There is a long history of supplements marketed to enhance memory, focus, overall cognitive function, and brain health. None of them are backed by quality scientific evidence, and they seem to go through the typical conveyor belt of claims – by the time one claim is collapsing, such as ginkgo biloba, the industry is happy to move on to the next.
The latest in this brain supplement story is creatine (specifically creatine monohydrate). The story here is a bit more complex than the typical supplement slop. The putative mechanism is reasonably plausible – creatine is converted into phosphocreatine and stored in neurons, which can be broken down into ATP to use as energy. The idea is that when the brain is stressed it can tap into this extra source of energy. At least there is no quantum vibrations or chi energy involved.
With these types of potential mechanisms, however, it is difficult to know if the effect is clinically significant. First, is the availability of ATP a rate-limiting step in brain function? Second, is the amount of ATP made available through phosphocreatine significant enough to affect function? To answer these questions we need clinical research.
A 2024 systematic review goes over all the relevant clinical studies – “Sixteen RCTs involving 492 participants aged 20.8-76.4 years.” That is a modest amount of data, but enough to get a preliminary idea of whether there is any potential here. The review found:
“Creatine supplementation showed significant positive effects on memory (SMD = 0.31, 95% CI: 0.18-0.44, Hedges’s g = 0.3003, 95% CI: 0.1778-0.4228) and attention time (SMD = -0.31, 95% CI: -0.58 to -0.03, Hedges’s g = -0.3004, 95% CI: -0.5719 to -0.0289), as well as significantly improving processing speed time (SMD = -0.51, 95% CI: -1.01 to -0.01, Hedges’s g = -0.4916, 95% CI: -0.7852 to -0.1980). However, no significant improvements were found on overall cognitive function or executive function. Subgroup analyses revealed that creatine supplementation was more beneficial in individuals with diseases, those aged 18-60 years, and females.”
I would characterize these findings as mixed. It seems to help memory, attention, and processing speed, but not overall cognitive function (that seems important) or executive function. Also, the effect was greater in women, those <60, and those with chronic illness. Generally, when we see mixed results like this with preliminary studies, that’s not a good sign.
The authors conclude that there is low to moderate confidence for a beneficial effect which requires “larger robust clinical trials” to validate. That is code for ‘not ready for prime time.’
There is also some evidence that creatine may be helpful for sleep deprivation specifically. This makes sense since a brain under stress, such as sleep deprivation, may make the availability of ATP a rate-limiting step.
Studies generally use a dose of 3-5 grams per day, or even 5-10 grams. For some applications, like sleep deprivation, a loading dose of 20 grams per day for a week is used. These doses are generally safe, but they can stress out the kidneys and should not be used in people with kidney disease. They can also worsen mania in bipolar disorder and worsen Parkinson’s disease when combined with caffeine.
What does all this mean for current recommendations for creatine for brain function? There are currently no published official recommendations from any medical body – so here’s my SBM-orientated take.
The claims for creatine are semi-plausible, and low-dose supplementation is likely safe (with the caveats above). But the clinical evidence is mixed and preliminary. I am especially concerned that the evidence shows no effect for “overall cognitive performance”. Given the overall false positive bias in the medical literature, especially for preliminary studies, the probability that creatine will turn out to be significantly effective is somewhat low, but non-zero.
Clearly, we need larger and more rigorous clinical research to provide more confident answers. There may also be a sub-population or specific indication where it is reasonably effective. That would be similar to melatonin – it is not really an effective general sleep aid, but it can be effective in treating jet lag. Perhaps creatine will turn out to only be effective for acute sleep deprivation.
I would not be surprised either way, but a more confident answer awaits larger clinical trials.
