Effects of LC n-3 PUFA Supplementation on Muscle Pain, Function, and Damage Markers in Healthy Young to Middle-Aged Adults Following Acute or Chronic Exercise: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Supplementation with long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may mitigate exercise-induced muscle damage (EIMD) and enhance post-exercise recovery. However, the systematic reviews/meta-analyses evaluating these effects across populations and exercise models are limited and do not provide dosing recommendations. Objective: This systematic review and meta-analysis aimed to evaluate the effects of LC n-3 PUFA supplementation on key post-exercise recovery outcomes, including muscle soreness, muscle function, and muscle damage biomarkers in healthy adults. Methods: Following the PRISMA guidelines, a comprehensive search of PubMed, Scopus, and clinical trial registry databases was conducted (to January 2025). All studies that met the inclusion criteria underwent appropriate methodological quality assessments using established tools. The data were extracted for inputting into random-effects models, with effect sizes reported as Hedges’ g and 95% confidence intervals (CIs). Heterogeneity was assessed using the I2 statistic. Results: Among the 2539 records, 43 studies met the inclusion criteria for the systematic review, and nine met the inclusion criteria for the meta-analysis. The effect of LC n-3 PUFA supplementation on recovery outcomes was equivocal, with significant methodological limitations noted across the literature. However, the meta-analysis of nine placebo-controlled, eccentric exercise trials demonstrated that LC n-3 PUFA supplementation significantly reduced delayed onset muscle soreness (DOMS) (Hedges’ g = −0.75; 95% CI: −1.14 to −0.36), creatine kinase (CK) (Hedges’ g = −0.40; 95% CI: −0.70 to −0.10), and muscle swelling (Hedges’ g = −0.45; 95% CI: −0.83 to −0.07), and significantly improved muscle strength (Hedges’ g = 0.45; 95% CI: 0.07 to 0.83) and range of motion (ROM) (Hedges’ g = 0.93; 95% CI: 0.33 to 1.53) at peak impairment compared with placebo. Conclusions: LC n-3 PUFA supplementation may support recovery from EIMD. However, due to the methodological limitations across the literature base it was not possible to assess effective dosing strategies. Future studies should address dose–response and duration requirements and incorporate objective assessments of omega-3 status (e.g., the Omega-3 Index [O3I] or comparable biomarkers) alongside standardized compliance measures. These approaches are necessary to determine effective dosing strategies and to test the relationship between omega-3 status and recovery outcomes.