Effects of Citrulline Malate Supplementation on Exercise Performance: A Systematic Review and Three-Level Meta-Analysis

Background: Citrulline malate (CM) is commonly used as an ergogenic supplement, but its effects on exercise performance and perceived exertion remain uncertain. This systematic review and meta-analysis evaluated the effects of CM supplementation, with attention paid to differences between acute and chronic protocols. Methods: Six databases were searched from inception to August 2025. Randomized controlled trials examining CM supplementation on exercise performance and/or perceived exertion were included. Hedges’ g was synthesized using three-level random-effects models to account for dependent effect sizes. Subgroup and moderator analyses explored supplementation protocol, exercise modality, sex, training status, dosage, and ingestion timing. Risk of bias, small-study effects, sensitivity analyses, and GRADE certainty were assessed. Results: Thirty randomized controlled trials contributed 138 effect sizes from 644 participants. CM supplementation was associated with a small improvement in overall exercise performance (g = 0.16, p = 0.01); however, prediction intervals were wide and statistical power was limited. The pooled effect on perceived exertion was not statistically significant. Current evidence appeared more stable for acute than chronic supplementation, although the protocol subgroup difference remained uncertain. Among acute studies, exploratory subgroup analyses suggested possible benefits for aerobic endurance and short anaerobic tasks, but these findings were not robust across sensitivity analyses. No significant between-subgroup differences were found for sex, training status, dosage, or ingestion timing. GRADE certainty ranged from low to very low. Conclusions: CM supplementation may be associated with small, context-dependent improvements in exercise performance, but current evidence remains limited and uncertain. Reliable dosing, timing, and target populations have not been established. Larger trials with verified supplement composition and standardized protocols are needed.