) are accreted in the brain. Since breastfeeding is associated with a better developmental outcome than formula feeding, and human milk in contrast to traditional standard formula contains LCPUFA, the question arose whether LCPUFA supplementation of infant formula may promote the neurodevelopmental outcome. The current paper reviews the evidence available in full-term infants. It concludes that postnatal supplementation of formula with LCPUFA is associated with a beneficial effect on short-term neurodevelopmental outcome. However, no evidence is available that LCPUFA supplementation enhances neurodevelopmental outcome in full-term infants beyond the age of four months. Nevertheless, it should be realized that very limited information is available on the effect of LCPUFA supplementation on neurodevelopmental outcome at school age or later. It is conceivable that effects of LCPUFA supplementation first emerge or re-emerge at school age when more complex neural functions are expressed. PMID:22254056
Hybrid striped bass feeds based on fish oil, beef tallow, and eicosapentaenoic acid/docosahexaenoic acid supplements: Insight regarding fish oil sparing and demand for -3 long-chain polyunsaturated fatty acids.
Bowzer, J; Jackson, C; Trushenski, J
Previous research suggests that saturated (SFA) and monounsaturated fatty acid (MUFA) rich lipids, including beef tallow, can make utilization or diet-to-tissue transfer of long-chain polyunsaturated fatty acids (LC-PUFA) more efficient. We hypothesized that using beef tallow as an alternative to fish oil may effectively reduce the LC-PUFA demand of hybrid striped bass × and allow for greater fish oil sparing. Accordingly, we evaluated growth performance and tissue fatty acid profiles of juvenile fish (23.7 ± 0.3 g) fed diets containing menhaden fish oil (considered an ideal source of LC-PUFA for this taxon), beef tallow (BEEF ONLY), or beef tallow amended with purified sources of eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA) to achieve levels corresponding to 50 or 100% of those observed in the FISH ONLY feed. Diets were randomly assigned to quadruplicate tanks of fish ( = 4; 10 fish/tank), and fish were fed assigned diets to apparent satiation once daily for 10 wk. Survival (98-100%) was equivalent among treatments, but weight gain (117-180%), specific growth rate (1.1-1.5% BW/d), feed intake (1.4-1.8% BW/d), thermal growth coefficient (0.50-0.70), and feed conversion ratio (FCR; 1.1-1.4, DM basis) varied. Except for FCR, no differences were observed between the FISH ONLY and BEEF ONLY treatments, but performance was generally numerically superior among fish fed the diets containing beef tallow supplemented with DHA at the 100% or both EPA and DHA at the 50% or 100% level. Tissue fatty acid composition was significantly distorted in favor among fish fed the beef tallow-based feeds; however, profile distortion was most overt in peripheral tissues. Results suggest that beef tallow may be used as a primary lipid source in practical diets for hybrid striped bass, but performance may be improved by supplementation with LC-PUFA, particularly DHA. Furthermore, our results suggest that -3 LC-PUFA requirements reported for hybrid striped bass may not be
Guillot, Nicolas; Caillet, Emilie; Laville, Martine; Calzada, Catherine; Lagarde, Michel; Véricel, Evelyne
Docosahexaenoic acid (DHA) can prevent cardiovascular events. However, few studies have addressed the effects of DHA on both platelet reactivity and redox status in healthy subjects, and dose-related studies are scarce. The main objectives of the present study were to determine the effects of increasing doses of DHA on platelets and redox status in humans. Twelve healthy male volunteers (aged 53-65 yr) were assigned to consume an intake of successively 200, 400, 800, and 1600 mg/d DHA, as the only omega-3 fatty acid, for 2 wk each dose. Blood and urine samples were collected before and after each dose of DHA and at 8 wk after arrest of supplementation. DHA was incorporated in a dose-response fashion in platelet phospholipids. After supplementation with 400 and 800 mg/d DHA, platelet reactivity was significantly decreased. Platelet vitamin E concentration increased only after 200 mg/d DHA, while p38 MAP kinase phosphorylation decreased. Urinary isoprostane was also significantly lowered after 200 mg/d DHA but was increased after 1600 mg/d. Therefore, supplementation with only 200 mg/d DHA for 2 wk induced an antioxidant effect. It is concluded that low consumption of DHA could be an effective and nonpharmacological way to protect healthy men from platelet-related cardiovascular events.
Sarkadi-Nagy, Eszter; Wijendran, Vasuki; Diau, Guan-Yeu; Chao, Angela Chueh; Hsieh, Andrea T; Turpeinen, Anu; Nathanielsz, Peter W; Brenna, J Thomas
Clinical studies show that docosahexaenoic acid (DHA) and arachidonic acid (ARA) supplemented formula improve visual function in preterm infants, however improved fatty acid status is known only for plasma and red blood cells (RBC) since target organs cannot be sampled from humans. Baboons were randomized to one of four groups: Term breast-fed (B); Term formula-fed (T-); Preterm formula-fed (P-); and Preterm DHA/ARA-supplemented formula-fed (P+). The P+ contained 0.61 +/- 0.03% DHA and 1.21 +/- 0.09% ARA, and breast milk had 0.68 +/- 0.22% and 0.62 +/- 0.12% as DHA and ARA, respectively. The B and P+ groups had significantly higher DHA concentration in all tissues than T- and P-. The P- group showed dramatically lower DHA content of 35%, 27%, 66%, and 75% in the brain, retina, liver, and plasma, respectively, compared with B. Supplementation prevented declines in DHA levels in the retina, and liver, and attenuated the decline in brain, plasma and RBC of preterm animals. In contrast, ARA was not significantly lower compared with B in any group in any tissue but was significantly elevated in liver and brain. RBC and plasma DHA were correlated with DHA in tissues; RBC/plasma ARA were uncorrelated with tissue ARA. We conclude that 1) DHA drops precipitously in term and preterm primates consuming formula without long chain polyunsaturates, while 22:5n-6 concentration rises; 2) tissue ARA levels are insensitive to dietary LCP supplementation or prematurity, 3) plasma and RBC levels of ARA are uncorrelated with total ARA levels; 4) DHA levels are correlated with group effects and are uncorrelated within groups.
Intrauterine and early life exposure to folic acid has significantly increased in North America owing to folic acid fortification, widespread supplemental use and periconceptional folic acid supplementation. The effect of maternal and postweaning folic acid supplementation on colorectal cancer risk ...
Corbee, R J; Barnier, M M C; van de Lest, C H A; Hazewinkel, H A W
The aim of this randomized, double-blinded, placebo-controlled, cross-over designed study was to demonstrate the clinical effect, registered by a survey, of a 10-week period of omega-3 fatty acid supplementation of the diet (1.53 g eicosapentaenoic acid (EPA) and 0.31 g DHA, both per 1000 kcal ME, equivalent to the complete diet) of 16 cats with radiologically documented, naturally occurring osteoarthritis (OA), in comparison with a 10-week period of supplementation with corn oil (0.00 g EPA and 0.00 g DHA, both per 1000 kcal ME). Cats on the fish oil revealed higher activity level (p = 0.07), more walking up and down the stairs (p = 0.07), less stiffness during gait (p = 0.03), more interaction with the owner (p = 0.07) and higher jumps (p = 0.03) compared to those on corn oil supplementation. In conclusion, supplementation of long-chain omega-3 polyunsaturated fatty acids changes the owner's perception of some aspects of behaviour and locomotion in cats with naturally occurring OA.
Capó, X; Martorell, M; Busquets-Cortés, C; Sureda, A; Riera, J; Drobnic, F; Tur, J A; Pons, A
Functional beverages based on almonds and olive oil and enriched with α-tocopherol and docosahexaenoic acid (DHA) could be useful in modulating oxidative stress and enhancing physical performance in sportsmen. The aim of this work was to evaluate the effects of supplementation with functional beverages on physical performance, plasma and erythrocyte fatty acids' and polyphenol handling, oxidative and nitrative damage, and antioxidant and mitochondrial gene expression in young and senior athletes. Athletes performed maximal exercise tests before and after one month of dietary supplementation and blood samples were taken immediately before and one hour after each test. The beverages did not alter performance parameters during maximal exercise. Supplementation increased polyunsaturated and reduced saturated plasma fatty acids while increasing the DHA erythrocyte content; it maintained basal plasma and blood polyphenol levels, but increased the blood cell polyphenol concentration in senior athletes. Supplementation protects against oxidative damage although it enhances nitrative damage in young athletes. The beverages enhance the gene expression of antioxidant enzymes in peripheral blood mononuclear cells after exercise in young athletes.
Penugonda, Kavitha; Lindshield, Brian L
Saw palmetto supplements are one of the most commonly consumed supplements by men with prostate cancer and/or benign prostatic hyperplasia (BPH). Some studies have found significant improvements in BPH and lower urinary tract symptoms (LUTS) with saw palmetto supplementation, whereas others found no benefits. The variation in the efficacy in these trials may be a result of differences in the putative active components, fatty acids and phytosterols, of the saw palmetto supplements. To this end, we quantified the major fatty acids (laurate, myristate, palmitate, stearate, oleate, linoleate) and phytosterols (campesterol, stigmasterol, β-sitosterol) in 20 commercially available saw palmetto supplements using GC-FID and GC-MS, respectively. Samples were classified into liquids, powders, dried berries, and tinctures. Liquid saw palmetto supplements contained significantly higher (p < 0.05) concentrations of total fatty acids (908.5 mg/g), individual fatty acids, total phytosterols (2.04 mg/g), and individual phytosterols, than the other supplement categories. Powders contained significantly higher (p < 0.05) concentrations of total fatty acids than tinctures, which contain negligible amounts of fatty acids (46.3 mg/g) and phytosterols (0.10 mg/g). Our findings suggest that liquid saw palmetto supplements may be the best choice for individuals who want to take a saw palmetto supplement with the highest concentrations of both fatty acids and phytosterols.
Penugonda, Kavitha; Lindshield, Brian L.
Saw palmetto supplements are one of the most commonly consumed supplements by men with prostate cancer and/or benign prostatic hyperplasia (BPH). Some studies have found significant improvements in BPH and lower urinary tract symptoms (LUTS) with saw palmetto supplementation, whereas others found no benefits. The variation in the efficacy in these trials may be a result of differences in the putative active components, fatty acids and phytosterols, of the saw palmetto supplements. To this end, we quantified the major fatty acids (laurate, myristate, palmitate, stearate, oleate, linoleate) and phytosterols (campesterol, stigmasterol, β-sitosterol) in 20 commercially available saw palmetto supplements using GC-FID and GC-MS, respectively. Samples were classified into liquids, powders, dried berries, and tinctures. Liquid saw palmetto supplements contained significantly higher (p < 0.05) concentrations of total fatty acids (908.5 mg/g), individual fatty acids, total phytosterols (2.04 mg/g), and individual phytosterols, than the other supplement categories. Powders contained significantly higher (p < 0.05) concentrations of total fatty acids than tinctures, which contain negligible amounts of fatty acids (46.3 mg/g) and phytosterols (0.10 mg/g). Our findings suggest that liquid saw palmetto supplements may be the best choice for individuals who want to take a saw palmetto supplement with the highest concentrations of both fatty acids and phytosterols. PMID:24067389
... slow cognitive decline? I've heard that folic acid supplements can improve cognitive function in older adults. ... those with Alzheimer's disease also benefit from folic acid? Answers from Paul Y. Takahashi, M.D. There's ...
Ali, Mehboob; Heyob, Kathryn M.; Velten, Markus; Tipple, Trent E.
We have previously shown that an adverse perinatal environment significantly alters lung growth and development and results in persistently altered cardiopulmonary physiology in adulthood. Our model of maternal LPS treatment followed by 14 days of neonatal hyperoxia exposure causes severe pulmonary disease characterized by permanent decreases in alveolarization and diffuse interstitial fibrosis. The current investigations tested the hypothesis that dysregulation of Notch signaling pathways contributes to the permanently altered lung phenotype in our model and that the improvements we have observed previously with maternal docosahexaenoic acid (DHA) supplementation are mediated through normalization of Notch-related protein expression. Results indicated that inflammation (IL-6 levels) and oxidation (F2a-isoprostanes) persisted through 8 wk of life in mice exposed to LPS/O2 perinatally. These changes were attenuated by maternal DHA supplementation. Modest but inconsistent differences were observed in Notch-pathway proteins Jagged 1, DLL 1, PEN2, and presenilin-2. We detected substantial increases in markers of apoptosis including PARP-1, APAF-1, caspase-9, BCL2, and HMGB1, and these increases were attenuated in mice that were nursed by DHA-supplemented dams during the perinatal period. Although Notch signaling is not significantly altered at 8 wk of age in mice with perinatal exposure to LPS/O2, our findings indicate that persistent apoptosis continues to occur at 8 wk of age. We speculate that ongoing apoptosis may contribute to persistently altered lung development and may further enhance susceptibility to additional pulmonary disease. Finally, we found that maternal DHA supplementation prevented sustained inflammation, oxidation, and apoptosis in our model. PMID:26138643
Pérez, Miguel Á; Terreros, Gonzalo; Dagnino-Subiabre, Alexies
Chronic stress leads to secretion of the adrenal steroid hormone corticosterone, inducing hippocampal atrophy and dendritic hypertrophy in the rat amygdala. Both alterations have been correlated with memory impairment and increased anxiety. Supplementation with ω-3 fatty acids improves memory and learning in rats. The aim of this study was to evaluate the effects of ω-3 supplementation on learning and major biological and behavioral stress markers. Male Sprague-Dawley rats were randomly assigned to three experimental groups: 1) Control, 2) Vehicle, animals supplemented with water, and 3) ω-3, rats supplemented with ω-3 (100 mg of DHA+25 mg of EPA). Each experimental group was divided into two subgroups: one of which was not subjected to stress while the other was subjected to a restraint stress paradigm. Afterwards, learning was analyzed by avoidance conditioning. As well, plasma corticosterone levels and anxiety were evaluated as stress markers, respectively by ELISA and the plus-maze test. Restraint stress impaired learning and increased both corticosterone levels and the number of entries into the open-arm (elevated plus-maze). These alterations were prevented by ω-3 supplementation. Thus, our results demonstrate that ω-3 supplementation had two beneficial effects on the stressed rats, a strong anti-stress effect and improved learning.
Maximin, Elise; Langelier, Bénédicte; Aïoun, Josiane; Al-Gubory, Kaïs H; Bordat, Christian; Lavialle, Monique; Heberden, Christine
Fatty acid binding protein 7 (FABP7), abundant in the embryonic brain, binds with the highest affinity to docosahexaenoic acid (DHA) and is expressed in the early stages of embryogenesis. Here, we have examined the consequences of the exposure to different DHA levels and of the in utero depletion of FABP7 on early rat brain development. Neurodevelopment was evaluated through the contents of two proteins, connexin 43 (Cx43) and cyclin-dependent kinase 5 (CDK5), both involved in neuroblast proliferation, differentiation, and migration. The dams were fed with diets presenting different DHA contents, from deficiency to supplementation. DHA brain embryos contents already differed at embryonic day 11.5 and the differences kept increasing with time. Cx43 and CDK5 contents were positively associated with the brain DHA levels. When FABP7 was depleted in vivo by injections of siRNA in the telencephalon, the enhancement of the contents of both proteins was lost in supplemented animals, but FABP7 depletion did not modify phospholipid compositions regardless of the diets. Thus, FABP7 is a necessary mediator of the effect of DHA on these proteins synthesis, but its role in DHA uptake is not critical, although FABP7 is localized in phospholipid-rich areas. Our study shows that high contents of DHA associated with FABP7 are necessary to promote early brain development, which prompted us to recommend DHA supplementation early in pregnancy.
Meyer, Barbara J; Hammervold, Tone; Rustan, Arild Chr; Howe, Peter R C
The objective of the study was to evaluate potential benefits of docosahexaenoic acid (DHA) rich fish oil supplementation as an adjunct to statin therapy for hyperlipidaemia. A total of 45 hyperlipidaemic patients on stable statin therapy with persistent elevation of plasma triglycerides (averaging 2.2 mmol/L) were randomised to take 4 g/day (n = 15) or 8 g/day (n = 15) of tuna oil or olive oil (placebo, n = 15) for 6 months. Plasma lipids, blood pressure and arterial compliance were assessed initially and after 3 and 6 months in 40 subjects who completed the trial. Plasma triglycerides were reduced 27% by 8 g/day DHA-rich fish oil (P < 0.05) but not by 4 g/day when compared with the placebo and this reduction was achieved by 3 months and was sustained at 6 months. Even though total cholesterol was already well controlled by the statin treatment (mean initial level 4.5 mmol/L), there was a further dose-dependent reduction with fish oil supplementation (r = -0.344, P < 0.05). The extent of total cholesterol reduction correlated (r = -0.44) with the initial total cholesterol levels (P < 0.005). In the subset with initial plasma cholesterol above 3.8 mmol/L, plasma very low density lipoprotein (VLDL), intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) were isolated and assayed for cholesterol and apolipoprotein B (apoB) at the commencement of the trial and at 3 months of intervention. Fish oil tended to lower cholesterol and apoB in VLDL and raise both in LDL. There were no changes in IDL cholesterol, IDL apoB and high-density lipoprotein cholesterol. The results demonstrate that DHA-rich fish oil supplementation (2.16 g DHA/day) can improve plasma lipids in a dose-dependent manner in patients taking statins and these changes were achieved by 3 months. Fish oil in addition to statin therapy may be preferable to drug combinations for the treatment of combined hyperlipidaemia.
Simón, María Victoria; Agnolazza, Daniela L; German, Olga Lorena; Garelli, Andrés; Politi, Luis E; Agbaga, Martin-Paul; Anderson, Robert E; Rotstein, Nora P
Oxidative stress is involved in activating photoreceptor death in several retinal degenerations. Docosahexaenoic acid (DHA), the major polyunsaturated fatty acid in the retina, protects cultured retina photoreceptors from apoptosis induced by oxidative stress and promotes photoreceptor differentiation. Here, we investigated whether eicosapentaenoic acid (EPA), a metabolic precursor to DHA, had similar effects and whether retinal neurons could metabolize EPA to DHA. Adding EPA to rat retina neuronal cultures increased opsin expression and protected photoreceptors from apoptosis induced by the oxidants paraquat and hydrogen peroxide (H2 O2 ). Palmitic, oleic, and arachidonic acids had no protective effect, showing the specificity for DHA. We found that EPA supplementation significantly increased DHA percentage in retinal neurons, but not EPA percentage. Photoreceptors and glial cells expressed Δ6 desaturase (FADS2), which introduces the last double bond in DHA biosynthetic pathway. Pre-treatment of neuronal cultures with CP-24879 hydrochloride, a Δ5/Δ6 desaturase inhibitor, prevented EPA-induced increase in DHA percentage and completely blocked EPA protection and its effect on photoreceptor differentiation. These results suggest that EPA promoted photoreceptor differentiation and rescued photoreceptors from oxidative stress-induced apoptosis through its elongation and desaturation to DHA. Our data show, for the first time, that isolated retinal neurons can synthesize DHA in culture. Docosahexaenoic acid (DHA), the major polyunsaturated fatty acid in retina photoreceptors, and its precursor, eicosapentaenoic acid (EPA) have multiple beneficial effects. Here, we show that retina neurons in vitro express the desaturase FADS2 and can synthesize DHA from EPA. Moreover, addition of EPA to these cultures protects photoreceptors from oxidative stress and promotes their differentiation through its metabolization to DHA.
Saunders, Angela V; Davis, Brenda C; Garg, Manohar L
While intakes of the omega-3 fatty acid α-linolenic acid (ALA) are similar in vegetarians and non-vegetarians, intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are low in vegetarians and virtually absent in vegans. Plasma, blood and tissue levels of EPA and DHA are lower in vegetarians than in non-vegetarians, although the clinical significance of this is unknown. Vegetarians do not exhibit clinical signs of DHA deficiency, but further research is required to ascertain whether levels observed in vegetarians are sufficient to support optimal health. ALA is endogenously converted to EPA and DHA, but the process is slow and inefficient and is affected by genetics, sex, age and dietary composition. Vegetarians can take practical steps to optimise conversion of ALA to EPA and DHA, including reducing intake of linoleic acid. There are no official separate recommendations for intake of fatty acids by vegetarians. However, we suggest that vegetarians double the current adequate intake of ALA if no direct sources of EPA and DHA are consumed. Vegetarians with increased needs or reduced conversion ability may receive some advantage from DHA and EPA supplements derived from microalgae. A supplement of 200-300 mg/day of DHA and EPA is suggested for those with increased needs, such as pregnant and lactating women, and those with reduced conversion ability, such as older people or those who have chronic disease (eg, diabetes).
Simón, María Victoria; Agnolazza, Daniela L.; German, Olga Lorena; Garelli, Andrés; Politi, Luis E.; Agbaga, Martin-Paul; Anderson, Robert E.; Rotstein, Nora P.
Oxidative stress is involved in activating photoreceptor death in several retinal degenerations. Docosahexaenoic acid (DHA), the major polyunsaturated fatty acid in the retina, protects cultured retina photoreceptors from apoptosis induced by oxidative stress and promotes photoreceptor differentiation. Here we investigated whether eicosapentaenoic acid (EPA), a metabolic precursor to DHA, had similar effects and whether retinal neurons could metabolize EPA to DHA. Adding EPA to rat retina neuronal cultures increased opsin expression and protected photoreceptors from apoptosis induced by the oxidants paraquat (PQ) and hydrogen peroxide (H2O2). Palmitic, oleic, and arachidonic acids had no protective effect, showing the specificity for DHA. We found that EPA supplementation significantly increased DHA percentage in retinal neurons, but not EPA percentage. Photoreceptors and glial cells expressed Δ6 desaturase (FADS2), which introduces the last double bond in DHA biosynthetic pathway. Pre-treatment of neuronal cultures with CP-24879 hydrochloride, a Δ5/Δ6 desaturase inhibitor, prevented EPA-induced increase in DHA percentage and completely blocked EPA protection and its effect on photoreceptor differentiation. These results suggest that EPA promoted photoreceptor differentiation and rescued photoreceptors from oxidative stress-induced apoptosis through its elongation and desaturation to DHA. Our data show, for the first time, that isolated retinal neurons can synthesize DHA in culture. PMID:26662863
acids ( PUFA ), particularly omega -3 fatty acids , inhibits SREBP-1 activation, resulting in a decreased transcription of FAS. 15. SUBJECT TERMS Prostate...Cancer; Lipid Metabolism; Clinical Trial; Omega -3 Fatty Acids 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES...controls, Menendez et al demonstrated that addition of omega -3 fatty acids (-3 FA), docosahexanoic acid (DHA), alpha- linolenic acid
Sarkadi-Nagy, Eszter; Wijendran, Vasuki; Diau, Guan Yeu; Chao, Angela Chueh; Hsieh, Andrea T; Turpeinen, Anu; Lawrence, Peter; Nathanielsz, Peter W; Brenna, J Thomas
Infant formulas supplemented with docosahexaenoic acid (DHA) and arachidonic acid (ARA) are now available in the United States; however, little is known about the factors that affect biosynthesis. Baboon neonates were assigned to one of four treatments: term, breast-fed; term, formula-fed; preterm (155 of 182 days gestation), formula-fed; and preterm, formula+DHA/ARA-fed. Standard formula had no DHA/ARA; supplemented formula had 0.61%wt DHA (0.3% of calories) and 1.21%wt ARA (0.6% of calories), and baboon breast milk contained 0.68 +/- 0.22%wt DHA and 0.62 +/- 0.12%wt ARA. At 14 days adjusted age, neonates received a combined oral dose of [U-13C]alpha-linolenic acid (LNA*) and [U-13C]linoleic acid (LA*), and tissues were analyzed 14 days after dose. Brain accretion of linolenic acid-derived DHA was approximately 3-fold greater for the formula groups than for the breast-fed group, and dietary DHA partially attenuated excess DHA synthesis among preterms. A similar, significant pattern was found in other organs. Brain linoleic acid-derived ARA accretion was significantly greater in the unsupplemented term group but not in the preterm groups compared with the breast-fed group. These data show that formula potentiates the biosynthesis/accretion of DHA/ARA in term and preterm neonates compared with breast-fed neonates and that the inclusion of DHA/ARA in preterm formula partially restores DHA/ARA biosynthesis to lower, breast-fed levels. Current formula DHA concentrations are inadequate to normalize long-chain polyunsaturated fatty acids synthesis to that of breast-fed levels.
Ulven, Stine M; Kirkhus, Bente; Lamglait, Amandine; Basu, Samar; Elind, Elisabeth; Haider, Trond; Berge, Kjetil; Vik, Hogne; Pedersen, Jan I
The purpose of the present study is to investigate the effects of krill oil and fish oil on serum lipids and markers of oxidative stress and inflammation and to evaluate if different molecular forms, triacylglycerol and phospholipids, of omega-3 polyunsaturated fatty acids (PUFAs) influence the plasma level of EPA and DHA differently. One hundred thirteen subjects with normal or slightly elevated total blood cholesterol and/or triglyceride levels were randomized into three groups and given either six capsules of krill oil (N = 36; 3.0 g/day, EPA + DHA = 543 mg) or three capsules of fish oil (N = 40; 1.8 g/day, EPA + DHA = 864 mg) daily for 7 weeks. A third group did not receive any supplementation and served as controls (N = 37). A significant increase in plasma EPA, DHA, and DPA was observed in the subjects supplemented with n-3 PUFAs as compared with the controls, but there were no significant differences in the changes in any of the n-3 PUFAs between the fish oil and the krill oil groups. No statistically significant differences in changes in any of the serum lipids or the markers of oxidative stress and inflammation between the study groups were observed. Krill oil and fish oil thus represent comparable dietary sources of n-3 PUFAs, even if the EPA + DHA dose in the krill oil was 62.8% of that in the fish oil.
Wietrak, Ewa; Kamiński, Krzysztof; Leszczyńska-Gorzelak, Bożena; Oleszczuk, Jan
Introduction. Observational studies confirm a higher incidence of preeclampsia in patients with low erythrocyte concentrations of omega-3 fatty acids. Observations point to an association of disorders of pregnancy, such as intrauterine growth restriction (IUGR) and preeclampsia, with excessive apoptosis. One potential mechanism of action of docosahexaenoic acid (DHA) promoting a reduction in the risk of pathological pregnancy may be by influencing these processes in the placenta. Materials and Methods. We investigated 28 pregnant women supplemented with a fish oil product containing 300 mg DHA starting from pregnancy week 20 until delivery (DHA group). The control group consisted of 50 women who did not receive such supplementation (control group). We determined the expression of Ki-67 and p21 as markers of proliferation and caspase 3 activity as a marker of apoptosis and DHA levels in umbilical cord blood. Results. Caspase 3 activity was significantly lower in the DHA group in comparison to the control group. Umbilical cord blood DHA concentration was higher in the DHA group. The expression of the proteins p21 and Ki-67 did not differ significantly between the groups. Conclusions. We observed an association between DHA supplementation and inhibition of placental apoptosis. We did not find an association between DHA and proliferation process in the placenta. PMID:26339616
Signorini, Cinzia; De Felice, Claudio; Leoncini, Silvia; Durand, Thierry; Galano, Jean-Marie; Cortelazzo, Alessio; Zollo, Gloria; Guerranti, Roberto; Gonnelli, Stefano; Caffarelli, Carla; Rossi, Marcello; Pecorelli, Alessandra; Valacchi, Giuseppe; Ciccoli, Lucia; Hayek, Joussef
This study mainly aims at examining the erythrocyte membrane fatty acid (FAs) profile in Rett syndrome (RTT), a genetically determined neurodevelopmental disease. Early reports suggest a beneficial effects of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on disease severity in RTT. A total of 24 RTT patients were assigned to ω-3 PUFAs-containing fish oil for 12 months in a randomized controlled study (average DHA and EPA doses of 72.9, and 117.1mg/kgb.w./day, respectively). A distinctly altered FAs profile was detectable in RTT, with deficient ω-6 PUFAs, increased saturated FAs and reduced trans 20:4 FAs. FAs changes were found to be related to redox imbalance, subclinical inflammation, and decreased bone density. Supplementation with ω-3 PUFAs led to improved ω-6/ω-3 ratio and serum plasma lipid profile, decreased PUFAs peroxidation end-products, normalization of biochemical markers of inflammation, and reduction of bone hypodensity as compared to the untreated RTT group. Our data indicate that a significant FAs abnormality is detectable in the RTT erythrocyte membranes and is partially rescued by ω-3 PUFAs.
Sarfaraz Alam, Mohammad; Ali, Mohammad Sajid; Zakir, Foziyah; Alam, Nawazish; Intakhab Alam, Mohammad; Ahmad, Faruque; Siddiqui, Masoom Raza; Ali, Mohammad Daud; Ansari, Mohammad Salahuddin; Ahmad, Sarfaraz; Ali, Maksood
The aim of the present study was to investigate the potential of nanoemulsion formulation for topical delivery of Clobetasol propionate (CP) using algal oil (containing omega-3 fatty acids) as the oil phase. CP has anti-inflammatory, immunomodulatory and antiproliferative activities. However, its clinical use is restricted to some extent due to its poor permeability across the skin. Algal oil was used as the oil phase and was also exploited for its anti-inﬂammatory effect along with CP in the treatment of inﬂammation associated with dermatitis. Nanoemulsion formulations were prepared by aqueous phase titration method, using algal oil, tween 20, PEG 200 and water as the oil phase, surfactant, co-surfactant and aqueous phase respectively. Furthermore, different formulations were subjected to evaluate for ex-vivo permeation and in-vivo anti-inflammatory, irritation and contact dermatitis studies. The optimized nanoemulsion was converted into hydrogel-thickened nanoemulsion system (HTN) using carbopol 971 and had a viscosity of 97.57 ± 0.04 PaS. The optimized formulation had small average diameter (120 nm) with zeta potential of -37.01 mV which indicated good long-term stability. In-vivo anti-inﬂammatory activity indicated 84.55% and 41.04% inhibition of inflammation for drug loaded and placebo formulations respectively. The assessment of skin permeation was done by DSC and histopathology studies which indicated changes in the structure of epidermal membrane of skin. Contact dermatitis reveals that the higher NTPDase activity in the treatment with the CP-loaded nanoemulsion could be related to the higher anti-inflammatory effect in comparison with placebo nanoemulsion gel. PMID:27610146
van der Meij, Barbara S; Langius, Jacqueline A E; Smit, Egbert F; Spreeuwenberg, Marieke D; von Blomberg, B Mary E; Heijboer, Annemieke C; Paul, Marinus A; van Leeuwen, Paul A M
Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), (n-3) fatty acids from fish oil, have immune-modulating effects and may improve nutritional status in cancer. The objective of this study was to investigate the effects of an oral nutritional supplement containing (n-3) fatty acids on nutritional status and inflammatory markers in patients with non-small cell lung cancer (NSCLC) undergoing multimodality treatment. In a double-blind experiment, 40 patients with stage III NSCLC were randomly assigned to receive 2 cans/d of a protein- and energy-dense oral nutritional supplement containing (n-3) fatty acids (2.0 g EPA + 0.9 g DHA/d) or an isocaloric control supplement. EPA in plasma phospholipids, energy intake, resting energy expenditure (REE), body weight, fat free mass (FFM), mid-upper arm circumference (MUAC), and inflammatory markers were assessed. Effects of intervention were analyzed by generalized estimating equations and expressed as regression coefficients (B). The intervention group (I) had a better weight maintenance than the control (C) group after 2 and 4 wk (B = 1.3 and 1.7 kg, respectively; P < 0.05), a better FFM maintenance after 3 and 5 wk (B = 1.5 and 1.9 kg, respectively; P < 0.05), a reduced REE (B = -16.7% of predicted; P = 0.01) after 3 wk, and a trend for a greater MUAC (B = 9.1; P = 0.06) and lower interleukin-6 production (B = -27.9; P = 0.08) after 5 wk. After 4 wk, the I group had a higher energy and protein intake than the C group (B = 2456 kJ/24 h, P = 0.03 and B = 25.0 g, P = 0.01, respectively). In conclusion, a protein- and energy-dense oral nutritional supplement containing (n-3) fatty acids beneficially affects nutritional status during multimodality treatment in patients with NSCLC.
Mateos, Hintsa T; Lewandowski, Paul A; Su, Xiao Q
This study was conducted to investigate the effects of fish oil (FO) supplements on fatty acid composition and the expression of ∆6 desaturase and elongase 2 genes in Jade Tiger abalone. Five test diets were formulated to contain 0.5, 1.0, 1.5, 2.0 and 2.5% of FO respectively, and the control diet was the normal commercial abalone diet with no additional FO supplement. The muscle, gonad and digestive glands (DG) of abalone fed with all of the five test diets showed significantly high levels of total n-3 polyunsaturated fatty acid (PUFA), eicosapentaenoic acid (EPA), docosapentaenoic acid n-3 (DPAn-3), and docosahexaenoic acid (DHA) than the control group. In all three types of tissue, abalone fed diet supplemented with 1.5% FO showed the highest level of these fatty acids (P < 0.05). For DPAn-3 the higher level was also found in muscle and gonad of abalone fed diet supplemented with 2% FO (P < 0.05). Elongase 2 expression was markedly higher in the muscle of abalone fed diet supplemented with 1.5% FO (P < 0.05), followed by the diet containing 2% FO supplement. For ∆6 desaturase, significantly higher expression was observed in muscle of abalone fed with diet containing 0.5% FO supplement (P < 0.05). Supplementation with FO in the normal commercial diet can significantly improve long chain n-3 PUFA level in cultured abalone, with 1.5% being the most effective supplementation level.
Interrelationships between maternal DHA in erythrocytes, milk and adipose tissue. Is 1 wt% DHA the optimal human milk content? Data from four Tanzanian tribes differing in lifetime stable intakes of fish.
Luxwolda, Martine F; Kuipers, Remko S; Koops, Jan-Hein; Muller, Stefan; de Graaf, Deti; Dijck-Brouwer, D A Janneke; Muskiet, Frits A J
Little is known about the interrelationships between maternal and infant erythrocyte-DHA, milk-DHA and maternal adipose tissue (AT)-DHA contents. We studied these relationships in four tribes in Tanzania (Maasai, Pare, Sengerema and Ukerewe) differing in their lifetime intakes of fish. Cross-sectional samples were collected at delivery and after 3 d and 3 months of exclusive breast-feeding. We found that intra-uterine biomagnification is a sign of low maternal DHA status, that genuine biomagnification occurs during lactation, that lactating mothers with low DHA status cannot augment their infants' DHA status, and that lactating mothers lose DHA independent of their DHA status. A maternal erythrocyte-DHA content of 8 wt% was found to correspond with a mature milk-DHA content of 1·0 wt% and with subcutaneous and abdominal (omentum) AT-DHA contents of about 0·39 and 0·52 wt%, respectively. Consequently, 1 wt% DHA might be a target for Western human milk and infant formula that has milk arachidonic acid, EPA and linoleic acid contents of 0·55, 0·22 and 9·32 wt%, respectively. With increasing DHA status, the erythrocyte-DHA content reaches a plateau of about 9 wt%, and it plateaus more readily than milk-DHA and AT-DHA contents. Compared with the average Tanzanian-Ukerewe woman, the average US woman has four times lower AT-DHA content (0·4 v. 0·1 wt%) and five times lower mature milk-DHA output (301 v. 60 mg/d), which contrasts with her estimated 1·8-2·6 times lower mobilisable AT-DHA content (19 v. 35-50 g).
Weiser, Michael J.; Butt, Christopher M.; Mohajeri, M. Hasan
Docosahexaenoic acid (DHA) is the predominant omega-3 (n-3) polyunsaturated fatty acid (PUFA) found in the brain and can affect neurological function by modulating signal transduction pathways, neurotransmission, neurogenesis, myelination, membrane receptor function, synaptic plasticity, neuroinflammation, membrane integrity and membrane organization. DHA is rapidly accumulated in the brain during gestation and early infancy, and the availability of DHA via transfer from maternal stores impacts the degree of DHA incorporation into neural tissues. The consumption of DHA leads to many positive physiological and behavioral effects, including those on cognition. Advanced cognitive function is uniquely human, and the optimal development and aging of cognitive abilities has profound impacts on quality of life, productivity, and advancement of society in general. However, the modern diet typically lacks appreciable amounts of DHA. Therefore, in modern populations, maintaining optimal levels of DHA in the brain throughout the lifespan likely requires obtaining preformed DHA via dietary or supplemental sources. In this review, we examine the role of DHA in optimal cognition during development, adulthood, and aging with a focus on human evidence and putative mechanisms of action. PMID:26901223
van Schalkwijk, Daniël B.; Pasman, Wilrike J.; Hendriks, Henk F. J.; Verheij, Elwin R.; Rubingh, Carina M.; van Bochove, Kees; Vaes, Wouter H. J.; Adiels, Martin; Freidig, Andreas P.; de Graaf, Albert A.
Dietary medium chain fatty acids (MCFA) and linoleic acid follow different metabolic routes, and linoleic acid activates PPAR receptors. Both these mechanisms may modify lipoprotein and fatty acid metabolism after dietary intervention. Our objective was to investigate how dietary MCFA and linoleic acid supplementation and body fat distribution affect the fasting lipoprotein subclass profile, lipoprotein kinetics, and postprandial fatty acid kinetics. In a randomized double blind cross-over trial, 12 male subjects (age 51±7 years; BMI 28.5±0.8 kg/m2), were divided into 2 groups according to waist-hip ratio. They were supplemented with 60 grams/day MCFA (mainly C8:0, C10:0) or linoleic acid for three weeks, with a wash-out period of six weeks in between. Lipoprotein subclasses were measured using HPLC. Lipoprotein and fatty acid metabolism were studied using a combination of several stable isotope tracers. Lipoprotein and tracer data were analyzed using computational modeling. Lipoprotein subclass concentrations in the VLDL and LDL range were significantly higher after MCFA than after linoleic acid intervention. In addition, LDL subclass concentrations were higher in lower body obese individuals. Differences in VLDL metabolism were found to occur in lipoprotein lipolysis and uptake, not production; MCFAs were elongated intensively, in contrast to linoleic acid. Dietary MCFA supplementation led to a less favorable lipoprotein profile than linoleic acid supplementation. These differences were not due to elevated VLDL production, but rather to lower lipolysis and uptake rates. PMID:25049048
Walker, Celia G.; Browning, Lucy M.; Mander, Adrian P.; Madden, Jackie; West, Annette L.; Calder, Philip C.; Jebb, Susan A.
The aims of this study were to determine whether age and sex influence both the status and the incorporation of EPA and DHA into blood plasma, cells and tissues. The study was a double-blind, randomised, controlled intervention, providing EPA+DHA equivalent to 0, 1, 2 or 4 portions of oily fish per week, for 12 months. Participants were stratified by age and sex. A linear regression model was used to analyse baseline outcomes, with covariates for age or sex groups, and adjusting for BMI. The change from baseline to 12 months in outcome was analysed with additional adjusting of treatment and average compliance. Fatty acid profiles were determined in plasma phosphatidylcholine (PC), cholesteryl esters (CE), NEFA and TAG, mononuclear cells (MNC), erythrocyte membranes (RBC), platelets (PLAT), buccal cells (BU) and adipose tissue (AT). At baseline, EPA concentration in plasma NEFA and DHA concentration in MNC, BU and AT was higher in females than males (all P<0.05). EPA in AT (P=0.003) and DHA in plasma TAG (P<0.01) and AT (P<0.001) were higher with increasing age. Following 12 months supplementation with EPA+DHA, adjusted mean difference for change in EPA in plasma TAG was significantly higher in females than males (P<0.05) and was greater with increasing age (P=0.02). Adjusted mean difference for change in DHA in AT was significantly smaller with increasing age (P=0.02). Although small differences in incorporation with age and sex were identified, these were not of sufficient magnitude to warrant a move away from population-level diet recommendations for n-3 PUFA. PMID:24063767
Walker, Celia G; Browning, Lucy M; Mander, Adrian P; Madden, Jackie; West, Annette L; Calder, Philip C; Jebb, Susan A
The aim of the present study was to determine whether age and sex influence both the status and incorporation of EPA and DHA into blood plasma, cells and tissues. The study was a double-blind, randomised, controlled intervention trial, providing EPA plus DHA equivalent to 0, 1, 2 or 4 portions of oily fish per week for 12 months. The participants were stratified by age and sex. A linear regression model was used to analyse baseline outcomes, with covariates for age or sex groups and by adjusting for BMI. The change in outcomes from baseline to 12 months was analysed with additional adjustment for treatment and average compliance. Fatty acid profiles in plasma phosphatidylcholine, cholesteryl esters, NEFA and TAG, mononuclear cells (MNC), erythrocyte membranes, platelets, buccal cells (BU) and adipose tissue (AT) were determined. At baseline, EPA concentrations in plasma NEFA and DHA concentrations in MNC, BU and AT were higher in females than in males (all P< 0·05). The concentrations of EPA in AT (P= 0·003) and those of DHA in plasma TAG (P< 0·01) and AT (P< 0·001) were higher with increasing age. Following 12-month supplementation with EPA plus DHA, adjusted mean difference for change in EPA concentrations in plasma TAG was significantly higher in females than in males (P< 0·05) and was greater with increasing age (P= 0·02). Adjusted mean difference for change in DHA concentrations in AT was significantly smaller with increasing age (P= 0·02). Although small differences in incorporation with age and sex were identified, these were not of sufficient magnitude to warrant a move away from population-level diet recommendations for n-3 PUFA.
Dietary supplementation of omega-3 fatty acid-containing fish oil suppresses F2-isoprostanes but enhances inflammatory cytokine response in a mouse model of ovalbumin-induced allergic lung inflammation.
Yin, Huiyong; Liu, Wei; Goleniewska, Kasia; Porter, Ned A; Morrow, Jason D; Peebles, R Stokes
Epidemiological and clinical evidence has suggested that increased dietary intake of fish oil containing omega-3 fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may be associated with a reduced risk of asthma. However, interventional studies on these effects have been equivocal and controversial. Free radical oxidation products of lipids and cyclooxygenases-derived prostaglandins are believed to play an important role in asthma, and fish oil supplementation may modulate the levels of these critical lipid mediators. We employed a murine model of allergic inflammation produced by sensitization to ovalbumin (OVA) to study the effects of fish oil supplementation on airway inflammation. Our studies demonstrated that omega-3 fatty acids were dose dependently incorporated into mouse lung tissue after dietary supplementation. We examined the oxidative stress status by measuring the levels of isoprostanes (IsoPs), the gold standard for oxidative stress in vivo. OVA challenge caused significant increase of F(2)-IsoPs in mouse lung, suggesting an elevated level of oxidative stress. Compared to the control group, fish oil supplementation led to a significant reduction of F(2)-IsoP (from arachidonic acid) with a concomitant increase of F(3)-IsoPs (from EPA) and F(4)-IsoPs (from DHA). Surprisingly, however, fish oil supplementation enhanced production of proinflammatory cytokine IL-5 and IL-13. Furthermore, fish oil supplementation suppressed the production of pulmonary protective PGE(2) in the bronchoalveolar lavage (BAL) while the level of urinary metabolites of the PGE(2) was increased. Our data suggest that augmented lung inflammation after fish oil supplementation may be due to the reduction of PGE(2) production in the lung and these dichotomous results bring into question the role of fish oil supplementation in the treatment of asthma.
Almeida, Cristine C; Alvares, Thiago S; Costa, Marion P; Conte-Junior, Carlos A
Whey protein (WP) supplements have received increasing attention by consumers due to the high nutritional value of the proteins and amino acids they provide. However, some WP supplements may not contain the disclosed amounts of the ingredients listed on the label, compromising the nutritional quality and the effectiveness of these supplements. The aim of this study was to evaluate and compare the contents of total protein (TP), α-lactalbumin (α-LA), β-lactoglobulin (β-LG), free essential amino acids (free EAA), and free branched-chain amino acids (free BCAA), amongst different WP supplements produced by U.S. and Brazilian companies. Twenty commercial brands of WP supplements were selected, ten manufactured in U.S. (WP-USA) and ten in Brazil (WP-BRA). The TP was analyzed using the Kjeldahl method, while α-LA, β-LG, free EAA, and free BCAA were analyzed using HPLC system. There were higher (p < 0.05) concentrations of TP, α-LA, β-LG, and free BCAA in WP-USA supplements, as compared to the WP-BRA supplements; however, there was no difference (p > 0.05) in the content of free EAA between WP-USA and WP-BRA. Amongst the 20 brands evaluated, four WP-USA and seven WP-BRA had lower (p < 0.05) values of TP than those specified on the label. In conclusion, the WP-USA supplements exhibited better nutritional quality, evaluated by TP, α-LA, β-LG, and free BCAA when compared to WP-BRA.
Bradley, M O; Swindell, C S; Anthony, F H; Witman, P A; Devanesan, P; Webb, N L; Baker, S D; Wolff, A C; Donehower, R C
Targeting an anti-cancer drug to tumors should increase the Area Under the drug concentration-time Curve (AUC) in tumors while decreasing the AUC in normal cells and should therefore increase the therapeutic index of that drug. Anti-tumor drugs typically have half-lives far shorter than the cell cycle transit times of most tumor cells. Tumor targeting, with concomitant long tumor exposure times, will increase the proportion of cells that move into cycle when the drug concentration is high, which should result in more tumor cell killing. In an effort to test that hypothesis, we conjugated a natural fatty acid, docosahexaenoic acid (DHA), through an ester bond to the paclitaxel 2'-oxygen. The resulting paclitaxel fatty acid conjugate (DHA-paclitaxel) does not assemble microtubules and is non-toxic. In the M109 mouse tumor model, DHA-paclitaxel is less toxic than paclitaxel and cures 10/10 tumored animals, whereas paclitaxel cures 0/10. One explanation for the conjugate's greater therapeutic index is that the fatty acid alters the pharmacokinetics of the drug to increase its AUC in tumors and decrease its AUC in normal cells. To test that possibility, we compared the pharmacokinetics of DHA-paclitaxel with paclitaxel in CD2F1 mice bearing approximately 125 mg sc M109 tumors. The mice were injected at zero time with a bolus of either DHA-paclitaxel or paclitaxel formulated in 10% cremophor/10% ethanol/80% saline. Animals were sacrificed as a function of time out to 14 days. Tumors and plasma were frozen and stored. The concentrations of paclitaxel and DHA-paclitaxel were analyzed by LC/MS/MS. The results show that DHA targets paclitaxel to tumors: tumor AUCs are 61-fold higher for DHA-paclitaxel than for paclitaxel at equitoxic doses and eight-fold higher at equimolar doses. Likewise, at equi-toxic doses, the tumor AUCs of paclitaxel derived from i.v. DHA-paclitaxel are 6.1-fold higher than for paclitaxel derived from i.v. paclitaxel. The tumor concentration of
Iglesia, I; Huybrechts, I; González-Gross, M; Mouratidou, T; Santabárbara, J; Chajès, V; González-Gil, E M; Park, J Y; Bel-Serrat, S; Cuenca-García, M; Castillo, M; Kersting, M; Widhalm, K; De Henauw, S; Sjöström, M; Gottrand, F; Molnár, D; Manios, Y; Kafatos, A; Ferrari, M; Stehle, P; Marcos, A; Sánchez-Muniz, F J; Moreno, L A
This study aimed to examine the association between vitamin B6, folate and vitamin B12 biomarkers and plasma fatty acids in European adolescents. A subsample from the Healthy Lifestyle in Europe by Nutrition in Adolescence study with valid data on B-vitamins and fatty acid blood parameters, and all the other covariates used in the analyses such as BMI, Diet Quality Index, education of the mother and physical activity assessed by a questionnaire, was selected resulting in 674 cases (43 % males). B-vitamin biomarkers were measured by chromatography and immunoassay and fatty acids by enzymatic analyses. Linear mixed models elucidated the association between B-vitamins and fatty acid blood parameters (changes in fatty acid profiles according to change in 10 units of vitamin B biomarkers). DHA, EPA) and n-3 fatty acids showed positive associations with B-vitamin biomarkers, mainly with those corresponding to folate and vitamin B12. Contrarily, negative associations were found with n-6:n-3 ratio, trans-fatty acids and oleic:stearic ratio. With total homocysteine (tHcy), all the associations found with these parameters were opposite (for instance, an increase of 10 nmol/l in red blood cell folate or holotranscobalamin in females produces an increase of 15·85 µmol/l of EPA (P value <0·01), whereas an increase of 10 nmol/l of tHcy in males produces a decrease of 2·06 µmol/l of DHA (P value <0·05). Positive associations between B-vitamins and specific fatty acids might suggest underlying mechanisms between B-vitamins and CVD and it is worth the attention of public health policies.
Based on the nitrogen balance (NB) data and the efficiency of amino acid utilization, optimum supplements of limiting amino acids (AA) to triticale were calculated and their effect on true N digestibility (TD), biological value of protein (BV) and net protein utilization (NPU) of a triticale-based diet was evaluated. To determine if AA balance must be considered in the calculation of the optimum supplements, the effect of a 20% or 40% excess of essential AA in lysine-, methionine-, threonine- or tryptophan-deficient diets was also studied. The AA excess had no significant effect on NB in diets deficient in lysine, methionine or threonine. However, NB in rats fed on the tryptophan-deficient diet increased as the AA excess increased. BV of the diet containing the optimized supplements of lysine, threonine, methionine and valine was comparable to that of lactalbumin or to the diet supplemented with all essential AA. The deletion of valine from the optimized supplement caused an insignificant decrease in BV. Due to the lower TD, NPU of diets containing the optimized AA supplements was lower than that of the diet containing all essential AA or of the lactalbumin-based diet.
Rathod, Richa S; Khaire, Amrita A; Kale, Anvita A; Joshi, Sadhana R
Vitamin B12 and omega-3 fatty acids are important nutrients required for neuronal functioning. We have demonstrated the beneficial effects of vitamin B12 and omega-3 fatty acid supplementation on brain neurotrophins and cognition in the first and second generation offspring. However, there is a need to examine if the effects are sustained in the third generation offspring. This study reports the effects of vitamin B12 and omega-3 fatty acid supplementation across three consecutive generations on brain neurotrophins like brain derived neurotrophic factor (BDNF); nerve growth factor (NGF) and cognitive performance in the third generation male offspring. Three successive generations of Wistar rats were assigned the following groups throughout pregnancy, lactation and adulthood: i) Control, ii) vitamin B12 deficient (BD), iii) vitamin B12 deficient + omega-3 fatty acid (BDO), iv) vitamin B12 supplemented (BS) and v) vitamin B12 supplemented + omega-3 fatty acid (BSO). The BD group demonstrated lower (p < 0.01) NGF in the cortex but not BDNF levels although the cognition was impaired (p < 0.01). In contrast, in the BDO group, higher NGF levels were observed in the hippocampus and animals demonstrated improved (p < 0.01) cognitive performance. Vitamin B12 supplementation showed comparable BDNF levels in the hippocampus while their levels were lower in the cortex as compared to the control (p < 0.05). These animals showed more reference and working memory errors (p < 0.01) as compared to the control group. A combined supplementation of vitamin B12 and omega-3 fatty acid showed higher (p < 0.01) levels of DHA and NGF in the hippocampus, higher BDNF in both hippocampus and cortex and improved cognitive performance. Our findings have implications for fortification of foods with vitamin B12 and omega-3 fatty acids in improving brain development.
Marcelo, C L; Dunham, W R
The effect of all-trans retinoic acid on the proliferation of essential fatty acid (EFA)-deficient and of EFA-supplemented adult human keratinocytes was investigated. EFA-deficient cell strains were supplied with one of four different fatty acid-supplemented media at the P0 to P1 passage. All-trans retinoic acid at 0.5 or 1.0 microM was added to the cultures at the P1 to P2 passage. At passage P3, and 3 and 7 d thereafter, the cell growth rate was determined. The fatty acid content of cultures grown in each medium was measured using gas chromatography. All the EFA media "normalized" the cellular fatty acid composition and drastically decreased the cell number and total DNA and protein of the cultures. All-trans retinoic acid at 1 microM prevented the loss of cell viability and growth usually associated with EFA supplementation but did not affect the control (EFA deficient) or 18:1 fatty acid-supplemented cultures. All-trans retinoic acid at 1 microM altered the fatty acid content of the EFA-supplemented cultures. A statistically significant increase in 14:0, 14:1, 16:1, 18:1, and 20:4 fatty acids occurred, whereas the amounts of 18:0 and 18:2 fatty acids decreased. The largest changes were in 16:1 fatty acid (8-14%) and 18:2 fatty acid (12-5%). All-trans retinoic acid at 0.5 microM also affected both cell growth and fatty acid composition without induction of the CRABP II message. These studies demonstrate that all-trans retinoic acid stimulates the growth of EFA-supplemented keratinocyte cultures while also altering the fatty acid composition of the cells.
Stein, Aryeh D; Wang, Meng; Rivera, Juan A; Martorell, Reynaldo; Ramakrishnan, Usha
The evidence relating prenatal supplementation with DHA to offspring neurological development is limited. We investigated the effect of prenatal DHA supplementation on infant brainstem auditory-evoked responses and visual- evoked potentials in a double-blind, randomized controlled trial in Cuernavaca, Mexico. Pregnant women were supplemented daily with 400 mg DHA or placebo from gestation wk 18-22 through delivery. DHA and placebo groups did not differ in maternal characteristics at randomization or infant characteristics at birth. Brainstem auditory-evoked responses were measured at 1 and 3 mo in 749 and 664 infants, respectively, and visual-evoked potentials were measured at 3 and 6 mo in 679 and 817 infants, respectively. Left-right brainstem auditory-evoked potentials were moderately correlated (range, 0.26-0.43; all P < 0.001) and left-right visual-evoked potentials were strongly correlated (range, 0.79-0.94; all P < 0.001) within any assessment. Correlations across visits were modest to moderate (range, 0.09-0.38; all P < 0.01). The offspring of DHA-supplemented women did not differ from those of control women with respect to any outcome measure (all comparisons P > 0.10). We conclude that DHA supplementation during pregnancy did not influence brainstem auditory-evoked responses at 1 and 3 mo or visual-evoked potentials at 3 and 6 mo.
Colombo, John; Kannass, Kathleen N.; Jill Shaddy, D.; Kundurthi, Shashi; Maikranz, Julie M.; Anderson, Christa J.; Blaga, Otilia M.; Carlson, Susan E.
Infants were followed longitudinally to document the relationship between docosahexaenoic acid (DHA) levels and the development of attention. Erythrocyte (red-blood cell; RBC) phospholipid DHA (percentage of total fatty acids) was measured from infants and mothers at delivery. Infants were assessed in infant-control habituation at 4, 6, and 8…
Liu, Meng-Jiao; Li, Hong-Tian; Yu, Li-Xia; Xu, Gao-Sheng; Ge, Hua; Wang, Lin-Lin; Zhang, Ya-Li; Zhou, Yu-Bo; Li, You; Bai, Man-Xi; Liu, Jian-Meng
We aimed to assess the correlation between docosahexaenoic acid (DHA) dietary intake and the plasma, erythrocyte and breast milk DHA concentrations in lactating women residing in the coastland, lakeland and inland areas of China. A total of 408 healthy lactating women (42 ± 7 days postpartum) were recruited from four hospitals located in Weihai (coastland), Yueyang (lakeland) and Baotou (inland) city. The categories of food containing DHA, the average amount consumed per time and the frequency of consumption in the past month were assessed by a tailored DHA food frequency questionnaire, the DHA Intake Evaluation Tool (DIET). DHA dietary intake (mg/day) was calculated according to the Chinese Food Composition Table (Version 2009). In addition, fasting venous blood (5 mL) and breast milk (10 mL) were collected from lactating women. DHA concentrations in plasma, erythrocyte and breast milk were measured using capillary gas chromatography, and were reported as absolute concentration (μg/mL) and relative concentration (weight percent of total fatty acids, wt. %). Spearman correlation coefficients were used to assess the correlation between intakes of DHA and its concentrations in biological specimens. The study showed that the breast milk, plasma and erythrocyte DHA concentrations were positively correlated with DHA dietary intake; corresponding correlation coefficients were 0.36, 0.36 and 0.24 for relative concentration and 0.33, 0.32, and 0.18 for absolute concentration (p < 0.05). The median DHA dietary intake varied significantly across areas (p < 0.05), which was highest in the coastland (24.32 mg/day), followed by lakeland (13.69 mg/day), and lowest in the inland (8.84 mg/day). The overall relative and absolute DHA concentrations in breast milk were 0.36% ± 0.23% and 141.49 ± 107.41 μg/mL; the concentrations were significantly lower in inland women than those from coastland and lakeland. We conclude that DHA dietary intake is positively correlated with DHA
Liu, Meng-Jiao; Li, Hong-Tian; Yu, Li-Xia; Xu, Gao-Sheng; Ge, Hua; Wang, Lin-Lin; Zhang, Ya-Li; Zhou, Yu-Bo; Li, You; Bai, Man-Xi; Liu, Jian-Meng
We aimed to assess the correlation between docosahexaenoic acid (DHA) dietary intake and the plasma, erythrocyte and breast milk DHA concentrations in lactating women residing in the coastland, lakeland and inland areas of China. A total of 408 healthy lactating women (42 ± 7 days postpartum) were recruited from four hospitals located in Weihai (coastland), Yueyang (lakeland) and Baotou (inland) city. The categories of food containing DHA, the average amount consumed per time and the frequency of consumption in the past month were assessed by a tailored DHA food frequency questionnaire, the DHA Intake Evaluation Tool (DIET). DHA dietary intake (mg/day) was calculated according to the Chinese Food Composition Table (Version 2009). In addition, fasting venous blood (5 mL) and breast milk (10 mL) were collected from lactating women. DHA concentrations in plasma, erythrocyte and breast milk were measured using capillary gas chromatography, and were reported as absolute concentration (μg/mL) and relative concentration (weight percent of total fatty acids, wt. %). Spearman correlation coefficients were used to assess the correlation between intakes of DHA and its concentrations in biological specimens. The study showed that the breast milk, plasma and erythrocyte DHA concentrations were positively correlated with DHA dietary intake; corresponding correlation coefficients were 0.36, 0.36 and 0.24 for relative concentration and 0.33, 0.32, and 0.18 for absolute concentration (p < 0.05). The median DHA dietary intake varied significantly across areas (p < 0.05), which was highest in the coastland (24.32 mg/day), followed by lakeland (13.69 mg/day), and lowest in the inland (8.84 mg/day). The overall relative and absolute DHA concentrations in breast milk were 0.36% ± 0.23% and 141.49 ± 107.41 μg/mL; the concentrations were significantly lower in inland women than those from coastland and lakeland. We conclude that DHA dietary intake is positively correlated with DHA
Pipingas, Andrew; Cockerell, Robyn; Grima, Natalie; Sinclair, Andrew; Stough, Con; Scholey, Andrew; Myers, Stephen; Croft, Kevin; Sali, Avni; Pase, Matthew P
The present randomized, placebo-controlled, double-blind, parallel-groups clinical trial examined the effects of fish oil and multivitamin supplementation on the incorporation of n-3 and n-6 fatty acids into red blood cells. Healthy adult humans (n = 160) were randomized to receive 6 g of fish oil, 6 g of fish oil plus a multivitamin, 3 g of fish oil plus a multivitamin or a placebo daily for 16 weeks. Treatment with 6 g of fish oil, with or without a daily multivitamin, led to higher eicosapentaenoic acid (EPA) composition at endpoint. Docosahexaenoic acid (DHA) composition was unchanged following treatment. The long chain LC n-3 PUFA index was only higher, compared to placebo, in the group receiving the combination of 6 g of fish oil and the multivitamin. Analysis by gender revealed that all treatments increased EPA incorporation in females while, in males, EPA was only significantly increased by the 6 g fish oil multivitamin combination. There was considerable individual variability in the red blood cell incorporation of EPA and DHA at endpoint. Gender contributed to a large proportion of this variability with females generally showing higher LC n-3 PUFA composition at endpoint. In conclusion, the incorporation of LC n-3 PUFA into red blood cells was influenced by dosage, the concurrent intake of vitamin/minerals and gender.
Bouchard-Mercier, Annie; Rudkowska, Iwona; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude
A large inter-individual variability in the plasma triglyceride (TG) response to an omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has been observed. The objective was to examine gene-diet interaction effects on the plasma TG response after a fish oil supplementation, between single-nucleotide polymorphisms (SNPs) within genes involved in fatty acid β-oxidation and dietary fat intakes. Two hundred and eight (208) participants were recruited in the greater Quebec City area. The participants completed a six-week fish oil supplementation (5 g fish oil/day: 1.9–2.2 g EPA and 1.1 g DHA). Dietary fat intakes were measured using three-day food records. SNPs within RXRA, CPT1A, ACADVL, ACAA2, ABCD2, ACOX1 and ACAA1 genes were genotyped using TAQMAN methodology. Gene-diet interaction effects on the plasma TG response were observed for SNPs within RXRA (rs11185660, rs10881576 and rs12339187) and ACOX1 (rs17583163) genes. For rs11185660, fold changes in RXRA gene expression levels were different depending on SFA intakes for homozygotes T/T. Gene-diet interaction effects of SNPs within genes involved in fatty acid β-oxidation and dietary fat intakes may be important in understanding the inter-individual variability in plasma TG levels and in the plasma TG response to a fish oil supplementation. PMID:24647074
del Puerto, Marta; Cabrera, M. Cristina
This investigation evaluated, in broiler chickens Pectoralis and Gastrocnemius muscles, the effect of the dietary supplementation with sodium selenite (0.3 ppm) versus selenomethionine (0.3 ppm), on the fatty acids composition, lipids indices, and enzymes indexes for desaturase, elongase, and thioesterase. The selenium reduced, in both muscles, the content of atherogenic fatty acids, C14:0 and C16:0, while it increased the C18:1 level. On the other hand, selenium increased, in both muscles, the content of C18:3n3 and EPA, but not DPA and DHA. No selenium effect was detected for PUFA/SFA, n-6, n-3, n-6/n-3, and atherogenic and thrombogenic indices. As for the enzyme indexes, a selenium effect is only detected for thioesterase. Taken together, the results highlight the potential effect of dietary selenium, mainly selenomethionine, in the modulation of the composition of fatty acids in chicken meat, in particular, reducing the content of atherogenic fatty acids and increasing the health promoting n-3 PUFA. PMID:28194404
Bandarra, Narcisa M; Lopes, Paula A; Martins, Susana V; Ferreira, Júlia; Alfaia, Cristina M; Rolo, Eva A; Correia, Jorge J; Pinto, Rui M A; Ramos-Bueno, Rebeca P; Batista, Irineu; Prates, José A M; Guil-Guerrero, José L
In this study, we hypothesized that the incorporation of docosahexaenoic acid (DHA) in tissues will be higher when it is ingested as triacylglycerols (TAG) structured at the sn-2 position, which enhances efficacy and health benefits of dietary DHA n-3 supplementation. Ten-week-old Golden Syrian male hamsters were randomly allocated into 4 dietary groups with 10 animals in each: linseed oil (LSO; control group), fish oil (FO), fish oil ethyl esters (FO-EE), and structured DHA at the sn-2 position of TAG (DHA-SL). After 12 weeks, there were no variations in the hamsters' body composition parameters across dietary groups. The DHA-SL diet had the lowest values of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total lipids, and aspartate aminotransferase activity, whereas the inverse was observed for the FO diet. Glucose was increased in the LSO diet without affecting insulin and insulin resistance markers. Whereas n-3 polyunsaturated fatty acid was increased in the brain of hamsters fed the DHA-SL diet, higher levels of n-6 polyunsaturated fatty acid were observed in the liver and erythrocytes of the LSO. The highest omega-3 index was obtained with the DHA-SL diet. The principal component analyses discriminated DHA from other metabolites and set apart 4 clusters matching the 4 diets. Similarly, liver, erythrocytes, and brain were separated from each other, pointing toward an individual signature on fatty acid deposition. The structured sn-2 position DHA-containing TAG ameliorated blood lipids and fatty acid incorporation, in particular eicosapentaenoic acid and DHA in liver, erythrocytes, and brain, relative to commercially FOs, thus improving the health benefits of DHA due to its higher bioavailability.
Replacement of fish oil with a DHA-rich algal meal derived from Schizochytrium sp. on the fatty acid and persistent organic pollutant levels in diets and flesh of Atlantic salmon (Salmo salar, L.) post-smolts.
Sprague, M; Walton, J; Campbell, P J; Strachan, F; Dick, J R; Bell, J G
The replacement of fish oil (FO) with a DHA-rich Schizochytrium sp. algal meal (AM) at two inclusion levels (11% and 5.5% of diet) was tested in Atlantic salmon post-smolts compared to fish fed a FO diet of northern (NFO) or southern hemisphere (SFO) origin. Fish were preconditioned prior to the 19-week experimental feeding period to reduce long-chain polyunsaturated fatty acid (LC-PUFA) and persistent organic pollutant levels (POPs). Dietary POP levels differed significantly between treatments in the order of NFO>SFO>11 AM/5.5 AM and were subsequently reflected in the flesh. Fish fed the 11 AM diet contained similar DHA levels (g 100 g(-1) flesh) to FO-fed fish, despite percentage differences. However, the low levels of EPA in the diets and flesh of algal-fed fish compromised the overall nutritional value to the final consumer. Nevertheless, further developments in microalgae culture offer a promising alternative lipid source of LC-PUFA to FO in salmon feeds that warrants further investigation.
Block, Robert C; Dier, Usawadee; Calderonartero, Pedro; Shearer, Gregory C; Kakinami, Lisa; Larson, Mark K; Harris, William S; Georas, Steve; Mousa, Shaker A
OBJECTIVE: In a recent study, we showed that the combination of aspirin plus the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) synergistically inhibited platelet function. As aspirin, EPA, and DHA have demonstrated anti-inflammatory properties, we hypothesized that the ingestion of EPA and DHA, with and without aspirin, would reduce plasma levels of inflammatory cytokines and angiogenesis factors more than aspirin alone and before aspirin was ingested. METHODS: Using multiplex technology, we investigated the effects of aspirin (single-dose 650 mg on day 1), EPA+DHA (3.4 g/d for days 2-29), and aspirin with EPA+DHA (day 30) on plasma levels of inflammatory cytokines and angiogenesis factors in healthy adults. RESULTS: Aspirin alone had no effect on any factor versus baseline, but EPA+DHA, with and without aspirin, significantly reduced concentrations of 8 of 9 factors. Although EPA+DHA plus aspirin reduced concentrations of a subset of the factors compared to baseline, neither aspirin alone nor the combination significantly reduced the level of any analyte more robustly than EPA+DHA alone. CONCLUSIONS: These data suggest that EPA+DHA has more pronounced down-regulatory effects on inflammation and angiogenesis than aspirin. The implications of these findings for the use of combined therapy for cardiovascular disease remain to be clarified.
Gao, Jingquan; Wang, Xuelai; Sun, Hongli; Cao, Yonggang; Liang, Shuang; Wang, Han; Wang, Yanming; Yang, Feng; Zhang, Fengyu; Wu, Lijie
Prenatal exposure to valproic acid (VPA) in rat offspring is capable of inducing experimental autism with neurobehavioral aberrations. This study investigated the effect of docosahexaenoic acid (DHA) on hippocampal cell death, learning and memory alteration in an experimental rat autism model. We found that DHA supplementation (75, 150 or 300 mg/kg/day, 21 days) rescued the VPA (600 mg/kg) induced DHA reduction in plasma and hippocampus in a dose-dependent manner, increased the levels of hippocampal p-CaMKII and p-CREB without affecting total protein level, and altered BDNF-AKT-Bcl-2 signaling pathway, as well as inhibited the activity of caspase-3. DHA also influenced the content of malondialdehyde (MDA) and the activities of antioxidant enzymes in the VPA-treated offspring. Consistent with the previous results, we also observed that 300 mg/kg DHA supplementation markedly increased the cell survival, decreased the cell apoptosis, and increased mature neuronal cell in the hippocampus in VPA-treated offspring. Utilizing the Morris water maze test, we found that DHA prevented cognitive impairment in offspring of VPA-treated rats. The data suggested that DHA may play a neuroprotective role in hippocampal neuronal cell and ameliorates dysfunctions in learning and memory in this rat autism model. Thus, DHA could be used as treatment intervention for mitigating behavioral dysfunctions in autism spectrum disorder (ASD).
Background: Concomitant supplementation of 1.5% docosahexaenoic acid (22:6 n-3; DHA) with 0.5% t10, c12- conjugated linoleic acid (18:2 n-6; CLA) prevented the CLA-induced increase in expression of hepatic genes involved in fatty acid synthesis and the decrease in expression of genes involved in fat...
Morrison, S Y; Campbell, J M; Drackley, J K
We determined the effects of calf milk replacers containing 0, 5, or 10% bovine plasma protein (PP), either without or with the supplemental amino acids (AA) Ile and Thr, on growth and health of male Holstein calves (n = 104) for 56 d. Milk replacers were formulated to contain 22% crude protein (CP), 20% fat, and 2.0% Lys. Milk replacers (12.5% solids) were fed at a rate of 1.5% of body weight (BW) on a dry matter basis during wk 1 and 1.75% of BW beginning on d 8. Starter was introduced on d 36 so that effects of PP and AA balance in milk replacers could be isolated. Intake, respiratory scores, and fecal scores were measured daily. Body weight and stature were measured weekly and blood serum samples were obtained during wk 4. Treatments had no effects on intakes of dry matter, CP, or metabolizable energy. During wk 6 and 8, BW was less as PP inclusion increased without AA supplementation compared with the other treatments. In wk 7, calves fed the higher level of PP without AA had lower BW than calves fed either the lower level of PP without supplemented AA or the higher inclusion of PP with supplemented AA. Average daily gain and gain:feed were lowest for calves fed the higher inclusion of PP without supplemented AA; heart girth in wk 7 was smallest for those calves. During the first 21 d, occurrence of scours was greater in calves fed the control milk replacer than in calves fed milk replacers containing the higher inclusion of PP either without or with supplemental AA. Occurrence of scours was also greater for the lower inclusion of PP compared with the higher inclusion of PP when AA were supplemented. Throughout the 56-d experiment, the chance of antibiotic treatment was greater for calves fed the control milk replacer than for all other treatments except the higher inclusion of PP without supplemental AA. Additionally, chance of antibiotic treatment was greater for the higher inclusion of PP without supplemental AA than for other milk replacers with PP. Calves
Introduction. Folic acid (FA) supplementation is recommended worldwide in the periconceptional period for the prevention of neural tube defects. Due to its involvement in a number of cellular processes, its role in other pregnancy outcomes such as miscarriage, recurrent miscarriage, low birth weight, preterm birth (PTB), preeclampsia, abruptio placentae, and stillbirth has been investigated. PTB is a leading cause of perinatal mortality and morbidity; therefore its association with FA supplementation is of major interest. The analysis of a small number of randomized clinical trials (RCTs) has not found a beneficial role of FA in reducing the rate of PTBs. Aim of the Study. The aim of this review was to examine the results from recent observational studies about the effect of FA supplementation on PTB. Materials and Methods. We carried out a search on Medline and by manual search of the observational studies from 2009 onwards that analyzed the rate of PTB in patients who received supplementation with FA before and/or throughout pregnancy. Results. The results from recent observational studies suggest a slight reduction of PTBs that is not consistent with the results from RCTs. Further research is needed to better understand the role of FA supplementation before and during pregnancy in PTB. PMID:24724083
Zwart, S. R.; Davis-Street, J. E.; Paddon-Jones, D.; Ferrando, A. A.; Wolfe, R. R.; Smith, S. M.
High-protein and acidogenic diets induce hypercalciuria. Foods or supplements with excess sulfur-containing amino acids increase endogenous sulfuric acid production and therefore have the potential to increase calcium excretion and alter bone metabolism. In this study, effects of an amino acid/carbohydrate supplement on bone resorption were examined during bed rest. Thirteen subjects were divided at random into two groups: a control group (Con, n = 6) and an amino acid-supplemented group (AA, n = 7) who consumed an extra 49.5 g essential amino acids and 90 g carbohydrate per day for 28 days. Urine was collected for n-telopeptide (NTX), deoxypyridinoline (DPD), calcium, and pH determinations. Bone mineral content was determined and potential renal acid load was calculated. Bone-specific alkaline phosphatase was measured in serum samples collected on day 1 (immediately before bed rest) and on day 28. Potential renal acid load was higher in the AA group than in the Con group during bed rest (P < 0.05). For all subjects, during bed rest urinary NTX and DPD concentrations were greater than pre-bed rest levels (P < 0.05). Urinary NTX and DPD tended to be higher in the AA group (P = 0.073 and P = 0.056, respectively). During bed rest, urinary calcium was greater than baseline levels (P < 0.05) in the AA group but not the Con group. Total bone mineral content was lower after bed rest than before bed rest in the AA group but not the Con group (P < 0.05). During bed rest, urinary pH decreased (P < 0.05), and it was lower in the AA group than the Con group. These data suggest that bone resorption increased, without changes in bone formation, in the AA group.
Wu, Aiguo; Noble, Emily E.; Tyagi, Ethika; Ying, Zhe; Zhuang, Yumei; Gomez-Pinilla, Fernando
Dietary deficiency of docosahexaenoic acid (C22: 6n-3; DHA) is linked to the neuropathology of several cognitive disorders, including anxiety. DHA, which is essential for brain development and protection, is primarily obtained through the diet or synthesized from dietary precursors, however the conversion efficiency is low. Curcumin (diferuloylmethane), which is a principal component of the spice turmeric, complements the action of DHA in the brain, and this study was performed to determine molecular mechanisms involved. We report that curcumin enhances the synthesis of DHA from its precursor, α-linolenic acid (C18: 3n-3; ALA) and elevates levels of enzymes involved in the synthesis of DHA such as FADS2 and elongase 2 in both liver and brain tissue. Furthermore, in vivo treatment with curcumin and ALA reduced anxiety-like behavior in rodents. Taken together, these data suggest that curcumin enhances DHA synthesis, resulting in elevated brain DHA content. These findings have important implications for human health and the prevention of cognitive disease, particularly for populations eating a plant-based diet or who do not consume fish, a primary source of DHA, since DHA is essential for brain function and its deficiency is implicated in many types of neurological disorders. PMID:25550171
Wu, Aiguo; Noble, Emily E; Tyagi, Ethika; Ying, Zhe; Zhuang, Yumei; Gomez-Pinilla, Fernando
Dietary deficiency of docosahexaenoic acid (C22:6 n-3; DHA) is linked to the neuropathology of several cognitive disorders, including anxiety. DHA, which is essential for brain development and protection, is primarily obtained through the diet or synthesized from dietary precursors, however the conversion efficiency is low. Curcumin (diferuloylmethane), which is a principal component of the spice turmeric, complements the action of DHA in the brain, and this study was performed to determine molecular mechanisms involved. We report that curcumin enhances the synthesis of DHA from its precursor, α-linolenic acid (C18:3 n-3; ALA) and elevates levels of enzymes involved in the synthesis of DHA such as FADS2 and elongase 2 in both liver and brain tissues. Furthermore, in vivo treatment with curcumin and ALA reduced anxiety-like behavior in rodents. Taken together, these data suggest that curcumin enhances DHA synthesis, resulting in elevated brain DHA content. These findings have important implications for human health and the prevention of cognitive disease, particularly for populations eating a plant-based diet or who do not consume fish, a primary source of DHA, since DHA is essential for brain function and its deficiency is implicated in many types of neurological disorders.
Busquets-Cortés, Carla; Capó, Xavier; Tur, Josep A.; Sureda, Antoni
Exercise training induces adaptations in mitochondrial metabolism, dynamics, and oxidative protection. Omega-3 fatty acids change membrane lipid composition and modulate mitochondrial function. The aim was to investigate the effect of 8-week training and docosahexaenoic acid (DHA) supplementation (1.14 g/day) on the mitochondria dynamics and antioxidant status in peripheral blood mononuclear cells (PBMCs) from sportsmen. Subjects were assigned to an intervention (N = 9) or placebo groups (N = 7) in a randomized double-blind trial. Nutritional intervention significantly increased the DHA content in erythrocyte membranes from the experimental group. No significant differences were reported in terms of circulating PBMCs, Mn-superoxide dismutase protein levels, and their capability to produce reactive oxygen species. The proteins related to mitochondrial dynamics were, in general, increased after an 8-week training and this increase was enhanced by DHA supplementation. The content in mitofusins Mtf-1 and Mtf-2, optic atrophy protein-1 (Opa-1), and mitochondrial transcription factor A (Tfam) were significantly higher in the DHA-supplemented group after intervention. Cytochrome c oxidase (COX-IV) activity and uncoupling proteins UCP-2 and UCP-3 protein levels were increased after training, with higher UCP-3 levels in the supplemented group. In conclusion, training induced mitochondrial adaptations which may contribute to improved mitochondrial function. This mitochondrial response was modulated by DHA supplementation. PMID:27698953
Taha, Ameer Y; Trepanier, Marc-Olivier; Ciobanu, Flaviu A; Taha, Nadeen M; Ahmed, Muaz; Zeng, Qiudi; Cheuk, Waiyin I; Ip, Bryan; Filo, Elvis; Scott, Brian W; Burnham, W M; Bazinet, Richard P
Complex partial seizures, which typically originate in limbic structures such as the amygdala, are often resistant to antiseizure medications. Our goal was to investigate the effects of chronic dietary supplementation with n-3 polyunsaturated fatty acids (PUFAs) derived from fish oil on seizure thresholds in the amygdala, as well as on blood and brain PUFA levels. The acute effects of injected n-3 PUFAs--eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)--were also tested in the maximal pentylenetetrazol (PTZ) seizure model. In amygdala-implanted subjects, fish oil supplementation significantly increased amygdaloid afterdischarge thresholds, as compared with controls at 3, 5, and 7 months after the start of supplementation. Fish oil supplementation also increased serum EPA and DHA concentrations. DHA concentration in the pyriform-amygdala area increased in the fish-oil treated group by 17-34%, but this effect did not reach statistical significance (P=0.065). DHA significantly increased the latency to seizure onset in the PTZ seizure model, whereas EPA had no significant effect. These observations suggest that chronic dietary fish oil supplementation can raise focal amygdaloid seizure thresholds and that this effect is likely mediated by DHA rather than by EPA.
Sharma, Sandeep; Zhuang, Yumei; Gomez-Pinilla, Fernando
To assess how the shift from a healthy diet rich in omega-3 fatty acids to a diet rich in saturated fatty acid affects the substrates for brain plasticity and function, we used pregnant rats fed with omega-3 supplemented diet from their 2nd day of gestation period as well as their male pups for 12 weeks. Afterwards, the animals were randomly assigned to either a group fed on the same diet or a group fed on a high-fat diet (HFD) rich in saturated fats for 3 weeks. We found that the HFD increased vulnerability for anxiety-like behavior, and that these modifications harmonized with changes in the anxiety-related NPY1 receptor and the reduced levels of BDNF, and its signalling receptor pTrkB, as well as the CREB protein. Brain DHA contents were significantly associated with the levels of anxiety-like behavior in these rats.
Gould, J F; Anderson, A J; Yelland, L N; Gibson, R A; Makrides, M
We explored the degree to which maternal and offspring outcomes resulting from consuming prenatal docosahexaenoic acid (DHA, 800mg/day) in a clinical trial were influenced by maternal characteristics. Among non-smokers, women who received DHA had heavier babies (adjusted mean difference (MD)=99g 95% CI 45-153, p<0.01; interaction p=0.01) and fewer low birth weight babies than control women (adjusted relative risk=0.43 95% CI 0.25-0.74, p<0.01; interaction p=0.01). From women who had not completed further education, children in the DHA group had higher cognitive scores at 18 months compared with control children (adjusted MD=3.15 95% CI 0.93-5.37, p=0.01; interaction p<0.01). Conversely, the children of women who completed further education in the DHA group had lower language scores than control children (adjusted MD -2.82 95% CI -4.90 to -0.73, p=0.01; interaction p=0.04). Our results support the notion that responsiveness to prenatal DHA may depend on the characteristics of specific population subgroups.
Wu, Lei; Roe, Charles L; Wen, Zhiyou
Polyunsaturated fatty acids, docosahexaenoic acid (DHA, 22:6, n-3), eicosapentaenoic acid (EPA, 20:5, n-3), and arachidonic acid (ARA, 20:4 n-6), have multiple beneficial effects on human health and can be used as an important ingredient in dietary supplements, food, feed and pharmaceuticals. A variety of microorganisms has been used for commercial production of these fatty acids. The microorganisms in the Pythium family, particularly Pythium irregulare, are potential EPA producers. The aim of this work is to provide a safety assessment of P. irregulare so that the EPA derived from this species can be potentially used in various commercial applications. The genus Pythium has been widely recognized as a plant pathogen by infecting roots and colonizing the vascular tissues of various plants such as soybeans, corn and various vegetables. However, the majority of the Pythium species (including P. irregulare) have not been reported to infect mammals including humans. The only species among the Pythium family that infects mammals is P. insidiosum. There also have been no reports showing P. irregulare to contain mycotoxins or cause potentially allergenic responses in humans. Based on the safety assessment, we conclude that P. irregulare can be considered a safe source of biomass and EPA-containing oil for use as ingredients in dietary supplements, food, feed and pharmaceuticals.
Cachaldora, P; García-Rebollar, P; Alvarez, C; De Blas, J C; Méndez, J
1. Laying hen performance and yolk fat fatty acid (FA) concentrations were evaluated with respect to the inclusion in the diet of different sources and levels of marine fish oil (MFO). 2. Twelve diets were arranged factorially, with three sources (MFO1, MFO2_EPA, MFO3_DHA) and four levels of inclusion (15, 30, 45 and 60 g/kg) of MFO. 3. Type of diet had little effect on egg production traits, although laying rate and shell thickness slightly decreased at the highest level of MFO supplementation. 4. An increase in level of inclusion of MFO from 15 to 60 g/kg linearly increased concentrations of C20:5 n-3, C22:5 n-3, C22:6 n-3 and total n-3 FA in yolk fat, but greatly impaired their efficiencies of deposition (g retained/g ingested). 5. An interaction between type and dietary concentration of MFO was found, as the reduction in efficiency of retention of n-3 FA in egg fat with level of MFO was less when the proportion of n-3 in total FA decreased or when that of DHA in total n-3 FA increased. 6. MFO3_ DHA was more efficiently used for total n-3 FA yolk deposition than MFO2_EPA at a similar total n-3 FA intake. 7. Dietary inclusion of MFO reduced LC n-6 FA yolk fat content, which additionally decreased the ratio between total n-6 and total n-3 FA in egg fat. 8. Regression equations were calculated in order to predict efficiency of retention and n-3 FA concentration of yolk fat in the range of diets studied.
Watson, Aaron M; Barrows, Frederic T; Place, Allen R
We examined growth performance and the lipid content in juvenile cobia, Rachycentron canadum, fed a taurine supplemented (1.5 %), plant protein based diet with two fish oil replacements. The first fish oil replacement was a thraustochytrid meal (TM + SOY) plus soybean oil (~9 % CL) and the second was a canola oil supplemented with the essential fatty acids (EFA) docosahexaenoic acid (DHA) and arachidonic acid (ARA) (~8 % CL). The diet using the thraustochytrid meal plus soybean oil performed equivalently to the fish oil diet; both resulting in significantly higher growth rates, lower feed conversion ratios, and higher survival than the supplemented canola oil diet, even though all three diets were similar in overall energy and met known protein and lipid requirements for cobia. The poor performance of the canola oil diet was attributed to insufficient addition of EFA in the supplemented canola oil source. Increasing levels of EFA in the supplemented canola oil above 0.5 g EFA kg(-1) would likely improve results with cobia. When fish fed either of the fish oil replacement diets were switched to the fish oil control diet, fatty acid profiles of the fillets were observed to transition toward that of the fish oil diet and could be predicted based on a standard dilution model. Based on these findings, a formulated diet for cobia can be produced without fish products providing 100 % survivorship, specific growth rates greater than 2.45 and feed conversion ratios less than 1.5, as long as taurine is added and EFA levels are above 0.5 g EFA kg(-1).
Veeranki, Sreenivas P.; Gebretsadik, Tebeb; Mitchel, Edward F.; Tylavsky, Frances A.; Hartert, Tina V.; Cooper, William O.; Dupont, William D; Dorris, Stacy L.; Hartman, Terryl J.; Carroll, Kecia N.
Background Asthma is one of the most common chronic childhood diseases. While folic acid supplementation around conception helps prevent neural tube defects, an animal model suggests it may be a risk factor for respiratory diseases; although epidemiologic studies have had conflicting results. We investigated the timing of folic acid-containing prescription filling during pregnancy and child asthma. Methods In a retrospective cohort study of 104,428 children, born 1996–2005, and their mothers enrolled in Tennessee Medicaid, we investigated the association of filling folic acid-containing prescriptions during pregnancy and childhood asthma at age 4.5–6 years. We categorized women into exposure groups based on prescription-filling centered around the first trimester: no folic acid prescription exposure, exposure in first trimester only, exposure after first trimester, and exposure in first trimester and beyond. We defined asthma using asthma-specific healthcare visits and medication fills. Using logistic regression models, we investigated the relationship adjusting for potential confounders. Results Overall 15% of children had asthma. Compared with children born to women with no folic acid prescription exposure, children born to women with exposures in the first trimester only or first trimester and later had increased relative odds of asthma [adjusted odds ratios (OR) 1.2, 95% confidence interval (CI) 1.1–1.3] and 1.2, 95% CI 1.2–1.3]; no association was seen in children born to women exposed after the first trimester. Conclusion Timing of folic acid-containing prescription filling during pregnancy was associated with childhood asthma. Our findings contribute to understanding of the role of prenatal nutritional supplements on child respiratory health. PMID:26360371
Attin, T; Meyer, K; Hellwig, E; Buchalla, W; Lennon, A M
The aim of this study was to evaluate the effect of mineral supplements to citric acid (1%; pH 2.21) on enamel erosion under controlled conditions in an artificial mouth. From each of 156 bovine incisors one polished enamel sample was prepared. The samples were divided among 13 experimental groups (n=12). In group 1 citric acid only was used (control). In groups 2-10 either calcium, phosphate or fluoride in various low concentrations was admixed to the citric acid. In groups 11-13 the citric acid was supplemented with a mixture of calcium, phosphate and fluoride. For demineralisation the specimens were rinsed with the respective solution for 1 min, immediately followed by a remineralisation period with artificial saliva (1 min). The specimens were cycled through this alternating procedure five times followed by rinsing for 8 h with artificial saliva. The de- and remineralisation cycle was repeated three times for each specimen interrupted by the 8 h-remineralisation periods. Before and after the experiments, the specimens were examined using microhardness testing (Knoop hardness) and laser profilometry. Hardness loss and enamel dissolution was significantly higher for the controls as compared to the remaining groups. Significantly lowest hardness loss for all groups was recorded for group 12 with admixture of calcium, phosphate and fluoride to citric acid. The significantly highest enamel loss was recorded for the controls compared to all other samples. Groups 3 and 4 revealed significantly lower and higher tissue loss compared to the remaining groups (2-13), respectively. The other groups did not differ significantly from each other. Modification of citric acid with calcium, phosphate and fluoride exerts a significant protective potential with respect to dental erosion. However, with the low concentrations applied enamel dissolution could not be completely prevented.
Kurt, Asuman; Andican, Gülnur; Siva, Zeynep Oşar; Andican, Ahat; Burcak, Gülden
In diabetes mellitus, chronic hyperglycemia leads to formation of advanced glycation end products (AGEs). Binding of AGEs to receptors of AGE (RAGE) causes deleterious effects. In populations with a high consumption of n-3 long-chain polyunsaturated fatty acids, a lower prevalence of diabetes mellitus has been reported. We aimed to investigate the effects of n-3 fatty acid (EPA and DHA) supplementation on the levels of AGEs (carboxymethyl lysine (CML) and pentosidine), sRAGE, and nuclear factor kappa B (NF-kB) in type 2 diabetes mellitus (T2DM). T2DM patients (n = 38) treated with oral hypoglycemic agents, without insulin were supplemented with n-3 fatty acids (1.2 g/day) for 2 months. Plasma CML, pentosidine, sRAGE, and NF-kB levels were measured by ELISA both before and after the supplementation. n-3 fatty acid supplementation significantly reduced fasting glucose (p < 0.01), glycated hemoglobin (HbA1c) (p < 0.05), and pentosidine (p < 0.05) levels. The supplementation induced percentage changes in pentosidine and HbA1c and in pentosidine and creatinine were observed to be correlated (r = 0.349, p < 0.05) and (r = 0.377, p < 0.05), respectively. Waist circumference and systolic and diastolic pressures were significantly decreased due to n-3 supplementation (p < 0.001, p < 0.01, p < 0.01), respectively. Our results show that supplementation with n-3 fatty acid has beneficial effects on waist circumference; systolic and diastolic blood pressures; and the levels of glucose, HbA1c, and pentosidine in T2DM patients. However, the supplementation failed to decrease these parameters to the reference ranges for healthy subjects. In addition, the supplementation did not appear to induce any significant differences in CML, sRAGE, or NF-kB.
Expanded abstract Citation Rice TW, Wheeler AP, Thompson BT, deBoisblanc BP, Steingrub J, Rock, P. Enteral Omega-3 Fatty Acid, γ-Linolenic Acid, and Antioxidant Supplementation in Acute Lung Injury. JAMA. 2011; 306(14):1574-1581. PubMed PMID: 21976613. Background The omega-3 (n-3) fatty acids docosahexaenoic acid and eicosapentaenoic acid, along with γ-linolenic acid and antioxidants, may modulate systemic inflammatory response and improve oxygenation and outcomes in patients with acute lung injury. Methods Objective: To determine if dietary supplementation of these substances to patients with acute lung injury would increase ventilator-free days to study day 28. Design: The OMEGA study, a randomized, double-blind, placebo-controlled, multicenter trial conducted from January 2, 2008, through February 21, 2009. All participants had complete follow-up. Setting: This trial occurred at 44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Subjects: Participants were 272 adults within 48 hours of developing acute lung injury requiring mechanical ventilation whose physicians intended to start enteral nutrition. Intervention: Twice-daily enteral supplementation of n-3 fatty acids, γ -linolenic acid, and antioxidants compared with an isocaloric control. Enteral nutrition, directed by a protocol, was delivered separately from the study supplement. Outcomes: Ventilator-free days to study day 28. Results The study was stopped early for futility after 143 and 129 patients were enrolled in the n-3 and control groups. Despite an 8-fold increase in plasma eicosapentaenoic acid levels, patients receiving the n-3 supplement had fewer ventilator-free days (14.0 vs 17.2; P=.02) (difference, −3.2 [95% CI, −5.8 to −0.7]) and intensive care unit-free days (14.0 vs 16.7; P=.04). Patients in the n-3 group also had fewer nonpulmonary organ failure-free days (12.3 vs 15.5; P=.02). Sixty-day hospital mortality was 26.6% in the n 3 group vs 16
Carney, Robert M.; Steinmeyer, Brian C.; Freedland, Kenneth E.; Rubin, Eugene H.; Rich, Michael W.; Harris, William S.
Objective Depression is associated with low red blood cell (RBC) levels of two omega-3 fatty acids (FAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), suggesting that omega-3 supplements might improve depression. However, clinical trials have produced mixed results. The purpose of this secondary analysis of data from a randomized controlled trial was to determine whether baseline blood levels of omega-3, which are known to vary widely among individuals, predict depression outcomes. Methods The percentages of EPA, DHA, and the omega-6 arachidonic acid (AA) were measured in RBCs at baseline and post-treatment in 122 participants with DSM-IV major depression who were randomized between May 2005 and December 2008 to receive either 50 mg/day of sertraline and 930 mg EPA/750 mg DHA/day or sertraline plus placebo. Associations between baseline RBC omega-3 levels and remission of depression (HAM-D≤7) were analyzed by treatment arm. Results Among participants in the omega-3 arm, baseline RBC levels of EPA+DHA (p=0.002) and the EPA+DHA:AA ratio (p=0.003) were significantly higher among those whose depression subsequently remitted compared with those whose depression did not remit. No associations were detected in the sertraline plus placebo arm. Baseline levels of EPA (p=0.03) and the EPA+DHA:AA ratio (p=0.04) moderated the relationship between treatment arm and depression outcomes. Conclusion High pre-treatment RBC levels of EPA and DHA, and a high EPA+DHA:AA ratio, predict favorable depression outcomes in patients receiving omega-3 supplements. Omega-3 supplementation may be an effective treatment for depression, but the requisite dosage and duration of treatment may depend on the patient's baseline level of omega-3. PMID:26930527
Jump, Donald B.; Depner, Christopher M.; Tripathy, Sasmita
Epidemiological studies on Greenland Inuits in the 1970s and subsequent human studies have established an inverse relationship between the ingestion of omega-3 fatty acids [C20–22 ω 3 polyunsaturated fatty acids (PUFA)], blood levels of C20–22 ω 3 PUFA, and mortality associated with cardiovascular disease (CVD). C20–22 ω 3 PUFA have pleiotropic effects on cell function and regulate multiple pathways controlling blood lipids, inflammatory factors, and cellular events in cardiomyocytes and vascular endothelial cells. The hypolipemic, anti-inflammatory, anti-arrhythmic properties of these fatty acids confer cardioprotection. Accordingly, national heart associations and government agencies have recommended increased consumption of fatty fish or ω 3 PUFA supplements to prevent CVD. In addition to fatty fish, sources of ω 3 PUFA are available from plants, algae, and yeast. A key question examined in this review is whether nonfish sources of ω 3 PUFA are as effective as fatty fish-derived C20–22 ω 3 PUFA at managing risk factors linked to CVD. We focused on ω 3 PUFA metabolism and the capacity of ω 3 PUFA supplements to regulate key cellular events linked to CVD. The outcome of our analysis reveals that nonfish sources of ω 3 PUFA vary in their capacity to regulate blood levels of C20–22 ω 3 PUFA and CVD risk factors. PMID:22904344
Morin, Caroline; Rousseau, Eric; Blier, Pierre U; Fortin, Samuel
ω-3 Fatty acid supplementation has been associated with lower blood pressure. Cardiovascular diseases are also known to be linked directly to an increase in ω-6 and a reduction in ω-3 fatty acid levels in blood circulation and tissues. To determine the effect of docosahexaenoic acid monoglycerides (MAG-DHA) on blood pressure, lipid profiles, and vascular remodeling in rats fed a high-fat/high-carbohydrate (HFHC) diet. Studies were performed in male rats subjected to 8 wk of HFHC diet supplemented or not with 3 g/day MAG-DHA. After 8 wk of daily MAG-DHA treatment, rats in the HFHC + MAG-DHA group had lower arterial blood pressure and heart rate compared with the HFHC group. Moreover, MAG-DHA prevented the increase aortic wall thickness, whereas lipid analysis of aortic tissues revealed an increase in DHA/AA ratio correlated with the production of resolvin D2 and D3 metabolites. Histological analysis revealed that MAG-DHA prevented the development of LVH in the HFHC group. Serum lipid profile analysis further showed a decrease in total cholesterol (TC) and LDL, including very low-density lipoprotein (VLDL) and triglyceride (TG) levels, together with an increase in HDL levels after 8 wk of MAG-DHA treatment compared with the HFHC group. Furthermore, daily MAG-DHA treatment resulted in reduced proinflammatory marker levels such as CRP, IL-6, TNFα, and IL-1β. Altogether, these findings revealed that per os administration of MAG-DHA prevents HFHC-diet induced hypertension and LVH in rats.
Long chain polyunsaturated fatty acids (LC-PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are considered essential omega-3 fatty acids in human nutrition. In marine microalgae EPA and/or DHA are allegedly involved in the regulation of membrane fluidity and thylakoid membrane functioning. The cellular content of EPA and DHA may therefore be enhanced at low temperature and irradiance conditions. As a result, polar and cold temperate marine microalgal species might potentially be suitable candidates for commercial EPA and DHA production, given their adaptation to low temperature and irradiance habitats. In the present study we investigated inter- and intraspecific EPA and DHA variability in five polar and (cold) temperate microalgae. Intraspecific EPA and DHA content did not vary significantly in an Antarctic (Chaetoceros brevis) and a temperate (Thalassiosira weissflogii) centric diatom after acclimation to a range of irradiance levels at two temperatures. Interspecific variability was investigated for two Antarctic (Chaetoceros brevis and Pyramimonas sp. (Prasinophyceae)) and three cold-temperate species (Thalassiosira weissflogii, Emiliania huxleyi (Prymnesiophyceae) and Fibrocapsa japonica (Raphidophyceae)) during exponential growth. Interspecific variability was shown to be much more important than intraspecific variability. Highest relative and absolute levels of DHA were measured in the prymnesiophyte E. huxleyi and the prasinophyte Pyramimonas sp., while levels of EPA were high in the raphidophyte F. japonica and the diatoms C. brevis and T. weissflogii. Yet, no significant differences in LC-PUFA content were found between polar and cold-temperate species. Also, EPA and DHA production rates varied strongly between species. Highest EPA production rate (174 μg L-1 day-1) was found in the Antarctic diatom Chaetoceros brevis, while DHA production was highest in the cold-temperate prymnesiophyte Emiliania huxleyi (164 μg L-1 day-1). We
Boelen, Peter; van Dijk, Roechama; Sinninghe Damsté, Jaap S; Rijpstra, W Irene C; Buma, Anita Gj
Long chain polyunsaturated fatty acids (LC-PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are considered essential omega-3 fatty acids in human nutrition. In marine microalgae EPA and/or DHA are allegedly involved in the regulation of membrane fluidity and thylakoid membrane functioning. The cellular content of EPA and DHA may therefore be enhanced at low temperature and irradiance conditions. As a result, polar and cold temperate marine microalgal species might potentially be suitable candidates for commercial EPA and DHA production, given their adaptation to low temperature and irradiance habitats.In the present study we investigated inter- and intraspecific EPA and DHA variability in five polar and (cold) temperate microalgae. Intraspecific EPA and DHA content did not vary significantly in an Antarctic (Chaetoceros brevis) and a temperate (Thalassiosira weissflogii) centric diatom after acclimation to a range of irradiance levels at two temperatures. Interspecific variability was investigated for two Antarctic (Chaetoceros brevis and Pyramimonas sp. (Prasinophyceae)) and three cold-temperate species (Thalassiosira weissflogii, Emiliania huxleyi (Prymnesiophyceae) and Fibrocapsa japonica (Raphidophyceae)) during exponential growth. Interspecific variability was shown to be much more important than intraspecific variability. Highest relative and absolute levels of DHA were measured in the prymnesiophyte E. huxleyi and the prasinophyte Pyramimonas sp., while levels of EPA were high in the raphidophyte F. japonica and the diatoms C. brevis and T. weissflogii. Yet, no significant differences in LC-PUFA content were found between polar and cold-temperate species. Also, EPA and DHA production rates varied strongly between species. Highest EPA production rate (174 μg L-1 day-1) was found in the Antarctic diatom Chaetoceros brevis, while DHA production was highest in the cold-temperate prymnesiophyte Emiliania huxleyi (164 μg L-1 day-1). We
Schuster, Gertrud U; Bratt, Jennifer M; Jiang, Xiaowen; Pedersen, Theresa L; Grapov, Dmitry; Adkins, Yuriko; Kelley, Darshan S; Newman, John W; Kenyon, Nicholas J; Stephensen, Charles B
Although the effects of fish oil supplements on airway inflammation in asthma have been studied with varying results, the independent effects of the fish oil components, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), administered separately, are untested. Here, we investigated airway inflammation and hyperresponsiveness using a mouse ovalbumin exposure model of asthma assessing the effects of consuming EPA (1.5% wt/wt), DHA (1.5% wt/wt), EPA plus DHA (0.75% each), or a control diet with no added omega-3 polyunsaturated fatty acids. Consuming these diets for 6 weeks resulted in erythrocyte membrane EPA contents (molar %) of 9.0 (± 0.6), 3.2 (± 0.2), 6.8 (± 0.5), and 0.01 (± 0.0)%; DHA contents were 6.8 (± 0.1), 15.6 (± 0.5), 12.3 (± 0.3), and 3.8 (± 0.2)%, respectively. The DHA group had the highest bronchoalveolar lavage (BAL) fluid eosinophil and IL-6 levels (P < 0.05). Similar trends were seen for macrophages, IL-4, and IL-13, whereas TNF-α was lower in omega-3 polyunsaturated fatty acid groups than the control (P < 0.05). The DHA group also had the highest airway resistance, which differed significantly from the EPA plus DHA group (P < 0.05), which had the lowest. Oxylipins were measured in plasma and BAL fluid, with DHA and EPA suppressing arachidonic acid-derived oxylipin production. DHA-derived oxylipins from the cytochrome P450 and 15-lipoxygenase pathways correlated significantly with BAL eosinophil levels. The proinflammatory effects of DHA suggest that the adverse effects of individual fatty acid formulations should be thoroughly considered before any use as therapeutic agents in asthma.
Roby, Mohamed H; Allouche, Ahmad; Dahdou, Layal; De Castro, Vanessa C; da Silva, Paulo H Alves; Targino, Brenda N; Huguet, Marion; Paris, Cédric; Chrétien, Françoise; Guéant, Rosa-Maria; Desobry, Stéphane; Oster, Thierry; Humeau, Catherine
Docosahexaenoic acid (DHA) is increasingly considered for its health benefits. However, its use as functional food ingredient is still limited by its instability. In this work, we developed an efficient and solvent-free bioprocess for the synthesis of a phenolic ester of DHA. A fed-batch process catalyzed by Candida antarctica lipase B was optimised, leading to the production of 440 g/L vanillyl ester (DHA-VE). Structural characterisation of the purified product indicated acylation of the primary OH group of vanillyl alcohol. DHA-VE exhibited a high radical scavenging activity in acellular systems. In vivo experiments showed increased DHA levels in erythrocytes and brain tissues of mice fed DHA-VE-supplemented diet. Moreover, in vitro neuroprotective properties of DHA-VE were demonstrated in rat primary neurons exposed to amyloid-β oligomers. In conclusion, DHA-VE synergized the main beneficial effects of two common natural biomolecules and therefore appears a promising functional ingredient for food applications.
Vafa, Toktam S.; Naserian, Abbas A.; Heravi Moussavi, Ali R.; Valizadeh, Reza; Mesgaran, Mohsen Danesh
This study examined the effects of supplementation of fish oil and canola oil in the diet on milk yield, milk components and fatty acid composition of Holstein dairy cows in early lactation. Eight multiparous early lactation Holstein cows (42±12 DIM, 40±6 kg daily milk yield) were fed a total mixed ration supplemented with either 0% oil (Control), 2% fish oil (FO), 1% canola oil +1% fish oil (FOCO), or 2% canola oil (CO) according to a double 4×4 Latin square design. Each period lasted 3 wk; experimental analyses were restricted to the last week of each period. Supplemental oils were added to a basal diet which was formulated according to NRC (2001) and consisted of 20% alfalfa, 20% corn silage and 60% concentrate. Milk yield was similar between diets (p>0.05), but dry matter intake (DMI) was lower (p<0.05) in cows fed FO diet compared to other diets. Milk fat percentage and daily yield decreased (p<0.01) with the supplementation of fish and canola oil. The daily yield and percentage of milk protein, lactose and solids-not-fat (SNF) were not affected by diets (p>0.05). The proportion (g/100 g fatty acids) of short chain fatty acids (SCFA) decreased and polyunsaturated fatty acids (PUFA) increased (p<0.05) in milk of all cows fed diets supplemented with oil. The proportions of 6:0, 8:0, 10:0 12:0 and 14:0 fatty acids in milk fat decreased (p<0.01) for all diets supplemented with oil, but the proportions of 14:1, 16:0 and 16:1 fatty acids were not affected by diets (p>0.05). The proportion of trans(t)-18:1 increased (p<0.01) in milk fat of cows fed FO and FOCO diets, but CO diet had the highest proportion of cis(c)-11 18:1 (p<0.01). The concentration of t-10, c-12 18:2, c-9 t-11 18:2, 18:3, eicosapentaenoic acid (EPA, 20:5) and docosahexaenoic acid (DHA, 22:6) increased (p<0.05) in FO and FOCO diets in comparison with the other two diets. These data indicate that including fish oil in combination with canola oil significantly modifies the fatty acid composition of
14. ABSTRACT: See next page. 15. SUBJECT TERMS Prostate Cancer; Lipid Medtabolism, Clinical Trial; Omega -3 Fatty Acids 16. SECURITY...AD_________________ Award Number: W81XWH-04-1-0296 TITLE: Fish Oil Supplementation and Fatty Acid ...SUBTITLE Fish Oil Supplementation and Fatty Acid Synthase Expression in the Prostate: A 5a. CONTRACT NUMBER Randomized
Fedorova-Dahms, I; Marone, P A; Bauter, M; Ryan, A S
The safety of DHA-rich Algal Oil from Schizochytrium sp. containing 40-45 wt% DHA and up to 10 wt% EPA was evaluated by testing for gene mutations, clastogenicity and aneugenicity, and in a subchronic 90-day Sprague-Dawley rat dietary study with in utero exposure, followed by a 4-week recovery phase. The results of all genotoxicity tests were negative. In the 90-day study, DHA-rich Algal Oil was administered at dietary levels of 0.5, 1.5, and 5 wt% along with two control diets: a standard low-fat basal diet and a basal diet supplemented with 5 wt% of concentrated Fish Oil. There were no treatment-related effects of DHA-rich Algal Oil on clinical observations, body weight, food consumption, behavior, hematology, clinical chemistry, coagulation, or urinalysis. Increases in absolute and relative weights of the liver, kidney, spleen and adrenals (adrenals and spleen with histological correlates) were observed in both the Fish Oil- and the high-dose of DHA-rich Algal Oil-treated females and were not considered to be adverse. The no observed adverse effect level (NOAEL) for DHA-rich Algal Oil under the conditions of this study was 5 wt% in the diet, equivalent to an overall average DHA-rich Algal Oil intake of 4260 mg/kg bw/day for male and female rats.
Chi, Zhanyou; Hu, Bo; Liu, Yan; Frear, Craig; Wen, Zhiyou; Chen, Shulin
Algal cultivation for converting cull potato to docosahexaenoic acid (DHA) was studied. Schizochytrium limacinum SR21 was selected as the better producing strain, compared with Thraustochytrium aureum because of higher cell density and DHA content. Used as both carbon and nitrogen source, an optimal ratio of hydrolyzed potato broth in the culture medium was determined as 50%, with which the highest production of 21.7 g/L dry algae biomass and 5.35 g/L DHA was obtained, with extra glucose supplemented. Repeat culture further improved the cell density but not fed batch culture, suggesting limited growth was most likely caused by metabolites inhibition.
Chi, Zhanyou; Hu, Bo; Liu, Yan; Frear, Craig; Wen, Zhiyou; Chen, Shulin
Algal cultivation for converting cull potato to docosahexaenoic acid (DHA) was studied. Schizochytrium limacinum SR21 was selected as the better producing strain, compared with Thraustochytrium aureum because of higher cell density and DHA content. Used as both carbon and nitrogen source, an optimal ratio of hydrolyzed potato broth in the culture medium was determined as 50%, with which the highest production of 21.7 g/L dry algae biomass and 5.35 g/L DHA was obtained, with extra glucose supplemented. Repeat culture further improved the cell density but not fed batch culture, suggesting limited growth was most likely caused by metabolites inhibition.
Freitas, Raquel D S; Costa, Kesiane M; Nicoletti, Natália F; Kist, Luiza W; Bogo, Maurício R; Campos, Maria M
This study investigated the effects of the long-term dietary fish oil supplementation or the acute administration of the omega-3 fatty acid docosahexaenoic acid (DHA) in the mouse hemorrhagic cystitis (HC) induced by the anticancer drug cyclophosphamide (CYP). HC was induced in mice by a single CYP injection (300mg/kg ip). Animals received four different diets containing 10% and 20% of corn or fish oil, during 21days. Separated groups received DHA by ip (1μmol/kg) or intrathecal (i.t.; 10μg/site) routes, 1h or 15min before CYP. The behavioral tests (spontaneous nociception and mechanical allodynia) were carried out from 1h to 6h following CYP injection. Bladder inflammatory changes, blood cell counts and serum cytokines were evaluated after euthanasia (at 6h). Immunohistochemistry analysis was performed for assessing spinal astrocyte and microglia activation or GPR40/FFAR1 expression. Either fish oil supplementation or DHA treatment (ip and i.t.) markedly prevented visceral pain, without affecting CYP-evoked bladder inflammatory changes. Moreover, systemic DHA significantly prevented the neutrophilia/lymphopenia caused by CYP, whereas this fatty acid did not significantly affect serum cytokines. DHA also modulated the spinal astrocyte activation and the GPR40/FFAR1 expression. The supplementation with fish oil enriched in omega-3 fatty acids or parenteral DHA might be interesting nutritional approaches for cancer patients under chemotherapy schemes with CYP.
Chaung, Hso-Chi; Chang, Chin-Dong; Chen, Pi-Hang; Chang, Chia-Jung; Liu, Shyh-Hwa; Chen, Chih-Cheng
Fish oil during early postnatal period may modulate the impact of oxidative stress in the developing brain and thus improve memory and cognitive behaviour. This study investigated the impacts of docosahexaenoic acid (DHA, C22:6, n-3) and/or phosphatidylserine (PS) on antioxidant activities in vitro, and the beneficial effects of feeding with DHA and/or PS on antioxidant activities in brain and liver tissues and on the cognitive functions of the developing brain. Results indicated that DHA and/or PS significantly enhanced antioxidant activities and increased cell viabilities in vitro. Feeding with DHA and/or PS supplementation not only significantly improved escape latency of animals, but it also improved the oxidative parameters in the brain, enhanced glutathione peroxidase activity as well as reduced nitric mono-oxide levels in the liver. DHA and PS may serve to protect cells from oxidative stress and further improve learning and memory ability in vivo.
Gdula-Argasińska, Joanna; Bystrowska, Beata
Endocannabinoids are synthetized as a results of demand from membrane phospholipids. The formation and actions of these lipid mediators depend to a great extent on the prevalence of precursor fatty acid (FA), and can be influenced by diet or supplementation. The purpose of this study was to evaluate the interactive effects of lipopolysaccharide (LPS) and benzo(a)pyrene (BaP) in RAW 264.7 cells supplemented with docosahexaenoic acid (DHA). After LPS and/or BaP treatment in macrophages pre-incubated with DHA, a significant decrease in the amount of fatty acid was observed. The highest content of monounsaturated fatty acids was detected in RAW 264.7 cells co-treated with LPS and BaP. Significant interactions between LPS and BaP co-treatment in terms of endocannabinoid levels were observed in RAW 264.7 cells after DHA supplementation. The highest amount of endocannabinoids was detected in macrophages supplemented with DHA and co-treated with BaP and LPS: arachidonoyl ethanolamine AEA (5.9μg/mL), docosahexaenoyl ethanolamide DHEA (10.6μg/mL) and nervonoyl ethanolamide NEA (16.5μg/mL). The highest expression of cyclooxygenase (COX-2) and cannabinoid receptor 2 (CB2) was noted in macrophages supplemented with DHA and activated with LPS and BaP. Our data suggested a novel, CB2 receptor-dependent, environmental stress reaction in macrophages co-treated with LPS and BaP after supplementation with DHA. Despite the synergistic LPS and BaP action DHA potentiates the anti-inflammatory response in RAW 264.7 cells.
Stephensen, Charles B
Eating fish or taking n-3 fatty acid supplements can decrease the risk and severity of cardiovascular disease. Such supplements also provide symptomatic relief for rheumatoid arthritis patients. Recent research suggests that asthma, another highly prevalent, chronic inflammatory disease, may also respond to fish oil supplements.
Hsieh, Andrea T; Brenna, J Thomas
The influence of dietary docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) on infant central nervous system (CNS) composition has implications for neural development, including vision, cognition, and motor function. We consider here combined results of three published studies of DHA/AA-containing formulas and breastfeeding to evaluate the CNS tissue response of baboon neonates with varied concentration and duration of DHA/AA consumption [G.Y. Diau, A.T. Hsieh, E.A. Sarkadi-Nagy, V. Wijendran, P.W. Nathanielsz, J.T. Brenna, The influence of long chain polyunsaturate supplementation on docosahexaenoic acid and arachidonic acid in baboon neonate central nervous system, BMC Med. 3 (2005) 11; A.T. Hsieh, J.C. Anthony, D.A. Diersen-Schade, et al., The influence of moderate and high dietary long chain polyunsaturated fatty acids (LCPUFA) on baboon neonate tissue fatty acids, Pediatr. Res. 61 (2007) 537-45; E. Sarkadi-Nagy, V. Wijendran, G.Y. Diau, et al., The influence of prematurity and long chain polyunsaturate supplementation in 4-week adjusted age baboon neonate brain and related tissues, Pediatr. Res. 54 (2003) 244-252]. A total of 43 neonates born spontaneously at term, or preterm by Cesarean section, consumed diets with DHA-AA (%w/w) at several levels: none (0,0), moderate (0.3, 0.6), or high (>0.6, 0.67 or 1.2). CNS fatty acids were analyzed at 4 and 12 weeks postpartum for term baboons and 7.5 weeks for preterm neonates. CNS DHA was consistently greater by 5-30% in neonates consuming DHA and nearer 30% for cortex. In contrast, CNS AA was unaffected by dietary AA and decreased in all structures with age. Dietary DHA consistently supports greater CNS DHA and maintenance of cortex DHA concentration with feeding duration, while CNS AA is not related to dietary supply. These data on structure-specific LCPUFA accretion may provide insight into neural mechanisms responsible for suboptimal functional outcomes in infants consuming diets that do not
Kim, Min Woo; Ahn, Ki Hoon; Ryu, Ki-Jin; Hong, Soon-Cheol; Lee, Ji Sung; Nava-Ocampo, Alejandro A.; Oh, Min-Jeong; Kim, Hai-Joong
Although there is accumulating evidence regarding the additional protective effect of folic acid against adverse pregnancy outcomes other than neural tube defects, these effects have not been elucidated in detail. We evaluated whether folic acid supplementation is associated with favorable maternal and fetal outcomes. This was a secondary analysis of 215 pregnant women who were enrolled in our prior study. With additional data from telephone interviews regarding prenatal folic acid supplementation, existing demographic, maternal and fetal data were statistically analyzed. The concentration of folic acid in maternal blood was significantly higher following folic acid supplementation (24.6 ng/mL vs.11.8 ng/mL). In contrast, homocysteine level in maternal blood decreased with folic acid supplementation (5.5 µmol/mL vs. 6.8 µmol/mL). The rates of both preeclampsia (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.09–0.76) and small for gestational age (SGA; 9.2% vs. 20.0%; OR, 0.42; 95% CI, 0.18–0.99) were lower in the folic acid supplementation group than those in the control group. Other pregnancy outcomes had no association with folic acid supplementation. The findings indicate that folic acid supplementation may help to prevent preeclampsia and SGA. Further studies are warranted to elucidate the favorable effects of folic acid supplementation on pregnancy outcomes. PMID:24842467
McDaniel, Jodi C.; Massey, Karen; Nicolaou, Anna
Chronic wounds often result from prolonged inflammation involving excessive polymorphonuclear leukocyte activity. Studies show that the ω-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found in fish oils generate bioactive lipid mediators that reduce inflammation and polymorphonuclear leukocyte recruitment in numerous inflammatory disease models. This study’s purpose was to test the hypotheses that boosting plasma levels of EPA and DHA with oral supplementation would alter lipid mediator levels in acute wound microenvironments and reduce polymorphonuclear leukocyte levels. Eighteen individuals were randomized to 28 days of either EPA + DHA supplementation (Active Group) or placebo. After 28 days, the Active Group had significantly higher plasma levels of EPA (p < 0.001) and DHA (p < 0.001) than the Placebo Group and significantly lower wound fluid levels of two 15-lipoxygenase products of ω-6 polyunsaturated fatty acids (9-hydroxyoctadecadienoic acid [p=0.033] and 15-hydroxyeicosatrienoic acid [p=0.006]), at 24 hours postwounding. The Active Group also had lower mean levels of myeloperoxidase, a leukocyte marker, at 12 hours and significantly more reepithelialization on Day 5 postwounding. We suggest that lipid mediator profiles can be manipulated by altering polyunsaturated fatty acid intake to create a wound microenvironment more conducive to healing. PMID:21362086
Omoruyi, F O; Budiaman, A; Eng, Y; Olumese, F E; Hoesel, J L; Ejilemele, A; Okorodudu, A O
In this study, the effect of phytic acid supplement on streptozotocin-induced diabetic rats was investigated. Diabetic rats were fed rodent chow with or without phytic acid supplementation for thirty days. Blood and organ samples were collected for assays. The average food intake was the highest and the body weight gain was the lowest in the group fed phytic acid supplement compared to the diabetic and normal control groups. There was a downward trend in intestinal amylase activity in the group fed phytic acid supplement compared to the other groups. The spike in random blood glucose was the lowest in the same group. We noted reduced serum triglycerides and increased total cholesterol and HDL cholesterol levels in the group fed phytic acid supplement. Serum alkaline phosphatase and alanine amino transferase activities were significantly (P < 0.05) increased by phytic acid supplementation. Systemic IL-1 β level was significantly (P < 0.05) elevated in the diabetic control and supplement treated groups. The liver lipogenic enzyme activities were not significantly altered among the groups. These results suggest that phytic acid supplementation may be beneficial in the management of diabetes mellitus. The observed adverse effect on the liver may be due to the combined effect of streptozotocin-induced diabetes and phytic acid supplementation.
Molloy, Carly; Doyle, Lex W; Makrides, Maria; Anderson, Peter J
Preterm children are at risk for a number of visual impairments which can be important for a range of other more complex visuocognitive tasks reliant on visual information. Despite the relatively high incidence of visual impairments in this group there are no good predictors that would allow early identification of those at risk for adverse outcomes. Several lines of evidence suggest that docosahexaenoic acid (DHA) supplementation for preterm infants may improve outcomes in this area. For example, diets deficient in the long-chain polyunsaturated fatty acid DHA have been shown to reduce its concentration in the cerebral cortex and retina, which interferes with physiological processes important for cognition and visual functioning. Further, various studies with pregnant and lactating women, as well as formula-fed infants, have demonstrated a general trend that supplementation with dietary DHA is associated with better childhood outcomes on tests of visual and cognitive development over the first year of life. However, research to date has several methodological limitations, including concentrations of DHA supplementation that have been too low to emulate the in utero accretion of DHA, using single measures of visual acuity to make generalised assumptions about the entire visual system, and little attempt to match what we know about inadequate DHA and structural ramifications with how specific functions may be affected. The objective of this review is to consider the role of DHA in the context of visual processing with a specific emphasis on preterm infants and to illustrate how future research may benefit from marrying what we know about structural consequences to inadequate DHA with functional outcomes that likely have far-reaching ramifications. Factors worth considering for clinical neuropsychological evaluation are also discussed.
Pratoomyot, Jarunan; Siranonthana, Nisa; Senanan, Wansuk
The giant river prawn (Macrobrachium rosenbergii) is one of the most farmed freshwater crustaceans in the world. Its global production has been stalling in the past decade due to the inconsistent quality of broodstock and hatchery-produced seeds. A better understanding of the role of nutrition in maturation diets will help overcome some of the production challenges. Arachidonic acid (20:4 n-6, ARA) is a fatty acid precursor of signaling molecules important for crustacean reproduction, prostaglandins E and F of the series II (PGE2 and PGF2α), and is often lacking in maturation diets of shrimp and prawns. We examined the effects of ARA in a combination of different fish oil (FO) and soybean oil (SO) blends on females’ reproductive performance and larval quality. Adult females (15.22 ± 0.13 g and 11.12 ± 0.09 cm) were fed six isonitrogenous and isolipidic diets containing one of two different base compositions (A or B), supplemented with one of three levels of Mortierella alpine-derived ARA (containing 40% active ARA): 0, 1 or 2% by ingredient weight. The two base diets differed in the percentages of (FO and SO with diet A containing 2% SO and 2% FO and diet B containing 2.5% SO and 1.5% FO, resulting in differences in proportional contents of dietary linoleic acid (18:2n-6, LOA) and docosahexaenoic acid (22:6n-3, DHA)). After the eight-week experiment, prawns fed diet B with 1 and 2% ARA supplement (B1 and B2) exhibited the highest gonadosomatic index (GSI), hepatosomatic index (HSI), egg clutch weight, fecundity, hatching rate, number of larvae, and reproductive effort compared to those fed other diets (p ≤ 0.05). Larvae from these two dietary treatments also had higher tolerance to low salinity (2 ppt). The maturation period was not significantly different among most treatments (p ≥ 0.05). ARA supplementation, regardless of the base diet, significantly improved GSI, HSI, egg clutch weight and fecundity. However, the diets with an enhanced ARA and LOA
Johnson, Elizabeth J; Schaefer, Ernst J
Dementia and age-related macular degeneration (AMD) are major causes of disability in the elderly. n-3 Fatty acids, particularly docosahexaenoic acid (DHA), are highly concentrated in brain and retinal tissue and may prevent or delay the progression of dementia and AMD. Low dietary intakes and plasma concentrations have been reported to be associated with dementia, cognitive decline, and AMD risk. The major dietary sources of DHA are fish and fish oils, although dietary supplements are available. At this point, it is not possible to make firm recommendations regarding n-3 fatty acids and the prevention of dementia and AMD. Our own unpublished observations from the Framingham Heart Study suggest that > or =180 mg/d of dietary DHA (approximately 2.7 fish servings/wk) is associated with an approximately 50% reduction in dementia risk. At least this amount of DHA is generally found in one commercially available 1-g fish oil capsule given daily.
Meher, Akshaya; Joshi, Asmita; Joshi, Sadhana
Nutritional status of the mother is known to influence various metabolic adaptations required for optimal fetal development. These may be mediated by transcription factors like peroxisome proliferator activated receptors (PPARs), which are activated by long chain polyunsaturated fatty acids. The objective of the current study was to examine the expression of different hepatic transcription factors and the levels of global methylation in the liver of the offspring born to dams fed micronutrient deficient (folic acid and vitamin B12) diets and supplemented with omega-3 fatty acids. Female rats were divided into five groups (n = 8/group) as follows; control, folic acid deficient (FD), vitamin B12 deficient (BD) and omega-3 fatty acid supplemented groups (FDO and BDO). Diets were given starting from pre-conception and continued throughout pregnancy and lactation. Pups were dissected at the end of lactation. Liver tissues were removed; snap frozen and stored at -80°C. Maternal micronutrients deficiency resulted in lower (p<0.05) levels of pup liver docosahexaenoic acid (DHA) and arachidonic acid (ARA) as compared to the control group. Pup liver PPARα and PPARγ expression was lower (p<0.05) in the BD group although there were no differences in the expression of SREBP-1c, LXRα and RXRα expression. Omega-3 fatty acids supplementation to this group normalized (p<0.05) levels of both PPARα and PPARγ but reduced (p<0.05) SREBP-1c, LXRα and RXRα expression. There was no change in any of the transcription factors in the pup liver in the FD group. Omega-3 fatty acids supplementation to this group reduced (p<0.05) PPARα, SREBP-1c and RXRα expression. Pup liver global methylation levels were higher (p<0.01) in both the micronutrients deficient groups and could be normalized (p<0.05) by omega-3 fatty acid supplementation. Our novel findings suggest a role for omega-3 fatty acids in the one carbon cycle in influencing the hepatic expression of transcription factors in the
Muralidharan, Pooja; Sarmah, Swapnalee; Marrs, James A.
Fetal Alcohol Spectrum Disorder (FASD) is caused by prenatal alcohol exposure, producing craniofacial, sensory, motor, and cognitive defects. FASD is highly prevalent in low socioeconomic populations, which are frequently accompanied by malnutrition. FASD-associated ocular pathologies include microphthalmia, optic nerve hypoplasia, and cataracts. The present study characterizes specific retinal tissue defects, identifies ethanol-sensitive stages during retinal development, and dissects the effect of nutrient supplements, such as retinoic acid (RA) and folic acid (FA) on ethanol-induced retinal defects. Exposure to pathophysiological concentrations of ethanol (during midblastula transition through somitogenesis; 2–24 hours post fertilization [hpf]) altered critical transcription factor expression involved in retinal cell differentiation, and produced severe retinal ganglion cell, photoreceptor, and Müller glial differentiation defects. Ethanol exposure did not alter retinal cell differentiation induction, but increased retinal cell death and proliferation. RA and FA nutrient co-supplementation rescued retinal photoreceptor and ganglion cell differentiation defects. Ethanol exposure during retinal morphogenesis stages (16–24 hpf) produced retinal defects like those seen with ethanol exposure between 2–24 hpf. Significantly, during an ethanol-sensitive time window (16–24 hpf), RA co-supplementation moderately rescued these defects, whereas FA co-supplementation showed significant rescue of optic nerve and photoreceptor differentiation defects. Interestingly, RA, but not FA, supplementation after ethanol exposure could reverse ethanol-induced optic nerve and photoreceptor differentiation defects. Our results indicate that various ethanol-sensitive events underlie FASD-associated retinal defects. Nutrient supplements like retinoids and folate were effective in alleviating ethanol-induced retinal defects. PMID:25541501
Muralidharan, Pooja; Sarmah, Swapnalee; Marrs, James A
Fetal Alcohol Spectrum Disorder (FASD) is caused by prenatal alcohol exposure, producing craniofacial, sensory, motor, and cognitive defects. FASD is highly prevalent in low socioeconomic populations, which are frequently accompanied by malnutrition. FASD-associated ocular pathologies include microphthalmia, optic nerve hypoplasia, and cataracts. The present study characterizes specific retinal tissue defects, identifies ethanol-sensitive stages during retinal development, and dissects the effect of nutrient supplements, such as retinoic acid (RA) and folic acid (FA) on ethanol-induced retinal defects. Exposure to pathophysiological concentrations of ethanol (during midblastula transition through somitogenesis; 2-24 h post fertilization [hpf]) altered critical transcription factor expression involved in retinal cell differentiation, and produced severe retinal ganglion cell, photoreceptor, and Müller glial differentiation defects. Ethanol exposure did not alter retinal cell differentiation induction, but increased retinal cell death and proliferation. RA and FA nutrient co-supplementation rescued retinal photoreceptor and ganglion cell differentiation defects. Ethanol exposure during retinal morphogenesis stages (16-24 hpf) produced retinal defects like those seen with ethanol exposure between 2 and 24 hpf. Significantly, during an ethanol-sensitive time window (16-24 hpf), RA co-supplementation moderately rescued these defects, whereas FA co-supplementation showed significant rescue of optic nerve and photoreceptor differentiation defects. Interestingly, RA, but not FA, supplementation after ethanol exposure could reverse ethanol-induced optic nerve and photoreceptor differentiation defects. Our results indicate that various ethanol-sensitive events underlie FASD-associated retinal defects. Nutrient supplements like retinoids and folate were effective in alleviating ethanol-induced retinal defects.
Markhus, Maria Wik; Rasinger, Josef Daniel; Malde, Marian Kjellevold; Frøyland, Livar; Skotheim, Siv; Braarud, Hanne Cecilie; Stormark, Kjell Morten; Graff, Ingvild Eide
Background Essential fatty acid status as well as docosahexaenoic acid (DHA, 22:6n-3) declines during pregnancy and lactation. As a result, the DHA status may not be optimal for child development and may increase the risk for maternal postpartum depression. The objective of this study was to assess changes in the maternal fatty acid status from pregnancy to 12 months postpartum, and to study the impact of seafood consumption on the individual fatty acid status. Methods Blood samples and seafood consumption habits (gestation week 28, and three-, six- and 12 months postpartum) were collected in a longitudinal observational study of pregnant and postpartum women (n = 118). Multilevel linear modeling was used to assess both changes over time in the fatty acid status of red blood cells (RBC), and in the seafood consumption. Results Six fatty acids varied the most (>80%) across the four time points analyzed, including the derivative of the essential α-linoleic acid (ALA, 18:3n-3), DHA; the essential linoleic acid (LA, 18:2 n-6); and the LA derivative, arachidonic acid (AA, 20:4n-6). Over all, a large variation in individuals’ DHA- and AA status was observed; however, over the 15-month study period only small inter-individual differences in the longitudinal trajectory of DHA- and AA abundance in the RBC were detected. The median intake of seafood was lower than recommended. Regardless, the total weekly frequency of seafood and eicosapentaenoic acid (EPA, 20:5n-3)/DHA-supplement intake predicted the maternal level of DHA (μg/g RBC). Conclusion The period of depletion of the maternal DHA status during pregnancy and lactation, seem to turn to repletion from about six months postpartum towards one year after childbirth, irrespective of RBC concentration of DHA during pregnancy. Seafood and EPA/DHA-supplement intake predicted the DHA levels over time. Trial Registration www.helseforskning.etikkom.no 2009/570/REC, project number: 083.09 PMID:26331947
Stein, Aryeh D.; Wang, Meng; Rivera, Juan A.; Martorell, Reynaldo; Ramakrishnan, Usha
The evidence relating prenatal supplementation with DHA to offspring neurological development is limited. We investigated the effect of prenatal DHA supplementation on infant brainstem auditory-evoked responses and visual- evoked potentials in a double-blind, randomized controlled trial in Cuernavaca, Mexico. Pregnant women were supplemented daily with 400 mg DHA or placebo from gestation wk 18–22 through delivery. DHA and placebo groups did not differ in maternal characteristics at randomization or infant characteristics at birth. Brainstem auditory-evoked responses were measured at 1 and 3 mo in 749 and 664 infants, respectively, and visual-evoked potentials were measured at 3 and 6 mo in 679 and 817 infants, respectively. Left-right brainstem auditory-evoked potentials were moderately correlated (range, 0.26–0.43; all P < 0.001) and left-right visual-evoked potentials were strongly correlated (range, 0.79–0.94; all P < 0.001) within any assessment. Correlations across visits were modest to moderate (range, 0.09–0.38; all P < 0.01). The offspring of DHA-supplemented women did not differ from those of control women with respect to any outcome measure (all comparisons P > 0.10). We conclude that DHA supplementation during pregnancy did not influence brainstem auditory-evoked responses at 1 and 3 mo or visual-evoked potentials at 3 and 6 mo. PMID:22739364
Toral, P G; Hervás, G; Gómez-Cortés, P; Frutos, P; Juárez, M; de la Fuente, M A
In an attempt to develop strategies for enhancing the nutritional value of sheep milk fat, dairy ewe diet was supplemented with 3 incremental levels of marine algae (MA), in combination with sunflower oil, to evaluate the effects of these marine lipids on milk fatty acid (FA) profile and animal performance. Fifty Assaf ewes in mid lactation were distributed in 10 lots of 5 animals each and allocated to 5 treatments (2 lots per treatment): no lipid supplementation (control) or supplementation with 25 g of sunflower oil/kg of DM plus 0 (SO), 8 (SOMA(1)), 16 (SOMA(2)), or 24 (SOMA(3)) g of MA (56.7% ether extract)/kg of DM. Milk production and composition, including FA profile, were analyzed on d 0, 3, 7, 14, 21, and 28 of treatment. Neither intake nor milk yield were significantly affected by lipid addition, but all MA supplements decreased milk fat content from d 14 onward, reaching a 30% reduction after 28 d on SOMA(3). This milk fat depression might be related not only to the joint action of some putative fat synthesis inhibitors, such as trans-9,cis-11 C18:2 and probably trans-10 C18:1, but also to the limited ability of the mammary gland to maintain a desirable milk fat fluidity, that would have been caused by the noticeable increase in trans-C18:1 together with the lowered availability of stearic acid for oleic acid synthesis through Delta(9)-desaturase. Furthermore, all lipid supplements, and mainly MA, reduced the secretion of de novo FA (C6:0-C14:0) without increasing the yield of preformed FA (>C16). Supplementation with sunflower oil plus MA resulted in larger increases in cis-9,trans-11 C18:2 than those observed with sunflower oil alone, achieving a mean content as high as 3.22% of total FA and representing a more than 7-fold increase compared with the control. Vaccenic acid (trans-11 C18:1) was also significantly enhanced (on average +794% in SOMA treatments), as was C22:6 n-3 (DHA) content, although the transfer efficiency of the latter, from the diets
Coëffier, Moïse; Marion-Letellier, Rachel; Déchelotte, Pierre
The pathophysiology of inflammatory bowel diseases (IBDs) is multifactorial and involves interactions of gut luminal content with mucosal barrier and especially immune cells. Malnutrition is a frequent issue during IBD flares, especially in Crohn's disease (CD) patients, and nutritional support is frequently used to treat malnutrition but also in an attempt to modulate intestinal inflammation. The use of oral or enteral nutrition intervention in IBDs may be effective, alone or in combination with drugs, to achieve and maintain remission. However, standard diets are less effective than new-generation biotherapies and could be improved by supplementation with specific immunomodulatory amino acids. Experimental studies evaluating glutamine, the preferential substrate for enterocytes, are promising. Some clinical studies with oral glutamine in CD are until now disappointing, but new formulations and targeting could enhance glutamine efficacy at the site of mucosal lesions. The role of arginine, involved in nitric oxide and polyamines synthesis, still remains debated. However, the effects of these amino acids in IBD have been poorly documented in humans. Other candidates like glycine, cysteine, histidine, or taurine should also be evaluated in the future.
Young, Genevieve; Conquer, Julie
Epidemiological evidence suggests that dietary consumption of the long chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), commonly found in fish or fish oil, may modify the risk for certain neuropsychiatric disorders. As evidence, decreased blood levels of omega-3 fatty acids have been associated with several neuropsychiatric conditions, including Attention Deficit (Hyperactivity) Disorder, Alzheimer's Disease, Schizophrenia and Depression. Supplementation studies, using individual or combination omega-3 fatty acids, suggest the possibility for decreased symptoms associated with some of these conditions. Thus far, however, the benefits of supplementation, in terms of decreasing disease risk and/or aiding in symptom management, are not clear and more research is needed. The reasons for blood fatty acid alterations in these disorders are not known, nor are the potential mechanisms by which omega-3 fatty acids may function in normal neuronal activity and neuropsychiatric disease prevention and/or treatment. It is clear, however, that DHA is the predominant n-3 fatty acid found in the brain and that EPA plays an important role as an anti-inflammatory precursor. Both DHA and EPA can be linked with many aspects of neural function, including neurotransmission, membrane fluidity, ion channel and enzyme regulation and gene expression. This review summarizes the knowledge in terms of dietary omega-3 fatty acid intake and metabolism, as well as evidence pointing to potential mechanisms of omega-3 fatty acids in normal brain functioning, development of neuropsychiatric disorders and efficacy of omega-3 fatty acid supplementation in terms of symptom management.
Lund, Ivar; Skov, Peter Vilhelm; Hansen, Benni Winding
The present study examined the effects of feeding pike perch larvae Artemia, enriched with either docosahexanoic acid (DHA), arachidonic acid (ARA), oleic acid (OA), olive oil (OO) or a commercial enrichment DHA Selco (DS) on tissue lipid deposition, stress tolerance, growth and development, and metabolic rate. There was higher tissue retention of ARA than DHA at comparable inclusion levels. No differences were observed between diets on the percentage contribution of ARA or DHA to the fatty acid profile of tissues (head and trunk). Total fatty acid content (mgg(-1)) was significantly higher in the head, reflecting its high content of neural tissue. Observations on larval erratic behaviour and mortality following exposure to salinity stress suggested that high inclusions levels of DHA had an alleviating effect, while ARA did not. Particularly larval groups reared for 16 days on diets enriched with OO and OA had mortality rates approaching 100% within two hours. Interestingly, this tendency, although not as pronounced, was also apparent in juvenile fish after 120 days of rearing on a common diet. Standard metabolic rate in larvae on an OO enriched diet was significantly elevated, but otherwise no groups had significant changes to their respiratory physiology. In addition to increased stress challenge sensitivity, early feeding with OA had long term impact on pike perch neural development indicated by a smaller brain size in juvenile fish. In conclusion, lack of DHA in the diet of pikeperch larvae suggests that this long chain polyunsaturated fatty acid is involved in processes that increase stress tolerance and that lack of dietary DHA in early larval stage caused increased stress sensitivity and long-term impaired neural development, while it does not appear to affect metabolic rate at rest.
Boles, J A; Kott, R W; Hatfield, P G; Bergman, J W; Flynn, C R
The objective of this study was to determine whether increasing levels of dietary safflower oil would alter unsaturated fat (especially CLA) and tocopherol content of lamb, animal performance, carcass characteristics, or color stability of lamb muscle tissue. Targhee x Rambouillet wethers (n = 60) were assigned to one of three diets (four pens per treatment with five lambs per pen) in a completely random design. Diets were formulated with supplemental safflower oil at 0 (control), 3, or 6% (as-fed basis) of the diet. Diets containing approximately 80% concentrate and 20% roughage were formulated, on a DM basis, to be isocaloric and isonitrogenous and to meet or exceed NRC requirements for Ca, P, and other nutrients. A subsample of 12 wethers per treatment was selected based on average BW (54 kg) and slaughtered. Carcass data (LM area, fat thickness, and internal fat content) and wholesale cut weight (leg, loin, rack, shoulder, breast, and foreshank), along with fatty acid, tocopherol, and color analysis, were determined on each carcass. The LM and infraspinatus were sampled for fatty acid profile. Increasing safflower oil supplementation from 0 to 3 or 6% increased the proportion of linoleic acid in the diet from 49.93 to 55.32 to 62.38%, respectively, whereas the percentage of oleic acid decreased from 27.94 to 23.80 to 20.73%, respectively. The percentage of oil in the diet did not (P > or = 0.11) alter the growth and carcass characteristics of lambs, nor did it alter the tocopherol content or color stability of meat. Increasing levels of safflower oil in lamb diets decreased (P < 0.01) the weight percentage of oleic acid in the infraspinatus and LM, and increased linoleic acid (P < 0.01). Oil supplementation increased (P < 0.01) the weight percentage of various isomers of CLA in muscle, with the greatest change in the cis-9,trans-11 isomer. Supplementation of sheep diets with safflower oil, up to 6% of the diet, resulted in increasing levels of unsaturated fatty
Lu, T; Harper, A F; Dibner, J J; Scheffler, J M; Corl, B A; Estienne, M J; Zhao, J; Dalloul, R A
The study was conducted to determine effects of dietary supplementation with a blend of antioxidants (ethoxyquin and propyl gallate) on carcass characteristics, meat quality, and fatty acid profile in finishing pigs fed a diet high in oxidants. A total of 100 crossbred barrows (10.9±1.4 kg BW, 36±2 d of age) were randomly allotted to 5 diet treatments (5 replicate pens per treatment, 4 pigs per pen). Treatments included: 1) HO: high oxidant diet containing 5% oxidized soy oil and 10% PUFA source which contributed 5.56% crude fat and 2.05% docosahexanoic acid (DHA) to the diet; 2) VE: the HO diet with 11 IU/kg of added vitamin E; 3) AOX: the HO diet with antioxidant blend (135 mg/kg); 4) VE+AOX: the HO diet with both vitamin E and antioxidant blend; and 5) SC: a standard corn-soy control diet with nonoxidized oil and no PUFA source. The trial lasted for 118 d; on d 83, the HO diet pigs were switched to the SC diet due to very poor health. From that point, the VE pigs displayed the poorest performance. On d 118, 2 pigs from each pen were harvested for sampling. Compared to pigs fed SC diet, the HO and VE pigs (P<0.05) showed lighter carcass weight, less back fat, less lean body mass, and smaller loin eye area. In addition, the VE pigs had decreased dressing percentage than the AOX and VE+AOX pigs (65.7 vs. 75.3 and 74.2%). Compared to the SC pigs, greater moisture percentage (74.7 vs. 77.4%) and less extractable lipid content (2.43 vs. 0.95%) were found in VE fed pigs (P<0.05). Drip loss of loin muscle in VE pigs was less than SC pigs (0.46 vs. 3.98%, P=0.02), which was associated with a trend for a greater 24-h muscle pH (5.74 vs. 5.54, P=0.07). The antioxidant blend addition in the high oxidant diet attenuated all of these effects to levels similar to SC (P>0.05), except a* value (redness) and belly firmness. Visible yellow coloration of backfat and lipofuscin in HO and VE pigs was observed at harvest at d 118. The high oxidant diet resulted in greater
Zhang, Xiaoyun; Qiao, Hua; Liu, Jianping; Dong, Haijun; Shen, Chenlin; Ni, Jingman; Shi, Yanbin; Xu, Ying
A simple and rapid LC-MS/MS method was established for the determination of dihydroartemisinin (DHA) in plasma and tissues of rats. Sample preparation was achieved by liquid-liquid extraction with aether and analysis was performed on LC-MS/MS in positive ion mode using electrospray ionization (ESI) as an interface. Target compounds were quantified in a single ion-monitoring (SIM) mode. DHA was monitored at m/z 267.1 and the internal standard finasteride at m/z 305.2. Chromatography was carried out using a Synergi fusion RP 80 column with a mixture of ethanol and 0.1% formic acid mixture (75:25) as the mobile phase. The pharmacokinetics and tissue distribution after intravenous administration of DHA in nanostructured lipid carrier (NLC) and in solution were then compared. The mean residence times (MRT) of the DHA-NLC was much longer than that of the DHA solution. In the tested organs, the AUC values of the DHA-NLC were higher than that of the DHA solution in liver, spleen, lung, brain and muscle, and lower than the DHA solution in heart and kidney. DHA-NLC prepared in this study is a promising sustained-release and drug-targeting system for antitumor drugs. It may also allow a reduction in dosage and a decrease in systemic toxicity.
To the Editors: We appreciate the interest and the comments of Chiu et al. concerning our recently published study investigating the effect of maternal docosahexaenoic acid (DHA) supplementation to prevent postpartum depression (PPD). We agree with many of their criticisms and, in fact, discussed th...
Champagne, Josee; Rennicks White, Ruth; Coyle, Doug; Fraser, William; Smith, Graeme; Fergusson, Dean; Walker, Mark C.
Preeclampsia (PE) is hypertension with proteinuria that develops during pregnancy and affects at least 5% of pregnancies. The Effect of Folic Acid Supplementation in Pregnancy on Preeclampsia: the Folic Acid Clinical Trial (FACT) aims to recruit 3,656 high risk women to evaluate a new prevention strategy for PE: supplementation of folic acid throughout pregnancy. Pregnant women with increased risk of developing PE presenting to a trial participating center between 80/7 and 166/7 weeks of gestation are randomized in a 1 : 1 ratio to folic acid 4.0 mg or placebo after written consent is obtained. Intent-to-treat population will be analyzed. The FACT study was funded by the Canadian Institutes of Health Research in 2009, and regulatory approval from Health Canada was obtained in 2010. A web-based randomization system and electronic data collection system provide the platform for participating centers to randomize their eligible participants and enter data in real time. To date we have twenty participating Canadian centers, of which eighteen are actively recruiting, and seven participating Australian centers, of which two are actively recruiting. Recruitment in Argentina, UK, Netherlands, Brazil, West Indies, and United States is expected to begin by the second or third quarter of 2013. This trial is registered with NCT01355159. PMID:24349782
Johansson, Ida; Monsen, Vivi Talstad; Pettersen, Kristine; Mildenberger, Jennifer; Misund, Kristine; Kaarniranta, Kai; Schønberg, Svanhild; Bjørkøy, Geir
Accumulation and aggregation of misfolded proteins is a hallmark of several diseases collectively known as proteinopathies. Autophagy has a cytoprotective role in diseases associated with protein aggregates. Age-related macular degeneration (AMD) is the most common neurodegenerative eye disease that evokes blindness in elderly. AMD is characterized by degeneration of retinal pigment epithelial (RPE) cells and leads to loss of photoreceptor cells and central vision. The initial phase associates with accumulation of intracellular lipofuscin and extracellular deposits called drusen. Epidemiological studies have suggested an inverse correlation between dietary intake of marine n-3 polyunsaturated fatty acids (PUFAs) and the risk of developing neurodegenerative diseases, including AMD. However, the disease-preventive mechanism(s) mobilized by n-3 PUFAs is not completely understood. In human retinal pigment epithelial cells we find that physiologically relevant doses of the n-3 PUFA docosahexaenoic acid (DHA) induce a transient increase in cellular reactive oxygen species (ROS) levels that activates the oxidative stress response regulator NFE2L2/NRF2 (nuclear factor, erythroid derived 2, like 2). Simultaneously, there is a transient increase in intracellular protein aggregates containing SQSTM1/p62 (sequestosome 1) and an increase in autophagy. Pretreatment with DHA rescues the cells from cell cycle arrest induced by misfolded proteins or oxidative stress. Cells with a downregulated oxidative stress response, or autophagy, respond with reduced cell growth and survival after DHA supplementation. These results suggest that DHA both induces endogenous antioxidants and mobilizes selective autophagy of misfolded proteins. Both mechanisms could be relevant to reduce the risk of developing aggregate-associate diseases such as AMD.
Naithani, Manisha; Saxena, Vartika; Mirza, Anissa Atif; Kumari, Ranjeeta; Sharma, Kapil; Bharadwaj, Jyoti
Background. Status of folic acid use in pregnant women of the hilly regions in North India was little known. This study was carried out to assess the folic acid use and estimate folate metabolites in pregnant women of this region. Materials and Methods. This cross-sectional study is comprised of 76 pregnant women, whose folic acid supplementation was assessed by a questionnaire and serum levels of homocysteine, tetrahydrofolic acid (THFA), and dihydrofolate reductase (DHFR) were estimated using Enzyme Linked Immunoassays. Results. The study data revealed awareness of folic acid use during pregnancy was present in 46.1% and 23.7% were taking folic acid supplements. The study depicted that there was no statistically significant difference between serum levels of THFA and DHFR in pregnant women with and without folic acid supplements (p = 0.790). Hyperhomocysteinemia was present in 15.78% of the participants. Conclusion. Less awareness about folic acid supplementation and low use of folic acid by pregnant women were observed in this region. Sufficient dietary ingestion may suffice for the escalated requirements in pregnancy, but since this cannot be ensured, hence folic acid supplementation should be made as an integral part of education and reproductive health programs for its better metabolic use, growth, and development of fetus.
Saxena, Vartika; Mirza, Anissa Atif; Kumari, Ranjeeta; Sharma, Kapil; Bharadwaj, Jyoti
Background. Status of folic acid use in pregnant women of the hilly regions in North India was little known. This study was carried out to assess the folic acid use and estimate folate metabolites in pregnant women of this region. Materials and Methods. This cross-sectional study is comprised of 76 pregnant women, whose folic acid supplementation was assessed by a questionnaire and serum levels of homocysteine, tetrahydrofolic acid (THFA), and dihydrofolate reductase (DHFR) were estimated using Enzyme Linked Immunoassays. Results. The study data revealed awareness of folic acid use during pregnancy was present in 46.1% and 23.7% were taking folic acid supplements. The study depicted that there was no statistically significant difference between serum levels of THFA and DHFR in pregnant women with and without folic acid supplements (p = 0.790). Hyperhomocysteinemia was present in 15.78% of the participants. Conclusion. Less awareness about folic acid supplementation and low use of folic acid by pregnant women were observed in this region. Sufficient dietary ingestion may suffice for the escalated requirements in pregnancy, but since this cannot be ensured, hence folic acid supplementation should be made as an integral part of education and reproductive health programs for its better metabolic use, growth, and development of fetus. PMID:27064332
Njoroge, Sarah W; Laposata, Michael; Boyd, Kelli L; Seegmiller, Adam C
Cystic fibrosis patients and model systems exhibit consistent abnormalities in metabolism of polyunsaturated fatty acids that appear to play a role in disease pathophysiology. Recent in vitro studies have suggested that these changes are due to overexpression of fatty acid desaturases that can be reversed by supplementation with the long-chain polyunsaturated fatty acids docosahexaenoate and eicosapentaenoate. However, these findings have not been tested in vivo. The current study aimed to test these results in an in vivo model system, the CFTR(-/-) knockout mouse. When compared with wild-type mice, the knockout mice exhibited fatty acid abnormalities similar to those seen in cystic fibrosis patients and other model systems. The abnormalities were confined to lung, ileum and pancreas, tissues that are affected by the disease. Similar to in vitro models, these fatty acid changes correlated with increased expression of Δ5- and Δ6-desaturases and elongase 5. Dietary supplementation with high-dose free docosahexaenoate or a combination of lower-dose docosahexaenoate and eicosapentaenoate in triglyceride form corrected the fatty acid abnormalities and reduced expression of the desaturase and elongase genes in the ileum and liver of knockout mice. Only the high-dose docosahexaenoate reduced histologic evidence of disease, reducing mucus accumulation in ileal sections. These results provide in vivo support for the hypothesis that fatty acid abnormalities in cystic fibrosis result from abnormal expression and activity of metabolic enzymes in affected cell types. They further demonstrate that these changes can be reversed by dietary n-3 fatty acid supplementation, highlighting the potential therapeutic benefit for cystic fibrosis patients.
Pratt, V C; Watanabe, S; Bruera, E; Mackey, J; Clandinin, M T; Baracos, V E; Field, C J
Metabolic demand and altered supply of essential nutrients is poorly characterised in patients with advanced cancer. A possible imbalance or deficiency of essential fatty acids is suggested by reported beneficial effects of fish oil supplementation. To assess fatty acid status (composition of plasma and neutrophil phospholipids) in advanced cancer patients before and after 14 days of supplementation (12+/-1 g day(-1)) with fish (eicosapentaenoic acid, and docosahexaenoic acid) or placebo (olive) oil. Blood was drawn from cancer patients experiencing weight loss of >5% body weight (n=23). Fatty acid composition of plasma phospholipids and the major phospholipid classes of isolated neutrophils were determined using gas liquid chromatography. At baseline, patients with advanced cancer exhibited low levels (<30% of normal values) of plasma phospholipids and constituent fatty acids and elevated 20 : 4 n-6 content in neutrophil phospholipids. High n-6/n-3 fatty acid ratios in neutrophil and plasma phospholipids were inversely related to body mass index. Fish oil supplementation raised eicosapentaenoic acid and docosahexaenoic acid content in plasma but not neutrophil phospholipids. 20 : 4 n-6 content was reduced in neutrophil PI following supplementation with fish oil. Change in body weight during the supplementation period related directly to increases in eicosapentaenoic acid in plasma. Advanced cancer patients have alterations in lipid metabolism potentially due to nutritional status and/or chemotherapy. Potential obstacles in fatty acid utilisation must be addressed in future trials aiming to improve outcomes using nutritional intervention with fish oils.
Moussa, Hind N; Hosseini Nasab, Susan; Haidar, Ziad A; Blackwell, Sean C; Sibai, Baha M
The association between folic acid supplementation, prior to conception and/or during pregnancy and pregnancy outcomes, has been the subject of numerous studies. The worldwide recommendation of folic acid is at least 0.4 mg daily for all women of reproductive age, and 4–5 mg in high-risk women. In addition, evidence shows that folic acid supplementation could modulate other adverse pregnancy outcomes, specifically, in pregnancies complicated by seizure disorders, preeclampsia, anemia, fetal growth restriction and autism. This review summarizes the available national and international guidelines, concerning the indications and dosage of folic acid supplementation during pregnancy. In addition, it describes the potential preventive benefits of folic acid supplementation on multiple maternal and fetal outcomes, as well as potential risks. PMID:28031963
Moussa, Hind N; Hosseini Nasab, Susan; Haidar, Ziad A; Blackwell, Sean C; Sibai, Baha M
The association between folic acid supplementation, prior to conception and/or during pregnancy and pregnancy outcomes, has been the subject of numerous studies. The worldwide recommendation of folic acid is at least 0.4 mg daily for all women of reproductive age, and 4-5 mg in high-risk women. In addition, evidence shows that folic acid supplementation could modulate other adverse pregnancy outcomes, specifically, in pregnancies complicated by seizure disorders, preeclampsia, anemia, fetal growth restriction and autism. This review summarizes the available national and international guidelines, concerning the indications and dosage of folic acid supplementation during pregnancy. In addition, it describes the potential preventive benefits of folic acid supplementation on multiple maternal and fetal outcomes, as well as potential risks.
Logan, Samantha L; Spriet, Lawrence L
Critical among the changes that occur with aging are decreases in muscle mass and metabolic rate and an increase in fat mass. These changes may predispose older adults to chronic disease and functional impairment; ultimately resulting in a decrease in the quality of life. Research has suggested that long chain omega-3 fatty acids, found predominantly in fatty fish, may assist in reducing these changes. The objective of this study was to evaluate the effect of fish oil (FO) supplementation in a cohort of healthy, community-dwelling older females on 1) metabolic rate and substrate oxidation at rest and during exercise; 2) resting blood pressure and resting and exercise heart rates; 3) body composition; 4) strength and physical function, and; 5) blood measures of insulin, glucose, c-reactive protein, and triglycerides. Twenty-four females (66 ± 1 yr) were recruited and randomly assigned to receive either 3g/d of EPA and DHA or a placebo (PL, olive oil) for 12 wk. Exercise measurements were taken before and after 12 wk of supplementation and resting metabolic measures were made before and at 6 and 12 wk of supplementation. The results demonstrated that FO supplementation significantly increased resting metabolic rate by 14%, energy expenditure during exercise by 10%, and the rate of fat oxidation during rest by 19% and during exercise by 27%. In addition, FO consumption lowered triglyceride levels by 29% and increased lean mass by 4% and functional capacity by 7%, while no changes occurred in the PL group. In conclusion, FO may be a strategy to improve age-related physical and metabolic changes in healthy older females. Trial registration: ClinicalTrials.gov NCT01734538.
Narayanankutty, Arunaksharan; Kottekkat, Anagha; Mathew, Shaji E; Illam, Soorya P; Suseela, Indu M; Raghavamenon, Achuthan C
Omega-3 fatty acids are well-known class of nutraceuticals with established health benefits. Recently, the oxidation products of these fatty acids are gaining attention, as they are likely to disturb body redox balance. Therefore, the efficacy of omega-3 fats under conditions of diminished antioxidant status, such as aging, is always a concern. Present study assessed the effects of omega-3 fats (DHA and EPA) together with or without vitamin-E in naturally aged rats. It was found that in omega-3 fats alone consumed rats the lipid profile was improved, while in omega-3 fat with vitamin-E-consumed group (OMVE), the hepato protective and antioxidant properties were pronounced, especially the redox status of brain tissue. It is possible that vitamin-E might have reduced the peroxidation of omega-3 fats, thereby allowing their synergistic effects. Hence, the use of vitamin-E along with omega-3 fat may be beneficial under aged conditions.
Izquierdo, M S; Scolamacchia, M; Betancor, M; Roo, J; Caballero, M J; Terova, G; Witten, P E
DHA deficiency has been related to skeletal malformations in fish, but high DHA levels have produced controversial results that could relate to the oxidative status of fish tissues in the different reports. In the present study, gilthead seabream (Sparus aurata) larvae were fed deficient, adequate or high DHA levels, or high DHA levels supplemented with the antioxidant α-tocopherol. Larvae fed deficient DHA levels tended to be smaller, and showed the highest incidence of urinary bladder calculi, lordosis and kyphosis and the lowest number of mineralised vertebrae for any given size class. Elevation of dietary DHA increased larval growth and significantly enhanced the expression of the insulin-like growth factor 1 (IGF-1) gene. However, a DHA level increase up to 5 % raised the degree of lipid oxidation in larval tissues and deformities in cranial endochondral bones and in axial skeletal haemal and neural arches. The increase in dietary α-tocopherol supplementation in high-DHA feeds reduced again the occurrence of skeletal deformities. Moreover, the expression of genes coding for specific antioxidants such as catalase, superoxide dismutase or glutathione peroxidase, which neutralised reactive oxygen substances formed by increased dietary DHA, was significantly decreased in larvae fed high α-tocopherol levels. These results denoted the importance of DHA for early bone formation and mineralisation. Low dietary DHA levels delay early mineralisation and increase the risk of cranial and axial skeletal deformities. Excessive DHA levels, without an adequate balance of antioxidant nutrients, increase the production of free radicals damaging cartilaginous structures before bone formation.
Asadi-Pooya, Ali A
Most experts agree that folic acid supplementation is a key preconception intervention, particularly in women with epilepsy who take anti-epileptic drugs (AEDs). Primary prevention of neural tube defect through folic acid supplementation results in reduction of risk in an otherwise healthy population. The current folic acid supplementation recommendation is that all women of childbearing potential be supplemented with at least 0.4 mg of folic acid daily prior to conception and during pregnancy. It is recommended that all women with epilepsy and of childbearing potential be supplemented with folic acid daily prior to conception and during pregnancy. However, considering the potential significant drug-drug interactions between high doses of folic acid and some AEDs in patients with epilepsy and also with the emerging evidence from animal studies that high levels of folic acid throughout gestation may have adverse effects on fetal brain development, it is not suggested to advocate high dose folic acid supplementation in women with epilepsy until more information is available about its appropriate, safe and optimal dosing.
Krzemińska, Izabela; Oleszek, Marta
This study evaluates the effect of different concentrations of glucose supplementation on growth, lipid accumulation, and the fatty acid profile in the Auxenochlorella protothecoides. Addition of glucose promoted the growth rate and decreased the chlorophyll content. Compared with photoautotrophic cells, an increase in the lipid content was observed in mixotrophic cells. The glucose addition induced changes in the fatty acid profile. Higher content of saturated fatty acids was found in the case of cells growing in the glucose-free medium. Oleic acid was the predominant component in mixotrophic cells supplemented with 5gL(-1) glucose, while linoleic acids dominated in cultures supplemented with both 1 and 3gL(-1) glucose. The use of glucose was associated with decreased levels of linolenic acid and PUFA. The changes in the fatty acid profile in mixotrophic cells are favourable for biodiesel production.
Conquer, J A; Holub, B J
The utilization of dietary docosahexaenoic acid (DHA; 22:6n-3) as a source of eicosapentaenoic acid (EPA; 20:5n-3) via retroconversion was investigated in both vegetarians and omnivores. For this purpose, an EPA-free preparation of DHA was given as a daily supplement (1.62 g DHA) over a period of 6 wk. The dietary supplement provided for a marked increase in DHA levels in both serum phospholipid (from 2.1 to 7.1 mol% in vegetarians and 2.2 to 7.6 mol% in omnivores) and platelet phospholipid (from 1.1 to 3.4 mol% in vegetarians and 1.4 to 3.9 mol% in omnivores). EPA levels rose to a significant but much lesser extent, while 20:4n-6, 22:5n-6, and 22:5n-3 all decreased. Based on the serum phospholipid data, the retroconversion of DHA to EPA in vivo was estimated to be 9.4% overall with no significant difference between omnivores and vegetarians.
Kimura, Rino; Takahashi, Nobuyuki; Lin, Shan; Goto, Tsuyoshi; Murota, Kaeko; Nakata, Rieko; Inoue, Hiroyasu; Kawada, Teruo
It is known that peroxisome proliferator-activated receptor (PPAR)α, whose activation reduces hyperlipidemia, is highly expressed in intestinal epithelial cells. Docosahexaenoic acid (DHA) could improve postprandial hyperlipidemia, however, its relationship with intestinal PPARα activation is not revealed. In this study, we investigated whether DHA can affect postprandial hyperlipidemia by activating intestinal PPARα using Caco-2 cells and C57BL/6 mice. The genes involved in fatty acid (FA) oxidation and oxygen consumption rate were increased, and the secretion of triacylglyceride (TG) and apolipoprotein B (apoB) was decreased in DHA-treated Caco-2 cells. Additionally, intestinal FA oxidation was induced, and TG and apoB secretion from intestinal epithelial cells was reduced, resulting in the attenuation of plasma TG and apoB levels after oral administration of olive oil in DHA-rich oil-fed mice compared with controls. However, no increase in genes involved in FA oxidation was observed in the liver. Furthermore, the effects of DHA on intestinal lipid secretion and postprandial hyperlipidemia were abolished in PPARα knockout mice. In conclusion, the present work suggests that DHA can inhibit the secretion of TG from intestinal epithelial cells via PPARα activation, which attenuates postprandial hyperlipidemia. PMID:24133194
Maki, Kevin C; Yurko-Mauro, Karin; Dicklin, Mary R; Schild, Arianne L; Geohas, Jeffrey G
In this double-blind, parallel trial, 93 healthy adults with hypertriglyceridemia (triacylglycerols [TAG] 150-499 mg/dL) were randomized to receive either a nutritional oil derived from marine algae (DHA-O; 2.4 g/day docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA] in a 2.7:1 ratio), fish oil (FO; 2.0 g/day DHA and EPA in a 0.7:1 ratio), or a corn oil/soy oil control as 4-1g softgel capsules/day with meals for 14 weeks; and were instructed to maintain their habitual diet. Percent changes from baseline for DHA-O, FO, and control, respectively, were TAG (-18.9, -22.9, 3.5; p<0.001 DHA-O and FO vs. control), low-density lipoprotein cholesterol (4.6, 6.8, -0.6; p<0.05 DHA-O and FO vs. control), and high-density lipoprotein cholesterol (4.3, 6.9, 0.6; p<0.05 FO vs. control). This study demonstrated that ingestion of microalgal DHA-O providing 2.4 g/day DHA+EPA lowered TAG levels to a degree that was not different from that of a standard fish oil product, and that was significantly more than for a corn oil/soy oil control.
Ostojic, Sergej M; Stojanovic, Marko; Drid, Patrik; Hoffman, Jay R; Sekulic, Damir; Zenic, Natasa
A variety of dietary interventions has been used in the management of chronic fatigue syndrome (CFS), yet no therapeutic modality has demonstrated conclusive positive results in terms of effectiveness. The main aim of this study was to evaluate the effects of orally administered guanidinoacetic acid (GAA) on multidimensional fatigue inventory (MFI), musculoskeletal soreness, health-related quality of life, exercise performance, screening laboratory studies, and the occurrence of adverse events in women with CFS. Twenty-one women (age 39.3 ± 8.8 years, weight 62.8 ± 8.5 kg, height 169.5 ± 5.8 cm) who fulfilled the 1994 Centers for Disease Control and Prevention criteria for CFS were randomized in a double-blind, cross-over design, from 1 September 2014 through 31 May 2015, to receive either GAA (2.4 grams per day) or placebo (cellulose) by oral administration for three months, with a two-month wash-out period. No effects of intervention were found for the primary efficacy outcome (MFI score for general fatigue), and musculoskeletal pain at rest and during activity. After three months of intervention, participants receiving GAA significantly increased muscular creatine levels compared with the placebo group (36.3% vs. 2.4%; p < 0.01). Furthermore, changes from baseline in muscular strength and aerobic power were significantly greater in the GAA group compared with placebo (p < 0.05). Results from this study indicated that supplemental GAA can positively affect creatine metabolism and work capacity in women with CFS, yet GAA had no effect on main clinical outcomes, such as general fatigue and musculoskeletal soreness.
TIAN, MING; LI, ZHI; WANG, GAO; PAN, WEIZHONG; LI, KEZHONG
The aim of the present study was to investigate the effects of docosahexaenoic acid (DHA) on the learning and memory ability of young rats exposed to propofol, and its underlying mechanisms. Sprague Dawley rats (n=60) were randomly divided into six groups: Control group (group A); solvent control group (group B); propofol group (group C); low-dose DHA + propofol group (group D); medium dose DHA + propofol group (group E); and high-dose DHA + propofol group (group F). The Morris water maze (MWM) test was performed to evaluate the rats' learning and memory ability, and tissue samples from the hippocampi of the rats were obtained for biochemical analysis. The results of the MWM test revealed that DHA supplementation administered to young rats led to an evident decrease in the latency to find the maze platform, and a significant increase in the number of platform crossings in groups E and F compared with group C (P<0.05). High-performance liquid chromatography indicated that glutamate concentration levels were significantly lower and γ-aminobutyric acid concentration levels were significantly higher in the hippocampi of group E and F rats treated with DHA compared with group C rats (P<0.05). Furthermore, DHA treatment alleviated the decrease in brain-derived neurotrophic factor levels (P<0.05), and superoxide dismutase (P<0.05) and glutathione peroxidase (P<0.05) activities induced by the administration of propofol. Additionally, DHA treatment decreased malondialdehyde levels in the hippocampi of rats (P<0.05). The aforementioned findings demonstrate that DHA was able to effectively improve learning and memory dysfunction induced by repeated propofol-induced anesthesia in young rats. This data suggests that DHA may be a potential candidate for further preclinical studies aimed at treating postoperative cognitive dysfunction. PMID:27073471
McNamara, Robert K
Over the past three decades a body of translational evidence has implicated dietary deficiency in long-chain omega-3 (LCn-3) fatty acids, including eicosapenaenoic acid (EPA) and docosahexaenoic acid (DHA), in the pathophysiology and etiology of major depressive disorder (MDD). Cross-national and cross-sectional data suggest that greater habitual intake of preformed EPA+DHA is associated with reduced risk for developing depressive symptoms and syndromal MDD. Erythrocyte EPA and DHA composition is highly correlated with habitual fish or fish oil intake, and case-control studies have consistently observed lower erythrocyte EPA and/or DHA levels in patients with MDD. Low erythrocyte EPA+DHA composition may also be associated with increased risk for suicide and cardiovascular disease, two primary causes of excess premature mortality in MDD. While controversial, dietary EPA+DHA supplementation may have antidepressant properties and may augment the therapeutic efficacy of antidepressant medications. Neuroimaging and rodent neurodevelopmental studies further suggest that low LCn-3 fatty acid intake or biostatus can recapitulate central pathophysiological features associated with MDD. Prospective findings suggest that low LCn-3 fatty acid biostatus increases risk for depressive symptoms in part by augmenting pro-inflammatory responsivity. When taken collectively, these translational findings provide a strong empirical foundation in support of dietary LCn-3 fatty acid deficiency as a modifiable risk factor for MDD. This review provides an overview of this translational evidence and then discusses future directions including strategies to translate this evidence into routine clinical screening and treatment algorithms.
Ma, Ai G; Schouten, Evert G; Zhang, Feng Z; Kok, Frans J; Yang, Fang; Jiang, Dian C; Sun, Yong Y; Han, Xiu X
In rural China, many pregnant women in their third trimester suffer from anemia (48%) and iron deficiency (ID; 42%), often with coexisting deficiencies of retinol and riboflavin. We investigated the effect of retinol and riboflavin supplementation in addition to iron plus folic acid on anemia and subjective well-being in pregnant women. The study was a 2-mo, double-blind, randomized trial. Subjects (n = 366) with anemia [hemoglobin (Hb) = 105 g/L] were randomly assigned to 4 groups, all receiving 60 mg/d iron and 400 mug/d folic acid. The iron+folic acid (IF) group (n = 93) served as reference, the iron+folic acid+retinol group (IFA) (n = 91) was treated with 2000 mug retinol, the iron+folic acid+riboflavin group (IFB) (n = 91) with 1.0 mg riboflavin, and the iron+folic acid+retinol+riboflavin group (IFAB) (n = 91) with retinol and riboflavin. After the 2-mo intervention, the Hb concentration increased in all 4 groups (P < 0.001). The increase in the IFAB group was 5.4 +/- 1.1 g/L greater than in the IF group (P < 0.001). The reduced prevalence of anemia (Hb < 110g/L) and ID anemia were significantly greater in the groups supplemented with retinol and /or riboflavin than in the IF group. Moreover, gastrointestinal symptoms were less prevalent in the IFA group than in the IF group (P < 0.05) and improved well-being was more prevalent in the groups receiving additional retinol and/or riboflavin than in the IF group (P < 0.05). Thus, a combination of iron, folic acid, retinol, and riboflavin was more effective than iron plus folic acid alone. Multimicronutrient supplementation may be worthwhile for pregnant women in rural China.
Background: Evidence from observational studies suggests that inadequate folate status enhances colorectal carcinogenesis, but results from some randomized trials do not support this hypothesis. Objective: To assess the effect of folic acid supplementation on recurrent colorectal adenoma, we conduc...
Ladesich, James B.; Pottala, James V.; Romaker, Ann; Harris, William S.
Background: Patients with obstructive sleep apnea (OSA) are at increased risk of cardiovascular disease (CVD). The omega-3 fatty acid docosahexaenoic acid (DHA) is a major component of neural tissues, and supplementation with fish oils improves autonomic tone and reduces risk for CVD. A link between low DHA status and less mature sleep patterns was observed in newborns. Methods: We investigated the relations between red blood cell (RBC) levels of DHA and OSA severity in 350 sequential patients undergoing sleep studies. Severity categories were defined as none/mild, moderate, and severe, based on apnea hypopnea index (AHI) scores of 0 to 14, 15 to 34, and > 34, respectively. Results: After controlling for age, sex, race, smoking, BMI, alcohol intake, fish intake, and omega-3 supplementation, RBC DHA was inversely related with OSA severity. For each 1-SD increase in DHA levels, a patient was about 50% less likely to be classified with severe OSA. The odds ratios (95% CI) were 0.47 (0.28 to 0.80) and 0.55 (0.31 to 0.99) for being in the severe group versus the none/mild or moderate groups, respectively. Conclusion: These findings suggest that disordered membrane fatty acid patterns may play a causal role in OSA and that the assessment of RBC DHA levels might help in the diagnosis of OSA. The effects of DHA supplementation on OSA should be explored. Citation: Ladesich JB; Pottala JV; Romaker A; Harris WS. Membrane level of omega-3 docosahexaenoic acid is associated with severity of obstructive sleep apnea. J Clin Sleep Med 2011;7(4):391-396. PMID:21897776
Cederholm, Tommy; Salem, Norman; Palmblad, Jan
The brain is a lipid-rich organ where docosahexaenoic acid (DHA) is enriched and where eicosapentaenoic acid (EPA) may have anti-inflammatory effects. The potential role for n-3 (ω-3) fatty acids such as DHA and EPA in the prevention of cognitive decline, including Alzheimer's disease (AD) has attracted major interest for the past 20 y. This review presents our understanding of recent observational, interventional, and experimental studies, with the aim of providing some answers to the following question: Can n-3 FA intake modulate cognitive function during aging? In longitudinal observation studies we mainly observe inverse relations between fish intake or serum concentrations of DHA and cognitive impairment. Intervention studies of EPA and DHA supplementation in healthy old individuals have been negative so far (i.e., after up to 2 years of treatment, no differences in cognitive decline between treated and nontreated participants have been observed). In studies that provided EPA and DHA to adults with mild cognitive impairment or age-related cognitive impairment the data seem to be positive. However, when patients with established AD were supplemented with EPA and DHA it appears no benefit was gained. For studies on healthy individuals, a major concern is that the treatment periods may have been too short. There might also be subgroup effects because of the carriage of apolipoprotein Eε4 alleles or risk factor burden. Experimental studies appear to be consistently positive (i.e., n-3 FA supplementation in rodents over a substantial portion of their lives reduces amyloid-β deposition and hippocampal neuron loss and improves cognitive functioning). We are getting closer to providing evidence-based recommendations on fish and fish oil intake to facilitate memory function during old age. In the meantime it is advised to follow the general CDC dietary recommendations of 2-3 fish meals per week or the equivalent intake of long chain n-3 fatty acids, particularly DHA.
Nobili, Valerio; Bedogni, Giorgio; Donati, Benedetta; Alisi, Anna; Valenti, Luca
The aim of this secondary analysis of a randomized controlled trial was to test whether the I148M variant of Patatin-like phospholipase domain-containing protein-3 (PNPLA3) is associated with the response to docosahexaenoic acid (DHA) in children with non-alcoholic fatty liver disease (NAFLD). Sixty children with NAFLD were randomized in equal numbers to DHA 250 mg/day, DHA 500 mg/day or placebo. Coherently with the primary analysis, the probability of more severe steatosis after 24 months of DHA supplementation was 50% lower [95% confidence interval (CI) -59% to -42%)] in the combined DHA 250 and 500 mg/day groups versus placebo. The present secondary analysis revealed an independent effect of PNPLA3 status on the response to DHA. In fact, the probability of more severe steatosis was higher (37%, 95% CI 26-48%) for the PNPLA3 M/M versus I/M genotype and lower (-12%, 95% CI -21% to -3%) for the I/I versus I/M genotype (Somers' D for repeated measures). We conclude that the 148M allele of PNPLA3 is associated with lower response, and the 148I allele with greater response, to DHA supplementation in children with NAFLD.
Park, Na-Young; Valacchi, Giuseppe; Lim, Yunsook
Inflammatory response is considered the most important period that regulates the entire healing process. Conjugated linoleic acid (CLA), a class of linoleic acid positional and geometric isomers, is well known for its antioxidant and anti-inflammatory properties. We hypothesized that dietary CLA supplementation accelerates cutaneous wound healing by regulating antioxidant and anti-inflammatory functions. To investigate wound closure rates and inflammatory responses, we used a full-thickness excisional wound model after 2-week treatments with control, 0.5%, or 1% CLA-supplemented diet. Mice fed dietary CLA supplementation had reduced levels of oxidative stress and inflammatory markers. Moreover, the wound closure rate was improved significantly in mice fed a 1% CLA-supplemented diet during early stage of wound healing (inflammatory stage). We conclude that dietary CLA supplementation enhances the early stage of cutaneous wound healing as a result of modulating oxidative stress and inflammatory responses. PMID:20871865
Bergman, J E H; Otten, E; Verheij, J B G M; de Walle, H E K
Periconceptional folic acid (FA) reduces neural tube defect (NTD) risk, but seems to have a varying effect per NTD subtype. We aimed to study the effect of FA supplementation on NTD subtype distribution using data from EUROCAT Northern Netherlands. We included all birth types with non-syndromal NTDs born in 1997-2012. By Fisher's exact test we analyzed possible differences in NTD subtype distribution between a correct FA supplementation group and incorrect FA supplementation group. We found proportionally fewer cervical/thoracic spina bifida cases and more lumbar/sacral spina bifida cases in the correct FA supplementation group, irrespective of the presence of the main NTD risk factors. The effect on NTD subtype distribution was only seen when FA supplementation was started before conception. We conclude that FA not only prevents the occurrence of a significant proportion of NTDs, but might also decrease the severity of NTDs, as long as supplementation is started before conception.
Fabian, Carol J; Kimler, Bruce F; Hursting, Stephen D
Women with evidence of high intake ratios of the marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) relative to the omega-6 arachidonic acid have been found to have a reduced risk of breast cancer compared with those with low ratios in some but not all case-control and cohort studies. If increasing EPA and DHA relative to arachidonic acid is effective in reducing breast cancer risk, likely mechanisms include reduction in proinflammatory lipid derivatives, inhibition of nuclear factor-κB-induced cytokine production, and decreased growth factor receptor signaling as a result of alteration in membrane lipid rafts. Primary prevention trials with either risk biomarkers or cancer incidence as endpoints are underway but final results of these trials are currently unavailable. EPA and DHA supplementation is also being explored in an effort to help prevent or alleviate common problems after a breast cancer diagnosis, including cardiac and cognitive dysfunction and chemotherapy-induced peripheral neuropathy. The insulin-sensitizing and anabolic properties of EPA and DHA also suggest supplementation studies to determine whether these omega-3 fatty acids might reduce chemotherapy-associated loss of muscle mass and weight gain. We will briefly review relevant omega-3 fatty acid metabolism, and early investigations in breast cancer prevention and survivorship.
Haubner, Laura Y; Stockard, Janet E; Saste, Monisha D; Benford, Valerie J; Phelps, Christopher P; Chen, Li T; Barness, Lewis; Wiener, Doris; Carver, Jane D
is sensitive for identifying effects of diet on neurodevelopment, and that diets supplemented with high levels of DHA may exert a negative influence on central nervous system development, potentially through effects on myelin. This study suggests the need for further studies of pre- and postnatal long chain polyunsaturated fatty acid dietary supplementation.
Background. Multiple micronutrient (MMN) supplements could increase hemoglobin and improve micronutrient status of pregnant women more than iron ± folic acid supplements alone. Objective. To compare the effects of MMN vs. iron ± folic acid supplements on hemoglobin and micronutrient status of pregn...
Dreyer, Hans C.; Strycker, Lisa A.; Senesac, Hilary A.; Hocker, Austin D.; Smolkowski, Keith; Shah, Steven N.; Jewett, Brian A.
Background. By the year 2030, 3.48 million older U.S. adults are projected to undergo total knee arthroplasty (TKA). Following this surgery, considerable muscle atrophy occurs, resulting in decreased strength and impaired functional mobility. Essential amino acids (EAAs) have been shown to attenuate muscle loss during periods of reduced activity and may be beneficial for TKA patients. Methods. We used a double-blind, placebo-controlled, randomized clinical trial with 28 older adults undergoing TKA. Patients were randomized to ingest either 20 g of EAAs (n = 16) or placebo (n = 12) twice daily between meals for 1 week before and 2 weeks after TKA. At baseline, 2 weeks, and 6 weeks after TKA, an MRI was performed to determine mid-thigh muscle and adipose tissue volume. Muscle strength and functional mobility were also measured at these times. Results. TKA patients receiving placebo exhibited greater quadriceps muscle atrophy, with a –14.3 ± 3.6% change from baseline to 2 weeks after surgery compared with –3.4 ± 3.1% for the EAA group (F = 5.16, P = 0.036) and a –18.4 ± 2.3% change from baseline to 6 weeks after surgery for placebo versus –6.2 ± 2.2% for the EAA group (F = 14.14, P = 0.001). EAAs also attenuated atrophy in the nonoperated quadriceps and in the hamstring and adductor muscles of both extremities. The EAA group performed better at 2 and 6 weeks after surgery on functional mobility tests (all P < 0.05). Change in quadriceps muscle atrophy was significantly associated with change in functional mobility (F = 5.78, P = 0.021). Conclusion. EAA treatment attenuated muscle atrophy and accelerated the return of functional mobility in older adults following TKA. Trial registration. Clinicaltrials.gov NCT00760383. Funding. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Office of the Director (OD), and the National Institutes of Health Office of Dietary Supplements (ODS), NIH grant K01HD057332, and the Medical
Zhang, De-Yong; Xu, Xiao-Lu; Shen, Xiu-Ying; Mei, Yu; Xu, Hui-Ying
The viscera of 10 kinds of marine fishes were collected for fish oil extraction and detection of DHA and EPA, two most important polyunsaturated fatty acids. The fish oil extraction ratio for the evaluated fishes varied from 0.95% to 10.18% (wt%). Pseudosciaena crocea presented the highest fish oil yield, followed by Mustelus manazo, Hippoglossus and Sciaenopsocellatus. A gas chromatography method was then established for analysis of EPA/DHA. The EPA concentration (in methyl ester form) in the fish oil varied from 1.39 to 10.65(mg/g). Epinephelus awoara presented the highest EPA concentration (p<0.05), followed by Epinephelussp, Sciaenopsocellatus and Hippoglossus. The DHA concentration (in methyl ester form) in the fish oil varied from 0.58 to 37.02 (mg/g). Epinephelus awoara presented the highest DHA concentration (p<0.05), followed by Sciaenopsocellatus, Pseudosciaena crocea and Hippoglossus. No strict positive correlation between the EPA/DHA concentration and the sea depth where the fish live was observed. The fishes living in middle depth presented highest EPA/DHA concentration.
Dietary saturated fat and docosahexaenoic acid differentially effect cardiac mitochondrial phospholipid fatty acyl composition and Ca(2+) uptake, without altering permeability transition or left ventricular function.
O'Connell, Kelly A; Dabkowski, Erinne R; de Fatima Galvao, Tatiana; Xu, Wenhong; Daneault, Caroline; de Rosiers, Christine; Stanley, William C
High saturated fat diets improve cardiac function and survival in rodent models of heart failure, which may be mediated by changes in mitochondrial function. Dietary supplementation with the n3-polyunsaturated fatty acid docosahexaenoic acid (DHA, 22:6n3) is also beneficial in heart failure and can affect mitochondrial function. Saturated fatty acids and DHA likely have opposing effects on mitochondrial phospholipid fatty acyl side chain composition and mitochondrial membrane function, though a direct comparison has not been previously reported. We fed healthy adult rats a standard low-fat diet (11% of energy intake from fat), a low-fat diet supplemented with DHA (2.3% of energy intake) or a high-fat diet comprised of long chain saturated fatty acids (45% fat) for 6 weeks. There were no differences among the three diets in cardiac mass or function, mitochondrial respiration, or Ca(2+)-induced mitochondrial permeability transition. On the other hand, there were dramatic differences in mitochondrial phospholipid fatty acyl side chains. Dietary supplementation with DHA increased DHA from 7% to ∼25% of total phospholipid fatty acids in mitochondrial membranes, and caused a proportional depletion of arachidonic acid (20:4n6). The saturated fat diet increased saturated fat and DHA in mitochondria and decreased linoleate (18:2n6), which corresponded to a decrease in Ca(2+) uptake by isolated mitochondria compared to the other diet groups. In conclusion, despite dramatic changes in mitochondrial phospholipid fatty acyl side chain composition by both the DHA and high saturated fat diets, there were no effects on mitochondrial respiration, permeability transition, or cardiac function.
Clark, Christine M; Monahan, Kevin D; Drew, Rachel C
Aging is associated with alterations of autonomic nerve activity, and dietary intake of omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found in fish oil (FO), can modulate autonomic nerve activity. However, the effect of omega-3 polyunsaturated fatty acid consumption on age-related cardiovascular responses at the onset of isometric handgrip exercise, a time of rapid autonomic adjustments, is unknown. Accordingly, 14 young (25 ± 1 years; mean ± SE) and 15 older (64 ± 2 years) healthy subjects ingested 4 g FO daily for 12 weeks. On pre- and postintervention visits, participants performed 15-sec bouts of isometric handgrip at 10%, 30%, 50%, and 70% maximal voluntary contraction (MVC) while beat-to-beat systolic, diastolic, and mean arterial blood pressure (SBP, DBP, MAP; Finometer) and heart rate (HR; electrocardiogram) were recorded. All baseline cardiovascular variables were similar between groups and visits, except DBP was higher in older subjects (P < 0.05). FO increased erythrocyte EPA and DHA content in both groups (P < 0.05). FO attenuated MAP and DBP increases in response to handgrip in both age groups (change from baseline during 70% MVC handgrip pre- and post-FO: young MAPΔ 14 ± 2 mmHg versus 10 ± 2 mmHg, older MAPΔ 14 ± 3 mmHg versus 11 ± 2 mmHg; young DBPΔ 12 ± 1 mmHg versus 7 ± 2 mmHg, older DBPΔ 12 ± 1 mmHg versus 7 ± 1 mmHg; P < 0.05). FO augmented the PP (SBP-DBP) increase with 70% MVC handgrip in both groups (P < 0.05), but did not alter SBP or HR increases with handgrip. These findings suggest that FO supplementation attenuates MAP and DBP increases at the onset of isometric handgrip exercise in healthy young and older humans.
Zeron, Yoel; Sklan, David; Arav, Amir
Fat supplementation in the diet influences reproductive performance of lactating ruminants. Changes in the fat supply alter fatty acid composition and this can affect physical properties of cell membranes. This study examined the effect of rumen bypass polyunsaturated fatty acid (PUFA) supplementation on oocyte quality, chilling sensitivity, and lipid phase transition in oocytes of the sheep. Ewes were fed a diet supplemented with calcium soaps of fish oil for 13 weeks. More follicles and oocytes were found in the ovaries of ewes supplemented with PUFA than in control ewes. The number of high-quality oocytes was higher in ewes fed PUFA than in control ewes (74.3 and 57.0%, P < 0.05, respectively). Evaluation of phospholipid fatty acid composition indicated that PUFA were present in small proportions in oocytes, and eicosapentaenoic acid and docosahexaenoic acid were absent. Supplementation with PUFA increased the proportion of long chain unsaturated fatty acid in the plasma and cumulus cells phospholipids by 7.4 and 12.7%, respectively (P < 0.05). Integrity of oocyte membranes following chilling (16 degrees C, 15 min) was improved by PUFA supplementation increasing from 62.5 to 90.0% (P < 0.05). Due to changes in the oocyte's fatty acid profile, physical properties of the membrane were changed and the midpoint temperature of lipid transition reduced by 11 degrees C. These results suggest that supplementation of rumen bypass PUFA to ruminant diets can change fatty acid composition of follicle components and influence parameters such as number and quality of oocytes and their chilling resistance.
Higa, R; Kurtz, M; Mazzucco, M B; Musikant, D; White, V; Jawerbaum, A
Maternal diabetes increases the risk of embryo malformations. Folic acid and safflower oil supplementations have been shown to reduce embryo malformations in experimental models of diabetes. In this study we here tested whether folic acid and safflower oil supplementations interact to prevent embryo malformations in diabetic rats, and analyzed whether they act through the regulation of matrix metalloproteinases (MMPs), their endogenous inhibitors (TIMPs), and nitric oxide (NO) and reactive oxygen species production. Diabetes was induced by streptozotocin administration prior to mating. From Day 0.5 of pregnancy, rats did or did not receive folic acid (15 mg/kg) and/or a 6% safflower oil-supplemented diet. Embryos and decidua were explanted on Day 10.5 of gestation for further analysis of embryo resorptions and malformations, MMP-2 and MMP-9 activities, TIMP-1 and TIMP-2 levels, NO production and lipid peroxidation. Maternal diabetes induced resorptions and malformations that were prevented by folic acid and safflower oil supplementation. MMP-2 and MMP-9 activities were increased in embryos and decidua from diabetic rats and decreased with safflower oil and folic acid supplementations. In diabetic animals, the embryonic and decidual TIMPs were increased mainly with safflower oil supplementation in decidua and with folic acid in embryos. NO overproduction was decreased in decidua from diabetic rats treated with folic acid alone and in combination with safflower oil. These treatments also prevented increases in embryonic and decidual lipid peroxidation. In conclusion, folic acid and safflower oil supplementations interact and protect the embryos from diabetes-induced damage through several pathways related to a decrease in pro-inflammatory mediators.
Saito, Hiroaki; Ishikawa, Satoru
The lipids and fatty acids of the neon flying squid (Ommastrephes bartramii) were an-alyzed to clarify its lipid physiology and health benefit as marine food. Triacylglycerols were the only major component in the digestive gland (liver). In all other organs (mantle, arm, integument, and ovary), sterols and phospholipids were the major components with noticeable levels of ceramide aminoethyl phosphonate and sphingomyelin. The significant levels of sphingolipids suggest the O. bartramii lipids is a useful source for cosmetics. Although the lipid content between the liver and all other tissues markedly differed from each other, the same nine dominant fatty acids in the triacylglycerols were found in all organs; 14:0, 16:0, 18:0, 18:1n-9, 20:1n-9, 20:1n-11, 22:1n-11, 20:5n-3 (icosapentaenoic acid, EPA), and 22:6n-3 (docosahexaenoic acid, DHA). Unusually high 20:1n-11 levels in the O. bartramii triacylglycerols were probably characteristic for western Pacific animal depot lipids, compared with non-detectable levels of 20:1n-11 reported in other marine animals. O. bartramii concurrently has high levels of DHA in their triacylglycerols. The major fatty acids in the phospholipids were 16:0, 18:0, 20:1n-9, EPA, and DHA without 20:1n-11. Markedly high levels of both EPA and DHA were observed in phosphatidylethanolamine, while only DHA was found as the major one in phosphatidylcholine. In particular, high levels of DHA were found both in its depot triacylglycerols and tissue phospholipids in all organs of O. bartramii, similar to that in highly migratory fishes. The high DHA levels in all its organs suggest that O. bartramii lipids is a healthy marine source for DHA supplements.
Rao, Shobha; Joshi, Sadhana; Kale, Anvita; Hegde, Mahabaleshwar; Mahadik, Sahebarao
Studies on fetal programming of adult diseases have highlighted the importance of maternal nutrition during pregnancy. Folic acid and long-chain essential polyunsaturated fatty acids (LC-PUFAs) have independent effects on fetal growth. However, folic acid effects may also involve alteration of LC-PUFA metabolism. Because marginal deficiency of LC-PUFAs during critical periods of brain growth and development is associated with risks for adult diseases, it is highly relevant to investigate how maternal supplementation of such nutrients can alter brain fatty acid levels. We examined the impact of folic acid supplementation, conventionally used in maternal intervention, on brain essential fatty acid levels and plasma corticosterone concentrations in adult offspring at 11 months of age. Pregnant female rats from 4 groups (6 in each) were fed with casein diets either with 18 g protein/100 g diet (control diet) or treatment diets that were marginal in protein (MP), such as 12 g protein/100 g diet supplemented with 8 mg folic acid (FAS/MP), 12 g protein/100 g diet without folic acid (FAD/MP), or 12 g protein/100 g diet (MP) with 2 mg folic acid. Pups were weaned to a standard laboratory diet with 18 g protein/100 g diet. All male adult offspring in the FAS/MP group showed lower docosahexaenoic acid (P<.05) as compared with control adult offspring (6.04+/-2.28 vs 10.33+/-0.86 g/100 g fatty acids) and higher n-6/n-3 ratio (P<.05). Docosahexaenoic acid levels in FAS/MP adult offspring were also lower (P<.05) when compared with the MP group. Plasma corticosterone concentrations were higher (P<.05) in male adult offspring from the FAS/MP group compared with control as well as the MP adult offspring. Results suggest that maternal folic acid supplementation at MP intake decreased brain docosahexaenoic acid levels probably involving corticosterone increase.
Das, Undurti N
Low blood folate and raised homocysteine concentrations are associated with poor cognitive function. Folic acid supplementation improves cognitive function. Folic acid enhances the plasma concentrations of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). EPA, DHA, and arachidonic acid (AA) are of benefit in dementia and Alzheimer's disease by up-regulating gene expression concerned with neurogenesis, neurotransmission and connectivity, improving endothelial nitric oxide (eNO) generation, enhancing brain acetylcholine levels, and suppressing the production of pro-inflammatory cytokines. EPA, DHA, and AA also form precursors to anti-inflammatory compounds such as lipoxins, resolvins, and neuroprotectin D1 (NPD1) that protect neurons from the cytotoxic action of various noxious stimuli. Furthermore, various neurotrophins and statins enhance the formation of NPD1 and thus, protect neurons from oxidative stress and prevent neuronal apoptosis Folic acid improves eNO generation, enhances plasma levels of EPA/DHA and thus, could augment the formation of NPD1. These results suggest that a combination of EPA, DHA, AA and folic acid could be of significant benefit in dementia, depression, and Alzheimer's disease and improve cognitive function.
White, N R; Burns, P D; Cheatham, R D; Romero, R M; Nozykowski, J P; Bruemmer, J E; Engle, T E
The objective of this experiment was to determine if dietary inclusion of fish meal would increase plasma and luteal tissue concentrations of eicosapentaenoic and docosahexaenoic acids. Seventeen nonlactating Angus cows (2 to 8 yr of age) were housed in individual pens and fed a corn silage-based diet for approximately 60 d. Diets were supplemented with fish meal at 5% DMI (a rich source of eicosapentaenoic acid and docosahexaenoic acid; n = 9 cows) or corn gluten meal at 6% DMI (n = 8 cows). Body weights and jugular blood samples were collected immediately before the initiation of supplementation and every 7 d thereafter for 56 d to monitor plasma n-3 fatty acid composition and BW. Estrous cycles were synchronized using 2 injections of PGF(2α) administered at 14-d intervals. The ovary bearing the corpus luteum was surgically removed at midcycle (between d 10 and 12) after estrus synchronization, which corresponded to approximately d 60 of supplementation. The ovary was transported to the laboratory, and approximately 1.5 g of luteal tissue was stored at -80°C until analyzed for n-3 fatty acid content. Initial and ending BW did not differ (P > 0.10) between cows supplemented with fish meal and those with corn gluten meal. Plasma eicosapentaenoic acid was greater (P < 0.05) beginning at d 7 of supplementation and docosahexaenoic was greater (P < 0.05) beginning at d 14 of supplementation for cows receiving fish meal. Luteal tissue collected from fish meal-supplemented cows had greater (P < 0.05) luteal n-3 fatty acids and reduced (P < 0.05) arachidonic acid and n-6 to n-3 ratio as compared with tissue obtained from cows supplemented with corn gluten meal. Our data show that fish meal supplementation increases luteal n-3 fatty acid content and reduces available arachidonic acid content, the precursor for PGF(2α). The increase in luteal n-3 fatty acids may reduce PGF(2α) intraluteal synthesis after breeding resulting in increased fertility in cattle.
Capó, Xavier; Martorell, Miquel; Sureda, Antoni; Batle, Juan Miguel; Tur, Josep Antoni; Pons, Antoni
Acute exercise induces changes in peripheral mononuclear cells' (PBMCs) capabilities to produce cytokines. The aim was to investigate the effect of docosahexaenoic acid (DHA) diet supplementation on cytokine production, by lipopolysaccharide (LPS)-stimulated PBMCs after exercise, and the in vitro influence of temperature. Fifteen male soccer players were randomly assigned to a placebo or an experimental group. The experimental group consumed an almond-based beverage enriched with DHA (1.16 g DHA/day) for 8 weeks, whereas the placebo group consumed a similar non-enriched beverage. Blood samples were taken before and after the nutritional intervention in basal conditions and 2 h after acute exercise. Nutritional intervention significantly increased the DHA content in erythrocytes only in experimental group (from 34 ± 3.6 to 43 ± 3.6 nmols DHA/10(9) erythrocytes). Exercise significantly increased Toll-like receptor 4 (TLR4) in PBMCs but only in the placebo group (203 %). Exercise also significantly increased IL6, IL8, VEGF, INFγ, TNFα, IL1α, IL1β, MCP1, and EGG production rates by LPS-stimulated PBMCs, and this response was attenuated by DHA supplementation. Temperature but not DHA also affected the pattern of cytokine production increasing IL6, IL8, IL1β, and MCP1 synthesis. The higher change was evidenced in IL1β increasing the production rate at 39.5 °C from 3.19 ± 0.77 to 22.4 ± 6.1 pg/h 10(6) PBMC in placebo and from 2.36 ± 0.11 to 10.6 ± 0.38 pg/h 10(6) PBMC in the supplemented group. The profile of affected cytokines differs between temperature and exercise, suggesting a different PBMC activation pathway. DHA diet supplementation only attenuated cytokine production after exercise and not that induced by temperature.
Gladyshev, Michail I; Sushchik, Nadezhda N; Makhutova, Olesia N
Most omnivorous animals, including humans, have to some degree relied on physiologically important polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from food. Only some taxa of microalgae, rather than higher plants can synthesize de novo high amounts of EPA and DHA. Once synthesized by microalgae, PUFA are transferred through trophic chain to organisms of higher levels. Thus, aquatic ecosystems play the unique role in the Biosphere as the principal source of EPA and DHA for most omnivorous animals, including inhabitants of terrestrial ecosystems. PUFA are transferred from aquatic to terrestrial ecosystems through riparian predators, drift of carrion and seaweeds, emergence of amphibiotic insects, and water birds. The essential PUFA are transferred through trophic chains with about twice higher efficiency than bulk carbon. Thereby, PUFA are accumulated, rather than diluted in biomass of organisms of higher trophic levels, e.g., in fish. Mankind is faced with a severe deficiency of EPA and DHA in diet. Although additional sources of PUFA supply for humans, such as aquaculture, biotechnology of microorganisms and transgenic terrestrial oil-seed producing plants are developed, natural fish production of aquatic ecosystems will remain one of the main sources of EPA and DHA for humans. Aquatic ecosystems have to be protected from anthropogenic impacts, such as eutrophication, pollution and warming, which reduce PUFA production.
Hammond, Bruce G; Mayhew, Dale A; Kier, Larry D; Mast, Richard W; Sander, Wayne J
The purpose of this series of studies was to assess the genotoxic potential of docosahexaenoic acid-rich microalgae from Schizochytrium sp. (DRM). DRM contains oil rich in highly unsaturated fatty acids (PUFAs). Docosahexaenoic acid (DHA n-3) is the most abundant PUFA component of the oil ( approximately 29% w/w of total fatty acid content). DHA-rich extracted oil from Schizochytrium sp. is intended for use as a nutritional ingredient in foods. All in vitro assays were conducted with and without mammalian metabolic activation. DRM was not mutagenic in the Ames reverse mutation assay using five different Salmonella histidine auxotroph tester strains. Mouse lymphoma suspension assay methodology was found to be inappropriate for this test material because precipitating test material could not be removed by washing after the intended exposure period and the precipitate interfered with cell counting. The AS52/XPRT assay methodology was not subject to these problems and DRM was tested and found not to be mutagenic in the CHO AS52/XPRT gene mutation assay. DRM was not clastogenic to human peripheral blood lymphocytes in culture. Additionally, DRM did not induce micronucleus formation in mouse bone marrow in vivo further supporting its lack of any chromosomal effects. Overall, the results of this series of mutagenicity assays support the conclusion that DRM does not have any genotoxic potential.
Luebeck, E Georg; Moolgavkar, Suresh H; Liu, Amy Y; Boynton, Alanna; Ulrich, Cornelia M
Folate is essential for nucleotide synthesis, DNA replication, and methyl group supply. Low-folate status has been associated with increased risks of several cancer types, suggesting a chemopreventive role of folate. However, recent findings on giving folic acid to patients with a history of colorectal polyps raise concerns about the efficacy and safety of folate supplementation and the long-term health effects of folate fortification. Results suggest that undetected precursor lesions may progress under folic acid supplementation, consistent with the role of folate role in nucleotide synthesis and cell proliferation. To better understand the possible trade-offs between the protective effects due to decreased mutation rates and possibly concomitant detrimental effects due to increased cell proliferation of folic acid, we used a biologically based mathematical model of colorectal carcinogenesis. We predict changes in cancer risk based on timing of treatment start and the potential effect of folic acid on cell proliferation and mutation rates. Changes in colorectal cancer risk in response to folic acid supplementation are likely a complex function of treatment start, duration, and effect on cell proliferation and mutations rates. Predicted colorectal cancer incidence rates under supplementation are mostly higher than rates without folic acid supplementation unless supplementation is initiated early in life (before age 20 years). To the extent to which this model predicts reality, it indicates that the effect on cancer risk when starting folic acid supplementation late in life is small, yet mostly detrimental. Experimental studies are needed to provide direct evidence for this dual role of folate in colorectal cancer and to validate and improve the model predictions.
De Velasco, P C; Sandre, P C; Tavares Do Carmo, M G; Faria-Melibeu, A C; Campello-Costa, P; Ferraz, A C; Andrade Da Costa, B L S; Serfaty, C A
Retinocollicular connections form precise topographical maps that are normally completed through the selective elimination of misplaced axons and the stabilization of topographically ordered axon terminals during early development. Omega-3 fatty acids, acquired exclusively through the diet, and its main metabolite, docosahexaenoic acid (DHA), are involved in brain development and synaptic maturation. We have previously shown that the nutritional restriction of omega-3/DHA results in abnormal retinocollicular topographical fine-tuning. Therefore, we studied the role of omega-3 fatty acids nutritional supplementation and the developmental time windows during which this postnatal supplementation would restore normal topographical maps in the visual system. Female rats and their litters were chronically fed with either control (soy oil) or restricted omega-3 (coconut oil) diets. Fish oil supplementation was introduced between either postnatal day (PND) 7-13, PND7-28 or PND21-42. At PND13, PND28 or PND42, animals received an anterograde eye injection of a neuronal tracer to visualize retinocollicular axons. Confirming previous observations we found that an omega-3/DHA deficiency resulted in an abnormally high innervation density of retinal axons at the visual layers of the superior colliculus (SC). Although a short-term fish oil supplementation between PND7-13 could not restore normal retinocollicular topography, an extended treatment between PND7-28 completely recovered normal innervation densities of retinotectal axons. However, a late onset supplementation protocol, between PND28-42, was no longer effective in the restoration of the abnormal topographical pattern induced by an early omega-3 nutritional malnutrition. The results suggest a critical period for omega3/DHA dietary intake for the proper development of visual topographical maps.
Zhao, Mei; Chen, Yuan-Hua; Chen, Xue; Dong, Xu-Ting; Zhou, Jun; Wang, Hua; Wu, Shu-Xian; Zhang, Cheng; Xu, De-Xiang
Folic acid is a water-soluble B-complex vitamin. Increasing evidence demonstrates that physiological supply of folic acid during pregnancy prevents folic acid deficiency-related neural tube defects (NTDs). Previous studies showed that maternal lipopolysaccharide (LPS) exposure caused NTDs in rodents. The aim of this study was to investigate the effects of high-dose folic acid supplementation during pregnancy on LPS-induced NTDs. Pregnant mice were intraperitoneally injected with LPS (20 μg/kg/d) from gestational day (GD) 8 to GD12. As expected, a five-day LPS injection resulted in 19.96% of fetuses with NTDs. Interestingly, supplementation with folic acid (3mg/kg/d) during pregnancy significantly alleviated LPS-induced NTDs. Additionally, folic acid significantly attenuated LPS-induced fetal growth restriction and skeletal malformations. Additional experiment showed that folic acid attenuated LPS-induced glutathione (GSH) depletion in maternal liver and placentas. Moreover, folic acid significantly attenuated LPS-induced expression of placental MyD88. Additionally, folic acid inhibited LPS-induced c-Jun NH2-terminal kinase (JNK) phosphorylation and nuclear factor kappa B (NF-κB) activation in placentas. Correspondingly, folic acid significantly attenuated LPS-induced tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in placentas, maternal serum and amniotic fluid. In conclusion, supplementation with high-dose folic acid during pregnancy protects against LPS-induced NTDs through its anti-inflammatory and anti-oxidative effects.
Hamilton, Mary L.; Warwick, Joanna; Terry, Anya; Allen, Michael J.; Napier, Johnathan A.; Sayanova, Olga
The marine diatom Phaeodactylum tricornutum can accumulate up to 30% of the omega-3 long chain polyunsaturated fatty acid (LC-PUFA) eicosapentaenoic acid (EPA) and, as such, is considered a good source for the industrial production of EPA. However, P. tricornutum does not naturally accumulate significant levels of the more valuable omega-3 LC-PUFA docosahexaenoic acid (DHA). Previously, we have engineered P. tricornutum to accumulate elevated levels of DHA and docosapentaenoic acid (DPA) by overexpressing heterologous genes encoding enzyme activities of the LC-PUFA biosynthetic pathway. Here, the transgenic strain Pt_Elo5 has been investigated for the scalable production of EPA and DHA. Studies have been performed at the laboratory scale on the cultures growing in up to 1 L flasks a 3.5 L bubble column, a 550 L closed photobioreactor and a 1250 L raceway pond with artificial illumination. Detailed studies were carried out on the effect of different media, carbon sources and illumination on omega-3 LC-PUFAs production by transgenic strain Pt_Elo5 and wild type P. tricornutum grown in 3.5 L bubble columns. The highest content of DHA (7.5% of total fatty acids, TFA) in transgenic strain was achieved in cultures grown in seawater salts, Instant Ocean (IO), supplemented with F/2 nutrients (F2N) under continuous light. After identifying the optimal conditions for omega-3 LC-PUFA accumulation in the small-scale experiments we compared EPA and DHA levels of the transgenic strain grown in a larger fence-style tubular photobioreactor and a raceway pond. We observed a significant production of DHA over EPA, generating an EPA/DPA/DHA profile of 8.7%/4.5%/12.3% of TFA in cells grown in a photobioreactor, equivalent to 6.4 μg/mg dry weight DHA in a mid-exponentially growing algal culture. Omega-3 LC-PUFAs production in a raceway pond at ambient temperature but supplemented with artificial illumination (110 μmol photons m-2s-1) on a 16:8h light:dark cycle, in natural seawater
Hamilton, Mary L; Warwick, Joanna; Terry, Anya; Allen, Michael J; Napier, Johnathan A; Sayanova, Olga
The marine diatom Phaeodactylum tricornutum can accumulate up to 30% of the omega-3 long chain polyunsaturated fatty acid (LC-PUFA) eicosapentaenoic acid (EPA) and, as such, is considered a good source for the industrial production of EPA. However, P. tricornutum does not naturally accumulate significant levels of the more valuable omega-3 LC-PUFA docosahexaenoic acid (DHA). Previously, we have engineered P. tricornutum to accumulate elevated levels of DHA and docosapentaenoic acid (DPA) by overexpressing heterologous genes encoding enzyme activities of the LC-PUFA biosynthetic pathway. Here, the transgenic strain Pt_Elo5 has been investigated for the scalable production of EPA and DHA. Studies have been performed at the laboratory scale on the cultures growing in up to 1 L flasks a 3.5 L bubble column, a 550 L closed photobioreactor and a 1250 L raceway pond with artificial illumination. Detailed studies were carried out on the effect of different media, carbon sources and illumination on omega-3 LC-PUFAs production by transgenic strain Pt_Elo5 and wild type P. tricornutum grown in 3.5 L bubble columns. The highest content of DHA (7.5% of total fatty acids, TFA) in transgenic strain was achieved in cultures grown in seawater salts, Instant Ocean (IO), supplemented with F/2 nutrients (F2N) under continuous light. After identifying the optimal conditions for omega-3 LC-PUFA accumulation in the small-scale experiments we compared EPA and DHA levels of the transgenic strain grown in a larger fence-style tubular photobioreactor and a raceway pond. We observed a significant production of DHA over EPA, generating an EPA/DPA/DHA profile of 8.7%/4.5%/12.3% of TFA in cells grown in a photobioreactor, equivalent to 6.4 μg/mg dry weight DHA in a mid-exponentially growing algal culture. Omega-3 LC-PUFAs production in a raceway pond at ambient temperature but supplemented with artificial illumination (110 μmol photons m-2s-1) on a 16:8h light:dark cycle, in natural seawater
Morin, Caroline; Cantin, André M; Rousseau, Éric; Sirois, Marco; Sirois, Chantal; Rizcallah, Edmond; Fortin, Samuel
Cystic fibrosis (CF) is a hereditary, chronic disease of the exocrine glands, characterized by the production of viscid mucus that obstructs the pancreatic ducts and bronchi, leading to infection and fibrosis. ω3 fatty acid supplementations are known to improve the essential fatty acid deficiency as well as reduce inflammation in CF. The objective of this study was to determine the effects of docosahexaenoic acid monoacylglyceride (MAG-DHA) on mucin overproduction and resolution of airway inflammation in two in vitro models related to CF. Isolated human bronchi reverse permeabilized with CF transmembrane conductance regulator (CFTR) silencing (si) RNA and stable Calu3 cells expressing a short hairpin (sh) RNA directed against CFTR (shCFTR) were used. Lipid analyses revealed that MAG-DHA increased DHA/arachidonic acid (AA) ratio in shCFTR Calu-3 cells. MAG-DHA treatments, moreover, resulted in a decreased activation of Pseudomonas aeruginosa LPS-induced NF-κB in CF and non-CF Calu-3 cells. Data also revealed a reduction in MUC5AC, IL-6, and IL-8 expression levels in MAG-DHA-treated shCFTR cells stimulated, or not, with LPS. Antiinflammatory properties of MAG-DHA were also investigated in a reverse-permeabilized human bronchi model with CFTR siRNA. After MAG-DHA treatments, messenger RNA transcript levels for MUC5AC, IL-6, and IL-8 were markedly reduced in LPS-treated CFTR siRNA bronchi. MAG-DHA displays antiinflammatory properties and reduces mucin overexpression in Calu-3 cells and human bronchi untreated or treated with P. aeruginosa LPS, a finding consistent with the effects of resolvinD1, a known antiinflammatory mediator.
Pasiakos, Stefan M; McClung, James P
Skeletal muscle protein synthesis (MPS) is regulated by a number of dietary factors, to include essential amino acids (EAAs). Leucine, a branched-chain amino acid, has been identified as a stimulator of MPS in many cell culture and animal studies. However, whether supplemental leucine exerts a unique stimulatory effect, as compared to other EAAs, on muscle anabolism in humans has not been clearly demonstrated. A recent study found no improvement in resting MPS in adults who consumed a 10 g EAA supplement providing added leucine (3.5 g leucine) when compared to a control 10 g EAA supplement (1.8 g leucine). These findings suggest that added leucine is unnecessary for the stimulation of MPS when sufficient EAAs are provided; however, the study of supplemental leucine during conditions such as endurance exercise, caloric deprivation, and ageing may be warranted.
Walz, O P; Pallauf, J
In a metabolic trial 4 groups of 8 piglets of 5 kg weight each were kept individually for 45 days (final weight 23 kg) and fed a practical diet. At the beginning of the experiment the body amino acid contents of an additional group of 8 piglets were determined by carcass analysis, and at the end of the experiment the body amino acid contents of the 4 test group piglets (A = control fed ad libitum, B and C = supplement of 1.5% fumaric acid fed ad libitum or restrictively, D = supplement of 1.5% citric acid fed ad libitum) were also analysed. The amino acid retention during the experimental period was determined by difference. The supplements of fumaric or citric acid did not influence the amount of the amino acid retention. The quotient of amino acid retention to amino acid consumed or the "productive amino acid value" was calculated and the maintenance requirements of essential amino acids for piglets were used to estimate the productive amino acid value for both retention and maintenance. The mean amino acid retention amounted to about 56 g/d, i.e. 3.49 g/kg W0.75.d of essential amino acids. The essential amino acid requirements for maintenance was 2.0 g, i.e. 0.29 g/kg W0.75.d, showing a variation of 4% (Leu) to 20% (Met+Cys) when related to the amount of the corresponding amino acid retention. With regard to the amino acid pattern for retention of the nutritionally most important amino acids, the following ratios were found: Lys, 100 (6.27 g/16 g N): Met+Cys, 48 (3.03 g): Thr, 56 (3.49 g): Trp, 13 (0.80 g). The productive amino acid values ranged from 40% (Trp), 55% (Thr), 66% (Met) to 80% (Lys). Under the conditions investigated, neither the supplements of organic acids nor the feed restriction influenced the amino acid utilization.
Bozzatello, Paola; Brignolo, Elena; De Grandi, Elisa; Bellino, Silvio
A new application for omega-3 fatty acids has recently emerged, concerning the treatment of several mental disorders. This indication is supported by data of neurobiological research, as highly unsaturated fatty acids (HUFAs) are highly concentrated in neural phospholipids and are important components of the neuronal cell membrane. They modulate the mechanisms of brain cell signaling, including the dopaminergic and serotonergic pathways. The aim of this review is to provide a complete and updated account of the empirical evidence of the efficacy and safety that are currently available for omega-3 fatty acids in the treatment of psychiatric disorders. The main evidence for the effectiveness of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been obtained in mood disorders, in particular in the treatment of depressive symptoms in unipolar and bipolar depression. There is some evidence to support the use of omega-3 fatty acids in the treatment of conditions characterized by a high level of impulsivity and aggression and borderline personality disorders. In patients with attention deficit hyperactivity disorder, small-to-modest effects of omega-3 HUFAs have been found. The most promising results have been reported by studies using high doses of EPA or the association of omega-3 and omega-6 fatty acids. In schizophrenia, current data are not conclusive and do not allow us either to refuse or support the indication of omega-3 fatty acids. For the remaining psychiatric disturbances, including autism spectrum disorders, anxiety disorders, obsessive-compulsive disorder, eating disorders and substance use disorder, the data are too scarce to draw any conclusion. Concerning tolerability, several studies concluded that omega-3 can be considered safe and well tolerated at doses up to 5 g/day. PMID:27472373
Bozzatello, Paola; Brignolo, Elena; De Grandi, Elisa; Bellino, Silvio
A new application for omega-3 fatty acids has recently emerged, concerning the treatment of several mental disorders. This indication is supported by data of neurobiological research, as highly unsaturated fatty acids (HUFAs) are highly concentrated in neural phospholipids and are important components of the neuronal cell membrane. They modulate the mechanisms of brain cell signaling, including the dopaminergic and serotonergic pathways. The aim of this review is to provide a complete and updated account of the empirical evidence of the efficacy and safety that are currently available for omega-3 fatty acids in the treatment of psychiatric disorders. The main evidence for the effectiveness of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been obtained in mood disorders, in particular in the treatment of depressive symptoms in unipolar and bipolar depression. There is some evidence to support the use of omega-3 fatty acids in the treatment of conditions characterized by a high level of impulsivity and aggression and borderline personality disorders. In patients with attention deficit hyperactivity disorder, small-to-modest effects of omega-3 HUFAs have been found. The most promising results have been reported by studies using high doses of EPA or the association of omega-3 and omega-6 fatty acids. In schizophrenia, current data are not conclusive and do not allow us either to refuse or support the indication of omega-3 fatty acids. For the remaining psychiatric disturbances, including autism spectrum disorders, anxiety disorders, obsessive-compulsive disorder, eating disorders and substance use disorder, the data are too scarce to draw any conclusion. Concerning tolerability, several studies concluded that omega-3 can be considered safe and well tolerated at doses up to 5 g/day.
Çelik, Fatma Çakmak; Aygün, Canan; Gülten, Sedat; Bedir, Abdulkerim; Çetinoğlu, Erhan; Küçüködük, Şükrü; Bek, Yüksel
Aim The adequacy of 50 mcg folic acid supplementation given to low-birth-weight babies was investigated. The folate levels of the mothers and infants, and breastmilk, and the optimum dose for folic acid supplementation were also investigated. Material and Methods After obtaining blood from 141 low-birth-weight infants on the 1st day of life for serum and red cell folate levels, the infants were randomly allocated into three groups according to the folic acid supplement dose. Forty-six infants were given 25 μg/d folic acid, 39 were given 50 μg/d folic acid, and 44 were given 75 μg/d folic acid. Folic acid could not be given to 12 infants. Follow-up blood samples were obtained at the end of folic acid supplementation. Maternal samples for red cell and serum folate levels and breast milk folate levels were obtained within the first 48 hours and the samples for measuring breastmilk folate level were obtained on the 3rd day postnatally. The feeding modes of the infants, maternal folic acid intake, and details of neonate intensive care unit course were recorded. Results The mean birth weight and gestational age of the infants were found as 1788.2±478.4 g and 33.5±2.9 weeks, respectively. The mean serum and red cell folate levels on admission were found as 21.2±12.2 ng/mL and 922.7±460.7 ng/mL, respectively. The mean maternal serum and red cell folate levels and the mean breast milk folate levels were found as 12.3±7.5 ng/mL, 845.5±301.4 ng/mL, and 30.6±33.0 ng/m, respectively. The breast milk folate levels of mothers who were supplemented with folic acid during pregnancy were significantly higher compared with mothers who were not supplemented with folic acid (p<0.001). Infants who were supplemented with folic acid had higher follow-up serum folate levels compared with the basal level in all groups, but there was no statistically significant difference between the groups. Conclusion This study showed that the folic acid doses of 25, 50, and 75 μcg/d affected
Lassek, William Day; Gaulin, Steven J C
Convergent evidence from neuronal biology and hominin brain hypertrophy suggests that omega-3 fatty acids are a limiting resource for neural and cognitive development in Homo sapiens, and therefore that children from populations with higher omega-3 availability should display superior cognitive performance. Using multiple regression, we tested this prediction in a sample of 28 countries, with Programme for International Student Assessment (PISA) math scores in 2009 as an index of cognitive performance, and country-specific breast milk levels of omega-3 docosahexaenoic acid (DHA) as an index of omega-3 availability. Breast milk DHA makes a highly significant contribution to math scores (β = 0.462, P = 0.006), greater in magnitude than the control variables of per capita Gross Domestic Product (PCGDP) and educational expenditures per pupil. Together, dietary fish (positively) and total fat (negatively) explain 61% of the variance in maternal milk DHA in a larger sample of 39 countries.
Uauy, Ricardo; Dangour, Alan D
The essential fatty acids (EFAs), particularly the n-3 long-chain polyunsaturated fatty acids (LCPs), are important for brain development during both the fetal and postnatal period. They are also increasingly seen to be of value in limiting the cognitive decline during aging. EFA deficiency was first shown over 75 years ago, but the more subtle effects of the n-3 fatty acids in terms of skin changes, a poor response to linoleic acid supplementation, abnormal visual function, and peripheral neuropathy were only discovered later. Both n-3 and n-6 LCPs play important roles in neuronal growth, development of synaptic processing of neural cell interaction, and expression of genes regulating cell differentiation and growth. The fetus and placenta are dependent on maternal EFA supply for their growth and development, with docosahexaenomic acid (DHA)-supplemented infants showing significantly greater mental and psychomotor development scores (breast-fed children do even better). Dietary DHA is needed for the optimum functional maturation of the retina and visual cortex, with visual acuity and mental development seemingly improved by extra DHA. Aging is also associated with decreased brain levels of DHA: fish consumption is associated with decreased risk of dementia and Alzheimer's disease, and the reported daily use of fish-oil supplements has been linked to improved cognitive function scores, but confirmation of these effects is needed.
Xiao, Ke; Ansari, Abdur Rahman; Rehman, Zia Ur; Khaliq, Haseeb; Song, Hui; Tang, Juan; Wang, Jing; Wang, Wei; Sun, Peng-Peng; Zhong, Juming; Peng, Ke-Mei
Foxn1 is essential for thymus development. The relationship between boric acid and thymus development, optimal dose of boric acid in ostrich diets, and the effects of boric acid on the expression of Foxn1 were investigated in the present study. Thirty healthy ostriches were randomly divided into six groups: Group I, II, III, IV, V, VI, and supplemented with boric acid at the concentration of 0 mg/L, 40 mg/L, 80 mg/L, 160 mg/L, 320 mg/L, 640 mg/L, respectively. The histological changes in thymus were observed by HE staining, and the expression of Foxn1 analyzed by immunohistochemistry and western blot. TUNEL method was used to label the apoptotic cells. Ostrich Foxn1 was sequenced by Race method. The results were as following: Apoptosis in ostrich thymus was closely related with boric acid concentrations. Low boric acid concentration inhibited apoptosis in thymus, but high boric acid concentration promoted apoptosis. Foxn1-positive cells were mainly distributed in thymic medulla and rarely in cortex. Foxn1 is closely related to thymus growth and development. The nucleotide sequence and the encoded protein of Foxn1 were 2736 bases and 654 amino acids in length. It is highly conserved as compared with other species. These results demonstrated that the appropriate boric acid supplementation in water would produce positive effects on the growth development of ostrich thymus by promoting Foxn1 expression, especially at 80 mg/L, and the microstructure of the thymus of ostrich fed 80 mg/L boric acid was well developed. The supplementation of high dose boron (>320 mg/L) damaged the microstructure of thymus and inhibited the immune function by inhibiting Foxn1 expression, particularly at 640 mg/L. The optimal dose of boric acid supplementation in ostrich diets is 80 mg/L boric acid. The genomic full-length of African ostrich Foxn1 was cloned for the first time in the study.
Tanghe, S; Millet, S; Missotten, J; Vlaeminck, B; De Smet, S
This study aimed to investigate the effects and possible interactions of birth weight and n-3 polyunsaturated fatty acid (PUFA) supplementation of the maternal diet on the fatty acid status of different tissues of newborn piglets. These effects are of interest as both parameters have been associated with pre-weaning mortality. Sows were fed a palm oil diet or a diet containing 1% linseed, echium or fish oil from day 73 of gestation. As fish oil becomes a scarce resource, linseed and echium oil were supplemented as sustainable alternatives, adding precursor fatty acids for DHA to the diet. At birth, the lightest and heaviest male piglet per litter were killed and samples from liver, brain and muscle were taken for fatty acid analysis. Piglets that died pre-weaning had lower birth weights than piglets surviving lactation (1.27±0.04 v. 1.55±0.02 kg; P<0.001), but no effect of diet on mortality was found. Lower DHA concentrations were observed in the brain of the lighter piglets compared with their heavier littermates (9.46±0.05 v. 9.63±0.04 g DHA/100 g fatty acids; P=0.008), suggesting that the higher incidence of pre-weaning mortality in low birth weight piglets may be related to their lower brain DHA status. Adding n-3 PUFA to the sow diet could not significantly reduce this difference in DHA status, although numerically the difference in the brain DHA concentration between the piglet weight groups was smaller when fish oil was included in the sow diet. Independent of birth weight, echium or linseed oil in the sow diet increased the DHA concentration of the piglet tissues to the same extent, but the concentrations were not as high as when fish oil was fed.
Zgheel, Faraj; Alhosin, Mahmoud; Rashid, Sherzad; Burban, Mélanie; Auger, Cyril; Schini-Kerth, Valérie B.
Aims Omega-3 fatty acid products containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have vasoprotective effects, in part, by stimulating the endothelial formation of nitric oxide (NO). This study determined the role of the EPA:DHA ratio and amount, and characterized the mechanism leading to endothelial NO synthase (eNOS) activation. Methods and Results EPA:DHA 6∶1 and 9∶1 caused significantly greater endothelium-dependent relaxations in porcine coronary artery rings than EPA:DHA 3∶1, 1∶1, 1∶3, 1∶6, 1∶9, EPA and DHA alone, and EPA:DHA 6∶1 with a reduced EPA + DHA amount, which were inhibited by an eNOS inhibitor. Relaxations to EPA:DHA 6∶1 were insensitive to cyclooxygenase inhibition, and reduced by inhibitors of either oxidative stress, Src kinase, PI3-kinase, p38 MAPK, MEK, or JNK. EPA:DHA 6∶1 induced phosphorylation of Src, Akt, p38 MAPK, ERK, JNK and eNOS; these effects were inhibited by MnTMPyP. EPA:DHA 6∶1 induced the endothelial formation of ROS in coronary artery sections as assessed by dihydroethidium, and of superoxide anions and hydrogen peroxide in cultured endothelial cells as assessed by electron spin resonance with the spin probe CMH, and the Amplex Red based assay, respectively. Conclusion Omega-3 fatty acids cause endothelium-dependent NO-mediated relaxations in coronary artery rings, which are dependent on the EPA:DHA ratio and amount, and involve an intracellular activation of the redox-sensitive PI3-kinase/Akt and MAPKs pathways to activate eNOS. PMID:25133540
Karunathilaka, Sanjeewa R; Mossoba, Magdi M; Chung, Jin Kyu; Haile, Ermias A; Srigley, Cynthia T
Using a portable field device, a Fourier transform infrared spectroscopy (FTIR) and partial least-squares regression (PLSR) method was developed for the rapid (<5 min) prediction of major and minor fatty acid (FA) concentrations in marine oil omega-3 dietary supplements. Calibration models were developed with 174 gravimetrically prepared samples. These models were tested using an independent validation set of dietary supplements. FAs analyzed included eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); the sums of saturated, branched-chain, and monounsaturated FAs; and n-6, n-4, n-3, n-1, and trans polyunsaturated FA. The spectral ranges 650-1500 or 650-1500 and 2800-3050 cm(-1) provided reliable predictions for FA components in 34 neat oil products: standard error of prediction, 0.73-1.58%; residual predictive deviation, 6.41-12.6. This simple, nondestructive quantitative method is a rapid screening tool and a time and cost-saving alternative to gas chromatography for verifying label declarations and in quality control.
McStay, Catrina L.; Prescott, Susan L.; Bower, Carol; Palmer, Debra J.
Since the early 1990s, maternal folic acid supplementation has been recommended prior to and during the first trimester of pregnancy, to reduce the risk of infant neural tube defects. In addition, many countries have also implemented the folic acid fortification of staple foods, in order to promote sufficient intakes amongst women of a childbearing age, based on concerns surrounding variable dietary and supplementation practices. As many women continue to take folic acid supplements beyond the recommended first trimester, there has been an overall increase in folate intakes, particularly in countries with mandatory fortification. This has raised questions on the consequences for the developing fetus, given that folic acid, a methyl donor, has the potential to epigenetically modify gene expression. In animal studies, folic acid has been shown to promote an allergic phenotype in the offspring, through changes in DNA methylation. Human population studies have also described associations between folate status in pregnancy and the risk of subsequent childhood allergic disease. In this review, we address the question of whether ongoing maternal folic acid supplementation after neural tube closure, could be contributing to the rise in early life allergic diseases. PMID:28208798
Garcia, Josel; Datol-Barrett, Eva; Dizon, Maynilad
After participating in a pilot project under a government-industry partnership to promote the adoption of weekly iron-folic acid supplementation among women of reproductive age in the Philippines in 1998, United Laboratories (UNILAB), the Philippines' largest private pharmaceutical company, decided in April 2002 to launch a weekly iron-folic acid supplement for pregnant and non-pregnant women under the brand name Femina. The business objective set for the Femina brand was to build the category of preventive iron-folic acid supplements in line with the Philippine Department of Health's advocacy on weekly supplementation as an alternate to daily dosing to reduce the prevalence of anemia in the country. The brand was supported with an integrated mix of traditional advertising media with complementary direct-to-consumer educational programs that aimed to create awareness of iron-deficiency anemia, its causes and effects, and the role of weekly intake of iron-folic acid in preventing the condition. Aggressive marketing support for 1 year was successful in creating awareness among the target women. Significant lessons derived from consumers identified opportunity areas that can be further addressed in developing advocacy programs on weekly iron supplementation implemented on a nationwide scale in the future.
Aliche-Djoudi, Fatiha; Podechard, Normand; Collin, Aurore; Chevanne, Martine; Provost, Emilie; Poul, Martine; Le Hégarat, Ludovic; Catheline, Daniel; Legrand, Philippe; Dimanche-Boitrel, Marie-Thérèse; Lagadic-Gossmann, Dominique; Sergent, Odile
Previously, we demonstrated that eicosapentaenoic acid enhanced ethanol-induced oxidative stress and cell death in primary rat hepatocytes via an increase in membrane fluidity and lipid raft clustering. In this context, another n-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA), was tested with a special emphasis on physical and chemical alteration of lipid rafts. Pretreatment of hepatocytes with DHA reduced significantly ethanol-induced oxidative stress and cell death. DHA protection could be related to an alteration of lipid rafts. Indeed, rafts exhibited a marked increase in membrane fluidity and packing defects leading to the exclusion of a raft protein marker, flotillin. Furthermore, DHA strongly inhibited disulfide bridge formation, even in control cells, thus suggesting a disruption of protein-protein interactions inside lipid rafts. This particular spatial organization of lipid rafts due to DHA subsequently prevented the ethanol-induced lipid raft clustering. Such a prevention was then responsible for the inhibition of phospholipase C-γ translocation into rafts, and consequently of both lysosome accumulation and elevation in cellular low-molecular-weight iron content, a prooxidant factor. In total, the present study suggests that DHA supplementation could represent a new preventive approach for patients with alcoholic liver disease based upon modulation of the membrane structures.
Chitayat, David; Matsui, Doreen; Amitai, Yona; Kennedy, Deborah; Vohra, Sunita; Rieder, Michael; Koren, Gideon
During the last decade critical new information has been published pertaining to folic acid supplementation in the prevention of neural tube defects (NTDs) and other folic acid-sensitive congenital malformations. These new data have important implications for women, their families, and health care professionals. We performed a review looking for the optimal dosage of folic acid that should be given to women of reproductive age who are planning or not avoiding conception to propose updated guidelines and thus help health care providers and patients. In addition to fortification of dietary staples with folic acid, women of reproductive age should supplement before conception with 0.4-1.0 mg of folic acid daily as part of their multivitamins. In the United States all enriched rice is also fortified with folic acid at 0.7 mg per pound of raw rice. However, this is not the case in many countries, and it has been estimated that only 1% of industrially milled rice is fortified with folic acid. In countries where rice is the main staple (eg, China), this does not allow effective folate fortification. Whereas the incidence of NTDs is around 1/1000 in the United States, it is 3- to 5-fold higher in Northern China and 3-fold higher in India. A recent population-based US study estimated that the reduction in NTD rates by folic acid is more modest than previously predicted. The potential of NTD prevention by folic acid is underutilized due to low adherence with folic acid supplementation, and calls for revising the policy of supplementation have been raised. We identified groups of women of reproductive age who may benefit from higher daily doses of folic acid, and this should be considered in current practice. These include women who have had previous pregnancies with NTDs, those who did not plan their pregnancy and hence did not supplement, and women with low intake or impaired adherence to daily folic acid supplementation. In addition, women with known genetic variations in
Sengupta, Namrata; Litoff, Elizabeth J.; Baldwin, William S.
HR96 is a CAR/PXR/VDR ortholog in invertebrates, and a promiscuous endo- and xenobiotic nuclear receptor involved in acclimation to toxicants. Daphnia HR96 is activated by chemicals such as atrazine and linoleic acid (LA) (n-6 fatty acid), and inhibited by triclosan and docosahexaenoic acid (DHA)(n-3 fatty acid). We hypothesized that inhibitors of HR96 may block the protective responses of HR96 based on previously performed luciferase assays. Therefore, we performed acute toxicity tests with two-chemical mixtures containing a HR96 inhibitor (DHA or triclosan) and a HR96 activator (LA or atrazine). Surprisingly, results demonstrate that triclosan and DHA are less toxic when co-treated with 20–80 μM atrazine. Atrazine provides concentration-dependent protection as lower concentrations have no effect and higher concentrations cause toxicity. LA, a weaker HR96 activator, did not provide protection from triclosan or DHA. Atrazine’s protective effects are presumably due to its ability to activate HR96 or other toxicologically relevant transcription factors and induce protective enzymes. Atrazine did not significantly induce glucosyltransferase, a crucial enzyme in triclosan detoxification. However, atrazine did increase antioxidant activities, crucial pathways in triclosan’s toxicity, as measured through GST activity and the TROLOX equivalence assay. The increase in antioxidant capacity is consistent with atrazine providing protection from a wide range of toxicants that induce ROS, including triclosan and unsaturated fatty acids predisposed to lipid peroxidation. PMID:25747156
Sengupta, Namrata; Litoff, Elizabeth J; Baldwin, William S
HR96 is a CAR/PXR/VDR ortholog in invertebrates, and a promiscuous endo- and xenobiotic nuclear receptor involved in acclimation to toxicants. Daphnia HR96 is activated by chemicals such as atrazine and linoleic acid (LA) (n-6 fatty acid), and inhibited by triclosan and docosahexaenoic acid (DHA) (n-3 fatty acid). We hypothesized that inhibitors of HR96 may block the protective responses of HR96 based on previously performed luciferase assays. Therefore, we performed acute toxicity tests with two-chemical mixtures containing a HR96 inhibitor (DHA or triclosan) and a HR96 activator (LA or atrazine). Surprisingly, results demonstrate that triclosan and DHA are less toxic when co-treated with 20-80 μM atrazine. Atrazine provides concentration-dependent protection as lower concentrations have no effect and higher concentrations cause toxicity. LA, a weaker HR96 activator, did not provide protection from triclosan or DHA. Atrazine's protective effects are presumably due to its ability to activate HR96 or other toxicologically relevant transcription factors and induce protective enzymes. Atrazine did not significantly induce glucosyltransferase, a crucial enzyme in triclosan detoxification. However, atrazine did increase antioxidant activities, crucial pathways in triclosan's toxicity, as measured through GST activity and the TROLOX equivalence assay. The increase in antioxidant capacity is consistent with atrazine providing protection from a wide range of toxicants that induce ROS, including triclosan and unsaturated fatty acids predisposed to lipid peroxidation.
Cipollina, Chiara; Di Vincenzo, Serena; Siena, Liboria; Di Sano, Caterina; Gjomarkaj, Mark; Pace, Elisabetta
Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function associated with increased local and systemic inflammatory markers, such as TNFα and IL-1β. Glucocorticoids are used to treat this chronic disease, however their efficacy is low and new drugs are very much required. 17-oxo-DHA is a cyclooxygenase-2-dependent, electrophilic, α,β-unsaturated keto-derivative of docosahexaenoic acid with anti-inflammatory properties. We evaluated the action of 17-oxo-DHA alone or in combination with the steroid fluticasone propionate (FP) in peripheral blood mononuclear cells (PBMCs) from COPD patients and healthy individuals exposed to lipopolysaccharide. We show that PBMCs from COPD patients released higher levels of TNFα and IL-1β compared to controls. 17-oxo-DHA displayed strong anti-inflammatory effects. The addition of 17-oxo-DHA in combination with FP showed enhanced anti-inflammatory effects through the modulation of transcriptional and post-transcriptional mechanisms. 17-oxo-DHA, but not FP, was able to suppress the release of mature IL-1β through inhibition of the NLRP3 inflammasome. Furthermore, 17-oxo-DHA inhibited inflammasome-dependent degradation of the glucocorticoid receptor (GR). Our findings suggest that 17-oxo-DHA in combination with FP or other steroids might achieve higher therapeutic efficacy than steroids alone. Combined treatment might be particularly relevant in those conditions where increased inflammasome activation may lead to GR degradation and steroid-unresponsive inflammation. PMID:27883019
Chitayat, David; Matsui, Doreen; Amitai, Yona; Kennedy, Deborah; Vohra, Sunita; Rieder, Michael
Abstract During the last decade critical new information has been published pertaining to folic acid supplementation in the prevention of neural tube defects (NTDs) and other folic acid–sensitive congenital malformations. These new data have important implications for women, their families, and health care professionals. We performed a review looking for the optimal dosage of folic acid that should be given to women of reproductive age who are planning or not avoiding conception to propose updated guidelines and thus help health care providers and patients. In addition to fortification of dietary staples with folic acid, women of reproductive age should supplement before conception with 0.4‐1.0 mg of folic acid daily as part of their multivitamins. In the United States all enriched rice is also fortified with folic acid at 0.7 mg per pound of raw rice. However, this is not the case in many countries, and it has been estimated that only 1% of industrially milled rice is fortified with folic acid. In countries where rice is the main staple (eg, China), this does not allow effective folate fortification. Whereas the incidence of NTDs is around 1/1000 in the United States, it is 3‐ to 5‐fold higher in Northern China and 3‐fold higher in India. A recent population‐based US study estimated that the reduction in NTD rates by folic acid is more modest than previously predicted. The potential of NTD prevention by folic acid is underutilized due to low adherence with folic acid supplementation, and calls for revising the policy of supplementation have been raised. We identified groups of women of reproductive age who may benefit from higher daily doses of folic acid, and this should be considered in current practice. These include women who have had previous pregnancies with NTDs, those who did not plan their pregnancy and hence did not supplement, and women with low intake or impaired adherence to daily folic acid supplementation. In addition, women with
Ismail, Adam; Rice, Harry B
The U.S. military may consider exploring the inclusion of the long-chain omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in the diets of active duty military personnel. To be successful, certain challenges must be overcome including determining appropriate dosage, ensuring cost efficiency, and optimizing stability. To increase EPA and DHA intake, the military should consider using one of three strategies, including mandates or recommendations on omega-3 supplement usage, contracts to purchase commercially available foods for distribution in the food supply chain, or direct addition of EPA and DHA into currently consumed foods. This review presents the challenges and strategies and provides potential suggestions to the military to increase the likelihood of success.
Ganesh, Vijayalakshmi; Hettiarachchy, Navam S
This paper focuses on the critical aspects of supplementation of foods with essential fatty acids (EFAs), the need, health benefits of supplementation and the constraints of the process. Current trend of supplementation of foods with EFAs has been gaining momentum and more research pioneers due to the health benefits in par with the direct intake of EFA supplements. Technologies including encapsulation, nanotechnology, molecular complexing, genetic engineering and more emerging means, hold promise to food supplementation with EFAs. Food trials with adoption of various technologies, studies of bioavailability and health benefits are still underway and crucial before EFA supplementation in foods can hit the market on a global scale.
Bo, Yacong; Zhang, Xueyuan; Wang, Youli; You, Jie; Cui, Han; Zhu, Yiwei; Pang, Wei; Liu, Wei; Jiang, Yugang; Lu, Quanjun
Objective: Intake of n-3 polyunsaturated fatty acids (n-3 PUFAs) may protect against mild cognitive impairment (MCI). However, there is still a lack of the n-3 PUFAs intervention in the elderly with MCI in China. The aim of the present study was to investigate the effect of n-3 PUFA supplementation on cognitive function in the Chinese elderly with MCI. Methods: Eighty six MCI individuals aged 60 years or older were randomly assigned to receive either n-3 PUFAs (480 mg DHA and 720 mg EPA per day, n = 44) or placebo (olive oil, n = 42) capsules. The changes of cognitive functions were assessed using Basic Cognitive Aptitude Tests (BCAT). Results: The mean age of participants was 71 years old, and 59% of the participants were men. n-3 PUFA supplementation was associated with improved total BCAT scores, perceptual speed, space imagery efficiency, and working memory (p < 0.01), but not with mental arithmetic efficiency or recognition memory (p > 0.05). Subgroup analysis by sex showed that n-3 PUFAs significantly improved perceptual speed (p = 0.001), space imagery efficiency (p = 0.013), working memory (p = 0.018), and total BCAT scores (p = 0.000) in males. However, in females, the significant beneficial effects can only be observed in perceptual speed (p = 0.027), space imagery efficiency (p = 0.006), and total BCAT scores (p = 0.015)—not working memory (p = 0.113). Conclusion: n-3 PUFAs can improve cognitive function in people with MCI. Further studies with different fish oil dosages, longer intervention periods, and larger sample sizes should be investigated before definite recommendations can be made. PMID:28075381
Kutzner, Laura; Ostermann, Annika I; Konrad, Thade; Riegel, Dieter; Hellhake, Stefan; Schuchardt, Jan Philipp; Schebb, Nils Helge
Supplementation products containing n-3 PUFA from marine sources serve a large market. Although the amount of eicosapentaenoic acid and docosahexaenoic acid in the products is provided by the manufacturer, no or little information is available on their lipid pattern. Therefore, we quantitatively analyzed the fatty acid pattern in the lipid fractions triglycerides, phospholipids, ethyl esters, and free fatty acids in supplementation products by means of solid phase extraction and gas chromatography. Twelve products from the European and U.S. markets containing fish, krill, algal, or plant oil were analyzed. Total n-3 PUFA content ranged from 68 g/100 g fat (fish oil) to 42 g/100 g fat (algal oil) to 17 g/100 g fat (krill oil). On the basis of the n-3 PUFA containing lipid class, the supplements can be separated dominantly in ethyl ester, re-esterified triglyceride, triglyceride, and phospholipid containing products. Algae-based products contained natural triglycerides, krill oils a complex mixture of phospholipids, triglycerides, and free fatty acids, and fish oil products either ethyl esters, re-esterified triglycerides, or triglycerides. Even products of the same class and source showed distinct differences in their lipid pattern. A specification of the lipid composition of n-3 PUFA products would allow distinguishing the different (qualities of) supplements.
Hoch, Anne Z.; Papanek, Paula; Szabo, Aniko; Widlansky, Michael E.; Gutterman, David D.
Objective To determine if folic acid supplementation improves vascular function (brachial artery flow-mediated dilation [FMD]) in professional dancers with known endothelial dysfunction. Design Prospective cross-sectional study. Setting Academic institution in the Midwestern United States. Subjects Twenty-two professional ballet dancers volunteered for this study. Main Outcome Measures Subjects completed a 3-day food record to determine caloric and micronutrient intake. Menstrual status was determined by interview and questionnaire. Endothelial function was determined as flow-induced vasodilation measured by high-frequency ultrasound of the brachial artery. A change in brachial diameter of <5% to hyperemic flow stimulus was defined a priori as endothelial dysfunction. Subjects with abnormal FMD took 10 mg of folic acid daily for 4 weeks, and FMD testing was then repeated. Serum whole blood was measured for folic acid levels before and after supplementation. Results Sixty-four percent of dancers (n = 14) had abnormal brachial artery FMD (<5%) (mean ± standard deviation, 2.9% ± 1.5%). After 4 weeks of folic acid supplementation (10 mg/day), FMD improved in all the subjects (7.1% ± 2.3%; P < .0001). Conclusions This study reveals that vascular endothelial function improves in dancers after supplementation with folic acid (10 mg/day) for at least 4 weeks. This finding may have clinically important implications for future cardiovascular disease risk prevention. PMID:21715240
Pham, Trong Khoa; Wright, Phillip C
Ethanol yield by Saccharomyces cerevisiae in very high glucose (VHG) media with an amino acid supplement was investigated. Amino acid supplementation led to positive cell responses, including reduced lag time and increased cell viability in VHG media. A quantitative shotgun proteomic analysis was used to understand how amino acid supplemented S. cerevisiae responds to high osmotic conditions. iTRAQ data revealed that most proteins involved in glycolysis and pentose phosphate pathways were up-regulated under high glucose shock. Reactivation of amino acid metabolism was also observed at the end of the lag phase. The relative abundance of most identified proteins, including aminoacyl-tRNA biosynthesis proteins, and heat-shock proteins, remained unchanged in the hours immediately following application of glucose shock. However, the expression of these proteins increased significantly at the end of the lag phase. Furthermore, the up-regulation of trehalose and glycogen biosynthesis proteins, first maintaining then latterly increasing glycolysis pathway activity was also observed. This was verified by enhanced ethanol yields at 10 and 12 h (0.43 and 0.45 g ethanol/g glucose) compared to 2 h (0.32 g ethanol/g glucose). These data combined with relevant metabolite measurements demonstrates that enhanced ethanol fermentation under VHG conditions can be achieved with the aid of amino acid supplementation.
Yao, Chien-An; Chen, Chin-Chu; Wang, Nai-Phog; Chien, Chiang-Ting
The use of a mixture of amino acids caused a selective apoptosis induction against a variety of tumor cell lines, reduced the adverse effects of anti-cancer drugs and increased the sensitivity of tumor cells to chemotherapeutic agents. We evaluated the effects and underlying mechanisms of soy-derived multiple amino acids’ oral supplementation on the therapeutic efficacy of low-dose cyclophosphamide (CTX) and on tumor growth, apoptosis, and autophagy in severe combined immunodeficiency (SCID) mice that were injected with sarcoma-180 (S-180) cells. 3-methyladenine or siRNA knockdown of Atg5 was used to evaluate its effect on sarcoma growth. A comparison of mice with implanted sarcoma cells, CTX, and oral saline and mice with implanted sarcoma cells, CTX, and an oral soy-derived multiple amino acid supplement indicated that the soy-derived multiple amino acid supplement significantly decreased overall sarcoma growth, increased the Bax/Bcl-2 ratio, caspase 3 expression, and apoptosis, and depressed LC3 II-mediated autophagy. Treatment with 3-methyladenine or Atg5 siRNA elicited similar responses as CTX plus soy-derived multiple amino acid in downregulating autophagy and upregulating apoptosis. A low dose of CTX combined with an oral soy-derived multiple amino acid supplement had a potent anti-tumor effect mediated through downregulation of autophagy and upregulation of apoptosis. PMID:27043621
Eneroth, Hanna; El Arifeen, Shams; Persson, Lars-Ake; Lönnerdal, Bo; Hossain, Mohammad Bakhtiar; Stephensen, Charles B; Ekström, Eva-Charlotte
Knowledge about the impact of maternal food and micronutrient supplementation on infant micronutrient status is limited. We examined the effect of maternal food and micronutrient supplementation on infant micronutrient status in the Maternal and Infant Nutrition Interventions in Matlab Trial. Pregnant women (n = 4436) were randomized to Early or Usual promotion of enrollment in a food supplementation program. In addition, they were randomly allocated to 1 of the following 3 types of daily micronutrient supplements provided from wk 14 of gestation to 3 mo postpartum: 1) folic acid and 30 mg iron (Fe30Fol); 2) folic acid and 60 mg iron; or 3) a multiple micronutrient including folic acid and 30 mg iron (MMS). At 6 mo, infant blood samples (n = 1066) were collected and analyzed for hemoglobin and plasma ferritin, zinc, retinol, vitamin B-12, and folate. The vitamin B-12 concentration differed between the micronutrient supplementation groups (P = 0.049). The prevalence of vitamin B-12 deficiency was lower in the MMS group (26.1%) than in the Fe30Fol group (36.5%) (P = 0.003). The prevalence of zinc deficiency was lower in the Usual food supplementation group (54.1%) than in the Early group (60.2%) (P = 0.046). There were no other differential effects according to food or micronutrient supplementation groups. We conclude that maternal multiple micronutrient supplementation may have a beneficial effect on vitamin B-12 status in infancy.
Ross, Brian M; Malik, Imran; Babay, Slim
A large body of evidence suggests that dietary supplementation with omega-3 fatty acids may ameliorate depressed mood. The magnitude of the effect varies between studies, however, ranging from none at all to being of clinical significance. Given that substantial comorbidity occurs between mood and anxiety disorders, suggesting that they have one or more pathophysiological mechanisms in common, we hypothesized that omega-3 fatty acids may be acting primarily to reduce anxiety rather than depression per se, a possibility which could underlie their variable effects on mood. To test this hypothesis rats were fed for 8 weeks with diets containing one of three types of omega-3 fatty acids, alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid, as well as a low omega-3 fatty acid control diet. Although brain omega-3 fatty acid concentrations were altered by dietary supplementation with eicospentaenoic acid and docosahexaenoic acid, no significant change in anxiety related behaviors were observed compared to the control group as assessed by the elevated-plus maze test. Our data therefore do not support an anxiolytic effect of omega-3 fatty acids and suggest that any effect of these lipids on mood likely occurs by a mechanism unrelated to reducing anxiety.
van Kooten, Maria J.; Veldhuizen, Maria G.; de Araujo, Ivan E.; O’Malley, Stephanie; Small, Dana M.
Compromised dopamine signaling in the striatum has been associated with the expression of impulsive behaviors in addiction, obesity and alcoholism. In rodents, Intragastric infusion of the fatty acid amide oleoylethanolamide increases striatal extracellular dopamine levels via vagal afferent signaling. Here we tested whether supplementation with PhosphoLean™, a dietary supplement that contains the precursor of the fatty acid amide oleoylethanolamide (N-oleyl-phosphatidylethanolamine), would reduce impulsive responding and alcohol use in heavy drinking young adults. Twenty-two individuals were assigned to a three-week supplementation regimen with PhosphoLean™ or placebo. Impulsivity was assessed with self-report questionnaires and behavioral tasks pre- and post-supplementation. Although self-report measures of impulsivity did not change, supplementation with PhosphoLean™, but not placebo, significantly reduced false alarm rate on a Go/No-Go task. In addition, an association was found between improved sensitivity on the Go/No-Go task and reduced alcohol intake. These findings provide preliminary evidence that promoting fatty acid derived gut-brain dopamine communication may have therapeutic potential for reducing impulsivity in heavy drinkers. PMID:26656766
Salkić, M.; Selimović, A.; Pašalić, H.; Keran, H.
A selective and accurate direct spectrophotometric method was developed for the determination of L-as cor bic acid in dietary supplements. Background correction was based on the oxidation of L-ascorbic acid by potassi um peroxydisulfate in an acidic medium. The molar absorptivity of the proposed method was 1.41 · 104 l/(mol · cm) at 265 nm. The method response was linear up to an L-ascorbic acid concentration of 12.00 μg/ml. The detection limit was 0.11 μg/ml, and the relative standard deviation was 0.9 % (n = 7) for 8.00 μg/ml L-ascorbic acid. Other compounds commonly found in the dietary supplements did not interfere with the detection of L-ascorbic acid. The proposed procedure was successfully applied to the determination of L-ascorbic acid in these supplements, and the results obtained agreed with those obtained by iodine titration.
Casanova, Ester; Baselga-Escudero, Laura; Ribas-Latre, Aleix; Cedó, Lídia; Arola-Arnal, Anna; Pinent, Montserrat; Bladé, Cinta; Arola, Lluís; Salvadó, M Josepa
Obesity has become a worldwide epidemic. The cafeteria diet (CD) induces obesity and oxidative-stress-associated insulin resistance. Polyunsaturated fatty acids and polyphenols are dietary compounds that are intensively studied as products that can reduce the health complications related to obesity. We evaluate the effects of 21 days of supplementation with grape seed proanthocyanidins extract (GSPE), docosahexaenoic-rich oil (DHA-OR) or both compounds (GSPE+DHA-OR) on skeletal muscle metabolism in diet-obese rats. The supplementation with different treatments did not reduce body weight, although all groups used more fat as fuel, particularly when both products were coadministered; muscle β-oxidation was activated, the mitochondrial functionality and oxidative capacity were higher, and fatty acid uptake gene expressions were up-regulated. In addition to these outcomes shared by all treatments, GSPE reduced insulin resistance and improved muscle status. Both treatments increased 5'-AMP-activated protein kinase (AMPK) phosphorylation, which was consistent with higher plasma adiponectin levels. Moreover, AMPK activation by DHA-OR was also correlated with an up-regulation of peroxisome proliferator-activated receptor alpha (Pparα). GSPE+DHA-OR, in addition to activating AMPK and enhancing fatty acid oxidation, increased the muscle gene expression of uncoupling protein 2 (Ucp2). In conclusion, GSPE+DHA-OR induced modifications that improved muscle status and could counterbalance the deleterious effects of obesity, and such modifications are mediated, at least in part, through the AMPK signaling pathway.
Lohner, Szimonetta; Fekete, Katalin; Decsi, Tamás
The mainstream of phenylketonuria (PKU) management is lifelong restriction of protein intake; however, this dietary restriction may be accompanied by insufficient dietary intake of long-chain polyunsaturated fatty acids (LCPUFA). The objective of this review was to assess whether significant depletion of LCPUFA can be detected in PKU patients on low-protein diet and whether LCPUFA supplementation is an effective way to increase the availability of LCPUFA in PKU patients. The method included structured search strategy on Ovid MEDLINE, Scopus, LILACS, and the Cochrane Library CENTRAL databases, with formal inclusion/exclusion criteria, data extraction procedure, and meta-analysis. We evaluated 9 case-control studies and 6 randomized controlled trials, dated from the inception of the databases to 2012. The meta-analysis of the case-control studies showed significantly lower values of both eicosapentaenoic acid and docosahexaenoic acid (DHA) in all biomarkers investigated and that of arachidonic acid in total plasma lipids in PKU patients as compared with healthy controls. There were sufficient data to demonstrate that dietary DHA supplementation of patients with PKU significantly increases the contribution of DHA to total plasma lipids. In summary, suboptimal LCPUFA status, especially that of n-3 LCPUFA, can be detected in PKU patients. Supplementing DHA to the diet of PKU patients may improve their LCPUFA status; however, further research is needed to determine the optimal supplementation dosage and to establish beneficial functional outcomes.
We previously reported better psychomotor development at 30 months of age in infants whose mothers received a docosahexaenoic acid (DHA) supplement for the first 4 months of lactation. We now assess neuropsychological and visual function of the same children at 5 years of age. Breastfeeding women w...
Minihane, Anne Marie
At a population level, cardioprotective and cognitive actions of the fish oil (FO) derived long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been extensively demonstrated. In addition to dietary intake, which is limited for many individuals, EPA and DHA status is dependent on the efficiency of their biosynthesis from α-linolenic acid. Gender and common gene variants have been identified as influencing the rate-limiting desaturase and elongase enzymes. Response to a particular intake or status is also highly heterogeneous and likely influenced by genetic variants which impact on EPA and DHA metabolism and tissue partitioning, transcription factor activity, or physiological end-point regulation. Here, available literature relating genotype to tissue LC n-3 PUFA status and response to FO intervention is considered. It is concluded that the available evidence is relatively limited, with much of the variability unexplained, though APOE and FADS genotypes are emerging as being important. Although genotype × LC n-3 PUFA interactions have been described for a number of phenotypes, few have been confirmed in independent studies. A more comprehensive understanding of the genetic, physiological and behavioural modulators of EPA and DHA status and response to intervention is needed to allow refinement of current dietary LC n-3 PUFA recommendations and stratification of advice to "vulnerable" and responsive subgroups.
Hekmati Azar Mehrabani, Zohreh; Ghorbanihaghjo, Amir; Sayyah Melli, Manizheh; Hamzeh-Mivehroud, Maryam; Fathi Maroufi, Nazila; Bargahi, Nasrin; Bannazadeh Amirkhiz, Maryam; Rashtchizadeh, Nadereh
Introduction:There are many ideas concerning the etiology and pathogenesis of preeclampsia including endothelial dysfunction, inflammation and angiogenesis. Elevated levels of total homocysteine (Hcy) and lipoprotein (a) [Lp(a)] are risk factors for endothelial dysfunction. This study aimed to evaluate the effect of high dose folic acid (FA) on serum Hcy and Lp(a) concentrations with respect to methylenetetrahydrofolate reductase (MTHFR) polymorphisms 677C→T during pregnancy. Methods: In a prospective uncontrolled intervention, 90 pregnant women received 5 mg FA supplementation before pregnancy till 36th week of pregnancy. The MTHFR polymorphisms 677C→T, serum lactate dehydrogenase activity, urine protein and creatinine concentrations were measured before starting folic acid administration. Serum levels of Hcy and Lp(a) were determined before and after completion of folic acid supplementation period. Results: Supplementation of the patients with FA for 36 week decreased the median (minimum– maximum) levels of serum Hcy from 11.40 μmol/L (4.40-28.70) to 9.70 (1.60-20.80) μmol/L (p=0.001). There was no significant change in serum Lp(a) after FA supplementation (p=0.17). The overall prevalence of genotypes in pregnant women that were under study for MTHFR C677T polymorphism was 53.3% CC, 26.7% CT and 20.0% TT. There was no correlation between decreasing level of serum Hcy in the patients receiving FA and MTHFR polymorphisms. Conclusion:Although FA supplementation decreased serum levels of Hcy in different MTHFR genotypes, serum Lp(a) was not changed by FA supplements. Our data suggests that FA supplementation effects on serum Hcy is MTHFR genotype independent in pregnant women. PMID:26929921
Finch, Emily R.; Kudva, Avinash K.; Quickel, Michael D.; Goodfield, Laura L.; Kennett, Mary J.; Whelan, Jay; Paulson, Robert F.; Prabhu, K. Sandeep
Current therapies for treatment of myeloid leukemia do not eliminate leukemia stem cells (LSC), leading to disease relapse. In this study, we supplemented mice with eicosapentaenoic acid (EPA, C20:5), a polyunsaturated omega-3 fatty acid, at pharmacological levels, to examine if the endogenous metabolite, cyclopentenone prostaglandin delta-12 PGJ3 (Δ12-PGJ3), was effective in targeting LSCs in experimental leukemia. EPA supplementation for eight weeks resulted in enhanced endogenous production of Δ12-PGJ3 that was blocked by indomethacin, a cyclooxygenase inhibitor. Using a murine model of chronic myelogenous leukemia (CML) induced by bone marrow transplantation of BCR-ABL-expressing hematopoietic stem cells, mice supplemented with EPA showed a decrease in the LSC population, reduced splenomegaly and leukocytosis, when compared to mice on an oleic acid diet. Supplementation of CML mice carrying the T315I mutation (in BCR-ABL) with EPA resulted in a similar effect. Indomethacin blocked the EPA effect and increased the severity of BCR-ABL-induced CML and decreased apoptosis. Δ12-PGJ3 rescued indomethacin-treated BCR-ABL mice and decreased LSCs. Inhibition of hematopoietic-prostaglandin D synthase (H-PGDS) by HQL-79 in EPA-supplemented CML mice also blocked the effect of EPA. In addition, EPA supplementation was effective in a murine model of acute myeloid leukemia. Supplemented mice exhibited a decrease in leukemia burden and a decrease in the LSC colony-forming unit (LSC-CFU). The decrease in LSCs was confirmed through serial transplantation assays in all disease models. The results support a chemopreventive role for EPA in myeloid leukemia, which is dependent on the ability to efficiently convert EPA to endogenous cyclooxygenase-derived prostanoids, including Δ12-PGJ3. PMID:26290393
Ganesh, Deepa; Sagayaraj, Benjamin M; Barua, Ravi Kumar; Sharma, Nidhi; Ranga, Upasana
In Arnold Chiari (kee-AHR-ee) II malformation elongated cerebellar tonsils are displaced inferiorly through the Foramen Magnum into the upper cervical spinal canal. It is a complex anomaly with skull, dura, brain, spine and cord manifestations. Meningomyelocele is seen in all cases. We present a case of type II Arnold Chiari Malformation diagnosed in utero in a pregnant lady .There was no periconceptional folic acid supplementation. As the role of the Methylene Tetra Hydro Folate Reductase gene polymorphism in neural tube defects is becoming evident, a simple opportunity as folic acid supplementation should not be missed. Folate supplementation as fortification of cereal grains will also prevent other conditions like congenital heart defects, urinary tract anomalies, orofacial defects, limb defects and pyloric stenosis.
Murphy, R A; Yeung, E; Mazurak, V C; Mourtzakis, M
Cancer cachexia is characterised by a progressive loss of muscle, resulting in functional impairment and shorter survival. Eicosapentaenoic acid, an n-3 polyunsaturated fatty acid found in fish, has been studied for its role as an anti-cachexia therapy. Initial results of eicosapentaenoic supplementation in advanced cancer were promising with improvements in lean body mass (LBM), appetite and quality of life. However, subsequent larger phase III clinical trials reported minimal benefits of supplementation. Recently, several studies have used different study designs, which may provide insight on the effectiveness of eicosapentaenoic in cancer cachexia and also on potential sources of divergent results in previous trials. This review examines the potential benefit of eicosapentaenoic supplementation on LBM and discusses limitations with current studies to identify methods which may aid in progressing the research of future clinical trials.
Effects of Perioperative Supplementation with Omega-3 Fatty Acids on Leukotriene B4 and Leukotriene B5 Production by Stimulated Neutrophils in Patients with Colorectal Cancer: A Randomized, Placebo-Controlled Intervention Trial
Sorensen, Lone S.; Thorlacius-Ussing, Ole; Rasmussen, Henrik H.; Lundbye-Christensen, Søren; Calder, Philip. C.; Lindorff-Larsen, Karen; Schmidt, Erik B.
Omega-3 fatty acids (n-3 FA) may have beneficial clinical and immune-modulating effects in surgical patients. In a randomized, double-blind, prospective, placebo-controlled trial, 148 patients referred for elective colorectal cancer surgery received an n-3 FA-enriched oral nutritional supplement (ONS) providing 2.0 g of eicosapentaenoic acid (EPA) and 1.0 g of docosahexaenoic acid (DHA) per day or a standard ONS for seven days before surgery. On the day of operation, there was a significant increase in the production of leukotriene B5 (LTB5) (p < 0.01) and 5-hydroxyeicosapentaenoic acid (5-HEPE) (p < 0.01), a significant decrease in the production of leukotriene B4 (LTB4) (p < 0.01) and a trend for a decrease in the production of 5-hydroxyeicosatetraenoic acid (5-HETE) (p < 0.1) from stimulated neutrophils in the active group compared with controls. There was no association between LTB4 values and postoperative complications. In conclusion, oral n-3 FA exerts anti-inflammatory effects in surgical patients, without reducing the risk of postoperative complications. PMID:25268838
Kałużna-Czaplińska, Joanna; Socha, Ewa; Rynkowski, Jacek
Urinary dicarboxylic acids are an important source of information about metabolism and potential problems especially connected with energy production, intestinal dysbiosis, and nutritional individuality in autistic children. A diet rich in vitamins and macroelements is a new idea of intervention in autism. The objective of the present study was to test the hypothesis that vitamin B2, vitamin B6, and magnesium supplementation is effective in reducing the level of dicarboxylic acids in the urine of autistic children. We examined the levels of succinic, adipic, and suberic acids in the urine of autistic children before and after vitamin supplementation. Thirty children with autism received magnesium (daily dose, 200 mg), vitamin B6 (pyridoxine; daily dose, 500 mg), and vitamin B2 (riboflavin; daily dose, 20 mg). The treatment was provided for a period of 3 months. Organic acids were determined using gas chromatography/mass spectrometry. Before supplementation, the levels of succinic, adipic, and suberic acids in the urine of autistic children were 41.47 ± 50.40 μmol/mmol creatinine, 15.61 ± 15.31 μmol/mmol creatinine, 8.02 ± 6.08 μmol/mmol creatinine; and after supplementation, the levels were 9.90 ± 8.26 μmol/mmol creatinine, 2.92 ± 2.41 μmol/mmol creatinine, and 2.57 ± 3.53 μmol/mmol creatinine, respectively. The results suggest that the supplementation reduces the level of dicarboxylic acid in the urine of autistic children.
Greenberg, James A; Bell, Stacey J; Guan, Yong; Yu, Yan-Hong
Folate (vitamin B(9)) is an essential nutrient that is required for DNA replication and as a substrate for a range of enzymatic reactions involved in amino acid synthesis and vitamin metabolism. Demands for folate increase during pregnancy because it is also required for growth and development of the fetus. Folate deficiency has been associated with abnormalities in both mothers (anemia, peripheral neuropathy) and fetuses (congenital abnormalities). This article reviews the metabolism of folic acid, the appropriate use of folic acid supplementation in pregnancy, and the potential benefits of folic acid, as well as the possible supplementation of l-methylfolate for the prevention of pregnancy-related complications other than neural tube defects.
Harvatine, K J; Allen, M S
Saturated and unsaturated fatty acid supplements (FS) were evaluated for effects on ruminal digestion kinetics, and ruminal and postruminal nutrient digestion. Eight early lactation ruminally and duodenally cannulated cows (77 +/- 12 days in milk, mean +/- SD) were used in a replicated 4 x 4 Latin square design experiment with 21-d periods. Treatments were control and a linear substitution of 2.5% fatty acids from supplemented saturated FS (SAT; prilled, hydrogenated free fatty acids) for partially unsaturated FS (UNS; calcium soaps of long-chain fatty acids). All rations contained identical forage and concentrate components including 37.2% forage and 13.5% cottonseed. Saturated FS linearly decreased ruminal digestibility of dry matter and organic matter and linearly decreased ruminal neutral detergent fiber (NDF) digestibility. The reduction in ruminal NDF digestibility was because of a linear decrease in digestion rate and a linear increase in passage rate of potentially digestible NDF with increasing saturated FS. Total tract digestibility of NDF was not different between treatments because of compensatory postruminal digestion. Ruminal fatty acid and C18 fatty acid digestibility tended to increase linearly with increasing unsaturated FS, and postruminal C18 fatty acid digestibility decreased with increasing saturated FS. Saturated FS linearly decreased ruminal organic matter digestibility and decreased intestinal long-chain fatty acid digestibility, although differences in fatty acid digestibility may be partially explained by fatty acid intake.
Dietary supplementation with methylseleninic acid reduces spontaneous metastasis of Lewis lung carcinoma in mice Lin Yan*, Lana C. DeMars The present study investigated the effects of dietary supplementation with methylseleninic acid (MSeA) on spontaneous metastasis of Lewis lung carcinoma (LLC) in...
Gottardo, E T; Prokoski, K; Horn, D; Viott, A D; Santos, T C; Fernandes, J I M
The aim of this study was to evaluate the regeneration of the intestinal mucosa in Eimeria and E. coli challenged broilers supplemented with glutamine, arginine, and threonine. Six hundred male broilers at one d of age from the Cobb strain were utilized. The design was completely randomized using a 2×3 factorial design (unchallenged and challenged and 3 diets). A commercial diet was used as a control and 2 other diets were formulated with glutamine (1.5 and 3% Aminogut®), arginine (1 and 2% L-Arginine), and threonine (1 and 2% L-threonine). The animals that consumed diets supplemented with amino acids presented better (P<0.05) feed conversion in the period from one to 42 d of age. The ability of cell proliferation and the villus:crypt ratio in response to enteric challenge were greater (P<0.05) for broilers that received diets supplemented with amino acids. High levels of amino acids in the experimental feeds reflected in greater protein levels in poultry house litter, and they did not interfere with ammonia production. The supplementation of diets with trophic amino acids can positively contribute to the regeneration and proliferation of the intestinal mucosa in broilers and to the maintenance of zootechnical performance when submitted to enteric challenges.
The need for supplemental folate can be traced to the initial phase of the discovery of this vitamin as a micronutrient for the prevention of pregnancy related anemia. In the post discovery era, folic acid was used primarily to prevent deficiency as manifested by low blood folate levels and megalob...
Park, Yoon Mee; Lee, Hwa Jeong; Jeong, Jae-Ho; Kook, Joong-Ki; Choy, Hyon E; Hahn, Tae-Wook; Bang, Iel Soo
Nitric oxide (NO) inactivates iron-sulfur enzymes in bacterial amino acid biosynthetic pathways, causing amino acid auxotrophy. We demonstrate that exogenous supplementation with branched-chain amino acids (BCAA) can restore the NO resistance of hmp mutant Salmonella Typhimurium lacking principal NO-metabolizing enzyme flavohemoglobin, and of mutants further lacking iron-sulfur enzymes dihydroxy-acid dehydratase (IlvD) and isopropylmalate isomerase (LeuCD) that are essential for BCAA biosynthesis, in an oxygen-dependent manner. BCAA supplementation did not affect the NO consumption rate of S. Typhimurium, suggesting the BCAA-promoted NO resistance independent of NO metabolism. BCAA supplementation also induced intracellular survival of ilvD and leuCD mutants at wild-type levels inside RAW 264.7 macrophages that produce constant amounts of NO regardless of varied supplemental BCAA concentrations. Our results suggest that the NO-induced BCAA auxotrophy of Salmonella, due to inactivation of iron-sulfur enzymes for BCAA biosynthesis, could be rescued by bacterial taking up exogenous BCAA available in oxic environments.
Bächler, Christoph; Schneider, Philipp; Bähler, Priska; Lustig, Ariel; Erni, Bernhard
Dihydroxyacetone (Dha) kinases are a sequence-conserved family of enzymes, which utilize either ATP (in animals, plants, bacteria) or the bacterial phosphoenolpyruvate carbohydrate phosphotransferase system (PTS) as a source of high-energy phosphate. The PTS-dependent kinase of Escherichia coli consists of three subunits: DhaK contains the Dha binding site, DhaL contains ADP as cofactor for the double displacement of phosphate from DhaM to Dha, and DhaM provides a phospho-histidine relay between the PTS and DhaL::ADP. DhaR is a transcription activator belonging to the AAA+ family of enhancer binding proteins. It stimulates transcription of the dhaKLM operon from a sigma70 promoter and autorepresses dhaR transcription. Genetic and biochemical studies indicate that the enzyme subunits DhaL and DhaK act antagonistically as coactivator and corepressor of the transcription activator by mutually exclusive binding to the sensing domain of DhaR. In the presence of Dha, DhaL is dephosphorylated and DhaL::ADP displaces DhaK and stimulates DhaR activity. In the absence of Dha, DhaL::ADP is converted by the PTS to DhaL::ATP, which does not bind to DhaR.
Jin, Fuxia; Nieman, David C; Sha, Wei; Xie, Guoxiang; Qiu, Yunping; Jia, Wei
Ten postmenopausal women (age 55.6 ± 0.8 years, BMI 24.6 ± 1.1 kg/m²) ingested 25 g/day milled chia seed during a 7-week period, with six plasma samples collected for measurement of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). Subjects operated as their own controls with overnight fasted blood samples taken at baseline (average of two samples), and then after 1, 2, 3, 5, and 7 weeks supplementation. Plasma ALA increased significantly after one week supplementation and was 138 % above baseline levels by the end of the study (overall time effect, P < 0.001). EPA increased 30 % above baseline (overall time effect, P = 0.019) and was correlated across time with ALA (r = 0.84, P = 0.02). No significant change in plasma DPA levels was measured (overall time effect, P = 0.067). Plasma DHA decreased slightly by the end of the study (overall time effect, P = 0.030) and was not correlated with change in ALA. In conclusion, ingestion of 25 g/day milled chia seeds for seven weeks by postmenopausal women resulted in significant increases in plasma ALA and EPA but not DPA and DHA.
Sanders, Thomas A B
Plants provide α-linolenic acid [ALA; 18:3n-3 (18:3ω-3)], which can be converted via eicosapentaenoic acid (EPA; 20:5n-3) to docosahexaenoic acid (DHA; 22:6n-3), which is required for normal visual and cognitive function. Dietary ALA is provided mainly by vegetable oils, especially soybean and rapeseed oils, but is destroyed by partial hydrogenation; it is also present in high amounts in walnuts and flaxseed. Dietary EPA and DHA are provided mainly by fish and so are absent from vegan diets and only present in trace amounts in vegetarian diets. Vegetarians and vegans have lower proportions of DHA in blood and tissue lipids compared with omnivores. High intakes of EPA and DHA (typically in the range of 3-5 g/d) but not ALA have favorable effects on several cardiovascular disease (CVD) risk factors and have been postulated to delay arterial aging and cardiovascular mortality, but these intakes are beyond the range of normal dietary intake. Arterial stiffness, which is a measure of arterial aging, appears to be lower in vegans than in omnivores; and risk of CVD in vegetarians and vegans is approximately one-third that in omnivores. Prospective cohort studies showed higher intakes of EPA+DHA, and less consistently ALA, to be associated with a lower risk of CVD, especially fatal coronary heart disease, but meta-analyses of randomized controlled trials of supplementation of EPA+DHA or ALA in secondary prevention of CVD showed no clear benefit. Current evidence is insufficient to warrant advising vegans and vegetarians to supplement their diets with EPA or DHA for CVD prevention.
Marean, Amber; Graf, Amanda; Zhang, Ying; Niswander, Lee
Neural tube defects (NTDs), a common birth defect in humans, result from the failure of the embryonic neural tube (NT) to close properly. NT closure is a complex, poorly understood morphogenetic process influenced by genes and environment. The most effective environmental influence in decreasing the risk for NTDs is folic acid (FA) fortification and supplementation, and these findings led to the recommendation of periconceptual FA intake and mandatory fortification of the US grain supply in 1998. To explore the relationship between genetics and responsiveness to FA supplementation, we used five mouse NTDs models-Zic2, Shroom3, Frem2, Grhl2 (Grainyhead-like 2) and L3P (Line3P)-and a long-term generational FA supplementation scheme. Contrary to expectations, we find that three genetic mutants respond adversely to FA supplementation with increased incidence of NTDs in homozygous mutants, occurrence of NTDs in heterozygous embryos and embryonic lethality prior to NT closure. Because of these unexpected responses, we examined NTD risk after short-term FA supplementation. Our results indicate that, for the same genetic allele, NTD risk can depend on the length of FA exposure. Our data indicate that, depending on the gene mutation, FA supplementation may adversely influence embryonic development and NT closure.
Yoshida, Shinya; Yasutomo, Koji; Watanabe, Toshiyuki
Atopic dermatitis (AD) is caused by both dysregulated immune responses and an impaired skin barrier. Although leukotriene B4 (LTB4) is involved in tissue inflammation that occurs in several disorders, including AD, therapeutic strategies based on LTB4 inhibition have not been explored. Here we demonstrate that progression of an AD-like skin disease in NC/Nga mice is inhibited when docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) is administered together with FK506. Treatment with DHA/EPA and FK506 decreases the clinical score of dermatitis in NC/Nga mice and lowers local LTB4 concentrations. The treatment also suppressed the infiltration of T cells, B cells, eosinophils and neutrophils, and promoted reduced serum IgE levels. Secretion of IL-13 and IL-17A in CD4(+) T cells was lower in DHA/EPA- and FK506-treated mice than in mice treated with FK506 alone. The inhibition of disease progression induced by DHA/EPA was reversed by local injection of LTB4, suggesting that the therapeutic effect of DHA/EPA is LTB4-dependent. Our results demonstrate that treatment of AD with DHA/EPA is effective for allergic skin inflammation and acts by suppressing LTB4 production. J. Med. Invest. 63: 187-191, August, 2016.
McManus, Seán; Tejera, Noemi; Awwad, Khader; Rigby, Neil; Fleming, Ingrid; Cassidy, Aedin; Minihane, Anne Marie
Our objective was to investigate the impact of EPA versus DHA on arterial stiffness and reactivity and underlying mechanisms (with a focus on plasma oxylipins) in the postprandial state. In a three-arm crossover acute test meal trial, men (n = 26, 35–55 years) at increased CVD risk received a high-fat (42.4 g) test meal providing 4.16 g of EPA or DHA or control oil in random order. At 0 h and 4 h, blood samples were collected to quantify plasma fatty acids, long chain n-3 PUFA-derived oxylipins, nitrite and hydrogen sulfide, and serum lipids and glucose. Vascular function was assessed using blood pressure, reactive hyperemia index, pulse wave velocity, and augmentation index (AIx). The DHA-rich oil significantly reduced AIx by 13% (P = 0.047) with the decrease following EPA-rich oil intervention not reaching statistical significance. Both interventions increased EPA- and DHA-derived oxylipins in the acute postprandial state, with an (1.3-fold) increase in 19,20-dihydroxydocosapentaenoic acid evident after DHA intervention (P < 0.001). In conclusion, a single dose of DHA significantly improved postprandial arterial stiffness as assessed by AIx, which if sustained would be associated with a significant decrease in CVD risk. The observed increases in oxylipins provide a mechanistic insight into the AIx effect. PMID:27170732
McManus, Seán; Tejera, Noemi; Awwad, Khader; Vauzour, David; Rigby, Neil; Fleming, Ingrid; Cassidy, Aedin; Minihane, Anne Marie
Our objective was to investigate the impact of EPA versus DHA on arterial stiffness and reactivity and underlying mechanisms (with a focus on plasma oxylipins) in the postprandial state. In a three-arm crossover acute test meal trial, men (n = 26, 35-55 years) at increased CVD risk received a high-fat (42.4 g) test meal providing 4.16 g of EPA or DHA or control oil in random order. At 0 h and 4 h, blood samples were collected to quantify plasma fatty acids, long chain n-3 PUFA-derived oxylipins, nitrite and hydrogen sulfide, and serum lipids and glucose. Vascular function was assessed using blood pressure, reactive hyperemia index, pulse wave velocity, and augmentation index (AIx). The DHA-rich oil significantly reduced AIx by 13% (P = 0.047) with the decrease following EPA-rich oil intervention not reaching statistical significance. Both interventions increased EPA- and DHA-derived oxylipins in the acute postprandial state, with an (1.3-fold) increase in 19,20-dihydroxydocosapentaenoic acid evident after DHA intervention (P < 0.001). In conclusion, a single dose of DHA significantly improved postprandial arterial stiffness as assessed by AIx, which if sustained would be associated with a significant decrease in CVD risk. The observed increases in oxylipins provide a mechanistic insight into the AIx effect.
To determine the potential for improving the conversion and deposition of the important omega-3 fatty acids docosahexaenoic acid (DHA; 22:6n-3) and eicosapentaenoic acid (EPA; 20:5n-3) in fish, forty-three families of rainbow trout were fed a diet low in these components and then evaluated for their...
Background Strenuous physical activity can alter the status of folic acid, a vitamin directly associated with homocysteine (Hcy); alterations in this nutrient are a risk factor for cardiovascular disease. Handball players are a population at risk for nutrient deficiency because of poor dietary habits. Objective The aims of this study were to evaluate nutritional status for macronutrients and folic acid in members of a high-performance handball team, and determine the effect of a nutritional intervention with folic acid supplementation and education. Design A total of 14 high-performance handball players were monitored by recording training time, training intensity (according to three levels of residual heart rate (RHR): <60%, 60%–80% and >80%), and subjective perceived exertion (RPE) during a 4-month training period. Nutritional, laboratory and physical activity variables were recorded at baseline (Week 0), after 2 months of dietary supplementation with 200 μg folic acid (50% of the recommended daily allowance) (Week 8) and after 2 months without supplementation (Week 16). We compared training load and analyzed changes in plasma concentrations of Hcy before and after the intervention. Results Bivariate analysis showed a significant negative correlation (P < 0.01) between Hcy and folic acid concentrations (r = −0.84) at Week 8, reflecting a significant change in Hcy concentration (P < 0.05) as a result of hyperhomocysteinemia following the accumulation of high training loads. At Week 16 we observed a significant negative correlation (P < 0.01) between Hcy concentration and training time with an RHR <60%, indicating that aerobic exercise avoided abrupt changes in Hcy and may thus reduce the risk of cardiovascular accidents in high-performance athletes. Conclusion Integral monitoring and education are needed for practitioners of handball sports to record their folic acid status, a factor that directly affects Hcy metabolism. Folic acid
Hwang, Jin-Ki; Yu, Hong-Nu; Noh, Eun-Mi; Kim, Jeong-Mi; Hong, On-Yu; Youn, Hyun Jo; Jung, Sung Hoo; Kwon, Kang-Beom; Kim, Jong-Suk; Lee, Young-Rae
Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is considered to have applications in cancer prevention and treatment. The beneficial effects of DHA against cancer metastasis are well established; however, the mechanisms underlying these effects in breast cancer are not clear. Cell invasion is critical for neoplastic metastasis, and involves the degradation of the extracellular matrix by matrix metalloproteinase (MMP)-9. The present study investigated the inhibitory effect of DHA on MMP-9 expression and cell invasion induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in the MCF-7 breast cancer cell line. DHA inhibited the TPA-induced activation of mitogen-activated protein kinase (MAPK) and the transcription of nuclear factor (NF)-κB, but did not inhibit the transcription of activator protein-1. DHA increased the activity of peroxisome proliferator-activated receptor (PPAR)-γ, an effect that was reversed by the application of the PPAR-γ antagonist GW9662. In addition, combined treatment with GW9662 and DHA increased NF-κB-related protein expression. These results indicate that DHA regulates MMP-9 expression and cell invasion via modulation of the MAPK signaling pathway and PPAR-γ/NF-κB activity. This suggests that DHA could be a potential therapeutic agent for the prevention of breast cancer metastasis. PMID:28123548
Pereira, Elzania S; Mizubuti, Ivone Y; Oliveira, Ronaldo L; Pinto, Andréa P; Ribeiro, Edson L A; Gadelha, Carla R F; Campos, Ana C N; Pereira, Marília F; Carneiro, Maria S S; Arruda, Paulo C; Silva, Luciano P
This study evaluates the effect of cashew nut meal (CNM), whole cottonseed (WCS), and calcium salts of long-chain fatty acids (Ca-LCFA) on the fatty acid profiles of meat from hair lambs. Thirty-five 60-d-old, male, noncastrated Santa Ines lambs with an initial average body weight of 13.00 ± 1.80 kg were used in a randomized complete-block design with 7 blocks and 5 treatments. The experimental treatments consisted of a control diet (CON) without supplemental lipids and 4 test diets with different lipid supplements that were selected according to the degree of protection from ruminal hydrogenation and their polyunsaturated fatty acid richness. The tests diets included the following modifications: supplementation with WCS, supplementation with CNM, supplementation with both cottonseed and CNM (CSCNM), and supplementation with Ca-LCFA. The C18:1n9c content was highest in the meat of the animals fed the CNM diet (42.00%). The meat from lambs fed the WCS and Ca-LCFA diets had higher C18:0 contents (25.23 and 22.80%, respectively). The C16:1 content was higher in the meat from the animals fed the CNM and CON diets (1.54 and 1.49%, respectively). C18:2c9t11 concentration was higher in the meat from the animals fed the Ca-LCFA and CNM diets. The estimated enzyme activity of Δ9-desaturase C18 was highest in the muscles of the lambs fed the CON, CNM, and CSCNM diets. The use of cashew nuts in the diet resulted in an increase in the C18:2c9t11 content of the lamb meat, which improved the nutritional characteristics of the fat.
Varnai, Veda Marija; Piasek, Martina; Blanusa, Maja; Juresa, Dijana; Sarić, Marija; Kostial, Krista
It was suggested that ascorbic acid as a natural chelating agent can influence lead toxicokinetics and improve chelating properties of dimercaptosuccinic acid (DMSA) in adult rats. In this paper potential benefits of ascorbic acid supplementation, alone or combined with DMSA, in decreasing lead retention in suckling rats were evaluated. Such data in young mammals are not available. L-Ascorbic acid (daily dose 650 mg/kg b.wt.) and/or DMSA (daily dose 91 mg/kg b.wt.) were administered orally to suckling Wistar rats either during ongoing 8-day oral lead exposure (as acetate; daily dose 2 mg lead/kg b.wt.) or after 3-day lead exposure (total dose 12 mg lead/kg b.wt.). Lead concentrations were analysed in the carcass (skeleton), liver, kidneys and brain by atomic absorption spectrometry. By ascorbic acid supplementation lead retention was not reduced under either lead exposure condition. Lead concentration was even increased in the carcass. Treatment with DMSA under both exposure conditions significantly reduced lead in all analysed tissues. Combined treatment with ascorbic acid and DMSA during ongoing lead exposure was substantially less effective than DMSA treatment alone, and did not affect DMSA efficacy when administered after lead exposure. It was concluded that ascorbic acid administered either during or after lead exposure in suckling rats has no beneficial effect on either lead retention or DMSA chelation effectiveness.
Valle-Rodríguez, Juan Octavio; Hernández-Cortés, Guillermo; Córdova, Jesús; Estarrón-Espinosa, Mirna; Díaz-Montaño, Dulce María
This study aimed to improve the fermentation efficiency of Kloeckera africana K1, in tequila fermentations. We investigated organic and inorganic nitrogen source requirements in continuous K. africana fermentations fed with Agave tequilana juice. The addition of a mixture of 20 amino-acids greatly improved the fermentation efficiency of this yeast, increasing the consumption of reducing sugars and production of ethanol, compared with fermentations supplemented with ammonium sulfate. The preference of K. africana for each of the 20 amino-acids was further determined in batch fermentations and we found that asparagine supplementation increased K. africana biomass production, reducing sugar consumption and ethanol production (by 30, 36.7 and 45%, respectively) over fermentations supplemented with ammonium sulfate. Therefore, asparagine appears to overcome K. africana nutritional limitation in Agave juice. Surprisingly, K. africana produced a high concentration of ethanol. This contrasts to poor ethanol productivities reported for other non-Saccharomyces yeasts indicating a relatively high ethanol tolerance for the K. africana K1 strain. Kloeckera spp. strains are known to synthesize a wide variety of volatile compounds and we have shown that amino-acid supplements influenced the synthesis by K. africana of important metabolites involved in the bouquet of tequila. The findings of this study have revealed important nutritional limitations of non-Saccharomyces yeasts fermenting Agave tequilana juice, and have highlighted the potential of K. africana in tequila production processes.
Mickleborough, Timothy D
Asthma prevalence continues to increase despite the progress that has been made in the treatment options for asthma. Alternative treatment therapies that reduce the dose requirements of pharmacological interventions would be beneficial, and could potentially reduce the public health burden of this disease. There is accumulating evidence that dietary modification has potential to influence the severity of asthma and reduce the prevalence and incidence of this condition. A possible contributing factor to the increased incidence of asthma in Western societies may the consumption of a pro-inflammatory diet. In the typical Western diet, 20-25-fold more omega (n)-6 polyunsaturated fatty acids (PUFA) than n-3 PUFA are consumed, which results in the release of pro-inflammatory arachidonic acid metabolites. Eicosapentaenoic acid and docosahexaenoic acid are n-3 PUFA derived from fish oil that competitively inhibit n-6 PUFA arachidonic acid (AA) metabolism and this reduce the generation of pro-inflammatory 4-series leukotrienes (LTs) and 2-series prostaglandins (PGs) and production of cytokines from inflammatory cells. These data are consistent with the proposed pathway by which dietary intake of n-3 PUFA modulates lung disease. This article will review the existing information concerning the relationship between n-3 PUFA supplementation and airway hyperresponsiveness in asthma. It includes studies assessing the efficacy of n-3 PUFA supplementation in exercise-induced bronchoconstriction. This review will also address the question as to whether supplementing the diet with n-3 PUFA represents a viable alternative treatment regimen for asthma.
Havazhagan, G.; Riar, S. S.; Kain, A. K.; Bardhan, Jaya; Thomas, Pauline
Two groups of male rats were exposed to simulated altitudes of 6060 m and 7576 m for 6 h/day for 7 days (intermittent exposure). In two additional groups of animals exposed to the same altitude, 100 mg of ascorbic acid (AA) was fed daily for 5 days prior to the exposure period and also during the exposure period. Rats that did not receive AA showed loss of body weight and weight of reproductive organs after exposure. Sex organs showed atrophy on histological examination and there was a deterioration in spermatozoal quality. There was an increase in alkaline and acid phosphatase, and decrease in protein, sialic acid and glyceryl phosphorylcholine content in various reproductive tissues after exposure. All the above changes in histology and biochemical composition could be partially prevented by AA supplementation. AA supplementation can therefore protect the male reproductive system from deleterious effects of hypoxia. The probable mechanism of action of AA is discussed.
Naqvi, A.Z.; Hasturk, H.; Mu, L.; Phillips, R.S.; Davis, R.B.; Halem, S.; Campos, H.; Goodson, J.M.; Van Dyke, T.E.; Mukamal, K.J.
Periodontitis is a common chronic inflammatory disease initiated by bacteria, resulting in bone resorption, tooth loss, and systemic inflammation. Long-chain omega-3 fatty acids such as docosahexaenoic acid (DHA) reduce periodontitis in animals. We aimed to determine whether DHA supplementation with low-dose aspirin would reduce periodontitis in humans. We conducted a double-blind placebo-controlled parallel trial lasting 3 mo. Fifty-five adults with moderate periodontitis were randomized to 2,000 mg of DHA or identical soy/corn oil capsules. All participants received 81 mg of aspirin but received no other treatments. We analyzed the primary outcome of per-pocket change in pocket depth using mixed models among teeth with pocket depth ≥5 mm. Secondary outcomes assessed with generalized estimating equations included gingival index, plaque index, and bleeding on probing. Gingival crevicular fluid samples were analyzed for changes in high-sensitivity C-reactive protein (hsCRP) and interleukins 6 and 1β (IL-6 and IL-1β). Plasma was analyzed for changes in systemic inflammatory markers, including hsCRP. We confirmed adherence with erythrocyte fatty acid measurement. Forty-six participants completed the trial. While similar at baseline, the proportion of DHA in red blood cell plasma membranes increased from 3.6% ± 0.9% to 6.2% ± 1.6% in the intervention group but did not change among controls. DHA supplementation decreased mean pocket depth (–0.29 ± 0.13; p = .03) and gingival index (–0.26 ± 0.13; p = .04). Plaque index and bleeding on probing did not change. Significant adjusted differences were found between DHA and control for both gingival crevicular fluid hsCRP (–5.3 ng/mL, standard error [SE] = 2.4, p = .03) and IL-1β (–20.1 pg/mL, SE = 8.2, p = .02) but not IL-6 (0.02 pg/mL, SE = 0.71, p = .98) or systemic hsCRP (–1.19 mg/L, SE = 0.90, p = .20). In this randomized controlled trial, aspirin-triggered DHA supplementation significantly improved
Jouris, Kelly B.; McDaniel, Jennifer L.; Weiss, Edward P.
Omega-3 fatty acids (omega-3) have anti-inflammatory properties. However, it is not known if omega-3 supplementation attenuates exercise-induced inflammation. We tested the hypothesis that omega-3 supplementation reduces inflammation that is induced by eccentric arm curl exercise. Healthy adult men and women (n=11; 35 ± 10 y) performed eccentric biceps curls on two occasions, once after 14d of dietary omega-3 restriction (control trial) and again after 7d of 3,000 mg/d omega-3 supplementation (omega-3 trial). Before and 48 h after eccentric exercise, signs of inflammation was assessed by measuring soreness ratings, swelling (arm circumference and arm volume), and temperature (infrared skin sensor). Arm soreness increased (p < 0.0001) in response to eccentric exercise; the magnitude of increase in soreness was 15% less in the omega-3 trial (p = 0.004). Arm circumference increased after eccentric exercise in the control trial (p = 0.01) but not in the omega-3 trial (p = 0.15). However, there was no difference between trials (p = 0.45). Arm volume and skin temperature did not change in response to eccentric exercise in either trial. These findings suggest that omega-3 supplementation decreases soreness, as a marker of inflammation, after eccentric exercise. Based on these findings, omega-3 supplementation could provide benefits by minimizing post-exercise soreness and thereby facilitate exercise training in individuals ranging from athletes undergoing heavy conditioning to sedentary subjects or patients who are starting exercise programs or medical treatments such as physical therapy or cardiac rehabilitation. Key points Dietary supplementation with omega-3 fatty acids has been shown to reduce inflammation in numerous inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, and Chrohn’s disease. Although strenuous exercise is known to cause acute increases in inflammation, it is not clear if omega-3 fatty acid supplementation attenuates this
D'Alessandro, Angelo; D'Amici, Gian Maria; Timperio, Anna Maria; Merendino, Nicolò; Zolla, Lello
Recent investigations have pointed out the ability of fatty acids, in particular of docosohaexanoic acid (DHA), to induce growth inhibition and apoptosis in the human PaCa-44 pancreatic cancer cell line through a series of mechanisms which has been hypothesized to mimic apoptosis. While preliminary evidences indicated the involvement of lipid-targeting oxidative stress in DHA-induced apoptotic processes, mainly through the alteration of the glutathione (GSH) homeostasis and oxidized-glutathione (GSSG) turn-over through their extra-cellular extrusion, no further molecular data have been hitherto accumulated. To this end, we hereby propose simultaneous protein-targeting and metabolite-oriented analyses, which have been integrated through the auxilium of in silico elaboration of those protein-protein interaction pathways and enrichment of biological/molecular functions. To determine the most suitable time window for the early onset of the DHA-triggered apoptosis phenomena we performed flow cytometry-based apoptotic assessment at 24, 48 and 72 h. Results indicated that the focus of apoptosis onset ranged from 48 to 72 h. From these analyses it emerges that the metabolism of control human PaCa-44 pancreatic cancer cell line mainly leans on glycolytic pathways, while it is promptly switched to Kreb's cycle activation (overexpression of Kreb's cycle enzymes in DHA-treated cells against controls) and modulation of the GSH homeostasis through an increased production of GSSG-reducing NADPH coenzyme via the shift of the glycolytic energy flux towards the pentose phosphate pathway. Interestingly, it also emerges a role for structural protein alteration in DHA-treated cells, which might be linked to cytoskeletal alterations occurring during apoptosis.
Ranjan, R; Ranjan, A; Dhaliwal, G S; Patra, R C
Cattle can synthesize L-ascorbic acid (or Vitamin C) from either D-glucose or D-galactose through glucuronic acid pathway in the liver. L-Ascorbic acid present in cattle diet is almost totally destroyed by rumen microorganisms making them essentially dependent on its endogenous synthesis, which is assumed sufficient to meet the physiological requirement. Therefore, the role of vitamin C in cattle health and disease has remained widely overlooked. However, there is mounting evidence that the level of L-ascorbic acid in blood and other tissues decreases in association with stress and disease, and Vitamin C supplementation revealed favorable response as evident from early recovery. The present review is an attempt to summarize the existing literature pertaining to the physiological role of L-ascorbic acid and the scope of its supplementation in the prevention and treatment of diseases in cattle. It should be realized that the aqueous solution of vitamin C is highly acidic and subcutaneous or intramuscular administration may cause tissue irritation and inflammation, whereas the sodium ascorbate solution is less acidic and might be used for intramuscular administration.
Khader, V; Rao, S V
The limiting amino acids of Bengal gram (Cicer arietinum) were determined from plasma amino acid score and ratio and growth response of weanling rats to supplements of amino acids. The results indicated that methionine, threonine and tryptophan are the most limiting amino acids. Protein efficiency ratio of raw and cooked Bengal gram fed at a dietary level of 10% protein increased from 2.7 to 3.7 and 2.4 to 3.4, respectively, on supplementing the diets with methionine, threonine and tryptophan. Plasma levels of lysine, methionine, threonine and tryptophan were similar in rats fed raw or cooked Bengal gram, indicating that the trypsin or other inhibitors that may be present in the raw gram do not affect the biological availability of these amino acids.
de Souza, J; Preseault, C L; Lock, A L
The objective of this study was to evaluate the response of mid-lactation dairy cows to a palmitic acid (C16:0)-enriched fatty acid supplement when replacing soyhulls or dry ground corn in the diet. Twenty-four multiparous Holstein cows (182 ± 60 d in milk; mean ± SD) were blocked by preliminary 3.5% fat-corrected milk and randomly assigned to treatment sequence in a replicated 3 × 3 Latin square design with 21-d periods. Treatments consisted of a control diet containing no supplemental fat (CON), and 2 C16:0-enriched fatty acid-supplemented treatments (PA; BergaFat F100, Berg & Schmidt, Hanover, Germany) as a replacement for either soyhulls (PA-SH) or dry ground corn (PA-CG). The C16:0-enriched supplement was fed at 1.5% of diet dry matter. The PA treatments did not affect dry matter intake, but PA-SH increased dry matter intake by 1.4 kg/d compared with PA-CG. The PA treatments did not affect milk yield; however, PA-SH increased milk yield by 2.4 kg/d compared with PA-CG. The PA treatments tended to decrease milk protein content (3.12 vs. 3.15%). In contrast, PA-SH increased milk protein content (3.14 vs. 3.10%) and milk protein yield (1.27 vs. 1.19 kg/d) compared with PA-CG. The PA treatments increased milk fat concentration (3.68 vs. 3.55%) and milk fat yield (1.46 vs. 1.38 kg/d). The increase in milk fat yield with PA treatments was due to the increase in the yield of 16-carbon fatty acid in milk fat. Furthermore, PA-SH tended to increase yield of de novo fatty acids and yield of 16-carbon fatty acids compared with PA-CG. The PA treatments tended to increase feed efficiency (3.5% fat-corrected milk/dry matter intake) compared with CON (1.51 vs. 1.46). The PA-SH treatment tended to increase insulin concentration compared with PA-CG (1.58 vs. 1.49 μg/L) and PA treatments increased nonesterified fatty acids compared with CON (110 vs. 99 μEq/L). Overall, PA treatments improved feed efficiency and increased milk fat yield and the response to the C16:0-enriched
Marzuca-Nassr, Gabriel Nasri; Vitzel, Kaio Fernando; De Sousa, Luís Gustavo; Murata, Gilson M; Crisma, Amanda Rabello; Rodrigues Junior, Carlos Flores; Abreu, Phablo; Torres, Rosângela Pavan; Mancini-Filho, Jorge; Hirabara, Sandro M; Newsholme, Philip; Curi, Rui
The effects of either eicosapentaenoic (EPA)- or docosahexaenoic (DHA)-rich fish oils on hindlimb suspension (HS)-induced muscle disuse atrophy were compared. Daily oral supplementations (0.3 mL/100 g b.w.) with mineral oil (MO) or high EPA or high DHA fish oils were performed in adult rats. After 2 weeks, the animals were subjected to HS for further 2 weeks. The treatments were maintained alongside HS At the end of 4 weeks, we evaluated: body weight gain, muscle mass and fat depots, composition of fatty acids, cross-sectional areas (CSA) of the soleus muscle and soleus muscle fibers, activities of cathepsin L and 26S proteasome, and content of carbonylated proteins in the soleus muscle. Signaling pathway activities associated with protein synthesis (Akt, p70S6K, S6, 4EBP1, and GSK3-beta) and protein degradation (atrogin-1/MAFbx, and MuRF1) were evaluated. HS decreased muscle mass, CSA of soleus muscle and soleus muscle fibers, and altered signaling associated with protein synthesis (decreased) and protein degradation (increased). The treatment with either fish oil decreased the ratio of omega-6/omega-3 fatty acids and changed protein synthesis-associated signaling. EPA-rich fish oil attenuated the changes induced by HS on 26S proteasome activity, CSA of soleus muscle fibers, and levels of p-Akt, total p70S6K, p-p70S6K/total p70S6K, p-4EBP1, p-GSK3-beta, p-ERK2, and total ERK 1/2 proteins. DHA-rich fish oil attenuated the changes induced by HS on p-4EBP1 and total ERK1 levels. The effects of EPA-rich fish oil on protein synthesis signaling were more pronounced. Both EPA- and DHA-rich fish oils did not impact skeletal muscle mass loss induced by non-inflammatory HS.
Richard, Caroline; Lewis, Erin D; Field, Catherine J
Long-chain polyunsaturated fatty acids (LCPUFA), especially the balance between arachidonic (AA) and docosahexaenoic (DHA) acids are known to have important immunomodulatory roles during the postnatal period when the immune system is rapidly developing. AA and DHA are required in infant formula in many countries but are optional in North America. The rationale for adding these LCPUFA to full-term formula is based on their presence in breast milk and randomized controlled studies that suggest improved cognitive function in preterm infants, but results are more variable in full-term infants. Recently, the European Food Safety Authority has proposed, based on a lack of functional evidence, that AA is not required in infant formula for full-term infants during the first year of life but DHA should remain mandatory. The purpose of this review is to review the evidence from epidemiological and intervention studies regarding the essentiality of AA and DHA in the postnatal infant and maternal diet (breast-feeding) for the immune system development early in life. Although studies support the essentiality of DHA for the immune system development, more research is needed to rule out the essentiality of AA. Nevertheless, intervention studies have demonstrated improvement in many markers of immune function in infants fed formula supplemented with AA and DHA compared with unsupplemented formula, which appears to consistently result in beneficial health outcomes including reduction in the risk of developing allergic and atopic disease early in life.
Partida, J A; Olleta, J L; Sañudo, C; Albertí, P; Campo, M M
This study measured the effect of replacing dietary fat from an animal source with palm oil supplements on the intramuscular fatty acid profile and sensory quality traits of the meat from young bulls. Thirty-six entire male Friesian calves (mean age=6.8±1.1 months, mean live weight=162.5±28.6kg) were assigned to one of four isoenergetic (1.03 MFU/kg DM) and isoproteinic (15.5% CP) diets, that differed in their fat additives: (D1) lard-tallow mix (control); (D2) hydrogenated palm oil fatty acids (PFA); (D3) calcium salt of partially hydrogenated PFA, and (D4) calcium salt of the fatty acid distillate from palm oil. Bulls (mean live weight=391.3±30.3kg) were slaughtered under commercial conditions and sensory tests were performed to evaluate the effects of the four diets and ageing time (1, 10, and 21d). Only the proportions of C16:0 and C18:0 were significantly affected by the palm oil dietary supplement. Ageing time affected grass odour, tenderness, juiciness, fibrosity, liver flavour, and acid flavour. Nevertheless, palm oil supplements did not negatively alter the organoleptic characteristics of the meat.
Bothma, C; Hugo, A; Osthoff, G; Joubert, C C; Swarts, J C; de Kock, H L
Pigs were fed diets containing 0, 0.25, 0.5 and 1% conjugated linoleic acid (CLA). Compared to controls, backfat from CLA fed pigs was firmer and extracted lipid contained increasing amounts of CLA, but a ±11% overall decrease in unsaturated fatty acids and a ±5% overall increase in each of C16:0 and C18:0 saturated fatty acids were noted. This resulted in a change in the melting properties of fat. The onset setting temperature increased from ±14°C to ±18°C for lipid of backfat of pigs from the 0.25 and 0.5% CLA supplementation groups, and to ±26°C for lipid from the 1% CLA supplementation group. The final melting temperatures increased from ±37°C to ±43°C and ±45°C, respectively. The presence of β'-crystals of C18:0-C16:0-C18:1c9 triacylglycerides in fat from CLA fed pigs and β-crystals in fat from 1% CLA fed pigs was observed. Fatty acid and melting point results explained the improvement in the technological quality of backfat as a result of dietary CLA supplementation.
Shin, Joo Young; Yu, Hyeong Gon
To evaluate the effect of chlorogenic acid supplementation in patients with retinitis pigmentosa, we evaluated objective change in visual function with multifocal electroretinography, along with visual acuity, visual field, standard electroretinography, and contrast sensitivity. Eighteen patients diagnosed with retinitis pigmentosa were enrolled in this prospective, non-comparative, single-arm study. Multifocal electroretinography, best-corrected visual acuity in Early Treatment Diabetic Retinopathy Study letters, total point score on visual field examination with Humphrey Field Analyzer II, electroretinography, and contrast sensitivity were measured and repeated after 3 months supplementation with chlorogenic acid. The amplitude of ring 5 was significantly higher on multifocal electroretinography after 3 months of chlorogenic acid supplementation (7.2 ± 9.5 vs 8.3 ± 10.8 nV/deg(2), mean ± standard deviation, P = 0.022). There were no significant changes in the best-corrected visual acuity, total point score on Humphrey Field Analyzer, 30 Hz flicker amplitude on standard electroretinography, or contrast sensitivity. Chlorogenic acid may have a beneficial effect on the peripheral area at the margins of retinal degeneration, and should be considered as an anti-oxidant for the management of retinitis pigmentosa.
Kelley, D S; Taylor, P C; Nelson, G J; Schmidt, P C; Ferretti, A; Erickson, K L; Yu, R; Chandra, R K; Mackey, B E
The purpose of this study was to examine the effects of feeding docosahexaenoic acid (DHA) as triacylglycerol on the fatty acid composition, eicosanoid production, and select activities of human peripheral blood mononuclear cells (PBMNC). A 120-d study with 11 healthy men was conducted at the Metabolic Research Unit of Western Human Nutrition Reach Center. Four subjects (control group) were fed the stabilization diet throughout the study; the remaining seven subjects were fed the basal diet for the first 30 d, followed by 6 g DHA/d for the next 90 d. DHA replaced an equivalent amount of linoleic acid; the two diets were comparable in their total fat and all other nutrients. Both diets were supplemented with 20 mg D alpha-tocopherol acetate per day. PBMNC fatty acid composition and eicosanoid production were examined on day 30 and 113; immune cell functions were tested on day 22, 30, 78, 85, 106, and 113. DHA feeding increased its concentration from 2.3 to 7.4 wt% in the PBMNC total lipids, and decreased arachidonic acid concentration from 19.8 to 10.7 wt%. It also lowered prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) production, in response to lipopolysaccharide, by 60-75%. Natural killer cell activity and in vitro secretion of interleukin-1beta and tumor necrosis factor alpha were significantly reduced by DHA feeding. These parameters remained unchanged in the subjects fed the control diet. B-cell functions as reported here and T-cell functions that we reported previously were not altered by DHA feeding. Our results show that inhibitory effects of DHA on immune cell functions varied with the cell type, and that the inhibitory effects are not mediated through increased production of PGE2 and LTB4.
Oliveira, Ronaldo Lopes; Neto, Severino Gonzaga; de Lima, Francisco Helton Sa; de Medeiros, Ariosvaldo Nunes; Bezerra, Leilson Rocha; Pereira, Elzania Sales; Bagaldo, Adriana Regina; de Pellegrini, Caius Barcellos; Correia, Braulio Rocha
This study compared the productive and nutritional parameters of milk from crossbred lactating cows managed on Panicum maximum Jacq. cv. Tanzania and with a diet supplemented with different pressed oilseed cakes. The supplements used were as follows: peanut cake, sunflower cake and palm kernel cake for replacement of soybean meal. Sixteen cows with an average weight of 544 ± 57 kg and producing 8 ± 1.4 L of milk per day were used in this study. The animals were randomly assigned to the treatments according to a Latin square design repeated over time, with four treatments, 16 animals and four experimental periods. Supplementation of the diet with peanut cake, sunflower cake and palm kernel cake compared with soybean meal in the diet of cows did not affect the average daily production or composition of the milk. The palm kernel cake promoted an increase in lauric fatty acids (C12:0 ) and palmitoleic acids (C16:1 ) (5.02 and 1.65%, respectively) compared with peanut cake and sunflower cake (4.13 and 4.01%, respectively). The levels of oleic fatty acids (C18:1 ) were higher for the sunflower cake and palm kernel cake supplements (26.01 and 25.01%, respectively) compared with peanut cake (23.11%). The replacement of soybean meal with sunflower cake and palm kernel cake improved the nutritional quality of the milk, with lower concentrations of saturated fatty acids and higher concentrations of unsaturated fatty acids, without compromising the production or nutritional composition of the milk. © 2015 Japanese Society of Animal Science.
Moreno-Indias, I; Morales-delaNuez, A; Hernández-Castellano, L E; Sánchez-Macías, D; Capote, J; Castro, N; Argüello, A
The effect of dietary docosahexaenoic acid (C22:6n3; DHA) supplementation on meat quality and immunity in goat (Capra hircus) kids was examined. Goat kids (n = 30) were fed 1 of 3 experimental diets: goat milk (GM), cow (Bos taurus) milk (CM), and CM supplemented with DHA (CM-DHA). Animals were fed ad libitum twice daily and weighed twice each week. Blood samples were collected by jugular venipuncture daily during the first 10 d of life and were subsequently collected every 5 d until slaughter at a BW of 8 kg. Carcass size (linear measurements) and weight, as well as meat pH, color, tenderness, and chemical composition were determined. Fatty acid profiles of intramuscular, peri-renal, pelvic, subcutaneous, and intermuscular fats were analyzed. Blood IgG and IgM concentrations, complement system activity (classical and alternative pathways), and chitotriosidase activity were recorded. Results indicated that the diet containing DHA did not affect (P > 0.05) carcass linear measurements, meat quality characteristics, or proximate composition of the meat. However, C22:6n3 fatty acid levels, mainly in intramuscular fat, were enriched (P < 0.05) in CM-DHA animals, and the n-6 to n-3 PUFA ratio was improved (P < 0.05). No differences (P > 0.05) in immune function were observed among groups. In conclusion, powdered whole CM is an effective option for feeding goat kids, and the inclusion of DHA to CM increases the quantity of this fatty acid in the meat.
Haque, A; Šaňková, B; Kvasilová, A; Krejčí, E; Sedmera, D
Endothelin (ET) signalling is essential for normal embryonic development. Disruption of this pathway leads to defects in the development of subsets of cranial and cephalic neural crest derivatives. Endothelin-converting enzyme 1 (ECE-1) is a ratelimiting step in the biosynthesis of ET-1. Recently, there has been considerable interest in the protective role of folic acid (FA) against congenital anomalies via increasing the expression of ET-1. We have tested whether FA supplementation can rescue craniofacial and cardiac defects observed in the ECE1-/- embryos. ECE1+/- mice were caged together to obtain litters containing embryos of all possible genotypes. The treatment group had the diet supplemented with 20 mg/kg of FA from the day of discovery of the vaginal plug. FA supplementation did not result in modified proportions of the genotypes, indicating no rescue of the embryonic mortality. There was also no effect on the litter size. Craniofacial and cardiac defects were likewise identical in the ECE1-/- embryos of both groups. There was a mild but significant reduction in the embryo size in wild-type and heterozygous FA-supplemented embryos, and there were haemorrhages in the wild-type supplemented embryos at ED14.5. Expression of ET receptor A detected by immunohistochemistry was up-regulated in the ECE1-/- embryos, but FA supplementation had no effects on the distribution of staining intensity. We conclude that FA is not able to rescue the phenotype in this model, suggesting an alternative pathway for its action. These results also caution against indiscriminate use of dietary supplements in attempts to prevent congenital anomalies.
Kanani, S J; Poojara, R H
The prevalence of anemia is high in adolescent girls in India, with over 70% anemic. Iron-folic acid (IFA) supplements have been shown to enhance adolescent growth elsewhere in the world. To confirm these results in India, a study was conducted in urban areas of Vadodora, India to investigate the effect of IFA supplements on hemoglobin, hunger and growth in adolescent girls 10-18 y of age. Results show that there was a high demand for IFA supplements and >90% of the girls consumed 85 out of 90 tablets provided. There was an increment of 17.3 g/L hemoglobin in the group of girls receiving IFA supplements, whereas hemoglobin decreased slightly in girls in the control group. Girls and parents reported that girls increased their food intake. A significant weight gain of 0.83 kg was seen in the intervention group, whereas girls in the control group showed little weight gain. The growth increment was greater in the 10- to 14-y-old age group than in the 15- to 18-y-old group, as expected, due to rapid growth during the adolescent spurt. IFA supplementation is recommended for growth promotion among adolescents who are underweight.
Adarme-Vega, T Catalina; Lim, David K Y; Timmins, Matthew; Vernen, Felicitas; Li, Yan; Schenk, Peer M
Omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) provide significant health benefits and this has led to an increased consumption as dietary supplements. Omega-3 fatty acids EPA and DHA are found in animals, transgenic plants, fungi and many microorganisms but are typically extracted from fatty fish, putting additional pressures on global fish stocks. As primary producers, many marine microalgae are rich in EPA (C20:5) and DHA (C22:6) and present a promising source of omega-3 fatty acids. Several heterotrophic microalgae have been used as biofactories for omega-3 fatty acids commercially, but a strong interest in autotrophic microalgae has emerged in recent years as microalgae are being developed as biofuel crops. This paper provides an overview of microalgal biotechnology and production platforms for the development of omega-3 fatty acids EPA and DHA. It refers to implications in current biotechnological uses of microalgae as aquaculture feed and future biofuel crops and explores potential applications of metabolic engineering and selective breeding to accumulate large amounts of omega-3 fatty acids in autotrophic microalgae.
Arsenault, Dany; Julien, Carl; Tremblay, Cyntia; Calon, Frédéric
Defects in neuronal activity of the entorhinal cortex (EC) are suspected to underlie the symptoms of Alzheimer's disease (AD). Whereas neuroprotective effects of docosahexaenoic acid (DHA) have been described, the effects of DHA on the physiology of EC neurons remain unexplored in animal models of AD. Here, we show that DHA consumption improved object recognition (↑12%), preventing deficits observed in old 3xTg-AD mice (↓12%). Moreover, 3xTg-AD mice displayed seizure-like akinetic episodes, not detected in NonTg littermates and partly prevented by DHA (↓50%). Patch-clamp recording revealed that 3xTg-AD EC neurons displayed (i) loss of cell capacitance (CC), suggesting reduced membrane surface area; (ii) increase of firing rate versus injected current (F-I) curve associated with modified action potentials, and (iii) overactivation of glutamatergic synapses, without changes in synaptophysin levels. DHA consumption increased CC (↑12%) and decreased F-I slopes (↓21%), thereby preventing the opposite alterations observed in 3xTg-AD mice. Our results indicate that cognitive performance and basic physiology of EC neurons depend on DHA intake in a mouse model of AD. PMID:21383850
Harvey, Lloyd D.; Yin, Yan; Attarwala, Insiya Y.; Begum, Gulnaz; Deng, Julia; Yan, Hong Q.; Dixon, C. Edward
We investigated the effects of the administration of docosahexaenoic acid (DHA) post-traumatic brain injury (TBI) on reducing neuroinflammation. TBI was induced by cortical contusion injury in Sprague Dawley rats. Either DHA (16 mg/kg in dimethyl sulfoxide) or vehicle dimethyl sulfoxide (1 ml/kg) was administered intraperitonially at 5 min after TBI, followed by a daily dose for 3 to 21 days. TBI triggered activation of microglia or macrophages, detected by an increase of Iba1 positively stained microglia or macrophages in peri-lesion cortical tissues at 3, 7, and 21 days post-TBI. The inflammatory response was further characterized by expression of the proinflammatory marker CD16/32 and the anti-inflammatory marker CD206 in Iba1+ microglia or macrophages. DHA-treated brains showed significantly fewer CD16/32+ microglia or macrophages, but an increased CD206+ phagocytic microglial or macrophage population. Additionally, DHA treatment revealed a shift in microglial or macrophage morphology from the activated, amoeboid-like state into the more permissive, surveillant state. Furthermore, activated Iba1+ microglial or macrophages were associated with neurons expressing the endoplasmic reticulum (ER) stress marker CHOP at 3 days post-TBI, and the administration of DHA post-TBI concurrently reduced ER stress and the associated activation of Iba1+ microglial or macrophages. There was a decrease in nuclear translocation of activated nuclear factor kappa-light-chain-enhancer of activated B cells protein at 3 days in DHA-treated tissue and reduced neuronal degeneration in DHA-treated brains at 3, 7, and 21 days after TBI. In summary, our study demonstrated that TBI mediated inflammatory responses are associated with increased neuronal ER stress and subsequent activation of microglia or macrophages. DHA administration reduced neuronal ER stress and subsequent association with microglial or macrophage polarization after TBI, demonstrating its therapeutic potential to
Background Health authorities in numerous countries recommend periconceptional folic acid to pregnant women to prevent neural tube defects. The objective of this study was to examine the association of folic acid supplementation during different periods of pregnancy and of dietary folate intake with the risk of spontaneous preterm delivery (PTD). Methods The Norwegian Mother and Child Cohort Study is a population-based prospective cohort study. A total of 65,668 women with singleton pregnancies resulting in live births in 1999–2009 were included. Folic acid supplementation was self-reported from 26 weeks before pregnancy until week 24 during pregnancy. At gestational week 22, the women completed a food frequency questionnaire, which allowed the calculation of their average total folate intake from foods and supplements for the first 4–5 months of pregnancy. Spontaneous PTD was defined as the spontaneous onset of delivery between weeks 22+0 and 36+6 (n = 1,628). Results The median total folate intake was 266 μg/d (interquartile range IQR 154–543) in the overall population and 540 μg/d (IQR 369–651) in the supplement users. Eighty-three percent reported any folic acid supplementation from <8 weeks before to 24 weeks after conception while 42% initiated folic acid supplementation before their pregnancy. Cox regression analysis showed that the amount of folate intake from the diet (hazard ratio HR 1.16; confidence interval CI 0.65-2.08) and from the folic acid supplements (HR 1.04; CI 0.95-1.13) was not significantly associated with the risk of PTD. The initiation of folic acid supplementation more than 8 weeks before conception was associated with an increased risk for PTD (HR 1.19; CI 1.05-1.34) compared to no folic acid supplementation pre-conception. There was no significant association with PTD when supplementation was initiated within 8 weeks pre-conception (HR 1.01; CI 0.88-1.16). All analyses were adjusted for maternal characteristics and
Zheng, Weilong; Wang, Xudong; Cao, Wenjing; Yang, Bowen; Mu, Ying; Dong, Yuesheng; Xiu, Zhilong
Many bioactive components such as poly-unsaturated fatty acids (e.g. EPA and DHA), phospholipids and astaxanthin are known in Antarctic krill (Euphausia superba) oil. The krill DHA and EPA are generally considered to be similar to natural ones. However, two chemical compounds which were separated from Antarctic krill oil and identified as EPA and DHA by HRESIMS and NMR acted much more effective inhibitive activities on growth of several cell lines (U937, K562, SMMC-7721, PC-3, MDA-MB-231, HL60 and MCF-7) than those from sturgeon liver and commercial fish oil. Taking MCF-7 as an example, the IC50 values of Antarctic krill EPA and DHA were 14.01 and 19.94μM，while the IC50 values of sturgeon liver and commercial fish EPA and DHA were 81.45, 73.13, 82.11 and 75.31μM, respectively. Raman spectra revealed that the Antarctic krill EPA and DHA have E-configuration structures, which were different from those in commercial fish oil. Additionally, the Antarctic krill EPA and DHA had no effects on human normal liver cell line HL7702. These results indicated that the Antarctic krill E-EPA and E-DHA had a great prospect in cancer therapy.
Singh, Shiva P; Häussler, Susanne; Heinz, Johanna F L; Saremi, Behnam; Mielenz, Birgit; Rehage, Jürgen; Dänicke, Sven; Mielenz, Manfred; Sauerwein, Helga
Decreasing insulin sensitivity (IS) in peripheral tissues allows for partitioning nutrients towards the mammary gland. In dairy cows, extensive lipid mobilization and continued insulin resistance (IR) are typical for early lactation. Adiponectin, an adipokine, promotes IS. Supplementation with conjugated linoleic acids (CLA) in rodents and humans reduces fat mass whereby IR and hyperinsulinemia may occur. In dairy cows, CLA reduce milk fat, whereas body fat, serum free fatty acids and leptin are not affected. We aimed to investigate the effects of CLA supplementation on serum and adipose tissue (AT) adiponectin concentrations in dairy cows during the lactation driven and parity modulated changes of metabolism. High yielding cows (n=33) were allocated on day 1 post partum to either 100 g/day of a CLA mixture or a control fat supplement (CON) until day 182 post partum. Blood and subcutaneous (sc) AT (AT) biopsy samples were collected until day 252 post partum to measure adiponectin. Serum adiponectin decreased from day 21 pre partum reaching a nadir at calving and thereafter increased gradually. The distribution of adiponectin molecular weight forms was neither affected by time, parity nor treatment. Cows receiving CLA had decreased serum adiponectin concentrations whereby primiparous cows responded about 4 weeks earlier than multiparous cows. The time course of adiponectin concentrations in sc AT (corrected for residual blood) was similar to serum concentrations, without differences between CLA and CON. CLA supplementation attenuated the post partum increase of circulating adiponectin thus acting towards prolongation of peripartal IR and drain of nutrients towards the mammary gland.
Lymperaki, E; Tsikopoulos, A; Makedou, K; Paliogianni, E; Kiriazi, L; Charisi, C; Vagdatli, E
The aim of the study was to assess serum total antioxidant capacity (TAC) and the impact of supplements on oxidative stress (OS) during pregnancy. Fifty volunteer pregnant women (21-40 years old), in the 12 ± 2 weeks' and 38 ± 2 weeks' gestation of pregnancy (study group), and 25 non-pregnant healthy women (control group) were enrolled. All pregnant women were divided into two age groups (A1: < 35 years and A2: ≥ 35 years) and four groups according to supplementation (B1: iron, B2: folic acid, B3: both and B4: none). Antioxidant activity was assayed using the TAC kit (Cayman Chemical Co.). Level of statistical significance was p < 0.05. Serum TAC values in all pregnant women in the first trimester were significantly lower, as compared with those of the control group. Levels of TAC increased significantly in the third trimester of pregnancy, especially with folic acid or no supplementation. In conclusion, pregnancy is associated with OS, which is promoted by the administration of iron supplementation.
Weiser, Michael J; Mucha, Brittany; Denheyer, Heather; Atkinson, Devon; Schanz, Norman; Vassiliou, Evros; Benno, Robert H
The prevalence of autism spectrum disorders over the last several decades has risen at an alarming rate. Factors such as broadened clinical definitions and increased parental age only partially account for this precipitous increase, suggesting that recent changes in environmental factors may also be responsible. One such factor could be the dramatic decrease in consumption of anti-inflammatory dietary omega-3 (n-3) polyunsaturated fatty acids (PUFAs) relative to the amount of pro-inflammatory omega-6 (n-6) PUFAs and saturated fats in the Western diet. Docosahexaenoic acid (DHA) is the principle n-3 PUFA found in neural tissue and is important for optimal brain development, especially during late gestation when DHA rapidly and preferentially accumulates in the brain. In this study, we tested whether supplementation of a low n-3 PUFA diet with DHA throughout development could improve measures related to autism in a mouse model of maternal immune activation. We found that dietary DHA protected offspring from the deleterious effects of gestational exposure to the viral mimetic polyriboinosinic-polyribocytidilic acid on behavioral measures of autism and subsequent adulthood immune system reactivity. These data suggest that elevated dietary levels of DHA, especially during pregnancy and nursing, may help protect normal neurodevelopment from the potentially adverse consequences of environmental insults like maternal infection.