How creatine went from the gym to becoming a promising product for the brain.

For nearly three decades, creatine was synonymous with muscle hypertrophy. It gained popularity in gyms in the 1990s and became one of the most studied and safest supplements, recognized for increasing strength and endurance in high-intensity exercises. In recent years, however, the focus of scientific—and commercial—attention has shifted: the same substance is now presented as capable of improving even mental performance. Is it true?

“Science has shown that the brain also depends on quick energy for functions such as memory, reasoning, and attention,” explains nutritionist Diogo Toledo, coordinator of the Nutrition Department at Einstein Hospital Israelita. “This discovery opened a new field: if creatine improves muscle energy availability, it could also have a positive impact on situations of brain stress, mental fatigue, or neurological diseases.”

The topic gained prominence after the publication, in 2024, of a German study in the journal Scientific Reports that reported a modest improvement in the cognitive performance of 15 volunteers deprived of sleep for 21 hours after ingesting a single, high dose of creatine monohydrate. Participants experienced small gains in memory, reaction time, and reasoning, as well as measurable changes in brain energy metabolism.

The study quickly gained traction on social media and health websites, where it circulated as supposed evidence that creatine "boosts the brain." Doctors, influencers, and wellness profiles reproduced the finding in a simplified way, often without mentioning that it was a small, short-term study conducted under extreme sleep deprivation conditions.

The promise of a colorless, odorless, and tasteless powder capable of improving physical and mental strength is tempting. But there is a lack of solid evidence that creatine fulfills this second role. "There are receptors that allow ingested creatine to reach the central nervous system," says nutritionist Igor Eckert, co-founder of Reviews, a platform that analyzes scientific studies.

But to then present it as a promise of a turbocharged mind is a whole different story. Eckert, author of a critical review published in October in The Journal of Nutrition , points out that this discussion has been marked by confirmation bias and a relaxation of evidence criteria.

Explosive force

The body produces creatine naturally from three amino acids — glycine, arginine, and methionine — synthesized in the liver, kidneys, and pancreas. The substance is also present in foods, mainly meats and fish. "It stores high-energy phosphates that help cells, especially muscle and brain cells, replenish energy in situations of intense exertion or high demand," explains Toledo.

Endogenous synthesis covers about 70% to 80% of the daily demand. The remainder comes from the diet, but it rarely reaches ideal saturation levels. To obtain the amount present in a single dose of supplement (3 to 5 grams), it would be necessary to eat more than a kilogram of beef per day. "It's as if we live in a world where the car produces part of its own gasoline, but never fills the tank completely," compares Eckert.

After being produced or ingested, creatine circulates in the blood and accumulates in tissues, mainly in muscles, where it acts as an energy buffer. It releases adenosine triphosphate (ATP), allowing intense physical exertion to last a few seconds longer. "It's reasonable to say that, for those who regularly engage in physical activity, supplementing with creatine is usually a good decision," says Eckert. "But the greatest benefit appears in sports that require explosive strength, such as weightlifting or short sprints."

From muscle to brain

The physical effect of creatine is widely proven. Since the 1990s, clinical trials have confirmed that the supplement increases the ability to generate force, improves performance in short-duration, high-intensity activities, and contributes to consistent gains in lean mass. One of the most recent studies, published in 2025 in the journal Nutrients , showed that healthy adults who received 5 grams of creatine per day experienced an average increase of 0.5 kg of lean mass after one week of use—an effect that remained stable, although without further increase, after 12 weeks of resistance training.

Another comprehensive review, published in the Journal of the International Society of Sports Nutrition , compiled data from hundreds of trials and concluded that creatine is one of the safest and most effective supplements available, with average gains of 5% to 15% in muscle strength and power. "In the brain, creatine performs the same function as in muscles: it acts on the release of ATP, the main energy currency of cells," explains Eckert.

Based on this logic, researchers began to investigate whether the brain could also benefit from supplementation. This hypothesis, formulated in the early 2000s, gave rise to a new front of studies on the role of creatine in cognition. Research from that time pointed to small gains in short-duration cognitive tasks, mainly in the elderly and sleep-deprived individuals. "There are about 25 studies, with inconsistent results," says Eckert. "In some, there is a benefit; in others, there isn't. And in the same study, sometimes a positive result appears in one test, but not in another."

The evidence — and the uncertainties

The hypothesis that creatine may benefit the brain has been tested for at least two decades in different experimental contexts—from sleep deprivation and psychological stress to aging. In a study published in 2023 in Nutrition Reviews , 90 healthy adults took 5 grams of creatine per day for six weeks and underwent a protocol that induced acute stress. The supplemented group performed slightly better on memory and attention tasks, but did not differ from the placebo in physiological markers of stress, such as cortisol levels and heart rate.

The authors suggest a possible compensatory effect limited to situations of mental overload, with no measurable impact on mood or cognitive functioning under normal conditions. However, the study has limitations: the period was short, there were no direct measurements of brain metabolism, and the sample was restricted to young, healthy adults.

“Furthermore, it’s unclear what a positive cognitive score on tests means in practice,” Eckert notes. “What does a 0.5-point increase on a memory test represent? Retaining more information? Even with very high-quality studies, there would still be uncertainty about what this type of result means.”

The nutritionist at Einstein Hospital acknowledges that there are indications of cognitive improvement in specific situations—such as sleep deprivation, mental fatigue, or in the elderly. According to him, creatine seems to act as support during times of higher energy demand from the brain, and not as an immediate stimulant. "But it's a myth to believe that the substance would transform any healthy person into someone with above-average mental performance, as if it were a miraculous nootropic," he cautions.

No effect on diseases

When it comes to neurological diseases, the scenario is even less promising. According to Eckert, 12 large clinical trials tested supplementation in conditions such as Parkinson's, Huntington's, amyotrophic lateral sclerosis (ALS), and multiple sclerosis—none showed relevant clinical benefits. "These studies were the nail in the coffin," he summarizes. "In the scientific literature, no one seriously discusses the effects of creatine on these diseases anymore."

The most robust study, published in 2015 in JAMA , followed 1,741 people with Parkinson's disease for five years. The trial was interrupted due to futility, after finding a total absence of effect on disease progression. "It's an exemplary study in terms of methodological rigor," Eckert points out. Even so, from 2021 onwards, reviews signed by experts linked to the creatine industry began to reappear. "These are texts that repeat the same ideas and studies to support the claim that the cognitive benefit is plausible, that it might work. But they systematically ignore the negative evidence in neurological diseases, precisely those that reduce the plausibility of this hypothesis," he states.

Since 2017, there have been no new large-scale clinical trials on the subject, only pilot studies, such as the one recently completed at the University of Kansas in the USA. Published in 2025 , the work was described as an early-stage, open-label, uncontrolled trial with 20 participants diagnosed with mild to moderate Alzheimer's disease. For eight weeks, the volunteers took 20 grams of creatine monohydrate daily and were assessed for adherence, safety, brain creatine concentration (by magnetic resonance spectroscopy), and cognitive performance.

Preliminary results showed good tolerability and an average increase of 11% in brain levels, as well as slight improvements in verbal fluency and short-term memory tests. However, the authors themselves classified the work only as evidence of feasibility, emphasizing that the small number of participants and the absence of a control group prevent any conclusions about clinical efficacy.

Safety margin

Creatine is among the most studied supplements in terms of safety, at least within recommended doses. "The longest studies have not shown relevant toxic effects on the kidneys or liver of healthy people," Toledo points out. "The limitation lies in some specific profiles: individuals with kidney disease or conditions affecting liver function need medical evaluation before using it. Another point is that there's no point in overdoing it, because the body has a saturation limit and the excess is eliminated."

The main point of attention is individual variability. "There is uncertainty about how much each person can tolerate and how much they need to supplement," compares Eckert. Even so, it's impossible to say that creatine is completely safe. Although available studies indicate low risk, most evaluated moderate doses for short periods. It is unknown what the effects of decades of continuous use or use far above the standard would be.

Therefore, new studies with more participants and prolonged follow-up are welcome. The challenge is to understand what doses are ideal, whether there are differences between men and women, young and old, and who actually benefits. "It is also essential to evaluate creatine in conjunction with other prevention and treatment strategies, to be seen as part of integrated care, and not as an isolated solution," says Diogo Toledo.

Eckert, in turn, warns of another risk of the current enthusiasm: the opportunity cost involved in choices based on unproven promises. "For example, someone with persistent cognitive difficulties might bet on a capsule advertised as beneficial and end up maintaining harmful habits instead of seeking the real cause of the problem," he exemplifies. For now, creatine remains on the borderline between a proven effective sports supplement and a potential brain ally that still lacks more solid evidence.

Source: Einstein Agency

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