BY Samuel Mathis MD
One of the core tenets of integrative medicine is diet and exercise. However, once patients start exercising with more regularity, additional questions begin to arise. One of the most common questions associated with exercise is the use of supplements to improve exercise quality and tolerance. One of the most used supplements for exercise is creatine. This supplement has some great uses in exercise, but new research shows the benefits may also extend beyond just improving exercise tolerance.
Creatine is a nitrogen-based modified amino acid molecule found mostly in skeletal muscles, where it plays a key role in the creation of ATP. A significant portion of our daily required creatine is obtained through our diets, mostly in red meats and seafood (1). Outside of dietary consumption, creatine is also synthesized in the liver and kidneys through arginine, glycine, and methionine. Creatine supplementation has been shown to increase the efficiency of the body’s ability to produce ATP through the P-CP pathway. This improvement in ATP production allows individuals to increase their training intensity, leading to improved muscle mass. This improvement in muscle mass translates into significant improvement in strength. A 2025 study evaluating the impact of creatine supplementation found that individuals utilizing creatine had significant improvement in muscle strength compared to the general population (1). The study found the best improvements were seen in low-dose supplementation that was paired with high-intensity exercise (1).
Beyond the well-known benefits of creatine supplementation, new research shows that supplementation has broader impacts on cognitive function and on at-risk populations. Regarding cognitive function, a recent systematic review of 16 studies (n=492) found that creatine monohydrate supplementation significantly improved memory, attention, and reaction speed compared with no supplementation (2). This benefit was seen in both short-term (< 4 wk) and long-term (> 4 wk) durations of supplementation. Interestingly, creatinine did not significantly impact overall cognitive or executive functioning (2). It is important to note that these were relatively small studies, and further evaluation is needed to fully assess the impact creatine has on memory and cognition.
Because creatine is found mostly in animal skeletal muscle, certain populations are at risk of low creatine stores. A 2024 study looked at the impact of creatine supplementation on these populations. It found that in vegan and vegetarian populations, creatine supplementation improved both cognitive and physical performance (3). Women are noted to have lower stores of creatine and supplementation can improve those stores as well as improve fatigue related to the early follicular and luteal phases of menstruation (3). In certain health conditions, creatine may improve symptoms of muscle wasting in patients with sarcopenia and cachexia, improve exercise tolerance in patients with cardiovascular disease, provide neuroprotective effects in patients with chronic neurological conditions such as Parkinsons and Huntington’s, and improve energy metabolism in patients with chronic fatigue and fibromyalgia (3).
When recommending creatine supplementation, the evidence indicates that low-dose creatine supplementation seems to be most effective. I typically recommend patients who choose to supplement take 3 – 5 mg of creatine monohydrate daily. This can be paired with carbohydrate loading to increase absorption, but it may cause GI upset (3). Creatine supplementation may also cause fluid retention in some patients, leading to edema. Creatine does increase levels of creatinine, but there has not been evidence that this impacts renal function. Of note, exogenous creatine supplementation will suppress the body’s own ability to synthesize creatine, but that effect returns to normal after 4-6 weeks. There are no reported complications with long-term creatine use, but there also have not been any specific studies looking at the health risks associated with creatine supplementation. This is an important point that should be discussed with patients seeking to utilize creatine. I often recommend using supplementation during periods of increased exercise, followed by supplementation holidays to ensure the body continues to create its own levels and may improve efficient use of creatine when taken (3).
References:
- Zhang H, Lan T, Yan X, Gu H, Li Y, He E. Effects of creatine supplementation on muscle strength gains-a meta-analysis and systematic review. PeerJ. 2025 Nov 27;13:e20380. doi: 10.7717/peerj.20380. PMID: 41328071; PMCID: PMC12665265.
- Xu C, Bi S, Zhang W, Luo L. The effects of creatine supplementation on cognitive function in adults: a systematic review and meta-analysis. Front Nutr. 2024;11:1424972. Published 2024 Jul 12. doi:10.3389/fnut.2024.1424972
- Gutiérrez-Hellín J, Del Coso J, Franco-Andrés A, et al. Creatine Supplementation Beyond Athletics: Benefits of Different Types of Creatine for Women, Vegans, and Clinical Populations-A Narrative Review. Nutrients. 2024;17(1):95. Published 2024 Dec 29. doi:10.3390/nu17010095