Showing papers on "Docosahexaenoic acid published in 2008"

The relationship between the fatty acid composition of immune cells and their function.

Abstract: The immune system, including its inflammatory components, is fundamental to host defence against pathogenic invaders. It is a complex system involving interactions amongst many different cell types dispersed throughout the body. Central to its actions are phagocytosis of bacteria, processing of antigens derived from intracellular and extracellular pathogens, activation of T cells with clonal expansion (proliferation) and production of cytokines that elicit effector cell functions such as antibody production and killing cell activity. Inappropriate immunologic activity, including inflammation, is a characteristic of many common human disorders. Eicosanoids produced from arachidonic acid have roles in inflammation and regulation of T and B lymphocyte functions. Eicosapentaenoic acid (EPA) also gives rise to eicosanoids and these may have differing properties from those of arachidonic acid-derived eicosanoids. EPA and docosahexaenoic acid (DHA) give rise to newly discovered resolvins which are anti-inflammatory and inflammation resolving. Human immune cells are typically rich in arachidonic acid, but arachidonic acid, EPA and DHA contents can be altered through oral administration of EPA and DHA. This results in a changed pattern of production of eicosanoids and probably also of resolvins, although the latter are not well examined in the human context. Changing the fatty acid composition of immune cells also affects phagocytosis, T cell signaling and antigen presentation capability. These effects appear to mediated at the membrane level suggesting important roles of fatty acids in membrane order, lipid raft structure and function, and membrane trafficking. Thus, the fatty acid composition of human immune cells influences their function and the cell membrane contents of arachidonic acid, EPA and DHA are important. Fatty acids influence immune cell function through a variety of complex mechanisms and these mechanisms are now beginning to be unraveled.

Polyunsaturated fatty acids, inflammatory processes and inflammatory bowel diseases

Abstract: With regard to inflammatory processes, the main fatty acids of interest are the n-6 PUFA arachidonic acid (AA), which is the precursor of inflammatory eicosanoids like prostaglandin E₂ and leukotriene B₄, and the n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA and DHA are found in oily fish and fish oils. EPA and DHA inhibit AA metabolism to inflammatory eicosanoids. They also give rise to mediators that are less inflammatory than those produced from AA or that are anti-inflammatory. In addition to modifying the lipid mediator profile, n-3 PUFAs exert effects on other aspects of inflammation like leukocyte chemotaxis and inflammatory cytokine production. Some of these effects are likely due to changes in gene expression, as a result of altered transcription factor activity. Fish oil has been shown to decrease colonic damage and inflammation, weight loss and mortality in animal models of colitis. Fish oil supplementation in patients with inflammatory bowel diseases results in n-3 PUFA incorporation into gut mucosal tissue and modification of inflammatory mediator profiles. Clinical outcomes have been variably affected by fish oil, although some trials report improved gut histology, decreased disease activity, use of corticosteroids and relapse.

Behavioral Deficits Associated with Dietary Induction of Decreased Brain Docosahexaenoic Acid Concentration

Abstract: Docosahexaenoic acid (DHA), an n-3 fatty acid, is rapidly deposited during the period of rapid brain development. The influence of n-3 fatty acid deficiency on learning performance in adult rats over two generations was investigated. Rats were fed either an n-3 fatty acid-adequate (n-3 Adq) or -deficient (n-3 Def) diet for three generations (F1-F3). Levels of total brain n-3 fatty acids were reduced in the n-3 Def group by 83 and 87% in the F2 and F3 generations, respectively. In the Morris water maze, the n-3 Def group showed a longer escape latency and delayed acquisition of this task compared with the n-3 Adq group in both generations. The acquisition and memory levels of the n-3 Def group in the F3 generation seemed to be lower than that of the F2 generation. The 22:5n-6/22:6n-3 ratio in the frontal cortex and dams' milk was markedly increased in the n-3 Def group, and this ratio was significantly higher in the F3 generation compared with the F2 generation. These results suggest that learning and cognitive behavior are related to brain DHA status, which, in turn, is related to the levels of the milk/dietary n-3 fatty acids.

Effect of fish oil on cognitive performance in older subjects A randomized, controlled trial

Abstract: Background: High intake of n-3 polyunsaturated fatty acids may protect against age-related cognitive decline. However, results from epidemiologic studies are inconclusive, and results from randomized trials in elderly subjects without dementia are lacking. Objective: To investigate the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation on cognitive performance. Methods: Double-blind, placebo-controlled trial involving 302 cognitively healthy (Mini-Mental State Examination score > 21) individuals aged 65 years or older. Participants were randomly assigned to 1,800 mg/d EPA–DHA, 400 mg/d EPA–DHA, or placebo capsules for 26 weeks. Cognitive performance was assessed using an extensive neuropsychological test battery that included the cognitive domains of attention, sensorimotor speed, memory, and executive function. Results: The mean age of the participants was 70 years, and 55% were male. Plasma concentrations of EPA–DHA increased by 238% in the high-dose and 51% in the low-dose fish oil group compared with placebo, reflecting excellent compliance. Baseline scores on the cognitive tests were comparable in the three groups. Overall, there were no significant differential changes in any of the cognitive domains for either low-dose or high-dose fish oil supplementation compared with placebo. Conclusions: In this randomized, double-blind, placebo-controlled trial, we observed no overall effect of 26 weeks of eicosapentaenoic acid and docosahexaenoic acid supplementation on cognitive performance.

Cognitive assessment of children at age 2(1/2) years after maternal fish oil supplementation in pregnancy: a randomised controlled trial.

Abstract: Objective To assess the effects of antenatal omega 3 long-chain polyunsaturated fatty acid (n-3 LC PUFA) on cognitive development in a cohort of children whose mothers received high-dose fish oil in pregnancy. Design A double-blind randomised placebo-controlled trial. Setting Perth, Western Australia, Australia. Patients 98 pregnant women received the supplementation from 20 weeks' gestation until delivery. Their infants (n = 72) were assessed at age 2(1/2) years. Interventions Fish oil (2.2 g docosahexaenoic acid (DHA) and 1.1 g eicosapentaenoic acid (EPA)/day) or olive oil from 20 weeks' gestation until delivery. Outcome measures Effects on infant growth and developmental quotients (Griffiths Mental Development Scales), receptive language (Peabody Picture Vocabulary Test) and behaviour (Child Behaviour Checklist). Results Children in the fish oil-supplemented group (n = 33) attained a significantly higher score for eye and hand coordination (mean ((SD) score 114 (10.2)) than those in the placebo group (n = 39, mean score 108 (SD 11.3); p = 0.021, adjusted p = 0.008). Eye and hand coordination scores correlated with n-3 PUFA levels in cord blood erythrocytes (EPA: r = 0.320, p = 0.007; DHA: r = 0.308, p = 0.009) and inversely correlated with n-6 PUFA (arachidonic acid 20:4n-6: r = -0.331, p = 0.005). Growth measurements in the two groups were similar at age 2(1/2) years. Conclusion Maternal fish oil supplementation during pregnancy is safe for the fetus and infant, and may have potentially beneficial effects on the child's eye and hand coordination. Further studies are needed to determine the significance of this finding.

Genetic variants of the FADS1 FADS2 gene cluster are associated with altered (n-6) and (n-3) essential fatty acids in plasma and erythrocyte phospholipids in women during pregnancy and in breast milk during lactation.

Abstract: The enzymes encoded by fatty acid desaturase (FADS) 1 and FADS2 are rate-limiting enzymes in the desaturation of linoleic acid [LA; 18:2(n-6)] to arachidonic acid [ARA; 20:4(n-6)], and alpha-linolenic acid [ALA; 18:3(n-3)] to eicosapentaenoic acid [EPA; 20:5(n-3)] and docosahexaenoic acid [DHA; 22:6(n-3)]. ARA, EPA, and DHA play central roles in infant growth, neural development, and immune function. The maternal ARA, EPA, and DHA status in gestation influences maternal-to-infant transfer and breast milk provides fatty acids for infants after birth. We determined if single nucleotide polymorphisms in FADS1 and FADS2 influence plasma phospholipid and erythrocyte ethanolamine phosphoglyceride (EPG) (n-6) and (n-3) fatty acids of women in pregnancy or their breast milk during lactation. We genotyped rs174553, rs99780, rs174575, and rs174583 in the FADS1 FADS2 gene cluster and analyzed plasma and erythrocyte fatty acids and dietary intake for 69 pregnant women and breast milk for a subset of 54 women exclusively breast-feeding at 1 mo postpartum. Minor allele homozygotes of rs174553(GG), rs99780(TT), and rs174583(TT) had lower ARA but higher LA in plasma phospholipids and erythrocyte EPG and decreased (n-6) and (n-3) fatty acid product:precursor ratios at 16 and 36 wk of gestation. Breast milk fatty acids were influenced by genotype, with significantly lower 14:0, ARA, and EPA but higher 20:2(n-6) in the minor allele homozygotes of rs174553(GG), rs99780(TT), and rs174583(TT) and lower ARA, EPA, 22:5(n-3), and DHA in the minor allele homozygotes G/G of rs174575. We showed that genetic variants of FADS1 and FADS2 influence blood lipid and breast milk essential fatty acids in pregnancy and lactation.

Omega-3 fatty acids for cardioprotection

Abstract: The most compelling evidence for the cardiovascular benefit provided by omega-3 fatty acids comes from 3 large controlled trials of 32,000 participants randomized to receive omega-3 fatty acid supplements containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or to act as controls These trials showed reductions in cardiovascular events of 19% to 45% These findings suggest that intake of omega-3 fatty acids, whether from dietary sources or fish oil supplements, should be increased, especially in those with or at risk for coronary artery disease Patients should consume both DHA and EPA The target DHA and EPA consumption levels are about 1 g/d for those with known coronary artery disease and at least 500 mg/d for those without disease Patients with hypertriglyceridemia benefit from treatment with 3 to 4 g/d of DHA and EPA, a dosage that lowers triglyceride levels by 20% to 50% Although 2 meals of oily fish per week can provide 400 to 500 mg/d of DHA and EPA, secondary prevention patients and those with hypertriglyceridemia must use fish oil supplements if they are to reach 1 g/d and 3 to 4 g/d of DHA and EPA, respectively Combination therapy with omega-3 fatty acids and a statin is a safe and effective way to improve lipid levels and cardiovascular prognosis beyond the benefits provided by statin therapy alone Blood DHA and EPA levels could one day be used to identify patients with deficient levels and to individualize therapeutic recommendations

Neurological Benefits of Omega-3 Fatty Acids

Abstract: The central nervous system is highly enriched in long-chain polyunsaturated fatty acid (PUFA) of the omega-6 and omega-3 series. The presence of these fatty acids as structural components of neuronal membranes influences cellular function both directly, through effects on membrane properties, and also by acting as a precursor pool for lipid-derived messengers. An adequate intake of omega-3 PUFA is essential for optimal visual function and neural development. Furthermore, there is increasing evidence that increased intake of the long-chain omega-3 PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may confer benefits in a variety of psychiatric and neurological disorders, and in particular neurodegenerative conditions. However, the mechanisms underlying these beneficial effects are still poorly understood. Recent evidence also indicates that in addition to the positive effects seen in chronic neurodegenerative conditions, omega-3 PUFA may also have significant neuroprotective potential in acute neurological injury. Thus, these compounds offer an intriguing prospect as potentially new therapeutic approaches in both chronic and acute conditions. The purpose of this article is to review the current evidence of the neurological benefits of omega-3 PUFA, looking specifically at neurodegenerative conditions and acute neurological injury.

Prescription omega-3 fatty acids and their lipid effects: physiologic mechanisms of action and clinical implications

Abstract: Hypertriglyceridemia is a risk factor for atherosclerotic coronary heart disease. Very high triglyceride (TG) levels (> or =500 mg/dl [5.65 mmol/l]) increase the risk of pancreatitis. One therapeutic option to lower TG levels is omega-3 fatty acids, which are derived from the oil of fish and other seafood. The American Heart Association has acknowledged that fish oils may decrease dysrhythmias, decrease sudden death, decrease the rate of atherosclerosis and slightly lower blood pressure, and has recommended fish consumption or fish oil supplementation as a therapeutic strategy to reduce cardiovascular disease. A prescription omega-3-acid ethyl esters (P-OM3) preparation has been available in many European nations for at least a decade, and was approved by the US FDA in 2004 to reduce very high TG levels (> or =500 mg/dl [5.65 mmol/l]). Mechanistically, most evidence suggests that omega-3 fatty acids reduce the synthesis and secretion of very-low-density lipoprotein (VLDL) particles, and increase TG removal from VLDL and chylomicron particles through the upregulation of enzymes, such as lipoprotein lipase. Omega-3 fatty acids differ mechanistically from other lipid-altering drugs, which helps to explain why therapies such as P-OM3 have complementary mechanisms of action and, thus, complementary lipid benefits when administered with statins. Additional human studies are needed to define more clearly the cellular and molecular basis for the TG-lowering effects of omega-3 fatty acids and their favorable cardiovascular effects, particularly in patients with hypertriglyceridemia.

Thraustochytrid Marine Protists: production of PUFAs and Other Emerging Technologies.

Abstract: Thraustochytrids, the heterotrophic, marine, straminipilan protists, are now established candidates for commercial production of the omega-3 polyunsaturated fatty acid (ω-3 PUFA), docosahexaenoic acid (DHA), that is important in human health and aquaculture. Extensive screening of cultures from a variety of habitats has yielded strains that produce at least 50% of their biomass as lipids, and DHA comprising at least 25% of the total fatty acids, with a yield of at least 5 g L−1. Most of the lipids occur as triacylglycerols and a lesser amount as phospholipids. Numerous studies have been carried out on salinity, pH, temperature, and media optimization for DHA production. Commercial production is based on a fed batch method, using high C/N ratio that favors lipid accumulation. Schizochytrium DHA is now commercially available as nutritional supplements for adults and as feeds to enhance DHA levels in larvae of aquaculture animals. Thraustochytrids are emerging as a potential source of other PUFAs such as arachidonic acid and oils with a suite of PUFA profiles that can have specific uses. They are potential sources of asataxanthin and carotenoid pigments, as well as other lipids. Genes of the conventional fatty acid synthesis and the polyketide-like PUFA synthesis pathways of thraustochytrids are attracting attention for production of recombinant PUFA-containing plant oils. Future studies on the basic biology of these organisms, including biodiversity, environmental adaptations, and genome research are likely to point out directions for biotechnology explorations. Potential areas include enzymes, polysaccharides, and secondary metabolites.

Lipid peroxidation products as oxidative stress biomarkers.

Abstract: Oxidative stress induced by reactive oxygen and nitrogen species has been implicated in the pathogenesis of various disorders and diseases Biomarkers are needed for assessment of oxidative stress status in vivo and also for health examination, diagnosis at early stage, prognosis, safe and efficient drug development, and evaluation of efficacy of drugs, foods, beverages, and supplements Lipids are susceptible to oxidation and lipid peroxidation products are potential biomarkers for oxidative stress status in vivo and its related diseases Recently, isoprostane, isoprostaglandin homologues from arachidonic acid, neuroprostanes from docosahexaenoic acid, hydroxyoctadecadienoic acid from linoleic acid, and oxysterols from cholesterol have received much attention as potential biomarkers for oxidative stress status in vivo The physiological levels of these lipid peroxidation products and potential application as biomarkers will be reviewed

Improved cognitive development among preterm infants attributable to early supplementation of human milk with docosahexaenoic acid and arachidonic acid.

Abstract: OBJECTIVE. The objective of our study was to evaluate the effect of supplementation with docosahexaenoic acid and arachidonic acid for human milk-fed preterm infants. The primary end point was cognitive development at 6 months of age. METHODS. The study was a randomized, double-blind, placebo-controlled study among 141 infants with birth weights of <1500 g. The intervention with 32 mg of docosahexaenoic acid and 31 mg of arachidonic acid per 100 mL of human milk started 1 week after birth and lasted until discharge from the hospital (on average, 9 weeks). Cognitive development was evaluated at 6 months of age by using the Ages and Stages Questionnaire and event-related potentials, a measure of brain correlates related to recognition memory. RESULTS. There was no difference in adverse events or growth between the 2 groups. At the 6-month follow-up evaluation, the intervention group performed better on the problem-solving subscore, compared with the control group (53.4 vs 49.5 points). There was also a nonsignificant higher total score (221 vs 215 points). The eventrelated potential data revealed that infants in the intervention group had significantly lower responses after the standard image, compared with the control group (8.6 vs 13.2). There was no difference in responses to novel images. CONCLUSIONS. Supplementation with docosahexaenoic acid and arachidonic acid for very preterm infants fed human milk in the early neonatal period was associated with better recognition memory and higher problem-solving scores at 6 months (Less)

Effect of Supplementing Pregnant and Lactating Mothers With n-3 Very-Long-Chain Fatty Acids on Children's IQ and Body Mass Index at 7 Years of Age

Abstract: OBJECTIVES. Arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6 n -3) are essential for brain growth and cognitive development. We have reported that supplementing pregnant and lactating women with n -3 very-long-chain polyunsaturated fatty acids promotes higher IQ scores at 4 years of age as compared with maternal supplementation with n -6 polyunsaturated fatty acids. In our present study, the children were examined at 7 years of age with the same cognitive tests as at 4 years of age. We also examined the relation between plasma fatty acid pattern and BMI in children, because an association between arachidonic acid and adipose tissue size has been suggested. METHODS. The study was randomized and double-blinded. The mothers took 10 mL of cod liver oil or corn oil from week 18 of pregnancy until 3 months after delivery. Their children were tested with the Kaufman Assessment Battery for Children at 7 years of age, and their height and weight were measured. RESULTS. We did not find any significant differences in scores on the Kaufman Assessment Battery for Children test at 7 years of age between children whose mothers had taken cod liver oil ( n = 82) or corn oil ( n = 61). We observed, however, that maternal plasma phospholipid concentrations of α-linolenic acid (18:3 n -3) and docosahexaenoic acid during pregnancy were correlated to sequential processing at 7 years of age. We observed no correlation between fatty acid status at birth or during the first 3 months of life and BMI at 7 years of age. CONCLUSION. This study suggests that maternal concentration of n-3 very-long-chain polyunsaturated fatty acids during pregnancy might be of importance for later cognitive function, such as sequential processing, although we observed no significant effect of n -3 fatty acid intervention on global IQs. Neonatal fatty acid status had no influence on BMI at 7 years of age.

Anti-inflammatory properties of omega-3 fatty acids in critical illness: novel mechanisms and an integrative perspective

Abstract: Fish oil-based nutrition is protective in severe critical care conditions. Regulation of the activity of transcription factor NF-κB is an important therapeutic effect of the major omega-3 fatty acids in fish oil, eicosapentaenoic and docosahexaenoic acid (EPA and DHA). Using the articles obtained by a Pubmed research, this article reviews three aspects of NF-κB/inflammatory inhibition by fish oil. (1) Inhibition of the NF-κB pathway at several subsequent steps: extracellular, free omega-3 inhibits the activation of the Toll-like receptor 4 by endotoxin and free saturated fatty acids. In addition, EPA/DHA blocks the signaling cascade between Toll-like/cytokine receptors and the activator of NF-κB, IKK. Oxidized omega-3 also interferes with the initiation of transcription by NF-κB. (2) The altered profile of lipid mediators generated during inflammation, with production of the newly identified, DHA-derived inflammation-resolving mediator classes (in addition to the formation of less pro-inflammatory eicosanoids from EPA). Resolvin D1 and Protectin D1 are potent, endogenous, DHA-derived lipid mediators that attenuate neutrophil migration and tissue injury in peritonitis and ischemia-reperfusion injury. Their production is increased in the later stages of an inflammatory response, at which time they enhance the removal of neutrophils. (3) Modulation of vagal tone with potential anti-inflammatory effects: vagal fibers innervating the viscera down-regulate inflammation by activating nicotinic receptors upon infiltrating and resident macrophages. Stimulation of the efferent vagus is therapeutic in experimental septic shock. Fish oil supplementation increases vagal tone following myocardial infarction and in experimental human endotoxinemia. It remains to be shown whether these pleiotropic actions of EPA/DHA contribute to fish oil’s therapeutic effect in sepsis.

The omega-6/omega-3 fatty acid ratio, genetic variation, and cardiovascular disease.

Abstract: A high omega-6/omega-3 ratio, as is found in today's Western diets, promotes the pathogenesis of many chronic diseases, including cardiovascular disease. Increased dietary intake of linoleic acid (LA) leads to oxidation of low-density lipoprotein (LDL), platelet aggregation, and interferes with the incorporation of essential fatty acids (EFA) in cell membrane phopholipids. Both omega-6 and omega-3 fatty acids influence gene expression. Omega-3 fatty acids have strong anti-inflammatory effects, suppress interleukin 1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6), whereas omega-6 fatty acids tend to be pro-inflammatory. Because inflammation is at the base of many chronic diseases, including coronary heart disease, dietary intake of omega-3 fatty acids plays an important role in the manifestation of disease, particularly in persons with genetic variation, as for example in individuals with genetic variants at the 5-lipoxygenase (5-LO). Increased dietary arachidonic acid (AA) significantly enhances the apparent atherogenic effect of genotype, whereas increased dietary intake of omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) blunts this effect. The diet-gene interaction further suggests that dietary omega-6 fatty acids promote, whereas marine omega-3 fatty acids EPA and DHA inhibit leukotriene-mediated inflammation that leads to atherosclerosis in this subpopulation.

Essential fatty acids and their metabolites could function as endogenous HMG-CoA reductase and ACE enzyme inhibitors, anti-arrhythmic, anti-hypertensive, anti-atherosclerotic, anti-inflammatory, cytoprotective, and cardioprotective molecules

Abstract: Lowering plasma low density lipoprotein-cholesterol (LDL-C), blood pressure, homocysteine, and preventing platelet aggregation using a combination of a statin, three blood pressure lowering drugs such as a thiazide, a β blocker, and an angiotensin converting enzyme (ACE) inhibitor each at half standard dose; folic acid; and aspirin-called as polypill- was estimated to reduce cardiovascular events by ~80%. Essential fatty acids (EFAs) and their long-chain metabolites: γ-linolenic acid (GLA), dihomo-GLA (DGLA), arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) and other products such as prostaglandins E1 (PGE1), prostacyclin (PGI2), PGI3, lipoxins (LXs), resolvins, protectins including neuroprotectin D1 (NPD1) prevent platelet aggregation, lower blood pressure, have anti-arrhythmic action, reduce LDL-C, ameliorate the adverse actions of homocysteine, show anti-inflammatory actions, activate telomerase, and have cytoprotective properties. Thus, EFAs and their metabolites show all the classic actions expected of the "polypill". Unlike the proposed "polypill", EFAs are endogenous molecules present in almost all tissues, have no significant or few side effects, can be taken orally for long periods of time even by pregnant women, lactating mothers, and infants, children, and adults; and have been known to reduce the incidence cardiovascular diseases including stroke. In addition, various EFAs and their long-chain metabolites not only enhance nitric oxide generation but also react with nitric oxide to yield their respective nitroalkene derivatives that produce vascular relaxation, inhibit neutrophil degranulation and superoxide formation, inhibit platelet activation, and possess PPAR-γ ligand activity and release NO, thus prevent platelet aggregation, thrombus formation, atherosclerosis, and cardiovascular diseases. Based on these evidences, I propose that a rational combination of ω-3 and ω-6 fatty acids and the co-factors that are necessary for their appropriate action/metabolism is as beneficial as that of the combined use of a statin, thiazide, a β blocker, and an angiotensin converting enzyme (ACE) inhibitor, folic acid, and aspirin. Furthermore, appropriate combination of ω-3 and ω-6 fatty acids may even show additional benefits in the form of protection from depression, schizophrenia, Alzheimer's disease, and enhances cognitive function; and serve as endogenous anti-inflammatory molecules; and could be administered from childhood for life long.

Intakes of long-chain omega-3 fatty acid associated with reduced risk for death from coronary heart disease in healthy adults.

Abstract: Numerous organizations and national health agencies have begun to recommend consumption of the long-chain omega-3 fatty acids (FAs) eicosapentaenoic acid and docosahexaenoic acid (EPA and DHA), respectively, in pill or fish form for general cardiovascular health The purpose of this article is to present a rationale for an official target intake of 400 to 500 mg/d of EPA + DHA in the United States Six epidemiologic studies reporting EPA + DHA intake and risk of coronary heart disease (CHD) death have been conducted in the United States, and five studies reported statistically significant inverse trends Meta-analysis of these data showed a significant dose-response relationship between risk for CHD death and intake (P = 003), with relative risk reductions of 37% at an average EPA + DHA intake of 566 mg/d Coincidentally, two servings per week of oily fish (the current American Heart Association recommendation) would provide 400 to 500 mg/d We conclude, therefore, that an intake of 400 to 500 mg/d of EPA + DHA is achievable by diet alone and would be expected to significantly reduce risk for death from CHD in healthy adults

The relationship of dietary omega-3 long-chain polyunsaturated fatty acid intake with incident age-related macular degeneration: AREDS report no. 23.

Abstract: Objective To examine the association of dietary ω-3 long-chain polyunsaturated fatty acid and fish intake with incident neovascular age-related macular degeneration (AMD) and central geographic atrophy (CGA). Methods Multicenter clinic-based prospective cohort study from a clinical trial including Age-Related Eye Disease Study (AREDS) participants with bilateral drusen at enrollment. Main outcome measures were incident neovascular AMD and CGA, ascertained from annual stereoscopic color fundus photographs (median follow-up, 6.3 years). We estimated nutrient and food intake from a validated food frequency questionnaire (FFQ) at baseline, with intake of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), c ombined EPA and DHA, and fish as primary exposures. Results After controlling for known covariates, we observed a reduced likelihood of progression from bilateral drusen to CGA among people who reported the highest levels of EPA (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.23-0.87) and EPA+DHA (OR, 0.45; 95% CI, 0.23-0.90) consumption. Levels of DHA were associated with CGA in age-, sex-, and calorie-adjusted models (OR, 0.51; 95% CI, 0.26-1.00); however, this statistical relationship did not persist in multivariable models. Conclusions Dietary lipid intake is a modifiable factor that may influence the likelihood of developing sight-threatening forms of AMD. Our findings suggest that dietary ω-3 long-chain polyunsaturated fatty acid intake is associated with a decreased risk of progression from bilateral drusen to CGA.