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

Sex hormones may regulate the biosynthesis of polyunsaturated fatty acids (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-3 (n-3) and omega-6 (n-6) PUFA biomarkers in healthy adults with mean age ≤50 years. We systematically searched Medline, Embase and Cochrane Central Register of Controlled Trials through to February 21, 2026 for cross-sectional reports of n-3 and n-6 PUFA levels for both sexes in plasma total lipids, phospholipids, triglycerides, cholesteryl esters (CE); erythrocyte total lipids, phosphatidylcholine, 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 synthesis of 71 PUFA biomarkers. By absolute difference in percentage of total fatty acids, we observed, in males versus females, higher n-3 docosapentaenoic acid (DPAn-3) (MD=0.19%, 95% CI: 0.10, 0.27, P<0.0001, I 2 =74%) and lower docosahexaenoic acid (DHA) (MD=-0.32%, 95% CI: -0.46, -0.18, P<0.00001, I 2 =59%) in total erythrocytes and in total plasma. Males had lower plasma LA, and higher CE gamma-linolenic acid and dihomo gamma 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 were 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 points to important biological differences in this portion of the n-3 PUFA biosynthesis pathway that requires further investigation. PROSPERO Registry Number CRD42023452859 Statement of Significance This systematic review and meta-analysis updates the evidence on sex differences in omega-3 and omega-6 PUFA biomarkers among adults of reproductive age, demonstrating higher DPAn-3 and lower DHA levels in males compared with females in plasma and erythrocyte total lipids. For the first time, study location explained heterogeneity for erythrocyte DHA, with sex differences driven by studies conducted in North America and Europe.