Creatine and the Brain: Promising Idea, Thin Evidence, Experts Warn

Creatine has a reputation that few supplements can claim: experts generally agree it helps people build slightly stronger muscles. Now a bigger claim is spreading, particularly on social media, that it can strengthen the brain too. Researchers say the idea is plausible. They also say the hype has run ahead of the science.

Stuart Phillips, a professor of kinesiology at McMaster University in Ontario, wants the conversation brought back down to earth. "Promise? Sure," he said. "But lots of things show promise." He argued that a dose of reality is needed on the brain-health side of things.

The theory starts with energy. Creatine plays a critical role in producing ATP, the body's main cellular fuel, which is why a person who lifts weights and takes creatine can train a little harder and get a little stronger. The brain is an especially hungry organ, using roughly 20% of the body's energy. From those two facts came the hypothesis that supplementing might energize brain cells, helping people focus, think more clearly and push through fatigue.

The brain, though, guards its creatine supply closely. It makes its own, to be sure it has enough. Creatine produced in the liver and elsewhere, or taken in through food or supplements, can cross the blood-brain barrier through a dedicated transporter protein, but only in very small amounts. Mehdi Boroujerdi, a pharmaceutical sciences expert and author of the "Handbook of Creatine and Creatinine In Vivo Kinetics," said the brain does not have an open gate saying "welcome all creatine." Assuming a higher dose will raise brain concentrations, he said, is a questionable concept.

The data are mixed. A few small studies found that a large dose, typically 20 grams, about four times the daily amount recommended for building muscle, raised brain creatine by roughly 5% to 10%. Other research found no increase at all. And whether a small rise would change how a person thinks, remembers or decides is an open question. Most studies of healthy adults, young and old, have found no cognitive benefit, which experts suspect is because the brain is already full on creatine.

There may be an exception. A few small studies suggest that under exhaustion or stress, such as after sleep deprivation or a demanding mental or physical workout, creatine may improve performance on some aspects of cognition, though that evidence is weaker. Darren Candow, a professor of kinesiology and health studies at the University of Regina who has conducted some of this research, said the average healthy person gets no cognitive benefit. But when the brain is metabolically stressed, in sleep deprivation, hypoxia or university students staying up all night, what it makes naturally might not be enough. Candow sits on the advisory boards of several supplement companies.

The other hope is that creatine could help a brain under attack from disease or injury. People with Alzheimer's, Parkinson's and other neurological disorders show evidence of impaired energy metabolism in the brain, so supplementing could in theory boost production. But clinical trials in Huntington's and Parkinson's patients were disappointing, showing no benefit for symptoms.

One recent study of 20 Alzheimer's patients looked more encouraging. A large dose for two months raised brain levels by 11%, and participants did better on cognitive tests at the end. But there was no placebo group, so the improvement could simply reflect a practice effect, since participants had seen the tests before. Matthew Taylor, an associate professor of dietetics and nutrition at the University of Kansas Medical Center who led the work, said he is not claiming memory improved. He described associated effects that could have other causes, but called it compelling evidence for continued study.

On that, experts agree. "Large-scale trials and long-term outcomes are nil at this point," Phillips said, adding that the honest truth is that science done so far is nowhere near what is needed to unpack the question.