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n-3 fatty acid dietary recommendations and food sources to achieve essentiality and cardiovascular benefits. Gebauer SK, Psota TL, Harris WS, Kris-Etherton PM. Am J Clin Nutr. 2006 Jun;83(6 Suppl):1526S-1535S. Review. PMID: 16841863 Dietary recommendations have been made for n-3 fatty acids, including {alpha}-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) to achieve nutrient adequacy and to prevent and treat cardiovascular disease. These recommendations are based on a large body of evidence from epidemiologic and controlled clinical studies. The n-3 fatty acid recommendation to achieve nutritional adequacy, defined as the amount necessary to prevent deficiency symptoms, is 0.6-1.2% of energy for ALA; up to 10% of this can be provided by EPA or DHA. To achieve recommended ALA intakes, food sources including flaxseed and flaxseed oil, walnuts and walnut oil, and canola oil are recommended. The evidence base supports a dietary recommendation of {approx}500 mg/d of EPA and DHA for cardiovascular disease risk reduction. For treatment of existing cardiovascular disease, 1 g/d is recommended. These recommendations have been embraced by many health agencies worldwide. A dietary strategy for achieving the 500-mg/d recommendation is to consume 2 fish meals per week (preferably fatty fish). Foods enriched with EPA and DHA or fish oil supplements are a suitable alternate to achieve recommended intakes and may be necessary to achieve intakes of 1 g/d.

Melanoma growth is reduced in fat-1 transgenic mice: impact of omega-6/omega-3 essential fatty acids. Xia S, Lu Y, Wang J, He C, Hong S, Serhan CN, Kang JX. Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12499-504. Epub 2006 Aug 3. PMID: 16888035 doi: 10.1073/pnas.0605394103 In vitro experiments showed that addition of the n-3 fatty acid eicosapentaenoic acid or PGE(3) inhibited the growth of B16 cell line and increased the expression of PTEN, which could be partially attenuated by inhibition of PGE(3) production, suggesting that PGE(3) may act as an antitumor mediator. These data demonstrate an anticancer (antimelanoma) effect of n-3 fatty acids through, at least in part, activation of PTEN pathway mediated by PGE(3).

Fungal treatment of a biodiesel byproduct can produce the omega-3 fatty acid EPA (eicosapentaenoic acid), offering a potentially economical source of EPA from microbes.\nGrowing the fungus Pythium irregulare in a crude glycerol and a yeast extract can lead to production of an EPA-rich biomass that could be used as an omega-3 fortified food, according to researchers from Virginia Polytechnic Institute and State University and the USDA's Agricultural Research Service.\n\nThe findings are published online ahead of print in the Journal of Agricultural and Food Chemistry.

March 7, 2005 Boston, MA - The anti-inflammatory effect of fish oils appears to be due to a powerful anti-inflammatory compound called resolvin (resolution-phase interaction product) E1, which is produced from eicosapentaenoic acid (EPA), Dr Makoto Arita (Brigham and Women's Hospital and Harvard Medical School, Boston, MA) and colleagues report in the March 7, 2005 issue of the Journal of Experimental Medicine [1]. Arita writes, "At nanomolar levels, resolvin E1 dramatically reduced dermal inflammation, peritonitis, dendritic cell migration, and interleukin (IL)-12 production.

Fish consumption and risk of subclinical brain abnormalities on MRI in older adults. Virtanen JK, Siscovick DS, Longstreth WT Jr, Kuller LH, Mozaffarian D. Neurology. 2008 Aug 5;71(6):439-46. PMID: 18678827 doi: 10.1212/01.wnl.0000324414.12665.b0 Conclusions: Among older adults, modest consumption of tuna/other fish, but not fried fish, was associated with lower prevalence of subclinical infarcts and white matter abnormalities on MRI examinations. Our results add to prior evidence that suggest that dietary intake of fish with higher eicosapentaenoic acid and docosahexaenoic acid content, and not fried fish intake, may have clinically important health benefits

Are omega-3 fatty acids options for prevention and treatment of cognitive decline and dementia? Cederholm T, Palmblad J. Curr Opin Clin Nutr Metab Care. 2009 Dec 16. [Epub ahead of print] PMID: 20019606 PURPOSE OF REVIEW: To report recent data on the potential role of omega-3 fatty acids (n-3 FA) found in oily fish, especially docosahexaenoic acid (DHA), to prevent and treat cognitive decline and Alzheimer's disease. RECENT FINDINGS: Observational studies still provide conflicting results, in which the majority indicate beneficial effects on cognition, both when assessed as a continuous variable or as incident dementia, mainly Alzheimer's disease. Experimental studies have demonstrated potentially ameliorating effects of eicosapentaenoic acid (EPA) and DHA on amyloid fragment formation, signal transduction including upregulation of the apolipoprotein receptor SorLA, as well as on angiogenesis. The role of EPA and DHA metabolites on Alzheimer's disease pathology is under investigation. Recently, three randomized intervention studies, with duration up to 6 months have been reported. In contrast to a small study from Taiwan, no positive overall effects were reported from the Swedish OmegAD Study or from a Dutch study, although post hoc analyses indicate that selected individuals with mild forms of Alzheimer's disease or cognitive decline may respond to treatment. SUMMARY: No firm conclusions can be drawn. Based on epidemiological data, fish including oily fish could be advised as part of a balanced diet for public health purpose, although the evidence for better cognition is only fairly consistent. It is unlikely that n-3 FA will emerge as a treatment option in general for improving cognitive function in patients with Alzheimer's disease. n-3 FA, especially DHA, may turn out as an adjuvant therapy in selected cases. Further long-term intervention studies on individuals with mild cognitive reductions are awaite"

"The omega-3 essential fatty acids commonly found in fatty fish and algae help animals avoid sensory overload, according to research published by the American Psychological Association. The finding connects low omega-3s to the information-processing problems found in people with schizophrenia; bipolar, obsessive-compulsive, and attention-deficit hyperactivity disorders; Huntington's disease; and other afflictions of the nervous system. The study, reported in the journal Behavioral Neuroscience, provides more evidence that fish is brain food. The key finding was that two omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) appear to be most useful in the nervous system, maybe by maintaining nerve-cell membranes. "It is an uphill battle now to reverse the message that 'fats are bad,' and to increase omega-3 fats in our diet," said Norman Salem Jr., PhD, who led this study at the Laboratory of Membrane Biochemistry and Biophysics at the National Institute on Alcohol Abuse and Alcoholism.

Quantitative analysis of the benefits and risks of consuming farmed and wild salmon. Foran JA, Good DH, Carpenter DO, Hamilton MC, Knuth BA, Schwager SJ. J Nutr. 2005 Nov;135(11):2639-43. PMID: 16251623 Contaminants in farmed Atlantic and wild Pacific salmon raise important questions about the competing health benefits and risks of fish consumption. A benefit-risk analysis was conducted to compare quantitatively the cancer and noncancer risks of exposure to organic contaminants in salmon with the (n-3) fatty acid-associated health benefits of salmon consumption. Recommended levels of (n-3) fatty acid intake, as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may be achieved by consuming farmed or wild salmon while maintaining an acceptable level of noncarcinogenic risk. However, the recommended level of EPA+DHA intake cannot be achieved solely from farmed or wild salmon while maintaining an acceptable level of carcinogenic risk. Although the benefit-risk ratio for carcinogens and noncarcinogens is significantly greater for wild Pacific salmon than for farmed Atlantic salmon as a group, the ratio for some subgroups of farmed salmon is on par with the ratio for wild salmon. This analysis suggests that risk of exposure to contaminants in farmed and wild salmon is partially offset by the fatty acid-associated health benefits. However, young children, women of child-bearing age, pregnant women, and nursing mothers not at significant risk for sudden cardiac death associated with CHD but concerned with health impairments such as reduction in IQ and other cognitive and behavioral effects, can minimize contaminant exposure by choosing the least contaminated wild salmon or by selecting other sources of (n-3) fatty acids.

n-3 fatty acids and cardiovascular disease. Breslow JL. Am J Clin Nutr. 2006 Jun;83(6 Suppl):1477S-1482S. Review. PMID: 16841857 The results of prospective cohort studies indicate that consuming fish or fish oil containing the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is associated with decreased cardiovascular death, whereas consumption of the vegetable oil-derived n-3 fatty acid {alpha}-linolenic acid is not as effective. Randomized control trials (RCTs) in the context of secondary prevention also indicate that the consumption of EPA plus DHA is protective at doses 3 g/d, EPA plus DHA can improve cardiovascular disease risk factors, including decreasing plasma triacylglycerols, blood pressure, platelet aggregation, and inflammation, while improving vascular reactivity. Mainly on the basis of the results of RCTs, the American Heart Association recommends that everyone eat oily fish twice per week and that those with coronary heart disease eat 1 g/d of EPA plus DHA from oily fish or supplements. Directions for future research include 1) RCTs to confirm the initial trials showing that EPA plus DHA decreases cardiovascular death and additional studies to determine whether this effect is due to EPA, DHA, or the combination; the dosage of the effective components; and whether the mechanism of action in humans is prevention of fatal arrhythmias. 2) Clinical studies to determine whether the reduction in cardiovascular disease risk factors is due to EPA, DHA, or the combination and the dosage of the effective components. 3) Clinical studies to determine whether vegetable oil-derived {alpha}-linolenic acid added to a diet enriched in n-6 fatty acids can effectively substitute for fish oil-derived EPA plus DHA.

Fish oil-derived fatty acids, docosahexaenoic acid and docosapentaenoic acid, and the risk of acute coronary events: the Kuopio ischaemic heart disease risk factor study. Rissanen T, Voutilainen S, Nyyssönen K, Lakka TA, Salonen JT. Circulation. 2000 Nov 28;102(22):2677-9. PMID: 11094031 Methods and Results-We studied this association in the Kuopio Ischaemic Heart Disease Risk Factor Study, a prospective population study in Eastern Finland. Subjects were randomly selected and included 1871 men aged 42 to 60 years who had no clinical coronary heart disease at baseline examination. A total of 194 men had a fatal or nonfatal acute coronary event during follow-up. In a Cox proportional hazards' model adjusting for other risk factors, men in the highest fifth of the proportion of serum DHA+DPA in all fatty acids had a 44% reduced risk (P=0.014) of acute coronary events compared with men in the lowest fifth. Men in the highest fifth of DHA+DPA who had a low hair content of mercury (2.0 µg/g). There was no association between proportion of eicosapentaenoic acid and the risk of acute coronary events. Conclusions-Our data provide further confirmation for the concept that fish oil-derived fatty acids reduce the risk of acute coronary events. However, a high mercury content in fish could attenuate this protective effect.

n-3 Fatty acids and cardiovascular disease: mechanisms underlying beneficial effects. Jung UJ, Torrejon C, Tighe AP, Deckelbaum RJ. Am J Clin Nutr. 2008 Jun;87(6):2003S-9S. PMID: 18541602 Dietary n-3 fatty acids, particularly eicosapentaenoic acid and docosahexaenoic acid, are important nutrients through the life cycle. Evidence from observational, clinical, animal, and in vitro studies indicates a beneficial role of n-3 fatty acids in the prevention and management of cardiovascular disease. Although the precise mechanisms are still unclear, clinical and preclinical studies indicate that the cardioprotective effects of n-3 fatty acids may be attributed to a number of distinct biological effects on lipid and lipoprotein metabolism, blood pressure, platelet function, arterial cholesterol delivery, vascular function, and inflammatory responses. Substantial evidence supports n-3 fatty acids as a practical, therapeutic adjuvant for promoting cardiovascular health and preventing and treating disease. n-3 Fatty acids modulate a number of important physiologic responses that can contribute to their cardioprotective effects. The multiple and complex mechanisms through which DHA and EPA exert their action appear to be distinct but also complementary. However, more studies are needed to quantify their protective effects and to define exact mechanisms of action.

"ScienceDaily (Dec. 16, 2009) - The omega-3 essential fatty acids commonly found in fatty fish and algae help animals avoid sensory overload, according to research published by the American Psychological Association. The finding connects low omega-3s to the information-processing problems found in people with schizophrenia; bipolar, obsessive-compulsive, and attention-deficit hyperactivity disorders; Huntington's disease; and other afflictions of the nervous system The study, reported in the journal Behavioral Neuroscience, provides more evidence that fish is brain food. The key finding was that two omega-3 fatty acids -- docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) -- appear to be most useful in the nervous system, maybe by maintaining nerve-cell membranes"

Omega-3 fatty acids: evidence basis for treatment and future research in psychiatry. Freeman MP, Hibbeln JR, Wisner KL, Davis JM, Mischoulon D, Peet M, Keck PE Jr, Marangell LB, Richardson AJ, Lake J, Stoll AL. J Clin Psychiatry. 2006 Dec;67(12):1954-67. Review. Erratum in: J Clin Psychiatry. 2007 Feb;68(2):338. PMID: 17194275 Conclusions: The preponderance of epidemiologic and tissue compositional studies supports a protective effect of omega-3 EFA intake, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in mood disorders. Meta-analyses of randomized controlled trials demonstrate a statistically significant benefit in unipolar and bipolar depression (p=.02). The results were highly heterogeneous, indicating that it is important to examine the characteristics of each individual study to note the differences in design and execution. There is less evidence of benefit in schizophrenia. EPA and DHA appear to have negligible risks and some potential benefit in major depressive disorder and bipolar disorder, but results remain inconclusive in most areas of interest in psychiatry. Treatment recommendations and directions for future research are described. Health benefits of omega-3 EFA may be especially important in patients with psychiatric disorders, due to high prevalence rates of smoking and obesity and the metabolic side effects of some psychotropic medications.

"July 9, 2008 | Michael O'Riordan Boston, MA - The consumption of a diet containing vegetable oils rich in alpha-linolenic acid (ALA) is associated with significant reductions in the risk of nonfatal MI, a new study has shown [1]. Investigators say the protective effect of ALA is evident among individuals with low intakes, suggesting the greatest benefit might be in developing countries, where fatty-acid consumption is limited. "The potential for benefit is great when the baseline intake is low," said lead investigator Dr Hannia Campos (Harvard Medical School, Boston, MA). "In countries where people eat very little fish-and some of these countries have almost no sources of omega-3 fatty acids because they cook with corn or sunflower oils-the consumption of vegetable oils with ALA could have a major impact on heart disease." In an editorial accompanying the published study [2], Dr William Harris (University of South Dakota, Sioux Falls) said that the data are suggestive and would be good news for individuals who will not or cannot eat fish, but more studies are still needed. "If ALA were able to do the same 'heavy lifting' that [eicosapentaenoic acid] EPA and [docosahexaenoic acid] DHA do, this would be welcomed news, because the capacity to produce ALA is essentially limitless, whereas there are only so many fish in the sea," he writes. "

October 17, 2006 | Steve Stiles Boston, MA - A review of the literature on the health effects of dietary fish or fish-oil intake has a reassuring message for seafood lovers, anyone eating fish for health reasons, and perhaps most everyone else [1]. Levels of mercury and other contaminants in commercially bought fish are low, and their potential risks are overwhelmed by likely reductions in cardiovascular mortality, according to a report in the October 18, 2006 issue of the Journal of the American Medical Association. "The main message is really that everybody should be eating one or two servings of fish or seafood per week for their health," Dr Dariush Mozaffarian (Harvard School of Public Health, Boston, MA) told heartwire. In his analysis, coauthored with Dr Eric B Rimm (Brigham and Women's Hospital, Boston, MA), regular "modest" intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the two long-chain n-3 polyunsaturated fatty acids (PUFAs) abundant in finfish and shellfish (collectively referred to as "fish" in the article), is associated with a 36% drop in coronary disease mortality (p Those potential benefits are immense compared with the highly publicized but apparently low health risks associated with methylmercury, dioxins, and polychlorinated biphenyls (PCBs) that have been found in some fish species, they write. The evidence suggests a potential for neurodevelopmental deficits from early exposure to methylmercury, but the risk is likely diminished by limiting intake of fish with high methylmercur

"June 21, 2006 | Michael O'Riordan Rome, Italy - One of the possible ways in which long-chain omega-3 fatty acids play a role in decreasing cardiovascular events is by entering advanced atherosclerotic plaques. According to the results of a new study, investigators were able to show that the incorporation of eicosapentaenoic acid (EPA) into advanced plaque was associated with a decreased expression of various matrix metalloproteinases (MMPs) involved in causing plaque instability, as well as with decreased plaque inflammation. These are results of the Omacor Carotid Endarterectomy Intervention (OCEAN) study, presented here this week at the International Symposium on Atherosclerosis by Dr Philip Calder (University of Southampton, UK). "By increasing the availability of omega-3 fatty acids, they appear in advanced atherosclerotic plaques, indicated in this study by the carotid artery, and this results in lower numbers of macrophages, foam cells, and T cells, as well as the lower expression of inflammatory markers," said Calder. "Histologically, this results in a plaque that appears to be less inflamed and more stable. This may contribute to reduced mortality in patients consuming omega-3 fatty acids, for example, in the GISSI Prevenzione trial.""

"Nov 14, 2005 | Michael O'Riordan. Dallas, TX - The addition of eicosapentaenoic acid (EPA) to low-dose statin therapy significantly reduced the incidence of major coronary events, largely driven by a reduction in unstable angina, when compared with patients taking statins alone. A subgroup analysis of the study, which involved a large number of primary-prevention patients, revealed that statin-treated secondary-prevention patients gained the most benefit from fish-oil supplementation. Dr Mitsuhiro Yokoyama Presenting the results of the Japan EPA Lipid Intervention Study (JELIS) during the late-breaking clinical-trials session at the American Heart Association Scientific Sessions 2005, Dr Mitsuhiro Yokoyama (Kobe University Graduate School of Medicine, Japan) said that the mechanism of benefit with EPA, a seafood-based, long-chain, n-3 polyunsaturated fatty acid, appears to be unrelated to the effects of cholesterol lowering. Commenting on the results of the study for heartwire, Dr Lawrence Appel (Johns Hopkins University School of Medicine, Baltimore, MD) said the findings are impressive given that the benefit of fish oil was observed on top of a regimen of statin therapy. He added that there are still some unknowns about which patient population would benefit most from fish oil."

"The Japan eicosapentaenoic acid (EPA) Lipid Intervention Study (JELIS) is a clinical trial that all Track Your Plaquers should know about. This enormous trial followed a simple design: Japanese men, between 40-75 years, and Japanese postmenopausal women aged

The effect of omega-3 FAs on tumour angiogenesis and their therapeutic potential. Spencer L, Mann C, Metcalfe M, Webb M, Pollard C, Spencer D, Berry D, Steward W, Dennison A. Eur J Cancer. 2009 Aug;45(12):2077-86. Epub 2009 Jun 1. Review. PMID: 19493674 Omega-3 fatty acid (omega-3 FA) consumption has long been associated with a lower incidence of colon, breast and prostate cancers in many human populations. Human trials have demonstrated omega-3 FA to have profound anti-inflammatory effects in those with cancer. In vitro and small animal studies have yielded a strong body of evidence establishing omega-3 FA as having anti-inflammatory, anti-apoptotic, anti-proliferative and anti-angiogenic effects. This review explores the evidence and the mechanisms by which omega-3 FA may act as angiogenesis inhibitors and identifies opportunities for original research trialling omega-3 FAs as anti-cancer agents in humans. The conclusions drawn from this review suggest that omega-3 FAs in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found principally in oily fish have potent anti-angiogenic effects inhibiting production of many important angiogenic mediators namely; Vascular Endothelial Growth Factor (VEGF), Platelet-Derived Growth Factor (PDGF), Platelet-Derived Endothelial Cell Growth Factor (PDECGF), cyclo-oxygenase 2 (COX-2), prostaglandin-E2 (PGE2), nitric oxide, Nuclear Factor Kappa Beta (NFKB), matrix metalloproteinases and beta-catenin

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