Manson · Circulation research 2020 · randomized controlled trial · n=25871

Vitamin D, Marine n-3 Fatty Acids, and Primary Prevention of Cardiovascular Disease Current Evidence.

Cited 76 times in the scientific literature.

Level 2 - randomized trial

Individual randomized controlled trial report/review

PubMed 31895658 · doi:10.1161/CIRCRESAHA.119.314541 · record verified 2026-08-30

What was done

This paper reviews results from the VITAL trial and related meta-analyses assessing marine omega-3 fatty acids and vitamin D3 for primary prevention of cardiovascular disease (CVD). VITAL was a nationwide, randomized, placebo-controlled, 2×2 factorial trial evaluating marine omega-3 fatty acids (1 g/day) and vitamin D3 (2000 IU/day) in 25,871 US men (aged ≥50) and women (aged ≥55), including 5,106 Black participants, over a median treatment duration of 5.3 years.

What was found

Omega-3 fatty acids did not significantly reduce the primary composite endpoint of major CVD events (HR 0.92, 95% CI 0.80-1.06). However, omega-3s were associated with significant reductions in total myocardial infarction (HR 0.72, 95% CI 0.59-0.90), percutaneous coronary intervention (HR 0.78, 95% CI 0.63-0.95), and fatal myocardial infarction (HR 0.50, 95% CI 0.26-0.97), with no effect on stroke. Benefit for major CVD events was observed in participants consuming <1.5 fish servings/week (HR 0.81, 95% CI 0.67-0.98; P interaction=0.045), and the greatest myocardial infarction reduction occurred in Black participants (HR 0.23, 95% CI 0.11-0.47; P interaction=0.001). Vitamin D3 supplementation did not reduce major CVD events (HR 0.97, 95% CI 0.85-1.12) or other cardiovascular endpoints.

Why it matters

Neither agent significantly lowered overall major CVD events in a primary prevention population, though marine omega-3 fatty acids demonstrated significant reductions in coronary endpoints, especially among individuals with low dietary fish intake.

Limits

The primary composite cardiovascular endpoints for both interventions were null. Secondary coronary endpoints and subgroup interactions (race, fish intake) are exploratory and require replication. Only a single fixed dose of each supplement was evaluated.

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