Temporal dynamics of the repeated bout effect on exercise-induced muscle damage: a systematic review and three-level meta-analysis

Objective The repeated bout effect (RBE) confers protection against exercise-induced muscle damage (EIMD). However, the temporal profile of this protective response both across post-exercise recovery and across different intervention-to-damage intervals remains poorly defined. This three-level meta-analysis aimed to quantify the time-course of RBE protective effects and to characterize potential temporal windows for intervention and measurement. Methods A systematic search of PubMed, Web of Science, Embase, and Scopus (inception to June 2025) identified 35 eligible studies. Three outcome measures, maximal voluntary contraction (MVC), delayed onset muscle soreness (DOMS), and creatine kinase (CK), were analyzed using three-level random-effects models. Effect sizes (Hedges’ g) were stratified by post-exercise measurement time (24, 48, 72, and 96 h) and intervention interval (<1 week, 1–2 weeks, 2–3 weeks, and >3 weeks). Results RBE significantly protected MVC (overall g = 1.18, 95% CI: 0.91–1.45) and reduced DOMS (g = −1.37, 95% CI: −1.70 to −1.05) and CK (g = −0.91, 95% CI: −1.33 to −0.50). Time-stratified analyses revealed distinct temporal patterns. MVC and DOMS showed their largest observed protective estimates at 72 h post-damage (g = 1.47 and −1.65, respectively), whereas CK showed its largest observed protective estimate at 96 h (g = −1.53). Direct comparisons accounting for within-study dependence showed a larger MVC estimate at 72 h than at 48 h and a more protective CK estimate at 48 h than at 24 h. Subgroup analyses revealed outcome-specific interval patterns, with pooled protective effects for MVC and DOMS numerically smallest in magnitude in the 2–3-week subgroup at all four assessed time points. Conclusion RBE-related protection showed time-dependent patterns across outcomes. Among the assessed time points, pooled protective effects were largest in magnitude at 72 h for functional (MVC) and perceptual (DOMS) outcomes, whereas biochemical (CK) effects increased progressively in magnitude through 96 h. The 2–3-week interval was characterized by numerically weaker pooled protective effects for MVC and DOMS. These findings provide an evidence-informed temporal framework for optimizing preconditioning and recovery-monitoring strategies in athletic training. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420251131290.