Creatine and Cognition in Healthy Adults: What Trials Show

Key points

• Creatine is part of the brain’s energy buffer, but supplemented creatine reaches the brain only modestly, and the biology is still more hypothesis than proof [1][2][17].
• Pooled results are mixed. A 2024 meta-analysis found a small memory benefit (moderate certainty) and low-certainty signals elsewhere; a 2023 meta-analysis found no memory effect in younger adults [4][6].
• The best-known positive trials are small, short, and mostly in vegetarians or sleep-deprived volunteers [8][9][10][12].
• In November 2024 EFSA found that a cause-and-effect link between creatine and improved cognitive function has not been established [18].
• Safety data in healthy people are reassuring for kidney markers, with caveats about trial size and unreconciled meta-analysis numbers [14][15][16].

Why a muscle supplement is studied for the brain

Creatine, phosphocreatine and the enzyme creatine kinase form an energy buffer: a reserve that helps regenerate ATP when demand spikes. A 2010 review in the Journal of Neurochemistry describes this system in the brain and notes that creatine crosses the blood-brain barrier poorly, so the brain makes part of its own [1]. Primary creatine deficiency syndromes, rare inherited disorders, hit the brain hardest, which is the clearest evidence that brain creatine matters [1].

A 2021 review by Roschel and colleagues proposes that brain creatine may fall under stressors such as sleep deprivation, aging, depression or brain injury, and that supplements could help most in those states. The same abstract says the best way to raise brain creatine is “still to be determined” [2]. A 2026 commentary goes further and calls creatine for cognition “a hypothesis rather than an established clinical practice” [17]. These are reviews, not trials: they explain why researchers test it, not that it works.

What the systematic reviews found

Review	Included	Main finding
Avgerinos 2018, Experimental Gerontology [3]	6 RCTs, 281 healthy people	Short-term memory and reasoning may improve; other domains conflicting; young people showed no change
Prokopidis 2023, Nutrition Reviews [6]	10 RCTs (8 pooled), healthy people	Memory SMD 0.29 (95% CI 0.04 to 0.53); older adults 0.88; adults aged 11-31: 0.03 (-0.14 to 0.20)
Xu 2024, Frontiers in Nutrition [4]	16 RCTs, 492 adults aged 21-76	Memory SMD 0.31 (0.18 to 0.44), moderate certainty; other domains low or very low

Avgerinos and colleagues (NIH intramural funding) concluded that creatine may help short-term memory and reasoning, with unclear effects elsewhere, and called for larger studies [3].

Prokopidis 2023 pooled memory results by age. The overall effect was small and the young-adult estimate was essentially zero [6]. Its record links a letter to the editor and an author reply whose title alleges double counting and inadequate statistics; we did not open either, so we cannot say whether the numbers changed [6].

Xu and colleagues (Guizhou Normal University; funded by the National Natural Science Foundation of China; no commercial conflicts declared) pooled 13 healthy-adult studies and 3 patient studies [4]. Memory was the one outcome with moderate certainty. Attention time (SMD -0.31) and processing-speed time (-0.51) reached significance, but with low certainty; attention and processing-speed scores, global cognition and executive function did not [4]. In subgroups, attention time was not significant in healthy people (-0.18, CI -0.62 to 0.27) but was in patients, and it was significant at ages 18-60 but not over 60 [4]. A February 2025 corrigendum clarified wording (“scores”) and left the conclusions unchanged [5]. The memory section cites 24 studies and 1,000 participants while the table lists 16, an inconsistency we could not resolve [4].

Sweden’s health-technology agency SBU searched in September 2025 and found seven systematic reviews on creatine and cognition, including these. It judged all seven at high risk of bias and so did not report their conclusions [7]. That judgement concerns the reviews, not creatine, but it limits how firmly any pooled number should be read.

The key randomized trials

Vegetarians. Rae and colleagues (2003) ran a double-blind crossover trial in 45 young adult vegetarians: 5 g a day or placebo for six weeks. Creatine improved backward digit span and Raven’s matrices (p < 0.0001 for both) [8]. The PubMed record lists no funder. Benton and Donohoe (2011, Swansea University) randomized 128 young women, vegetarians and meat-eaters, to 20 g of creatine or placebo for five days. Memory improved in vegetarians but not meat-eaters; verbal fluency and vigilance did not change; reaction-time variability fell regardless of diet [9]. No funder is listed in the record. Both trials were short and small, and we found no large replication.

Sleep deprivation. McMorris and colleagues published two trials in which volunteers took creatine for seven days and then stayed awake. In the 2006 trial, 19 people (10 creatine, 9 placebo) showed less deterioration at 24 hours on random movement generation, choice reaction time, balance and mood, with no difference in stress hormones [10]. The 2007 trial found a benefit on a central executive task only at 36 hours and no group difference on the other variables [11]; its abstract gives no sample size. Funders are not stated in either record.

In 2024 Gordji-Nejad and colleagues (Forschungszentrum Julich funding listed) gave 15 adults aged 20-28 a single high oral dose of 0.35 g/kg or placebo during about 21 hours of sleep deprivation, in a crossover design. Brain scans showed shifts in phosphate metabolites, and cognitive performance and processing speed improved [12]. The sample size and design come from NutraIngredients’ report of the paper; we could not open the full text, and that report notes the article gives no exact test values or limitations section [13]. Alzchem, a creatine manufacturer, is named there as the supplier of the product; no conflict statement was found [13]. It is a proof-of-concept study, not a test of everyday performance.

What is and is not shown for healthy young adults

Shown: in small trials, creatine can change some cognitive scores under metabolic stress (sleep loss) or low dietary creatine (vegetarians), and a pooled memory signal exists in older adults [4][6][8][9][10][12].

Not shown: a reliable benefit in well-rested, omnivorous young adults. The Prokopidis estimate for young adults is near zero, Avgerinos found no change in young people, and Xu’s healthy-only attention estimate crossed zero [3][4][6]. EFSA’s panel reviewed 21 human intervention studies plus two from a meta-analysis’s reference list. It reported that working-memory benefits appeared only in short high-dose studies and not at lower doses or with continuous use, that a response-inhibition result was isolated among 10 healthy-adult studies, and that three patient studies showed no effect [18].

Gaps: we found no large, preregistered, independent trial in healthy adults; little data on real-world tasks; and unclear brain uptake [17].

Regulatory status

In the EU, EFSA’s NDA Panel published its opinion on 19 November 2024 (EFSA Journal 22(11):e9100) on a claim submitted by Alzchem Trostberg GmbH under Article 13(5) of Regulation (EC) No 1924/2006. It concluded that a cause-and-effect relationship between creatine supplementation and improved cognitive function has not been established [18][19]. A search listing pointed to a Commission regulation of 26 May 2026 refusing the claim; we could not open the text and do not rely on it. We did not verify the FDA, UK or German status of creatine supplements (not checked). “Research use only” does not apply to creatine.

Risks and unknowns

The 2017 International Society of Sports Nutrition position stand says supplementation of up to 30 g a day for up to five years was safe and well tolerated in healthy people and some patient groups [14]. It was funded by the Council for Responsible Nutrition, a supplement trade association, and several authors list supplement-industry affiliations [14].

For kidneys, a 2011 review of safety studies reported no change in liver or kidney function measures in healthy people over several months; its authors caution that people with existing kidney disease or risk factors should avoid high intakes and say screening seems unnecessary in healthy people [15]. A randomized trial of 18 healthy men over three months found no signs of renal dysfunction on cystatin C [16]. A 2019 meta-analysis (15 studies reviewed, 6 pooled) reported standardized increases in serum creatinine (0.48, CI 0.24 to 0.73) and urea (1.10, CI 0.34 to 1.85) while its abstract states no significant alteration. We could not reconcile those statements and flag them as unresolved [22].

Not covered by the studies we opened: people with kidney disease, interactions, pregnancy, and product purity.

What the source posts claim

For the broader context see our tier-list checks: cognitive enhancement tier list and cope supplements tier list.

@Hoostethics (15 October 2026) posted “ranking the most cope supplements.” as a tier-list image. Creatine monohydrate sits in “somewhat cope”, the mildest tier, with turmeric, collagen peptides and noopept [20]. The image has no citations. Verdict: partly supported. Placing it low on cognition matches EFSA and the mixed meta-analyses [4][6][18]. The label overlooks the small trials in vegetarians and sleep-deprived adults and the moderate-certainty memory result [4][8][12].

@dex7official (20 October 2026) posted “THE ONLY TRUE COGNITIVE ENHANCEMENT TIER LIST (NO COPES EDITION)”. Creatine is in F, with BPC-157, pinealon, cannabis, pregabalin, insulin and phenibut [21]. Verdict: partly supported. As a claim that creatine is unproven for healthy-adult cognition, it fits the evidence. F is shared with substances of very different safety profiles, and the image does not say whether F means ineffective or harmful The safety reviews and trial above reported no kidney harm in healthy adults [14][15][16]. The list cites no evidence.

Frequently asked questions

Does creatine improve memory? A 2024 meta-analysis of 16 randomized trials found a small effect on memory with moderate certainty [4]. A 2023 meta-analysis found the effect concentrated in older adults and near zero in younger ones [6].

Does creatine help after poor sleep? Small trials of 19 and 15 volunteers reported better performance on some tasks during sleep deprivation [10][12][13]. They were short, and none tested ordinary tiredness.

Has a regulator approved a cognition claim for creatine? No. EFSA concluded in November 2024 that a cause-and-effect relationship has not been established [18].

Is creatine safe for the kidneys? In healthy adults, trials and reviews found no sign of kidney damage on the markers measured, though trials were small and short [15][16]. People with kidney disease are the group authors flag for caution [15].

Sources

1. Béard E, Braissant O, Journal of Neurochemistry, “Synthesis and transport of creatine in the CNS: importance for cerebral functions” (2010). Abstract read via the Europe PMC search API (europepmc.org).
2. Roschel H, Gualano B, Ostojic SM, Rawson ES, Nutrients, “Creatine Supplementation and Brain Health” (2021). https://doi.org/10.3390/nu13020586 (abstract via Europe PMC)
3. Avgerinos KI et al., Experimental Gerontology, “Effects of creatine supplementation on cognitive function of healthy individuals: A systematic review of randomized controlled trials” (2018). https://pubmed.ncbi.nlm.nih.gov/29704637/ (abstract read via Europe PMC)
4. Xu C, Bi S, Zhang W, Luo L, Frontiers in Nutrition, “The effects of creatine supplementation on cognitive function in adults: a systematic review and meta-analysis” (12 July 2024). https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2024.1424972/full
5. Frontiers in Nutrition, “Corrigendum: The effects of creatine supplementation on cognitive function in adults” (17 February 2025). https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2025.1570800/full
6. Prokopidis K et al., Nutrition Reviews, “Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials” (2023). Abstract read via Europe PMC.
7. SBU (Swedish Agency for Health Technology Assessment), “Creatine supplementation to enhance cognitive functions” (5 November 2025). https://www.sbu.se/en/publications/responses-from-the-sbu-enquiry-service/creatine-supplementation-to-enhance-cognitive-functions/
8. Rae C et al., Proceedings of the Royal Society B, “Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial” (2003). https://doi.org/10.1098/rspb.2003.2492 (abstract via Europe PMC)
9. Benton D, Donohoe R, British Journal of Nutrition, “The influence of creatine supplementation on the cognitive functioning of vegetarians and omnivores” (2011). https://pubmed.ncbi.nlm.nih.gov/21118604/ (abstract via Europe PMC)
10. McMorris T et al., Psychopharmacology, “Effect of creatine supplementation and sleep deprivation, with mild exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol” (2006). PMID 16416332, abstract via Europe PMC.
11. McMorris T et al., Physiology & Behavior, “Creatine supplementation, sleep deprivation, cortisol, melatonin and behavior” (2007). PMID 17046034, abstract via Europe PMC.
12. Gordji-Nejad A et al., Scientific Reports, “Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation” (28 February 2024). https://doi.org/10.1038/s41598-024-54249-9 (abstract via Europe PMC; full text not opened)
13. NutraIngredients, “Study finds single high dose of creatine boosts cognitive performance during sleep deprivation” (3 April 2024). https://www.nutraingredients.com/Article/2024/04/03/single-high-dose-of-creatine-boosts-cognition-during-sleep-deprivation/ (secondary source for sample size)
14. Kreider RB et al., Journal of the International Society of Sports Nutrition, “International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine” (13 June 2017). https://doi.org/10.1186/s12970-017-0173-z
15. Kim HJ, Kim CK, Carpentier A, Poortmans JR, Amino Acids, “Studies on the safety of creatine supplementation” (2011). Abstract via Europe PMC.
16. Gualano B et al., European Journal of Applied Physiology, “Effects of creatine supplementation on renal function: a randomized, double-blind, placebo-controlled clinical trial” (2008). PMID 18188581, abstract via Europe PMC.
17. Machado M, Nutrition and Health, “Creatine supplementation and cognitive aging: The challenge of crossing the blood-brain barrier” (1 May 2026, online 8 December 2025). Abstract via Europe PMC.
18. EFSA NDA Panel, EFSA Journal 22(11):e9100, “Creatine and improvement in cognitive function: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006” (19 November 2024). https://doi.org/10.2903/j.efsa.2024.9100 (abstract via Europe PMC; the publisher page returned 403)
19. RegASK, “EFSA Issues Scientific Opinion on Creatine and Cognitive Function Health Claim” (December 2024). https://regask.com/efsa-issues-scientific-opinion-on-creatine-supplements/ (trade source for applicant and date)
20. @Hoostethics, “ranking the most cope supplements.” (15 October 2026). https://x.com/Hoostethics/status/2110728908735979632 (text read through the fxtwitter mirror; tier placement from our transcription of the image)
21. @dex7official, “THE ONLY TRUE COGNITIVE ENHANCEMENT TIER LIST (NO COPES EDITION)” (20 October 2026). https://x.com/dex7official/status/2112691493261484516 (text read through the fxtwitter mirror; tier placement from our transcription of the image)
22. de Souza e Silva A et al., Journal of Renal Nutrition, “Effects of Creatine Supplementation on Renal Function: A Systematic Review and Meta-Analysis” (2019). https://doi.org/10.1053/j.jrn.2019.05.004 (abstract via Europe PMC)

This article is information, not medical advice.