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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^1,2,3

¹ From the Tufts–New England Medical Center Evidence-based Practice Center, Institute for Clinical Research and Health Policy Studies, Tufts–New England Medical Center, Boston, MA (CW, MC, EMB, BK, and JL); the University of Missouri–Kansas City and the Mid America Heart Institute, Saint Luke's Hospital, Kansas City, MO (WSH); the Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA (AHL); and Abt Associates Inc, Cambridge, MA (HSJ)

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 -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 -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.

Key Words: n–3 Fatty acids • eicosapentaenoic acid • docosahexaenoic acid • fish oil • linolenic acid • cardiovascular disease • adverse events • systematic review

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