Erythrocyte Omega-3 Index as a Biomarker for Skeletal Muscle Omega-3 Composition: A 22-Week Study

Omega-3 fatty acid supplementation has been shown to positively influence various biological processes including immune function, cognition and neuromuscular performance, with recent evidence suggesting beneficial effects in human skeletal muscle. Measurement of omega-3 fatty acids in skeletal muscle requires skeletal muscle biopsies that are invasive and require specialized training. In contrast, measurements of erythrocyte and plasma omega-3 saturation require minimally invasive venous blood draws. This novel analysis, conducted as part of a larger study (, investigated the correlation between the relative abundance of eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) in human skeletal muscle, red blood cells and plasma. Using a repeated measures design, 15 females and 14 males supplemented 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 draws were obtained at weeks 0, 6, 8, 16, 20, 22. Analysis revealed a strong correlation between EPA in skeletal muscle and erythrocytes at week-0 (p < 0.001; r2 = 0.721) which weakened over the supplementation and washout periods. For DHA, there was a moderate correlation at week-0 (p < 0.001; r2 = 0.505) which remained consistent through the 22-week course. For EPA+DHA, there was a strong correlation between skeletal muscle and erythrocytes peaking at week-8 (p < 0.001; r2 = 0.813), before weakening slightly throughout the washout period. Finally, there was no significant association between skeletal muscle and plasma levels throughout the supplementation and washout periods. This analysis provides insights into the association and incorporation of the omega-3 fatty acids EPA and DHA on a tissue-dependent basis. Our results suggest that the Omega-3 Index (EPA+DHA) may be a useful, non-invasive bio-marker of skeletal muscle omega-3 composition during supplementation.