The influence of biological sex on skeletal muscle phospholipid membrane composition in response to omega n-3 polyunsaturated fatty acid supplementation and washout in humans.
Level 3 - non-randomized controlled study
Prospective repeated-measures cohort study comparing sex-stratified groups without randomization
PubMed 40663806 · doi:10.1016/j.plefa.2025.102696
What was done
In a repeated-measures design, 15 females and 14 males consumed 5 g/day of EPA+DHA (3.75 g EPA, 1.25 g DHA) for 8 weeks, followed by a 14-week washout period. Skeletal muscle biopsies and venous blood samples were collected at weeks 0 (baseline), 6, 8, 16, 20, and 22 to assess fatty acid incorporation and clearance in plasma, erythrocytes, and muscle phospholipid membranes.
What was found
At 6 weeks of supplementation, females had significantly greater skeletal muscle EPA phospholipid composition (p = 0.035), higher erythrocyte EPA phospholipid composition (p = 0.034), and higher whole plasma DHA composition (p = 0.033) compared to males. After 14 weeks of washout, skeletal muscle EPA (p < 0.001) and erythrocyte EPA (p = 0.005) remained significantly elevated above baseline, whereas whole plasma EPA was not significantly different from baseline (p = 0.381). Absolute concentration values and percentage changes were not reported in the abstract.
Why it matters
This study shows that omega-3 fatty acid incorporation kinetics vary by biological sex and that skeletal muscle tissue retains incorporated EPA long after supplementation ceases, even after circulating plasma levels return to baseline.
Limits
The sample size was small (29 participants). The abstract does not report baseline dietary controls, participant age or health status, exact quantitative effect sizes, or whether these membrane changes translate into meaningful physiological or functional differences in muscle.
Cited by
- supports Supplementation with approximately 5 grams of omega-3s takes about 4 weeks to induce a significant change in skeletal muscle phospholipid profile, plateauing between 6 and 8 weeks.