Impact of creatine supplementation on inflammation: evidence from a systematic review and meta-analysis of randomized double-blind placebo trials

Introduction Creatine supplementation is widely recognized for its ergogenic effects on strength and body composition. Recent studies have explored its potential anti-inflammatory properties, particularly in exercise-induced stress and aging-related chronic inflammation. However, results across randomized trials remain inconsistent. This systematic review and meta-analysis aimed to assess the effects of creatine supplementation on inflammatory biomarkers in human populations. Methods A systematic review and meta-analysis were conducted following PRISMA 2020 guidelines and registered in PROSPERO (CRD420251027784). Eight randomized controlled trials were included, evaluating creatine supplementation (various dosages and durations) versus placebo in healthy individuals, athletes, and clinical populations. The primary outcomes were inflammatory markers, including C-reactive protein (CRP), interleukin-6 (IL-6), IL-1β, TNF-α, and prostaglandin E 2 . Data extraction and risk of bias assessments were performed by two independent reviewers. The certainty of evidence was rated using the GRADE framework. Results Pooled analysis showed no significant acute effects of creatine on CRP (SMD = 0.32; 95% CI: -0.29 to 0.94; p = 0.30; I² = 28%). Chronic effects of creatine on CRP (SMD = -0.11; 95% CI: -0.69 to 0.48; p = 0.73; I² = 0%) and IL-6 (SMD = -0.06; 95% CI: -0.64 to 0.53; p = 0.84; I² = 0%) were also no significant. The certainty of evidence was rated as moderate for all outcomes. Risk of bias varied, with missing outcome data being the most frequent limitation. Conclusion Creatine supplementation does not significantly reduce inflammatory biomarkers in humans based on current evidence. Although certain benefits were observed under intense endurance conditions, results remain inconsistent across populations. Future well-powered trials with standardized protocols are needed to clarify creatine’s role in modulating inflammation. Systematic review registration https://www.crd.york.ac.uk/prospero/ , identifier CRD420251027784.