Impact of creatine supplementation on inflammation: evidence from a systematic review and meta-analysis of randomized double-blind placebo trials
de Camargo KMR, Bruna-Mejías A, Valenzuela-Fuenzalida JJ, Gonzaga LA, Barbalho SM, Barroca AL, Porto AA, Raimundo RD, de Abreu LC, Valenti VE
Frontiers in immunology · 3 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- Meta-analysis (indexed by PubMed)
- Studied in
- People
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Independent funding
- Government
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Government
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Grants
- Fundação de Amparo à Pesquisa do Estado de São Paulo (25/06769-1)
Based on 2 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2026-02-19 · Front Immunol · vol. 17 · p. 1743603
- Publisher
- Frontiers Media
- Cited
- 3 citations · more than 95% of similar papers · 4.9× the field average
- Impact
- Top 10% most cited in its field
- References
- 31 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Muscle metabolism and nutrition · Exercise and Physiological Responses · Biochemical effects in animals
- Keywords
- Placebo, Randomized controlled trial, Creatine, Meta-analysis, Clinical trial, Data extraction, Relative risk, C-reactive protein
- MeSH
- humans, inflammation, creatine, c-reactive protein, double-blind method, dietary supplements, randomized controlled trials as topic, biomarkers
10 authors
From CL, AR, BR, IE
- Kell Mazzini Ribeiro de Camargo
- Alejandro Bruna-MejíasUniversidad de Playa Ancha de Ciencias de la Educación; Fundación Ciencias Exactas y Naturales
- Juan Jose Valenzuela-FuenzalidaUniversidad Bernardo O'Higgins
- Luana Almeida [UNESP] Gonzaga
- Sandra Maria BarbalhoFaculdade de Medicina de Marília; Universidade de Marília
- Alexandre L. Barroca
Abstract
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 E2. 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.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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