Long considered a staple in muscle and strength building pursuits, creatine has shown promise in burnishing neurocognitive health and performance in recent years.

Creatine is a naturally occurring substance that is extrapolated from three amino acids: methionine, glycine, and arginine and synthesized within the liver, kidneys, and pancreas. Since it encompasses a linkage of two or more amino acids, creatine is technically classified as a peptide. Peptides are a cluster of molecules that interact with a range of tissues throughout the body and govern cellular growth, development, and differentiation.

Nearly all our body’s creatine supply is stored within skeletal muscle in free and phosphorylated forms. Trace amounts of creatine are also found within cardiac tissue, testes, and the brain. Creatine’s phosphorylated form, known as phosphocreatine (PCr), regenerates adenosine triphosphate (ATP), our body’s energy currency, by donating a phosphate group to adenosine diphosphate (ADP) to sustain intense physical activities involving great effort that are characterized by substantial muscular forces.

To date, most investigations of creatine’s efficacy have been premised on its role in facilitating improvements in muscular power, strength, and power endurance, or the ability to engage in multiple bouts performed at high intensities over an extended course of time. This attribute is reflected in repeat sprint ability, which is critical to success in a gamut of sports.

However, recent research has suggested that brain function can be influenced by creatine levels. Creatine replenishes ATP within the cerebral cortex, just as it does in skeletal muscle tissue, but in this environment, it is chiefly responsible for supporting neurotransmission. Creatine that is synthesized within the body is transported to the brain through the blood-brain barrier via the creatine transporter protein, which have been both shown to regulate creatine levels. Lower levels of creatine may result in impaired neurocognitive health and may be linked to a host of neurological disorders and the development and progression of Alzheimer's disease (Candow et al., 2023; Smith et al., 2025).

Lower cortical creatine levels can be overcome by daily creatine supplementation. Daily consumption of 20 grams per day (or four rounded teaspoons), a dose consistent with established recommendations to increase intramuscular PCr stores and eventuating muscular performance, has been shown to improve cognitive task performance among adults (Candow et al., 2023). Improved neurocognitive function was observed among subjects exposed to acute hypoxia (Turner et al., 2015), suggesting its utility as a possible adjunctive measure in supporting acclimatization to increased altitudes. Further, a single dose of creatine was shown to improve cognitive test performance amid sleep deprivation (Gordji-Nejad et al., 2024). An earlier study involving a single dose of creatine demonstrated improvements in mood and prefrontal cortex functioning following 24 hours of sleep deprivation (McMorris et al., 2006). Though the findings from theses studies are encouraging, the impact of creatine supplementation on chronically sleep deprived individuals, whom are estimated to represent one-third of Americans, remains to be ascertained.

Dietary Sources of Creatine

Creatine is found in abundant amounts in animal proteins, specifically red meat and various fish, including herring, salmon, and tuna. Additionally, moderate amounts are present in dairy products. Smaller amounts of creatine are found in seeds, nuts, and legumes. Lower creatine content in the latter two sources bear implications for those ascribing to vegetarian and vegan lifestyles, respectively, and therefore may warrant creatine supplementation.

Creatine Supplements

Though multiple forms of creatine are commercially available, many share key differences in both composition and efficacy. Further, large variations in purity have been documented across products (Escalante et al., 2022).

Creatine Monohydrate is creatine linked with a single water molecule, permitting it to be readily absorbed into liquid for consumption. Creatine Monohydrate is the most popular form of creatine due to its cost-effectiveness.

Creatine Ethyl Ester, another common form of creatine, dissolves better in phospholipids and fats, presumably making it active for a longer period of time. Creatine Ethyl Ester is commonly sold in pill or serum form as it does not mix well in water-based beverages.

Creatine Hydrochloride is composed of both creatine and hydrochloric acid, which enhances its solubility and thus requires smaller doses due to improved absorption.

Creatine Citrate, like Creatine Monohydrate, dissolves in water-based beverages rapidly. Its structure is derived from the binding of creatine molecules with citric acid.

Creatine Nitrate, similar to Creatine Monohydrate and Creatine Citrate, is highly water soluble. Its structure is derived from the binding of creatine molecules with a nitrate group.

Creatine Phosphate is a highly water-soluble form derived from the combination of creatine and a phosphate molecule.

Micronized Creatine is Creatine Monohydrate that has undergone a micronization process to reduce its particle size enabling ingestion of greater concentrations of creatine.

Conclusion

Upon review of the research, inclusive of the recent shift of exploring the association between creatine and neurocognitive function, incorporating sources of creatine within the dietary pattern and supplementation merit consideration. Increased daily creatine consumption is recommended for individuals aiming to improve muscular and neurocognitive performance with potential implications for those transitioning to higher altitudes as well as those struggling with sleep deprivation, though the long-term effects of creatine on chronically sleep deprived populations in unknown.

References

Candow, D.G., Forbes, S.C., Ostojic, S.M., Prokopidis, K., Stock, M.S., Harmon, K.K., & Faulkner, P. (2023). “Heads Up” for creatine supplementation and its potential applications for brain health and function. Sports Medicine, 53(1), 49-65. https://doi.org/10.1007/s40279-023-01870-9

Escalante, G., Gonzalez, A.M., St. Mart, D., Torres, M., Echols, J., Islas, M., & Schoenfeld, B.J. (2022). Analysis of the efficacy, safety, and cost of alternative forms of creatine available for purchase on Amazon.com: are label claims supported by science? Heliyon, 8(12), e12113. https://doi.org/10.1016/j.heliyon.2022.e12113

Gordji-Nejad, A., Matusch, A., Kleedörfer, S., Jayeshkumar Patel, H., Drzezga, A., Elmenhorst, D., Binkofski, F., & Bauer, A. (2024). Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation. Scientific Reports, 14(1), 4937. https://doi.org/10.1038/s41598-024-54249-9

McMorris, T., Harris, R.C., Swain, J., Corbett, J., Collard, K., Dyson, R.J., Dye, L., Hodgson, C., & Draper, N. (2006). Effect of creatine supplementation and sleep deprivation, with mild exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol. Psychopharmacology, 185(1), 93–103. https://doi.org/10.1007/s00213-005-0269-z

Smith, A.N., Choi, I.-Y., Lee, P., Sullivan, D.K., Burns, J.M., Swerdlow, R.H., Kelly, E., & Taylor, M.K. (2025). Creatine monohydrate pilot in Alzheimer’s: Feasibility, brain creatine, and cognition. Alzheimer’s and Dementia: Translational Research and Clinical Interventions, 11(2), e70101. https://doi.org/10.1002/trc2.70101

Turner, C.E., Byblow, W.D., & Gant, N. (2015). Creatine supplementation enhances corticomotor excitability and cognitive performance during oxygen deprivation. Journal of Neuroscience, 35(4), 1773–1780. https://doi.org/10.1523/jneurosci.3113-14.2015

About the author

Joseph Giandonato, PhD, MBA, CSCS is an Assistant Professor of Exercise Science at an institution in the Northeastern US. Previously, Giandonato supported an award-winning employee wellness program at a major university in the Mid-Atlantic US while serving as an adjunct faculty member at several colleges and universities where he taught exercise physiology, statistics, and research methods. Giandonato previously served as a strength and conditioning coach and has extensive experience working with professional, collegiate, and high school athletes. His research interests include ergogenic aids, concurrent training, and exploring health behaviors of non-traditional undergraduate students.