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Mayo Clinic: How Creatine Supports Brain Health
October 30, 2025
It’s widely accepted that as a supplement, creatine monohydrate can increase the body’s natural creatine stores in muscle. That extra boost has been shown to support lean muscle mass, enhance strength and power during workouts, and improve recovery.*1-3
But research is shining light on creatine’s impact beyond building a better bicep. Turns out this well-known muscle supplement might benefit the most important organ in your body – the brain.*
Over the past several years, there’s been an increase in research investigating creatine’s potential to support energy for the brain, protect brain cells, and benefit cognitive or psychological function.*
Here’s what we know (and don’t know) about creatine’s impact on maintaining brain health.
What is creatine and how does it supply energy?
Creatine is created from three amino acids. The body's liver, pancreas, and kidneys make about 1 gram of creatine per day. It can also be obtained through supplementation and diet, particularly from seafood and red meat.3
The body stores about 95% of creatine within muscle cells. Approximately 66% is stored as phosphocreatine (PCr) – creatine with high-energy phosphate attached to it – and the remainder as free creatine without phosphate. About 5% of creatine is stored in tissues outside of skeletal muscles, like the brain and heart.4,5
When you do short, intense activities – like sprinting or lifting something heavy – your muscles use up energy in the form of adenosine triphosphate (ATP) very quickly.
That’s where creatine comes in.
As ATP breaks down into adenosine diphosphate (ADP) and phosphate, it releases energy. When your muscle cells suddenly need more energy – like when you’re pushing through one more rep – the phosphocreatine that’s stored in your body donates phosphate to ADP to form new ATP.6,7
In this way, creatine supports energy by quickly recycling ATP so that your muscles can keep working.
Creatine’s role in brain health
Creatine plays several critical roles in the brain, most of them centered on maintaining energy balance, supporting cellular signaling, and protecting neurons from stress or injury.
Even though the brain is an organ primarily made of neurons and glial cells – not muscle tissue – it relies on creatine for energy in many of the same ways as muscle.
By fueling the production of ATP, creatine supports the cellular energy your brain needs for everything from memory to mood.6 This is no small undertaking because, even though the brain accounts for about 2% of your body weight, it uses 20% of your total energy, primarily in the form of ATP.8
Creatine’s effect on cognitive performance
There’s evidence that creatine might support cognitive performance, especially under stressful conditions like sleep deprivation and mental fatigue.*6,9,10 Neurons have high energy demands during active thinking, learning, and stressful situations. Creatine helps neurons regenerate ATP faster, supporting consistent signaling and neurotransmission during prolonged or stressful activity.6,8,9
A 2024 systematic review and meta-analysis of 16 randomized clinical trials suggests that creatine supported memory and improved reaction time on certain timed attention and processing tasks.* But supplementing with creatine did not improve overall cognition or executive function skills like planning and switching tasks.10
Other studies indicate that creatine might benefit memory, especially in older adults and vegetarians – two groups that can be low in creatine.*11,12
Conclusive research results for cognitive gains in healthy, unstressed adults are lacking due to variations in study designs, dosages, and experimental protocols. Many researchers caution that evidence supporting creatine’s ability to support brain health is not definitive, especially for executive function and overall cognition.6,10,13
Creatine’s use for mood support
There’s promising – but preliminary – evidence in humans that 5 grams per day of creatine along with standard medicinal treatment14 or cognitive behavioral therapy (CBT)15 might provide support for low mood.*
In one study involving adult participants, those who took 5 grams of creatine daily alongside standard care showed earlier and greater overall improvements in self-reported well-being compared to those receiving a placebo along with standard treatment.14 Another eight-week study found that individuals taking creatine in combination with CBT experienced more noticeable positive mood changes than those who received a placebo.15
It’s important to note that larger clinical trials are still needed and that current studies are investigating whether creatine can provide a supporting role for improving mood, not replace current therapies.
Creatine’s impact on neurological health
Scientists continue to explore whether creatine might protect brain cells.
Inside every brain cell is an energy network called the creatine-creatine kinase (CK) system. This system helps mitochondria (the cell’s power plants) make and store energy so that neurons can work efficiently.16-18
When the CK system breaks down, brain cells can’t keep up with energy demands. Over time, this can lead to cellular stress and imbalanced inflammatory processes.16,18
Studies in animals suggest that creatine might protect brain cells by supporting mitochondrial function. While some results are promising, successful lab and animal studies don’t always translate to the same benefits in humans.16-21
Creatine: More to explore
Additional research is needed to understand and leverage the use of creatine monohydrate in brain health, especially regarding optimal dosages and long-term effects. Benefits might depend on baseline creatine levels, genetics, or even diet.
Although creatine monohydrate is generally regarded as safe for long-term use at 3-5 grams a day, it’s always best to speak with your health-care professional before starting a supplement, especially if you have preexisting health issues.
A word from Thorne
Thorne carries a variety of Creatine products to support your individual needs: unflavored in jars and on-the-go stick packs, flavored in jars (strawberry or pineapple orange), and flavored combined with branched-chain amino acids (peach mango).
References
Kreider RB, Kalman DS, Antonio J, et al. International Society of Sports Nutrition position stand: Safety and efficacy of creatine supplementation in exercise, sport, and medicine. J Int Soc Sports Nutr. 2017;14:18.
Forbes SC, Candow DG, Ostojic SM, et al. Meta-analysis examining the importance of creatine ingestion strategies on lean tissue mass and strength in older adults. Nutrients. 2021;13(6):1912
Edenfield KM. Sports supplements: Pearls and pitfalls. Prim Care. 2020;47(1):37-48.
Fernández-Landa J, Santibañez-Gutierrez A, Todorovic N, et al. Effects of creatine monohydrate on endurance performance in a trained population: A systematic review and meta-analysis. Sports Med. 2023;53(5):1017-1027.
Bonilla DA, Kreider RB, Stout JR, et al. Metabolic basis of creatine in health and disease: A bioinformatics-assisted review. Nutrients. 2021;13(4):1238.
Sandkühler JF, Kersting X, Faust A, et al. The effects of creatine supplementation on cognitive performance – a randomised controlled study. BMC Med. 2023;21(1):440.
Kazak L, Cohen P. Creatine metabolism: Energy homeostasis, immunity and cancer biology. Nat Rev Endocrinol. 2020;16(8):421-436.
Padamsey Z, Rochefort NL. Paying the brain's energy bill. Curr Opin Neurobiol. 2023;78:102668.
Gordji-Nejad A, Matusch A, Kleedörfer S, et al. Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation. Sci Rep. 2024;14(1):4937.
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.
Prokopidis K, Giannos P, Triantafyllidis KK, et al. Effects of creatine supplementation on memory in healthy individuals: A systematic review and meta-analysis of randomized controlled trials. Nutr Rev. 2023;81(4):416-427.
Kaviani M, Shaw K, Chilibeck PD. Benefits of creatine supplementation for vegetarians compared to omnivorous athletes: A systematic review. Int J Environ Res Public Health. 2020;17:3041.
McMorris T, Hale BJ, Pine BS, Williams TB. Creatine supplementation research fails to support the theoretical basis for an effect on cognition: Evidence from a systematic review. Behav Brain Res. 2024;466:114982.
Lyoo IK, Yoon S, Kim TS, et al. A randomized, double-blind placebo-controlled trial of oral creatine monohydrate augmentation for enhanced response to a selective serotonin reuptake inhibitor in women…. Am J Psychiatry. 2012;169(9):937-945.
Sherpa NN, De Giorgi R, Ostinelli EG, et al. Efficacy and safety profile of oral creatine monohydrate in add-on to cognitive-behavioural therapy…: An 8-week pilot, double-blind, randomised, placebo-controlled feasibility and exploratory trial in an under-resourced area. Eur Neuropsychopharmacol. 2025;90:28-35.
Smith AN, Morris JK, Carbuhn AF, et al. Creatine as a therapeutic target…. Curr Dev Nutr. 2023;7(11):102011.
Smith AN, Choi IY, Lee P, et al. Creatine monohydrate pilot…: Feasibility, brain creatine, and cognition. Alzheimers Dement (N Y). 2025;11(2):e70101.
Marques EP, Wyse ATS. Creatine as a neuroprotector: An actor that can play many parts. Neurotox Res. 2019;36(2):411-423.
Kieburtz K, Tilley BC, Elm JJ, et al. Effect of creatine monohydrate…: A randomized clinical trial. JAMA. 2015;313(6):584-93.
Hersch SM, Schifitto G, Oakes D, et al. The CREST-E study of creatine…: A randomized controlled trial. Neurology. 2017;89(6):594-601.
Pastula DM, Moore DH, Bedlack RS. Creatine…. Cochrane Database of Systematic Reviews 2012, Issue 12. Art. No.: CD005225. [Accessed October 1, 2025].
