CREATINE supplementation fails to reduce systemic inflammatory biomarkers such as C-reactive protein in adults with osteoarthritis. A systematic review and meta-analysis of randomized controlled trials evaluating creatine supplementation and inflammation demonstrated that the popular ergogenic supplement exerts no significant modulatory effect on circulating markers of chronic, low-grade inflammation. While creatine remains widely recognized for enhancing muscle mass and cellular bioenergetics, these latest findings clarify that its therapeutic reach does not extend to suppressing systemic immune cascades in rheumatic disorders.
Evaluating data across eight double-blind trials, researchers examined whether creatine alters key inflammatory mediators, including C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1beta. In clinical populations with mild to moderate knee osteoarthritis, twelve weeks of creatine supplementation yielded no measurable changes in systemic CRP, IL-6, or TNF-α compared to placebo. Similar null findings emerged in older adults participating in resistance training, where creatine produced no additive reductions in circulating cytokines.
Quantitative synthesis further underscored this absence of systemic effect. The pooled analysis revealed no significant reduction in chronic CRP levels (mean difference: -0.41 mg/L; 95% confidence interval: -2.39 to 1.58; p = 0.69) or chronic IL-6 concentrations (mean difference: -0.02 pg/mL; 95% confidence interval: -0.54 to 0.49; p = 0.93), with negligible heterogeneity between trials. Acute loading protocols likewise failed to generate meaningful reductions in circulating CRP.
To contextualize the evidence regarding creatine supplementation and inflammation, researchers highlighted differing underlying physiological mechanisms. Benefits documented in endurance athletes, such as attenuated post-exercise spikes in prostaglandin E2 and TNF-α, appear driven by transient cellular swelling and cytoprotective stabilization against acute mechanical trauma. In contrast, rheumatologic conditions and aging-related joint degeneration arise from sustained immunometabolic signaling, which remains unresponsive to intracellular energy buffering.
For rheumatologists and primary care physicians, these findings provide essential guidance for patient counseling. Creatine supplementation demonstrated an excellent safety profile with no adverse renal, hepatic, or gastrointestinal events across cohorts. Although clinicians can endorse creatine as an adjunctive intervention to combat sarcopenia, frailty, and periarticular muscle weakness, it should not be positioned as an anti-inflammatory or disease-modifying therapy for joint pathology.
Reference
de Camargo KMR et al. Impact of creatine supplementation on inflammation: evidence from a systematic review and meta-analysis of randomized double-blind placebo trials. Front Immunol. 2026;17:1743603.
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