Abstract
Eccentric exercise-induced muscle damage (EIMD) impairs muscle function and recovery. While omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has shown promise in mitigating EIMD, the role of their oxidation products (oxylipins) remains unclear. This study investigated the effects of 8-week n-3 PUFA supplementation on muscle recovery and its relationship with blood oxylipin profiles after EIMD in healthy men. Eighteen participants were randomly assigned into two groups: OMEGA (n = 9 28.0 ± 2.5 y; 2.5 g/d of DHA and 0.5 g/d of EPA) and PLACEBO (n = 9 21.4 ± 0.6 y; maltodextrin). Participants performed one bout of 100 unilateral isokinetic eccentric maximal voluntary contractions of the knee extensor muscles before and after an 8-week supplementation period. N-3 PUFA supplementation augmented plasma EPA- and DHA-derived oxylipins (p < 0.05) in the OMEGA group, which showed an attenuation of peak muscle maximum voluntary contraction loss (-15.4 ± 5.2%; p = 0.05) post-exercise compared to the PLACEBO group (1.3 ± 6.0%). There were no differences in muscles soreness between groups. Multivariate analyses identified body fat percentage and specific n-3 and n-6 PUFA-derived oxylipins as predictors of MVC loss after EIMD. In conclusion, the increased plasma levels of n-3 PUFA derived oxylipins following supplementation suggest a possible role for these lipid mediators in promoting muscle recovery. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-44339-1.