The fish oil story remains fishy.

T here is substantial evidence, mostly observational, that diets that include fish reduce the risk of coronary heart disease. 1– 4 Yet, a major question remains as to whether this benefit is due entirely to the omega-3, or long-chain, n-3 fatty acids such as docosahexaenoic acid (DHA) and eicosapenta-enoic acid (EPA) and/or other nutrient contents in fish. An alternative explanation is that people who consume more fish are already consuming a heart-healthy diet. Although an effect of omega-3 fatty acids on cardiac sudden death has been suggested, 5–7 minimal evidence exists to support their use in the setting of an acute myocardial infarction (AMI). The Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)–Prevenzione was a trial in patients surviving a recent (Ͻ3 months earlier) AMI. 5 In that trial, 11 323 patients were randomly assigned to 1-g supplements of n-3 polyunsaturated fatty acids, vitamin E (300 mg/d), both, or no treatment on top of the optimal pharmacological treatment and lifestyle advice at the time. Survival curves for n-3 polyunsaturated fatty acid treatment diverged early after randomization, and total mortality was significantly lowered after 3 months of treatment (risk reduction, 0.59; 95% confidence interval, 0.36 to 0.97; Pϭ0.037), and the reduction in risk of sudden death was particularly relevant and statistically significant at 4 months (risk reduction, 0.47; 95% confidence interval, 0.219 to 0.995; Pϭ0.048). Although this study was implemented 10 years ago, it set the stage for the OMEGA Trial, a double-blind, randomized, placebo-controlled trial of earlier administration of omega-3 fatty acids in patients with AMI who were receiving more recent and aggressive state-of-the-art and guidelines-based therapy. The OMEGA Trial 8 set out to evaluate the effect of highly purified omega-3-acid ethyl esters (DHA, 380 mg; EPA, 460 mg) versus placebo administered 3 to 14 days after an AMI (ST-elevation or non–ST-elevation MI) on the rate of sudden cardiac death within 1 year after the infarct. Sudden death was defined as death within 1 hour of the first symptoms or an unwitnessed event occurring overnight. Also included was sudden cardiac arrest with initially successful resuscitation and subsequent death during the hospital stay. The secondary end points tested included all-cause mortality, nonfatal car-diovascular events, rhythm abnormalities, and depression score. On the basis of the GISSI-Prevenzione Trial, 5 a 45% projected reduction in the number of total deaths resulting from sudden death by omega-3 fatty acids was expected. Importantly, because …