Marklund · Circulation 2019 · pooled individual-participant meta-analysis of prospective cohort studies · n=68659

Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality.

Cited 339 times in the scientific literature.

Level 3 - non-randomized controlled study

Meta-analysis of prospective observational cohort studies

PubMed 30971107 · doi:10.1161/CIRCULATIONAHA.118.038908 · record verified 2026-08-28

What was done

Consortium-based harmonized individual-level analysis of 30 prospective observational studies across 13 countries evaluating biomarkers of linoleic acid (LA) and arachidonic acid (AA) in circulating blood and adipose tissue. Multivariable-adjusted hazard ratios were pooled via inverse-variance-weighted meta-analysis for incident total cardiovascular disease (CVD), coronary heart disease, ischemic stroke, and cardiovascular mortality across 2.5 to 31.9 years of median follow-up.

What was found

Among 68,659 participants with 15,198 incident CVD events, higher LA levels per interquintile range were significantly associated with lower risks of total CVD (HR 0.93; 95% CI, 0.88-0.99), cardiovascular mortality (HR 0.78; 95% CI, 0.70-0.85), and ischemic stroke (HR 0.88; 95% CI, 0.79-0.98), and nonsignificantly with coronary heart disease (HR 0.94; 95% CI, 0.88-1.00). Higher AA levels were not associated with increased CVD risk and were associated with lower total CVD in extreme quintile comparison (HR 0.92; 95% CI, 0.86-0.99).

Why it matters

These findings challenge concerns that omega-6 polyunsaturated fatty acids promote cardiovascular disease and support dietary recommendations that include linoleic acid for CVD prevention.

Limits

The observational design cannot establish causality or eliminate residual confounding. Biomarker compartments varied across included cohorts, and findings may reflect broader healthy lifestyle patterns.

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