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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. 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.

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.

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.

Synergistic anti-inflammatory effects of low doses of curcumin in combination with polyunsaturated fatty acids: docosahexaenoic acid or eicosapentaenoic acid. Saw CL, Huang Y, Kong AN. Biochem Pharmacol. 2010 Feb 1;79(3):421-30. Epub 2009 Sep 8. PMID: 19744468

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.

"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. "

Yukihisa TANAKA, Takashi OHKUBO, Nobuo FUKUDA and Hidehiko HIBINO, "Effect of Molecular Forms on Distribution of Docosahexaenoic Acid into Organs in Mice", J. Oleo Sci., Vol. 52, 89-97 (2003) .

Song JH, Fujimoto K, Miyazawa T. Polyunsaturated (n-3) fatty acids susceptible to peroxidation are increased in plasma and tissue lipids of rats fed docosahexaenoic acid-containing oils. J Nutr. 2000 Dec;130(12):3028-33. PMID: 11110863 [PubMed - index

Docosahexaenoic acid-enriched egg consumption induces accretion of arachidonic acid in erythrocytes of elderly patients. Payet M, Esmail MH, Polichetti E, Le Brun G, Adjemout L, Donnarel G, Portugal H, Pieroni G. Br J Nutr. 2004 May;91(5):789-96. PMID: 15137931 doi:10.1079/BJN20041106

Why fish oils may not always be adequate treatments for depression or other inflammatory illnesses: docosahexaenoic acid, an omega-3 polyunsaturated fatty acid, induces a Th-1-like immune response. Maes M, Mihaylova I, Kubera M, Bosmans E. Neuro Endocrinol Lett. 2007 Dec;28(6):875-80. PMID: 18063921

DHA and EPA generally modulated different sets of genes, although a few common effects were noted. In our approach, we used preneoplastic adenoma cells which are a relevant model for target cells of chemoprevention. If verified with real time PCR, these results identify genes and targets for chemoprevention of colon cancer. Modulation of gene expression in eicosapentaenoic acid and docosahexaenoic acid treated human colon adenoma cells. Habermann N, Lund EK, Pool-Zobel BL, Glei M. Genes Nutr. 2009 Mar;4(1):73-6. Epub 2009 Feb 21. PMID: 19234733 doi: 10.1007/s12263-009-0112-y.

Antioxidative and anti-inflammatory actions of docosahexaenoic acid and eicosapentaenoic acid in renal epithelial cells and macrophages. Kim YJ, Chung HY. J Med Food. 2007 Jun;10(2):225-31. PMID: 17651056 doi:10.1089/jmf.2006.092.

Docosahexaenoic acid induces an anti-inflammatory profile in lipopolysaccharide-stimulated human THP-1 macrophages more effectively than eicosapentaenoic acid. Weldon SM, Mullen AC, Loscher CE, Hurley LA, Roche HM. J Nutr Biochem. 2007 Apr;18(4):250-8. Epub 2006 Jun 16. PMID: 16781858 doi:10.1016/j.jnutbio.2006.04.003

Docosahexaenoic acid suppresses arachidonic acid-induced proliferation of LS-174T human colon carcinoma cells. Habbel P, Weylandt KH, Lichopoj K, Nowak J, Purschke M, Wang JD, He CW, Baumgart DC, Kang JX. World J Gastroenterol. 2009 Mar 7;15(9):1079-84. PMID: 19266600 doi: 10.3748/wjg.15.1079.

Hemostatic factors and platelet aggregation after a fish-enriched diet or fish oil or docosahexaenoic acid supplementation. Agren JJ, Väisänen S, Hänninen O, Muller AD, Hornstra G. Prostaglandins Leukot Essent Fatty Acids. 1997 Oct;57(4-5):419-21. PMID: 9430389 doi:10.1016/S0952-3278(97)90421-X    

Arachidonic acid and docosahexaenoic acid supplementation increases coronary flow velocity reserve in Japanese elderly individuals. Oe H, Hozumi T, Murata E, Matsuura H, Negishi K, Matsumura Y, Iwata S, Ogawa K, Sugioka K, Takemoto Y, Shimada K, Yoshiyama M, Ishikura Y, Kiso Y, Yoshikawa J. Heart. 2008 Mar;94(3):316-21. Epub 2007 Jun 25. PMID: 17591648 doi:10.1136/hrt.2006.113159

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.

"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"