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

Li D, Shum C, Khoo A, Shi T, Green MR, Blanco Mejia S, Khan TA, Chiavaroli L et al.

Advances in nutrition (Bethesda, Md.), 2026

Abstract

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 2 = 74%] and lower DHA (MD = -0.32%, 95% CI: -0.46%, -0.18%, P 2 = 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…

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