Cardiovascular Impact of Nutritional Supplementation With Omega-3 Fatty Acids

JACC Focus Seminar

Richard L. Weinberg, MD, PHD; Robert D. Brook, MD; Melvyn Rubenfire, MD; Kim A. Eagle, MD


J Am Coll Cardiol. 2021;77(5):593-608. 

In This Article

Abstract and Introduction


Omega-3 polyunsaturated fatty acids (PUFAs) are a key component of a heart-healthy diet. For patients without clinical atherosclerotic cardiovascular disease, 2 or more servings of fatty fish per week is recommended to obtain adequate intake of omega-3 PUFAs. If this not possible, dietary supplementation with an appropriate fish oil may be reasonable. Supplementation with omega-3 PUFA capsules serves 2 distinct but overlapping roles: treatment of hypertriglyceridemia and prevention of cardiovascular events. Marine-derived omega-3 PUFAs reduce triglycerides and have pleiotropic effects including decreasing inflammation, improving plaque composition and stability, and altering cellular membranes. Clinical trial data have shown inconsistent results with omega-3 PUFAs improving cardiovascular outcomes. In this paper, the authors provide an overview of PUFAs and a summary of key clinical trial data. Recent trial data suggest the use of prescription eicosapentaenoic acid ethyl ester for atherosclerotic cardiovascular disease event reduction in selected populations.


A heart-healthy diet is paramount in the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). Observational studies and some randomized controlled trials (RCTs) have shown beneficial cardiovascular (CV) effects of omega-3 polyunsaturated fatty acids (PUFAs). In this review, we offer a survey of omega-3 and other PUFAs, recommendations for their consumption, mechanisms of action on the CV system, and evidence related to the CV benefits of prescription omega-3 PUFAs. We highlight the knowledge gaps with omega-3 PUFAs and CV risk reduction in the context of newly published and ongoing RCTs.