For the past 30 years, omega-3 fatty acids (ω-3 FAs) (eicosapentaenoic [EPA] and docosahexaenoic [DHA] acids) have been associated with reduced rates of myocardial infarction. Several prospective studies examining fish intake and coronary heart disease (CHD) confirmed that regular fish consumption (one or more meals per week) was associated with a risk-adjusted reduction in sudden death compared with low consumption. Other studies, however, have failed to document benefits from fish consumption. O'Keefe and Harris review the clinical implications of studies evaluating ω-3 FA supplementation.

Three prospective, randomized, controlled studies evaluated the benefits of ω-3 FA intake in the secondary prevention of heart disease. The Diet and Reinfarction Trial randomized 2,013 men to usual care or a diet high in ω-3 FAs following myocardial infarction. Patients in the latter group showed a 29 percent reduction in overall mortality over the next two years. The incidence of fatal myocardial infarctions decreased significantly as well. Another trial randomized a similar population to usual care or fish oil supplementation. After one year, there was a significant decrease in serious ventricular arrhythmias and total cardiac events in patients taking the fish oil supplement. The largest study was the GISSI Prevenzione Trial, in which most patients were randomized to usual care or increased intake of ω-3 FA following myocardial infarction. After 3.5 years, patients consuming an increased amount of dietary ω-3 FAs had a statistically significant reduction in total mortality and sudden death. This last study also suggested that the difference in outcome appeared to be independent of traditional risk factors such as lipids and blood pressure, and was additive to the benefit conferred by standard preventive therapies. None of the studies reported serious adverse events associated with increased ω-3 FA intake.

The mechanisms responsible for the protective effect of increased ω-3 FA intake include antidysrhythmic effects, decreased fibrinogen levels and platelet counts, modestly reduced blood pressure and decreased cell proliferation. Improvements in arterial compliance and endothelial function, as well as antiplatelet and anti-inflammatory effects also have been documented. The U.S. Food and Drug Administration has concluded that dietary intake of up to 3 g per day of EPA plus DHA is “Generally Recognized as Safe.” Even though ω-3FA supplementation results in a modest increase in low-density lipoprotein, it is more than offset by marked reductions in atherogenic very-low-density lipoprotein triglyceride levels.

The authors conclude that ω-3 FA supplementation should be considered in patients with documented CHD, especially if they have risk factors for sudden cardiac death. For a list of these risk factors, see the accompanying table. The recommended intake of 1 g per day may be appropriate for all adults with a high CHD risk factor profile. A dietary approach can include four 3-oz servings of oily fish (e.g., salmon, herring, mackerel) weekly. Fish oil capsules can be used as well. The benefits of ω-3 FA supplementation appear to be independent of and additive to those of other therapeutic interventions for CHD, such as statins, aspirin and antihypertensive agents.