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

Recommendations for use of Omega-3 PUFAs

Based on the results of the REDUCE-IT trial, several guidelines have incorporated the use of IPE. The National Lipid Association recommends the use of IPE in patients ≥45 years of age with clinical ASCVD and in patients ≥50 years of age with diabetes and 1 or more risk additional risk factors for ASCVD, with fasting triglycerides 135 to 499 mg/dl already on high intensity or maximally tolerated statin therapy with or without ezetimibe.[89] Similar recommendations are endorsed by the American Diabetes Association and the 2019 European Society for Cardiology/European Atherosclerosis Society Guidelines for the management of dyslipidemias.[90] The 2018 American College of Cardiology/American Heart Association Guideline on the Management of Blood Cholesterol did not include a recommendation for IPE; however, the results of the REDUCE-IT trial were not available at the time of this publication.[91] Additionally, the use of prescription omega-3 PUFAs (4 g/day) is recommended for reducing triglycerides in patients in whom underlying causes have been addressed and lifestyle changes implemented.[19] For patients with ASCVD without hypertriglyceridemia or at high risk for ASCVD, 1 g/day of omega-3 PUFA supplementation may be considered; however, prescribers should acknowledge that there is a lack of consensus for this recommendation and that the benefit is less clear.[17,18] Additionally, when considering high-dose omega-3 PUFAs, the possibility of increased atrial fibrillation (EPA and EPA + DHA formulations) and increased bleeding (EPA formulation) should be discussed with patients.

Replacing saturated fats with polyunsaturated fats is part of a healthy diet.[92] Current recommendations focus on dietary omega-3 PUFA intake from fish, ideally at least 2 servings per week (total weekly intake of ≥8 oz; average of at least 250 mg/day of EPA + DHA). Given that the typical American dietary consumption of omega-3 PUFAs is below 250 mg/day, it is reasonable to supplement with fish oil should fish intake be inadequate. Should patients not meet clinical indications for prescription-strength omega-3 PUFAs and use fish oil dietary supplements, they should be educated on how to identify formulations with appropriate amounts of EPA and DHA. In addition, health care providers should educate patients how to identify fish oil products that contain minimal amounts of non–omega-3 fatty acids and expressly state are free of persistent organic pollutants and mercury.