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  1. Kris-Etherton PM, Harris WS, Appel LJ. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002; 106(21):2747-2757.


*Quick Summary of Study: Fish oil was found to have beneficial effects against cardiovascular disease.


Since the first AHA Science Advisory “Fish Consumption, Fish Oil, Lipids, and Coronary Heart Disease,”1 important new findings, including evidence from randomized controlled trials (RCTs), have been reported about the beneficial effects of omega-3 (or n-3) fatty acids on cardiovascular disease (CVD) in patients with preexisting CVD as well as in healthy individuals.2 New information about how omega-3 fatty acids affect cardiac function (including antiarrhythmic effects), hemodynamics (cardiac mechanics), and arterial endothelial function have helped clarify potential mechanisms of action. The present Statement will address distinctions between plant-derived (α-linolenic acid, C18:3n-3) and marine-derived (eicosapentaenoic acid, C20:5n-3 [EPA] and docosahexaenoic acid, C22:6n-3 [DHA]) omega-3 fatty acids. (Unless otherwise noted, the term omega-3 fatty acids will refer to the latter.) Evidence from epidemiological studies and RCTs will be reviewed, and recommendations reflecting the current state of knowledge will be made with regard to both fish consumption and omega-3 fatty acid (plant- and marine-derived) supplementation. This will be done in the context of recent guidance issued by the US Environmental Protection Agency and the Food and Drug Administration (FDA) about the presence of environmental contaminants in certain species of fish.

2.Hu FB, Bronner L, Willett WC, et al. Fish and omega-3 fatty acid intake and risk of coronary heart disease in women. JAMA. 2002; 287: 1815�182.


*Quick Summary of Study: Fish oil consumption in women was found to reduce the risk of coronary heart disease.


Context �Higher consumption of fish and omega-3 fatty acids has been associated with a lower risk of coronary heart disease (CHD) in men, but limited data are available regarding women.

Objective �To examine the association between fish and long-chain omega-3 fatty acid consumption and risk of CHD in women.

Design, Setting, and Participants �Dietary consumption and follow-up data from 84 688 female nurses enrolled in the Nurses' Health Study, aged 34 to 59 years and free from cardiovascular disease and cancer at baseline in 1980, were compared from validated questionnaires completed in 1980, 1984, 1986, 1990, and 1994.

Main Outcome Measures �Incident nonfatal myocardial infarction and CHD deaths.

Results �During 16 years of follow-up, there were 1513 incident cases of CHD (484 CHD deaths and 1029 nonfatal myocardial infarctions). Compared with women who rarely ate fish (<1 per month), those with a higher intake of fish had a lower risk of CHD. After adjustment for age, smoking, and other cardiovascular risk factors, the multivariable relative risks (RRs) of CHD were 0.79 (95% confidence interval [CI], 0.64-0.97) for fish consumption 1 to 3 times per month, 0.71 (95% CI, 0.58-0.87) for once per week, 0.69 (95% CI, 0.55-0.88) for 2 to 4 times per week, and 0.66 (95% CI, 0.50-0.89) for 5 or more times per week (P for trend = .001). Similarly, women with a higher intake of omega-3 fatty acids had a lower risk of CHD, with multivariable RRs of 1.0, 0.93, 0.78, 0.68, and 0.67 (P<.001 for trend) across quintiles of intake. For fish intake and omega-3 fatty acids, the inverse association appeared to be stronger for CHD deaths (multivariate RR for fish consumption 5 times per week, 0.55 [95% CI, 0.33-0.90] for CHD deaths vs 0.73 [0.51-1.04]) than for nonfatal myocardial infarction.

Conclusion �Among women, higher consumption of fish and omega-3 fatty acids is associated with a lower risk of CHD, particularly CHD deaths.

3. Hu FB, Stampfer MJ, Manson JE, et al. Dietary intake of alpha-linolenic acid and risk of ischemic heart disease among women. Am J Clin Nutr.1999;69:890-897


*Quick Summary of Study: Omega 3 consumption was shown to provide protection against ischemic heart disease.


Background: Experimental studies in laboratory animals and humans suggest that α-linolenic acid (18:3n-3) may reduce the risk of arrhythmia.

Objective: The objective was to examine the association between dietary intake of α-linolenic acid and risk of fatal ischemic heart disease (IHD).

Design: This was a prospective cohort study. The intake of α-linolenic acid was derived from a 116-item food-frequency questionnaire completed in 1984 by 76283 women without previously diagnosed cancer or cardiovascular disease.

Results: During 10 y of follow-up, we documented 232 cases of fatal IHD and 597 cases of nonfatal myocardial infarction. After adjustment for age, standard coronary risk factors, and dietary intake of linoleic acid and other nutrients, a higher intake of α-linolenic acid was associated with a lower relative risk (RR) of fatal IHD; the RRs from the lowest to highest quintiles were 1.0, 0.99, 0.90, 0.67, and 0.55 (95% CI: 0.32, 0.94; P for trend = 0.01). For nonfatal myocardial infarction there was only a modest, nonsignificant trend toward a reduced risk when extreme quintiles were compared (RR: 0.85; 95% CI: 0.61, 1.19; P for trend = 0.50). A higher intake of oil and vinegar salad dressing, an important source of α-linolenic acid, was associated with reduced risk of fatal IHD when women who consumed this food ≥5�6 times/wk were compared with those who rarely consumed this food (RR: 0.46; 95% CI: 0.27, 0.76; P for trend = 0.001).

Conclusions: This study supports the hypothesis that a higher intake of α-linolenic acid is protective against fatal IHD. Higher consumption of foods such as oil-based salad dressing that provide polyunsaturated fats, including α-linolenic acid, may reduce the risk of fatal IHD.

Key Words: Ischemic heart disease � diet � α-linolenic acid � risk � Nurses' Health Study � trans fatty acids � women

4. Wang C, Harris W, Chung M, Lichtenstein A, Balk E, Kupelnick B, Jordan H La J. �N-3 Fatty acids from fish or fish-oil supplements, but not �linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review. Am J Clin Nutr. July 2006; 84(1): 5-17.

*Quick Summary of Study: Fish oil supplementation was found to have lower rates of cardiovascular disease among those individuals



Studies on the relation between dietary n�3 fatty acids (FAs) and cardiovascular disease vary in quality, and the results are inconsistent. A systematic review of the literature on the effects of n�3 FAs (consumed as fish or fish oils rich in eicosapentaenoic acid and docosahexaenoic acid or as α-linolenic acid) on cardiovascular disease outcomes and adverse events was conducted. Studies from MEDLINE and other sources that were of ≥1 y in duration and that reported estimates of fish or n�3 FA intakes and cardiovascular disease outcomes were included. Secondary prevention was addressed in 14 randomized controlled trials (RCTs) of fish-oil supplements or of diets high in n�3 FAs and in 1 prospective cohort study. Most trials reported that fish oil significantly reduced all-cause mortality, myocardial infarction, cardiac and sudden death, or stroke. Primary prevention of cardiovascular disease was reported in 1 RCT, in 25 prospective cohort studies, and in 7 case-control studies. No significant effect on overall deaths was reported in 3 RCTs that evaluated the effects of fish oil in patients with implantable cardioverter defibrillators. Most cohort studies reported that fish consumption was associated with lower rates of all-cause mortality and adverse cardiac outcomes. The effects on stroke were inconsistent. Evidence suggests that increased consumption of n�3 FAs from fish or fish-oil supplements, but not of α-linolenic acid, reduces the rates of all-cause mortality, cardiac and sudden death, and possibly stroke. The evidence for the benefits of fish oil is stronger in secondary- than in primary-prevention settings. Adverse effects appear to be minor.

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