SYSTEMATIC REVIEW article
Front. Immunol.
Sec. Nutritional Immunology
This article is part of the Research TopicPreventative Nutritional Approaches Against Inflammatory DiseasesView all articles
Impact of Creatine Supplementation on Inflammation: Evidence from a Systematic Review and Meta-Analysis of Randomized Double-Blind Placebo Trials
Provisionally accepted
Kell Mazzini Ribeiro de Camargo1Alejandro Bruna-Mejías1,2
Juan Valenzuela1,2Luana A. Gonzaga1Sandra Maria Barbalho1,3Alexandre L. Barroca1
Andrey Porto1
Rodrigo Daminello Raimundo1,4*Luiz Carlos de Abreu1,5
Vitor E. Valenti1- 1Universidade Estadual Paulista Julio de Mesquita Filho, São Paulo, Brazil
- 2Universidad de Playa Ancha, Playa Ancha, Chile
- 3Universidade de Marilia, Marília, Brazil
- 4Faculdade de Medicina do ABC, Santo André, Brazil
- 5Universidade Federal do Espirito Santo, Vitoria, Brazil
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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.
Keywords: Creatine, crp, Cytokines, IL-6, Inflammation, Meta-analysis, supplementation
Received: 10 Nov 2025; Accepted: 02 Jan 2026.
Copyright: © 2026 Camargo, Bruna-Mejías, Valenzuela, Gonzaga, Barbalho, Barroca, Porto, Raimundo, de Abreu and Valenti. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Rodrigo Daminello Raimundo
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