The Influence of Biological Sex on Skeletal Muscle Phospholipid Membrane Composition in Response to Omega-3 Fatty Acid Supplementation and Washout in Humans

Abstract

Omega-3 fatty acid intake is associated with reduced inflammation, protection against cardiovascular disease, and improved cognitive function. There is also evidence that omega-3 fatty acid intake impacts skeletal muscle, potentially with greater effects in females than males. Sex-specific responses to omega-3 fatty acid intake may be linked to the incorporation of eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) into skeletal muscle phospholipid membranes. However, no study has characterized the effect of biological sex on human skeletal muscle phospholipid composition in response to EPA+DHA supplementation, and washout of EPA and DHA from skeletal muscle phospholipids following the cessation of supplementation. In a repeated measures design, 15 females and 14 males consumed 5 g/d of EPA+DHA (3.2 g EPA; 1.8 g DHA) for 8 weeks followed by 14 weeks of washout. Skeletal muscle biopsies and venous blood samples were obtained at weeks 0 (baseline), 6, 8, 16, 20, and 22. Females displayed higher skeletal muscle EPA phospholipid composition (p = 0.048), greater erythrocyte EPA phospholipid composition (p = 0.034), and plasma DHA composition (p = 0.035) compared to males. At 14 weeks of washout, skeletal muscle and erythrocyte EPA phospholipid composition (p < 0.001 and p = 0.005) remained elevated above baseline, whereas plasma EPA composition (p = 0.381) was not different from baseline. We demonstrate that 5 g/d EPA+DHA supplementation influences human fatty acid composition in a manner that is both sex and tissue-dependant.