The science of creatine supplementation
By Austin Perlmutter, MD
Creatine May Have Brain and Muscle Benefits: Initially popular among athletes for muscle growth and performance, creatine is now recognized for its potential positive effects on brain function. Naturally occurring in the body, especially in muscles, supplementation can significantly boost its levels.
Enhancing Brain Function: Studies suggest that creatine supplementation increases brain creatine levels, which may counter mental fatigue and enhance brain energy metabolism. It's particularly noted for improving memory, especially in older adults, and may also boost intelligence and reasoning abilities.
Specific Benefits and Safety: Research indicates notable benefits of creatine supplementation for older adults, women, and those under metabolic stress. Concerns regarding kidney health have been largely dispelled, with studies suggesting safety in young adults and chronic renal disease patients.
Optimal Use and Dosage: The most studied and accessible form of creatine is creatine monohydrate, with a general consensus on a dosage of around 5 grams per day. This dosage is believed to support both muscle and brain wellness effectively.
Creatine: A Key Player in Brain Health and Function
Over the last years it’s likely you’ve heard mention of a compound called creatine. Often found in supplemental form as a white powder, creatine monohydrate is found naturally in our bodies, especially in our muscles. It’s been prized for decades by athletes for its role in muscle growth and athletic performance, but we’re now learning that creatine supplementation may have positive effects on multiple aspects of brain function.
What is creatine?
Creatine is a compound made up of carbon, oxygen, nitrogen and hydrogen. It was first discovered in 1832 in muscle, and the vast majority (over 90%) of our body’s creatine is stored in our muscle. It is made from the amino acids glycine, methionine and arginine. Even though we have natural creatine in our bodies, supplementation can dramatically increase our levels by 50-fold or higher.
How did creatine get popular?
Around 80 years after its discovery, researchers at Harvard University demonstrated that consumption of creatine leads to an increase in the muscle content of creatine, and later, scientists showed that creatine can help create more energy in the form of ATP. In the 1990s, athletes had been using creatine to enhance athletic performance. This led to higher-potency supplementation becoming more readily available. A number of review articles have concluded that creatine supplementation can improve multiple measures of muscle performance in men and women and may enhance muscle recovery after exercise. This has since been expanded to a number of other domains, and by now over 1000 peer-reviewed papers have been published on creatine supplementation.
What about creatine and the brain?
Creatine and brain energy metabolism
Our brains are incredibly energy intensive, using up over 20% of our body’s energy despite only making up around 2% of our weight. With this in mind, creatine’s energy supplementing effect could in theory present a significant benefit for the brain. Research has revealed that supplemental oral creatine does increase the brain’s creatine levels, and may help counteract mental fatigue. Having access to extra brain fuel may help explain the diverse brain benefits associated with creatine supplementation, as explored below.
Creatine and memory
Despite the litany of claims on the market, very few supplements have been shown to statistically enhance memory. Creatine is rather unique in this regard. In a powerful 2022 meta-analysis, it was concluded that creatine supplementation significantly improved memory (compared to placebo). This improvement was particularly impressive among older adults (aged 66-77 years).
Creatine and intelligence/reasoning
Like memory, there are very few supplement-based interventions linked to improved intelligence scores. That’s what makes the data on creatine all the more interesting. In a systematic review of randomized trials published in 2018, researchers concluded that oral creatine supplementation may improve the intelligence and reasoning abilities of healthy individuals
Who might benefit most from creatine
To date, the best data for the brain benefits of creatine supplementation appear to be in older adults, and potentially especially those who are vegan or vegetarian. Given what we know about its role in brain energy, it may be worthy of special consideration when our brains are under higher levels of metabolic stress (for example, if we’re sleep deprived or psychologically stressed).
Creatine supplementation in women
A common question around creatine supplementation concerns its use in women. As is so often the case, there is less research available on the topic of creatine use in women than men. It is known that creatine stores in our body are partly under the control of hormones, and that hormonal shifts occurring in women may have an important role in availability of natural creatine in the body. In a review paper published by scientists at the University of North Carolina in 2021, it was suggested that “creatine supplementation may be even more effective for females by supporting a pro-energetic environment in the brain,” and that “the current body of literature that has evaluated the effect of creatine supplementation in females suggests that the risk-to-benefit ratio is low.”
Creatine and kidney issues
Another popular question about creatine relates to the potential that it could harm our kidneys, or that it should be avoided in people with kidney issues. This particular question was addressed by researchers who published a review in the Journal of Renal Nutrition in 2021. After analyzing all the relevant published studies, they conclude: “…we are of the opinion that creatine supplements are safe for young adults and patients with chronic renal diseases,” and while they generally believe the supplements to be overall safe, they suggested there may be a value in continued investigation of the effects on elderly patients with kidney issues.
What type and how much?
There are several forms of creatine on the market. These include creatine ethyl ester, creatine hydrochloride, buffered creatine and creatine monohydrate. By far the most studied and most available form is creatine monohydrate (it’s also usually the most cost effective). Regarding optimal dosing, there is some variability, but generally around 5 grams seems to be the consensus, and this does seem to generalize to many of the brain-specific studies. Some exercise research suggests that for maximum performance effects, it should be taken after exercise and with food.
Creatine has emerged as a frontrunner among supplements scientifically studied for their benefits on brain function. While most research indicates that supplementation with creatine is safe, it’s always worth speaking with a healthcare practitioner about any sort of supplement intervention and ensuring the product comes from a trusted, quality company. Generally speaking, most of the published research appears to support a dose of roughly 5 grams a day of creatine monohydrate as a way of supporting muscle and brain wellness.