Impact of creatine supplementation on inflammation: evidence from a systematic review and meta-analysis of randomized double-blind placebo trials.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 41798953 · doi:10.3389/fimmu.2026.1743603
What was done
A systematic review and meta-analysis (registered in PROSPERO: CRD420251027784) evaluated the effects of creatine supplementation versus placebo on inflammatory biomarkers. Eight randomized, double-blind, placebo-controlled trials encompassing healthy individuals, athletes, and clinical populations were synthesized. Primary inflammatory outcomes included C-reactive protein (CRP), interleukin-6 (IL-6), IL-1β, TNF-α, and prostaglandin E2. Risk of bias and GRADE certainty were evaluated by two independent reviewers.
What was found
Pooled analysis revealed no statistically significant acute effect of creatine on CRP (SMD = 0.32; 95% CI: -0.29 to 0.94; p = 0.30; I² = 28%). Chronic creatine supplementation also demonstrated no significant effect on CRP (SMD = -0.11; 95% CI: -0.69 to 0.48; p = 0.73; I² = 0%) or IL-6 (SMD = -0.06; 95% CI: -0.64 to 0.53; p = 0.84; I² = 0%). Numerical meta-analytic estimates were not reported in the abstract for IL-1β, TNF-α, or prostaglandin E2. Certainty of evidence was rated as moderate for all outcomes.
Why it matters
This review indicates that current clinical trial evidence does not support an anti-inflammatory benefit of creatine supplementation on circulating biomarkers like CRP or IL-6 in human populations.
Limits
The analysis included only eight studies with heterogeneous dosing, durations, and populations ranging from athletes to clinical cohorts. Total participant count was not reported in the abstract. Missing outcome data was the most frequent risk of bias limitation across the included trials.
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