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

Adverse Effects

Omega-3 PUFAs are well tolerated, and side effects occur typically in <5% of persons.[19] Common adverse events are belching, nausea, and dysgeusia (fishy taste), in addition to skin eruptions, eczema, and itching. Increases in low-density lipoprotein cholesterol, particularly with DHA consumption, also occur.[86] There was an increased incidence of atrial fibrillation in the REDUCE-IT trial (5.3% in the IPE group vs. 3.9% in the placebo group; p = 0.004) and the STRENGTH study (2.2% in the omega-3 PUFA group vs. 1.3% in the placebo group; p < 0.001).[20,63] Owing to antiplatelet and membrane fluidity effects, there has been an association of omega-3 PUFAs and bleeding. In the JELIS study, there was a small but significant increase in total bleeding events (1.1% for EPA compared with 0.6% in the usual-care arm; p = 0.0006).[79] In the REDUCE-IT trial, there was an increase in bleeding events in the IPE arm compared with the placebo arm (2.7% vs 2.1%; p = 0.06), which approached but did not meet statistical significance.[20] Given that omega-3 PUFAs are highly purified oils, they do not appear to be allergenic, and patients who are allergic to seafood typically need not avoid these products. U.S. Food and Drug Administration labels recommend using omega-3 PUFAs with caution in these patients, and they should be administered under the guidance of a health care provider.[87]