What to Tell Your Patients: A Critical Review of the JAMA Cardiology Meta-Analysis “Associations of Omega-3 Fatty Acid Supplement use with Cardiovascular Disease Risks”
Alex Vasquez, DC, ND, DO, FACN
Director, International Conference on Human Nutrition and Functional Medicine, 6801 Biotics Research Dr., Rosenberg, TX 77471, USA
Elizabeth Sutherland, ND
Adjunct Faculty, National University of Natural Medicine, Portland, Oregon, USA


omega-3 fatty acids
cardiovascular health
heart disease


Authors of a meta-analysis recently published in JAMA Cardiology concluded that omega-3 fatty acids have no significant association with fatal or nonfatal coronary heart disease or any major vascular events. This critical review examines participant profile, intervention dosage, bioavailability of intervention, and duration of therapy for the cited trials and determines that the conclusion of the meta-analysis is tentative at best.



Aung T, Halsey J, Kromhout D, et al. Omega-3 Treatment Trialists’ Collaboration. Associations of omega-3 fatty acid supplement use with cardiovascular disease risks: meta-analysis of 10 trials involving 77 917 individuals. JAMA Cardiol. 2018;3:225–34.

Greene SJ, Temporelli PL, Campia U, et al. Effects of polyunsaturated fatty acid treatment on post discharge outcomes after acute myocardial infarction. Am J Cardiol. 2016;117:340–6.

GISSI-Prevenzione Investigators (Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico). Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet. 1999;354:447–55. Published errata appear in Lancet. 2001;357:642; and Lancet. 2007;369:106.

Siscovick DS, Barringer TA, Fretts AM, et al.; on behalf of the American Heart Association Nutrition Committee of the Council on Lifestyle and Cardiometabolic Health; Council on Epidemiology and Prevention; Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology. Omega-3 polyunsaturated fatty acid (fish oil) supplementation and the prevention of clinical cardiovascular disease: a science advisory from the American Heart Association. Circulation. 2017;135:e867–84.

Harris WS, Del Gobbo L, Tintle NL. The Omega-3 Index and relative risk for coronary heart disease mortality: estimation from 10 cohort studies. Atherosclerosis. 2017;262:51–4.

Flock MR, Skulas-Ray AC, Harris WS, et al. Determinants of erythrocyte omega-3 fatty acid content in response to fish oil supplementation: a dose-response randomized controlled trial. J Am Heart Assoc. 2013;2:e000513.

Allaire J, Harris WS, Vors C, et al. Supplementation with high-dose docosahexaenoic acid increases the Omega-3 Index more than high-dose eicosapentaenoic acid. Prostaglandins Leukot Essent Fatty Acids. 2017;120:8–14.

von Schacky C. Omega-3 Index and cardiovascular health. Nutrients. 2014;6:799–814.

Del Gobbo LC, Imamura F, Aslibekyan S, et al.; Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Fatty Acids and Outcomes Research Consortium (FORCe). ω-3 Polyunsaturated fatty acid biomarkers and coronary heart disease: pooling project of 19 cohort studies. JAMA Intern Med. 2016;176:1155–66.
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