Manson · The New England journal of medicine 2019 · randomized placebo-controlled trial · n=25871

Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer.

Cited 978 times in the scientific literature.

Level 2 - randomized trial

Individual randomized controlled trial.

PubMed 30415637 · doi:10.1056/NEJMoa1811403 · record verified 2026-08-29

What was done

In a randomized, placebo-controlled, 2-by-2 factorial trial across the United States, 25,871 adults (men aged 50 or older, women aged 55 or older, including 5,106 Black participants) were assigned to receive marine n-3 fatty acids (1 g per day) or placebo for the primary prevention of cardiovascular disease and cancer. Vitamin D3 (2000 IU per day) was tested as the other factorial arm. Participants were followed for a median of 5.3 years. Co-primary endpoints were major cardiovascular events (composite of myocardial infarction, stroke, or cardiovascular death) and invasive cancer of any type.

What was found

Major cardiovascular events occurred in 386 participants in the n-3 group versus 419 in the placebo group (hazard ratio, 0.92; 95% CI, 0.80 to 1.06; P=0.24). Invasive cancer occurred in 820 participants in the n-3 group versus 797 in the placebo group (hazard ratio, 1.03; 95% CI, 0.93 to 1.13; P=0.56). For secondary endpoints, total myocardial infarction was reduced in the n-3 group (hazard ratio, 0.72; 95% CI, 0.59 to 0.90), but no significant differences were observed for total stroke (hazard ratio, 1.04; 95% CI, 0.83 to 1.31), cardiovascular death (hazard ratio, 0.96; 95% CI, 0.76 to 1.21), cancer death (hazard ratio, 0.97; 95% CI, 0.79 to 1.20), or all-cause mortality (hazard ratio, 1.02; 95% CI, 0.90 to 1.15). No excess bleeding or serious adverse events were seen.

Why it matters

This large primary-prevention trial shows that routine dietary supplementation with 1 g daily of marine omega-3 fatty acids does not reduce overall cardiovascular events or cancer incidence in a general population at average risk.

Limits

The trial tested only a single 1 g daily dose of mixed marine n-3 fatty acids, so higher doses or specific purified formulations were not evaluated. The median follow-up of 5.3 years may be insufficient to capture longer-term cancer latency, and results cannot be generalized to secondary prevention in patients with established disease.

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