Effect of Omega-3 Dosage on Cardiovascular Outcomes: An Updated Meta-Analysis and Meta-Regression of Interventional Trials
Bernasconi AA, Wiest MM, Lavie CJ, Milani RV, Laukkanen JA
Published in Mayo Clinic Proceedings
Abstract
This systematic review examines the cardiovascular effects of omega-3 fatty acids, demonstrating significant reductions in cardiovascular disease risk, particularly in populations with elevated triglycerides and low baseline omega-3 intake.
Methodology
Systematic review, meta-analysis and dose-response meta-regression of randomised controlled trials of marine EPA/DHA supplementation reporting cardiovascular outcomes.
Key Findings
Across 40 randomised trials with 149,051 participants, EPA/DHA supplementation was associated with a 13% reduction in myocardial infarction risk, a 9% reduction in coronary heart disease mortality, a 10% reduction in coronary heart disease events and a 35% reduction in fatal myocardial infarction. Meta-regression showed benefit increased with dose - roughly a further 9% risk reduction per additional gram per day of EPA plus DHA. No significant effect on stroke was found.
Conclusions
Marine omega-3 supplementation lowers coronary heart disease risk in a dose-dependent manner, with clearest benefit at doses well above the roughly 1 g/day used in most neutral trials.
Limitations
Pooled trials differ widely in dose, EPA:DHA ratio, formulation, comparator oil and baseline risk, which drives heterogeneity; the dose-response signal comes from meta-regression across trials rather than randomised dose comparison; a large share of the benefit is driven by high-dose EPA trials such as REDUCE-IT, whose mineral oil comparator remains contested; no stroke benefit was observed.
Study Details
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