Amino Acid Derivative
Creatine (Monohydrate)
Strong EvidenceOne of the most heavily studied supplements in existence: the International Society of Sports Nutrition position stand reports no evidence of renal harm across protocols from 1-80 g/day lasting 5 days to 60 months. The cognitive evidence is narrower than that safety record. A systematic review of six randomised trials in 281 healthy people found short-term memory and reasoning may improve, with young people's task performance largely unchanged and vegetarians responding better (Avgerinos 2018). A meta-analysis of eight trials put the memory effect at a standardised mean difference of 0.29 overall, 0.88 in adults aged 66–76 and 0.03 in those aged 11–31 (Prokopidis 2023) — a published letter argued its statistics double-counted, so treat the size as uncertain — and a 2024 meta-analysis of 16 trials in 492 adults, some with illnesses, found gains in memory, attention and processing speed but not in overall cognition or executive function (Xu 2024). The individual trials show where it helps: 20 g a day for five days improved memory in young vegetarian women but not in meat-eaters (Benton 2011); 5 g a day for six weeks improved working memory and reasoning in 45 young vegetarians (Rae 2003); and a 20 g-a-day loading week blunted the fall in reaction time and mood after 24 hours without sleep (McMorris 2006). Compared with CoQ10 and ALCAR, the other cellular-energy entries here, creatine has by far the larger trial base and the clearer safety data. Verdict: worth taking at 5 g a day if you eat little meat, are older, or face sleep loss; for a well-fed young meat-eater, expect little measurable change in cognition.
Recommended Dose
5 g creatine monohydrate daily
Timing
Any time, with water
Mechanism of Action
Creatine, found mostly in meat, fish and other animal foods, combines with phosphate to form phosphocreatine, a reserve of high-energy phosphate that regenerates ATP quickly in muscle and brain cells; vegetarians are known to have lower muscle creatine (Benton 2011). Supplementation does reach the brain, but less than it reaches muscle: in six young volunteers, 20 g a day for four weeks raised average total brain creatine by 8.7%, ranging from 3.5% to 13.3% between people, and the change had reversed when they were re-measured at least three months after stopping (Dechent 1999). That extra energy buffer matters most when the brain is under strain — sleep deprivation is the best-tested case (McMorris 2006).
Side Effects & Safety
Initial water retention. Very well-studied safety profile. Rare GI discomfort. Does not cause kidney damage in healthy individuals despite persistent myths.
Do not use / talk to a doctor first
- Chronic kidney disease, or any diagnosed renal impairment
- Concurrent use of potentially nephrotoxic medication
Interactions
Potentially nephrotoxic medications
The ISSN position stand advises against creatine in people taking these, not because creatine is itself nephrotoxic but because renal monitoring becomes harder to interpret
Source: Kreider 2017, J Int Soc Sports Nutr (PMC5469049)
Serum creatinine blood tests (a measurement interaction, not a drug one)
Creatine supplementation transiently RAISES serum creatinine, which can mimic kidney disease on a routine panel and has led to unnecessary investigation. Tell whoever orders the test that you take creatine
Source: Kreider 2017, J Int Soc Sports Nutr (PMC5469049)
Pregnancy & breastfeeding
Evidence in pregnancy and breastfeeding is lacking rather than negative - it has not been adequately studied. Not recommended without medical advice.
Who should avoid / see a doctor
Anyone with diagnosed kidney disease or taking nephrotoxic medication. For everyone else the renal-damage claim is not supported: the concern that persists in practice is the blood test, because creatine raises serum creatinine and the result can be misread.
Synergies
Used in These Stacks
See Creatine (Monohydrate) inside a full protocol — the stack pages cover when and why to combine it.
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References
- 1.Kreider 2017, Journal of the International Society of Sports Nutrition — No evidence of renal function impairment across supplementation protocols spanning 1-80 g/day for 5 days to 60 months, assessed by eGFR, serum and urinary creatinine, urea, proteinuria and albuminuria. (position stand / evidence review)
- 2.Kreider 2017, Journal of the International Society of Sports Nutrition — Creatine should not be used by people with chronic renal disease or taking potentially nephrotoxic medication, and it can transiently raise serum creatinine in a way that mimics kidney disease. (position stand / evidence review)
- 3.Dechent 1999, Am J Physiol — 6 healthy young volunteers, proton MR spectroscopy: creatine monohydrate 4 x 5 g/day for 4 weeks raised mean total brain creatine by 8.7% (0.6 mM, p<0.001), with inter-individual range 3.5–13.3%; changes were reversible at control measurements at least 3 months later.
- 4.Benton 2011, Br J Nutr — 128 young adult women, vegetarian or omnivore, randomised double-blind: 20 g creatine/day for 5 days improved memory in vegetarians but not omnivores; no effect on verbal fluency or vigilance; reduced variability of choice reaction time in both groups.
- 5.Avgerinos 2018, Exp Gerontol — Systematic review of 6 randomised trials (281 healthy individuals): short-term memory and intelligence/reasoning may improve; other domains conflicting; performance unchanged in young individuals; vegetarians responded better on memory tasks. (systematic review)
- 6.Prokopidis 2023, Nutr Rev — Meta-analysis of 8 RCTs in healthy people: creatine improved memory versus placebo (SMD 0.29, 95% CI 0.04–0.53); older adults 66–76 SMD 0.88, younger 11–31 SMD 0.03 (not significant); dose 2.2–20 g/day and duration 5 days to 24 weeks did not change the result. (a letter (Eckert & Pascher 2023, PMID 36644917) argued double-counting produced false-positive findings; the authors replied)
- 7.Xu 2024, Front Nutr — Meta-analysis of 16 RCTs (492 adults aged 20.8–76.4, healthy and with diseases): creatine monohydrate improved memory (SMD 0.31), attention time and processing speed time, but not overall cognitive function or executive function. (a corrigendum was published in 2025)
- 8.Rae 2003, Proc Biol Sci — 45 young adult vegetarians, double-blind placebo-controlled crossover: 5 g/day for 6 weeks improved backward digit span and Raven's Advanced Progressive Matrices (p<0.0001).
- 9.McMorris 2006, Psychopharmacology — 19 subjects loaded 5 g creatine four times daily (or placebo) for 7 days, then 24 h of sleep deprivation with mild exercise: the creatine group showed less decline in random movement generation, choice reaction time, balance and mood.
