Creatine, one of the most popular supplements among gym-goers and athletes, does not appear to have the anti-inflammatory effect that many imagine. This conclusion comes from a systematic review and meta-analysis conducted in Brazil by researchers at São Paulo State University (UNESP), which evaluated clinical trials in humans. The study indicates that, to date, there is no consistent evidence that creatine reduces inflammatory markers in the body.
Supported by FAPESP , the study was conducted at UNESP’s Center for Systematic Review Studies in Cardiovascular and Metabolic Health in Marília. The results were published in the scientific journal Frontiers in Immunology . The researchers analyzed data from eight randomized, placebo-controlled clinical trials to investigate the effects of creatine supplementation on the most common inflammatory biomarkers.
Since the 1990s, creatine has been widely recognized for its ergogenic effects – that is, its ability to improve physical performance by helping the body train better, generate more strength, resist fatigue longer, and recover faster. However, the growing popularity of the supplement has led to misconceptions about its potential benefits, including its supposed anti-inflammatory effect.
“Many people claim that creatine is anti-inflammatory based on the results of studies done on animals or isolated cells in a lab. The problem is that these basic research findings don’t always translate into clinical effects in humans,” explains Vitor Engrácia Valenti , group coordinator and study advisor.
As Valenti explains, there is some evidence that creatine has anti-inflammatory properties that may help preserve muscle integrity and reduce inflammatory markers after intense exercise, though the exact mechanisms responsible have yet to be fully defined.
The results of the analyzed studies were heterogeneous and varied according to the population and type of intervention. Some studies pointed to the anti-inflammatory effects of creatine in contexts of intense and long-duration exercise. For example, research with athletes who took short-duration, high-dose creatine supplements (about 20 g per day for five days) observed reductions in inflammatory markers after strenuous events such as long-distance runs and triathlons. These studies observed decreases in prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), and interleukin-1β, suggesting a protective effect against muscle damage and the acute inflammatory response induced by strenuous exercise.
However, this benefit was not replicated across different population profiles and clinical conditions. For example, studies conducted with patients with osteoarthritis and older adults found no significant reductions in inflammatory markers, such as C-reactive protein (CRP), interleukins, and other cytokines, even after weeks of supplementation.
In some cases, the observed improvements, such as reductions in certain markers or gains in strength, were attributed to the exercise itself rather than the creatine supplementation. Furthermore, molecular-level and muscle-recovery investigations also failed to identify a significant impact of creatine on inflammation, suggesting that its effects may be limited to specific contexts.
Of the most frequently evaluated biomarkers in the studies, C-reactive protein (CRP) and interleukin-6 (IL-6) stood out. The results showed very small reductions among participants who used creatine; these differences were not considered statistically or clinically significant. For example, the average reduction in CRP was only 0.41 mg/dL. “The magnitude of the difference was small,” the researcher explains. The reduction in IL-6 among those taking regular creatine supplementation was even smaller. “There was a minimal decrease, which isn’t significant from a statistical or clinical standpoint,” he states.
However, Valenti offers a caveat: the absence of evidence does not necessarily mean that the anti-inflammatory effect does not exist. “Given these findings, we recommend conducting more randomized, placebo-controlled clinical trials to confirm the observed data. Our study serves as a stimulus, a challenge to the scientific community, by highlighting the need for more robust investigations on the topic.”
The researcher also points out that inflammation is not always harmful. During physical exercise, for instance, the body produces inflammatory molecules that are crucial for muscle adaptation. “This acute and transient inflammatory response, along with other exercise-induced molecular signals, contributes to muscle repair, remodeling, and adaptation processes,” he explains.
Safety
Overall, the review of studies concluded that creatine supplementation is safe, even across different populations and contexts. Athletes undergoing intense and prolonged exercise did not report significant adverse effects, such as cramps, dehydration, or gastrointestinal discomfort, when taking high doses of creatine (20 g per day for five days) in short-term protocols, while maintaining performance within expected ranges. Similar results were observed in experimental studies with healthy individuals, in which the substance was well tolerated.
This pattern was also replicated in clinical populations and older adults, including in longer-term interventions. For example, in patients with osteoarthritis and older adults engaged in strength training, creatine was not associated with clinically relevant adverse events or unfavorable metabolic or functional changes. Taken together, the data reinforce the idea that creatine is safe and well-tolerated when used appropriately.
In practice, the findings do not change current recommendations regarding the use of the supplement, which is still considered safe for most people and may improve physical performance. “Creatine can enhance muscle strength and performance during exercise and, in some contexts, may indirectly contribute to functionality,” states Valenti.
Nevertheless, a healthcare professional should guide the use of creatine. “It’s important to consult a doctor, nutritionist, or physical educator before using it because everyone’s needs are different,” the researcher recommends. For Valenti, the main impact of the study lies in paving the way for new research. “The great importance of this review is to show that there are still few clinical trials on the subject and to encourage the scientific community to advance in this area,” he concludes.
About São Paulo Research Foundation (FAPESP)
The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at www.fapesp.br/en and visit FAPESP news agency at www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe.
Frontiers in Immunology
Impact of creatine supplementation on inflammation: evidence from a systematic review and meta-analysis of randomized double-blind placebo trials
18-Feb-2026