Effects of Creatine Supplementation on Oxidative Stress Biomarkers in Exercising Individuals: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Introduction This systematic review and meta-analysis evaluated the effects of creatine supplementation on oxidative stress biomarkers in humans performing exercise. The review examined the effects of creatine within an exercise context. Methods Following the PRISMA 2020 guidelines, searches were conducted in EMBASE, LILACS, CINAHL, MEDLINE/PubMed, Cochrane Library, Scopus, and Web of Science through August 2026. Eligible studies were randomized controlled trials involving exercise in which creatine supplementation was compared with placebo, no supplementation, or an exercise-only control condition. The primary outcomes were oxidative stress biomarkers, particularly 8-hydroxy-2′-deoxyguanosine (8-OHdG), malondialdehyde (MDA), and total antioxidant capacity (TAC). Risk of bias was assessed using the RoB 2 tool, and certainty of evidence was evaluated using GRADE. Results Nine trials met the inclusion criteria. For 8-OHdG, the pooled analysis showed no statistically significant effect of creatine supplementation (MD = − 1.22; 95% CI: −4.38 to 1.94; p > 0.05). Substantial heterogeneity was observed (I² = 58.4%; p = 0.121), indicating notable between-study variability. For MDA, creatine supplementation also had no significant effect (Hedges’ g = − 0.67; 95% CI: −5.13 to 3.80; p = 0.586). Heterogeneity was very high (I² = 91.8%; p < 0.0001), and the wide prediction interval indicated substantial uncertainty regarding the effect expected in future studies. Creatine supplementation did not significantly affect TAC (MD = 0.28; 95% CI: −0.57 to 1.13; p > 0.05), with no evidence of heterogeneity (I² = 0.0%; p = 0.888). The certainty of the evidence was very low for all outcomes because of the small number of studies, imprecision, methodological limitations, and inconsistency, particularly for MDA. Conclusion Very-low-certainty evidence indicates that creatine supplementation during exercise does not significantly affect 8-OHdG, MDA, or total antioxidant capacity. Findings were limited by imprecision, substantial inconsistency for MDA, and small sample sizes. Larger randomized controlled trials with standardized supplementation, exercise, biomarker, and sampling protocols are required.