CREATINE SUPPLEMENTATION AS A STRATEGY FOR COGNITIVE SUPPORT AND NEUROPROTECTION

Authors

DOI:

https://doi.org/10.31435/ijitss.2(50).2026.5794

Keywords:

Creatine Monohydrate, Supplementation, Cognitive Function, Neuroprotection, Neuroplasticity, Blood-Brain Barrier

Abstract

Creatine (methylguanidine-acetic acid) is an organic compound formed from reactions involving the amino acids arginine, glycine and methionine. Synthesized endogenously in the kidneys and liver, it is concentrated in skeletal muscle and tendons, as well as in the brain, liver, kidneys and testes. Since the 1990s, creatine has been a widely used sports supplement, known to enhance muscle strength, endurance and recovery.  It is one of the most extensively researched supplements in the world, and its efficacy and safety profile have been confirmed in thousands of peer-reviewed publications. With an increasing number of publications highlighting the effects of creatine on the central nervous system (CNS), this article aims to review the most recent literature.

Objective: This review evaluates scientific evidence concerning creatine’s effects on cognitive function and neuroprotection in healthy adults while analyzing the underlying neurobiological mechanisms.

Methodology: A literature review was performed using PubMed, Scopus, and Google Scholar, encompassing meta-analyses, randomized controlled trials, and neuroimaging data.

Results: Analysis of the current literature indicates that creatine supplementation can increase brain phosphocreatine levels, thereby enhancing cellular bioenergetics. In healthy adults, improvements in short-term memory, fluid intelligence, and reduced mental fatigue represent the most pronounced cognitive benefits observed primarily under conditions of metabolic stress, including sleep deprivation or demanding cognitive tasks.

Conclusions: Creatine represents a promising, safe intervention for supporting CNS function. Especially since its safety and effectiveness have been extensively studied. However, further research must establish definitive dosing protocols to optimize cognitive outcomes.

References

Almeida, L. S., Salomons, G. S., Hullaert, T., Jakobs, C., & Gajja, S. J. (2006). Creatine-dependent glutamate release. Journal of Neurochemistry, 97(1), 207–216. https://doi.org/10.1111/j.1471-4159.2006.03723.x

Avgerinos, K. I., Spyrou, N., Bougioukas, K. I., & Kapogiannis, D. (2018). Effects of creatine supplementation on cognitive function of healthy individuals: A systematic review of randomized controlled trials. Experimental Gerontology, 108, 166–173. https://doi.org/10.1016/j.exger.2018.04.013

Balestrino, M. (2021). Role of creatine in the heart and brain. Nutrients, 13(4), Article 1155. https://doi.org/10.3390/nu13041155

Braissant, O., Henry, H., Béard, E., & Uldry, J. P. (2011). Creatine deficiency syndromes and the importance of creatine synthesis in the brain. Amino Acids, 40(5), 1315–1324. https://doi.org/10.1007/s00726-011-0852-z

Brinton, R. D., Yao, J., Yin, F., Mack, W. J., & Cadenas, E. (2015). Perimenopause as a neurological transition state. Nature Reviews Endocrinology, 11(7), 393–405. https://doi.org/10.1038/nrendo.2015.82

Bürli, T., Harneit, A., & Moulin, M. (2013). Creatine as a neuromodulator in the central nervous system. Amino Acids, 44(4), 1085–1094. https://doi.org/10.1007/s00726-012-1386-8

Candow, D. G., Forbes, S. C., Roberts, M. D., Young, K. C., Ziegenfuss, T. N., & Antonio, J. (2022). Creatine o’clock: Does timing of ingestion really influence muscle mass and performance? Frontiers in Sports and Active Living, 4, Article 893714. https://doi.org/10.3389/fspor.2022.893714

Dechent, P., Pouwels, P. J., Wilken, B., Hanefeld, F., & Frahm, J. (1999). Increase of total creatine in human brain after oral supplementation of creatine-monohydrate. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 277(3), R698–R704. https://doi.org/10.1152/ajpregu.1999.277.3.R698

Ellery, S. J., Walker, D. W., & Dickinson, H. (2016). Creatine for women: A review of the relationship between creatine and the reproductive cycle and female-specific benefits of creatine therapy. Amino Acids, 48(8), 1807–1817. https://doi.org/10.1007/s00726-016-2199-y

Forbes, S. C., Cordingley, D. M., Cornish, S. M., Gualano, B., Roschel, H., Ostojic, S. M., Rawson, E. S., & Candow, D. G. (2022). Effects of creatine supplementation on brain function and health. Nutrients, 14(5), Article 921. https://doi.org/10.3390/nu14050921

Galbraith, R. A., Furukawa, M., & Li, M. (2006). Creatine responsiveness and the effects of creatine transport in the hypothalamus. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 291(1), R270–R276. https://doi.org/10.1152/ajpregu.00270.2006

Gordji-Nejad, A., Matusch, A., Kleedörfer, S., Scharrer, I., Shah, N. J., & Langen, K. J. (2024). Effects of creatine monohydrate supplementation on brain energetics and cognitive function. Scientific Reports, 14(1), Article 2172. https://doi.org/10.1038/s41598-024-52261-3

Guidi, C., Potenza, L., Sestili, P., Mariani, F., Pagliarani, S., Martinelli, C., Stocchi, V., & Fimognari, C. (2008). Creatine supplementation prevents oxidative DNA damage and adaptation in muscle cells exposed to ROS. British Journal of Nutrition, 99(5), 962–971. https://doi.org/10.1017/S000711450785315X

Hemmer, W., & Wallimann, T. (1993). Functional aspects of creatine kinase in brain. Developmental Neuroscience, 15(3–5), 249–260. https://doi.org/10.1159/000111340

Kreider, R. B., & Stout, J. R. (2021). Creatine in health and disease. Nutrients, 13(2), Article 447. https://doi.org/10.3390/nu13020447

Matthews, R. T., Ferrante, R. J., Klivenyi, P., Yang, L., Klein, A. M., Mueller, G., Kieburtz, K., & Beal, M. F. (1999). Creatine and cyclocreatine attenuate MPTP neurotoxicity. Experimental Neurology, 157(1), 142–149. https://doi.org/10.1006/exne.1999.6841

McMorris, T., Harris, R. C., Swain, J., Corbett, J., Collard, K., Dyson, R. J., Dye, L., Hodgson, C., & Draper, N. (2007). Creatine supplementation, sleep deprivation, cortisol, melatonin and behavior. Physiology & Behavior, 90(1), 21–28. https://doi.org/10.1016/j.physbeh.2006.08.024

O’Gorman, E., Beutner, G., Wallimann, T., & Brdiczka, D. (1997). The role of creatine kinase in inhibition of mitochondrial permeability transition. FEBS Letters, 414(2), 253–257. https://doi.org/10.1016/S0014-5793(97)01045-3

Perasso, L., Lunardi, G., Strangio, A., Cupello, A., & Balestrino, M. (2013). Role of creatine in synaptic plasticity and long-term potentiation. Amino Acids, 45(1), 33–39. https://doi.org/10.1007/s00726-013-1484-2

Rae, C., Digney, A. L., McEwan, S. R., & Bates, T. C. (2003). Oral creatine monohydrate supplementation improves brain performance: A double-blind, placebo-controlled, cross-over trial. Proceedings of the Royal Society of London. Series B: Biological Sciences, 270(1529), 2147–2150. https://doi.org/10.1098/rspb.2003.2492

Roschel, H., Gualano, B., Ostojic, S. M., & Rawson, E. S. (2021). Creatine supplementation and brain health. Nutrients, 13(2), Article 586. https://doi.org/10.3390/nu13020586

Royes, L. F., Fighera, M. R., Furian, A. F., Oliveira, M. S., Myskiw, J. C., Fiúza, M. C., Petry, J. C., Coelho, R. C., & Mello, C. F. (2006). Effectiveness of creatine in preventing seizures and memory deficit induced by pentylenetetrazol. Pharmacology Biochemistry and Behavior, 83(1), 136–148. https://doi.org/10.1016/j.pbb.2006.01.002

Sahlin, K., & Harris, R. C. (2011). The creatine kinase reaction: A simple reaction with functional complexity. Amino Acids, 40, 1363–1367. https://doi.org/10.1007/s00726-011-0856-8

Sandretti, L., & Adriano, E. (2023). Creatine and brain health: More than just an energy provider. Frontiers in Cellular Neuroscience, 17, Article 1215444. https://doi.org/10.3389/fncel.2023.1215444

Schulze, A. (2003). Creatine deficiency syndromes. Molecular and Cellular Biochemistry, 244(1–2), 143–150. https://doi.org/10.1023/A:1022443503883

Sestili, P., Martinelli, C., Colombo, E., Barbieri, E., Potenza, L., Sartini, S., & Fimognari, C. (2011). Creatine as an antioxidant. Amino Acids, 40, 1385–1396. https://doi.org/10.1007/s00726-011-0875-5

Smith-Ryan, A. E., Cabre, H. E., Eckerson, J. M., & Candow, D. G. (2021). Creatine supplementation in women’s health: A lifespan perspective. Nutrients, 13(3), Article 815. https://doi.org/10.3390/nu13030815

Snow, T. M., Forbes, S. C., Cordingley, D. M., Ostojic, S. M., Gualano, B., Rawson, E. S., & Candow, D. G. (2024). Creatine supplementation and brain health: A scoping review of contemporary literature. Nutrients, 16(11), Article 1662. https://doi.org/10.3390/nu16111662

Turner, C. P., Swift, J., McMorris, T., Corbett, J., & Theisen, T. (2015). Creatine supplementation and brain health: Effects of hypoxia. Physiology & Behavior, 141, 1–10. https://doi.org/10.1016/j.physbeh.2014.12.036

Wallimann, T., Wyss, M., Brdiczka, D., Nicolay, K., & Eppenberger, H. M. (1992). Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: The “phosphocreatine circuit” for cellular energy homeostasis. Biochemical Journal, 281(1), 21–40. https://doi.org/10.1042/bj2810021

Wyss, M., & Kaddurah-Daouk, R. (2000). Creatine and creatinine metabolism. Physiological Reviews, 80(3), 1107–1213. https://doi.org/10.1152/physrev.2000.80.3.1107

Xu, C., Zhang, H., & Wang, Y. (2024). The effects of creatine supplementation on cognitive function in adults: A systematic review and meta-analysis. Frontiers in Nutrition, 11, Article 1424972. https://doi.org/10.3389/fnut.2024.1424972

Downloads

Published

2026-06-16

How to Cite

Ławniczak, A., Prządka, J., Tomaszewska, A., Kaczmarek, M., Pojawa, M., Łazor, N., Witkowska, W., Wagner, E., Chudzik, A., & Buzek, E. (2026). CREATINE SUPPLEMENTATION AS A STRATEGY FOR COGNITIVE SUPPORT AND NEUROPROTECTION. International Journal of Innovative Technologies in Social Science, 2(2(50). https://doi.org/10.31435/ijitss.2(50).2026.5794