Creatine: A Treatment for Memory and Mental Health?

If you've ever heard of creatine—a powdery nonsteroidal supplement sold in most health food stores—you likely link creatine to bodybuilders or weightlifters. Both of the latter groups often consume creatine to increase strength and muscle size. If a swole gym bro was the first mental image the mention of creatine conjured for you, you're correct: Creatine is arguably the most effective legal performance supplement for athletes¹.

Although small amounts of creatine can be obtained directly from food (primarily fish and beef), our muscles also readily absorb creatine from oral supplementation (e.g., mixing creatine in drinking water). Why? Because muscles can use creatine to create adenosine triphosphate (ATP), the life-enabling energy source vital to cellular and muscular function. In brief, muscle cells containing more creatine can produce more energy for activities such as running, jumping, and lifting. With thousands of studies supporting the safety and efficacy of creatine for muscle function, creatine use by recreational and competitive athletes has been common for decades.

Brain creatine

In 1999², a paper showed something that was at the time surprising even to scientists: Creatine was also present in the human brain. Further, oral creatine intake increased brain creatine levels (suggesting that at least some creatine passed through the notoriously finicky blood-brain barrier).

Like muscle, human brain function is highly energy intensive. Therefore, it makes sense that the brain would also use creatine as a supplemental energy source. In fact, research revealed that creatine is so important to human brain function that the brain even synthesizes its own creatine.

The knowledge that creatine was a bioactive substance in the brain inspired a new generation of research questions: Could creatine supplementation, proven to improve muscle function, also improve brain function? If so, which brain functions and people are most likely to benefit?

With nearly two decades of creatine research on brain function now complete, the initial results appear promising (see Figure 1³):

Source: Thomas Rutledge

• A 2023 systematic review and meta-analysis of placebo-controlled clinical trials indicated that creatine supplementation moderately improved memory function in healthy adults⁴. Memory benefits described in this review were, on average, larger for older adults and smaller for younger adults.
• There is some evidence from creatine reviews that supplementation may be more beneficial for people experiencing acute/chronic stress or who consume smaller amounts of creatine through diet (e.g., vegans and vegetarians)³.
• Because anxiety, PTSD, and depression symptoms are associated with metabolic dysfunction and impaired energy levels in the brain—mechanisms improved by creatine—it is plausible that creatine supplementation can be beneficial⁵. Population studies reliably show higher depressive symptoms among people with lower creatine levels. Initial human creatine interventional trials indicate small to moderate symptom improvements for individuals with these mental health conditions.
• Animal studies and initial human trials likewise indicate potential benefits of creatine supplementation in people with mild traumatic brain injury (mTBI)³. Impaired metabolic function is a common side effect of TBI. This process could potentially be improved by higher creatine intake.
• At this point, the optimal dosing schedule (i.e., how much creatine/how often to take/how long to take) for brain benefits remains unclear. Most brain creatine trials borrow from protocols established for studies testing creatine for physical performance, where consistent regimens of 5 grams of creatine/day are consumed or "pre-loading" regimens of 10-20 grams of creatine/day for 1-2 weeks followed by a 5-gram/day "maintenance" dose are used.

Summary

Once limited to populations seeking better athletic performance, creatine has come full circle as a health supplement. Although additional clinical trials are required to optimize dosing patterns and to identify persons most likely to benefit, evolving creatine research is showing promise as a supplement potentially helpful for a range of mood and cognitive symptoms.

*As with all health supplements, if you are considering creatine use, favor brands that submit to third-party testing to ensure product quality. There is also no scientific basis to use any form of creatine for brain health other than creatine monohydrate—the cheapest and most proven form of creatine (other forms of creatine are more expensive and may not provide the same effects⁶).