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Am Fam Physician. 2019;100(6):374-375

Clinical Question

Do marine n-3 fatty acids (also called omega-3 fatty acids) reduce the risk of cardiovascular events or cancer in patients without known vascular disease or cancer?

Bottom Line

This is the second large, well-designed study (the first one included patients with diabetes mellitus; this one included patients without diabetes) that found no benefit from a 1-g daily dosage of marine n-3 fatty acid supplementation for the primary prevention of cardiovascular disease or cancer. This study featured more than 20 comparisons, so the small reduction found in myocardial infarctions may be due to chance alone. (Level of Evidence = 1b)


A recent POEM reported that a U.K. trial of marine n-3 fatty acids in 15,000 patients with diabetes found no evidence of benefit as primary prevention of cardiovascular disease or cancer. The current study is the first adequately powered U.S. trial of marine n-3 (omega-3) fatty acids for primary prevention. The researchers recruited a total of 25,871 men 50 years and older and women 55 years and older who had no history of cardiovascular disease or cancer. The groups were balanced at the start of the study, with a mean age of 67 years, 51% women, and 14% with diabetes. The investigators used a three-month placebo run-in period to exclude patients who were noncompliant, which was approximately one-third of those initially recruited. This could overestimate the potential benefit seen in clinical practice. Participants were randomly assigned to a 1-g daily dosage of marine n-3 fatty acids or placebo. The median follow-up was 5.3 years. There was no reduction in the likelihood of cancer diagnosis or the primary composite cardiovascular outcome (i.e., cardiovascular death, nonfatal myocardial infarction, or ischemic stroke). There was no difference between groups regarding cardiovascular or all-cause mortality. There was a reduction in total myocardial infarctions (hazard ratio = 0.72; 95% CI, 0.59 to 0.90), although the absolute reduction was small (145 vs. 200 total myocardial infarctions with more than 12,000 patients in each group). It is important not to make too much of this finding because there were 24 comparisons made in the primary analysis, so this one could be caused by chance alone. There was no difference between groups regarding adverse events. A subgroup analysis found a modest, but statistically significant, reduction in the primary composite outcome for persons who ate fewer than 1.5 servings of fish per week, but not in those who ate more.

Study design: Randomized controlled trial (double-blinded)

Funding source: Government

Allocation: Concealed

Setting: Population-based

Reference: Manson JE, Cook NR, LeeI M, et al.; VITAL Research Group. Marine n-3 fatty acids and prevention of cardiovascular disease and cancer. N Engl J Med. 2019;380(1):23–32.

Editor's Note: Dr. Ebell is Deputy Editor for Evidence-Based Medicine for AFP and cofounder and Editor-in-Chief of Essential Evidence Plus, published by Wiley-Blackwell.

POEMs (patient-oriented evidence that matters) are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, see Copyright Wiley-Blackwell. Used with permission.

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