Sex Differences in Omega-3 and Omega-6 PUFA Status: A Systematic Review and Meta-analysis of Cross-Sectional...

Sex hormones may regulate the biosynthesis of PUFAs; however, the extent and consistency of sex differences in different lipid pools remain unclear. We aimed to update and synthesize evidence on sex differences in circulating and tissue omega (ω)-3 (n-3) and ω-6 (n-6) PUFA biomarkers in healthy adults with a mean age ≤50 y. We systematically searched Medline, Embase, and Cochrane Central Register of Controlled Trials through to 21 February, 2026, for cross-sectional reports of n-3 and n-6 PUFA levels for both sexes in plasma total lipids, phospholipids, triglycerides, and cholesteryl esters (CE); erythrocyte total lipids, phosphatidylcholine, and phosphatidylethanolamine; or adipose tissue. Unadjusted mean differences (MD) between male and female n-3 and n-6 PUFA levels were pooled using random-effects meta-analysis. We identified 67 eligible publications, including 85 comparisons from observational studies and clinical trials, yielding a synthesis of 71 PUFA biomarkers. By absolute difference in percentage of total fatty acids, we observed, in males compared with females, higher n-3 docosapentaenoic acid (DPAn-3) [MD = 0.19%, 95% confidence interval (CI): 0.10%, 0.27%, P < 0.0001, I² = 74%] and lower DHA (MD = -0.32%, 95% CI: -0.46%, -0.18%, P < 0.00001, I² = 59%) in total erythrocytes and in total plasma. Males had lower plasma linoleic acid and higher CE γ-linolenic acid and dihomo-γ-linolenic acid. Heterogeneity in total erythrocyte EPA and DHA was explained by study location, with sex differences in erythrocyte DHA driven by studies in North America and Europe. The certainty of the evidence for all outcomes was graded as low or very low. Future studies should consider sex as a modifier of n-3 and n-6 PUFA status in adult males and females of childbearing age. Higher DPAn-3 and lower DHA in males point to important biological differences in this portion of the n-3 PUFA biosynthesis pathway that require further investigation. This trial was registered at PROSPERO as CRD42023452859.