Creatine
amino-acid · also known as creatine monohydrate, methylguanidine-acetic acid
This is general information, not medical advice. Supplements can interact with medicines and health conditions. Always check with your doctor or pharmacist before starting or changing supplements.
What it is
Creatine is the best-evidenced sports supplement there is. Your body synthesises it from three amino acids and stores it in muscle as phosphocreatine, a rapid-recycling energy reserve for short, hard efforts. Supplementing raises muscle stores by 20-40%, and hundreds of trials — including multiple meta-analyses — show consistent gains in strength, high-intensity performance and lean mass when combined with resistance training, in young and older adults alike. Evidence for brain benefits is younger and more mixed: memory effects look most convincing in older adults and under sleep deprivation. The persistent worry — that creatine damages the kidneys — is largely unfounded. Controlled trials and a meta-analysis of renal outcomes show no harm to kidney function in healthy people at standard doses. The confusion arises because creatine breaks down into creatinine, the very marker blood tests use to estimate kidney function, so supplementation can make a routine test look worse without any true change in the kidneys. If you take medicines monitored by creatinine-based tests, tell your doctor you use creatine. Choose plain creatine monohydrate: no fancier form has beaten it.
Which form to choose
Grades here rate how well the evidence supports choosing a form, which is not the same as how much that form has been studied: a well-studied form can be graded low precisely because the studies argue against it. This is a different scale from the claim grades below — see our editorial policy.
The trial-standard form: essentially all of an oral dose is absorbed, and 3-5 g daily raises muscle creatine stores by roughly 20-40% within about four weeks (faster with a loading phase). It is also the cheapest form per gram. Dissolves slowly in cold water; warm water or a shaker fixes this.
The form used in virtually every positive creatine trial — hundreds of randomised controlled trials and multiple meta-analyses of strength, performance and body-composition outcomes rest on monohydrate. The grade reflects both this overwhelming trial use and head-to-head comparisons in which no alternative form has outperformed it.
Chemically identical to standard creatine monohydrate, milled to a smaller particle size so it mixes and stays suspended better in liquid. Absorption and muscle uptake are those of monohydrate; pay for it only if mixability bothers you.
Grade inherited from creatine monohydrate: micronisation changes particle size, not the molecule, so the entire monohydrate trial base applies. No evidence suggests any outcome difference from standard monohydrate.
A creatine salt marketed on much higher water solubility, with the claim that smaller doses therefore work as well as monohydrate. Solubility is genuinely higher, but solubility is not the limiting step — monohydrate is already almost completely absorbed — and no human data show better uptake into muscle.
Little human outcome data. One small 8-week randomised trial (n=40) found creatine HCl improved strength and body composition alongside resistance training but showed no benefit over creatine monohydrate. The grade rests on that single small comparison plus mechanistic solubility claims — not on any demonstrated advantage — so there is no evidence-based reason to pay its premium over monohydrate.
Creatine monohydrate blended with alkaline buffer, marketed on the claim that it survives stomach acid better and works at lower doses with fewer side effects. A well-controlled head-to-head trial found none of this: no advantage in muscle creatine content, body composition, strength or anaerobic capacity, and no fewer side effects.
The grade rests on direct comparative evidence: a 28-day randomised double-blind trial (n=36 resistance-trained participants) found buffered creatine no better than monohydrate at equal doses, and at the manufacturer's low recommended dose (1.5 g/day) muscle creatine tended to rise less than with monohydrate loading. It works only insofar as it is creatine; the marketing claims are unsupported.
An esterified form once marketed as better absorbed. The opposite is true: it is unstable and degrades substantially to creatinine (the inert waste product) before reaching muscle, so it raises serum and muscle creatine less effectively than monohydrate while raising blood creatinine more.
Head-to-head evidence of inferiority: in a 7-week randomised trial against monohydrate and placebo (n=30), creatine ethyl ester produced lower serum creatine than monohydrate, higher serum creatinine than both other groups, and no advantage in body composition, strength or power. Graded D because the comparative evidence argues against choosing it, not merely an absence of data.
Evidence-based benefits
At 3-5 g daily (with or without a short loading phase), creatine improves strength and performance in short, high-intensity exercise — one of the most replicated findings in sports nutrition.
A meta-analysis of 100 controlled studies found significant effect sizes for high-intensity tasks under 30 seconds (ES 0.24) and 30-150 seconds (ES 0.19), with larger effects for repetitive bouts and upper-body work; no benefit was seen for endurance tasks such as running and swimming. Meta-analyses restricted to randomised placebo-controlled trials confirm this: lower-limb strength ES 0.235 (95% CI 0.125-0.346; 60 studies, 1,297 participants) and upper-limb strength ES 0.317 (95% CI 0.185-0.449; 53 studies, 1,138 participants), independent of age, sex, training status, dose or loading protocol.
Taken at 3-5 g daily alongside resistance training, creatine increases lean mass beyond training alone — including in older adults, where it also improves functional strength.
In a meta-analysis of 22 randomised controlled trials in older adults (721 participants, mean ages 57-70, training 7-52 weeks), creatine added 1.37 kg of lean tissue over resistance training alone (95% CI 0.97-1.76 kg) and improved chest-press (SMD 0.35, 95% CI 0.16-0.53) and leg-press strength (SMD 0.24, 95% CI 0.05-0.43). An earlier meta-analysis of 357 older adults found greater gains in fat-free mass, one-repetition-maximum strength and 30-second chair-stand performance versus training alone. In younger trainees, the Branch meta-analysis found small but significant lean-mass effects, largest with loading protocols.
Creatine (typically 5-20 g daily in trials) may support memory and cognitive performance, most convincingly in older adults and under sleep deprivation; effects in rested young adults are small or absent.
A meta-analysis of 8 randomised controlled trials found improved memory overall (SMD 0.29, 95% CI 0.04-0.53) driven almost entirely by older adults aged 66-76 (SMD 0.88, 95% CI 0.22-1.55), with no effect in those aged 11-31 (SMD 0.03, 95% CI -0.14 to 0.20); its statistics were later disputed in a published letter, so treat the pooled figure cautiously. A systematic review of 6 RCTs (281 individuals) reported benefits mainly for short-term memory and reasoning. Under stress the signal is clearer: after 24-hour sleep deprivation, 7 days of 20 g/day preserved choice-reaction time, balance and mood (n=19), and a single 0.35 g/kg dose improved processing speed and cerebral high-energy phosphates during 21-hour sleep deprivation.
Risks & contraindications
Creatine does not impair kidney function in healthy people at standard doses (3-5 g daily, or short loading phases) — but it raises serum creatinine, which can make routine creatinine-based kidney tests (eGFR) look falsely abnormal. People with existing kidney disease should consult a doctor before use.
A systematic review and meta-analysis of renal outcomes (15 studies qualitative, 6 quantitative) concluded creatine does not induce renal damage at studied doses and durations. A 3-month randomised placebo-controlled trial of ~10 g/day used cystatin C — a kidney marker unaffected by creatine — and found no decline in kidney function. A study of athletes using creatine for 10 months to 5 years found no impairment of glomerular filtration or tubular function versus controls. The catch: creatine degrades to creatinine, so supplementation typically nudges serum creatinine up by roughly 0.1-0.2 mg/dL without any true change in kidney function — a laboratory artefact, not injury.
Expect roughly 1-2 kg of water-related weight gain during a loading phase, and possible stomach upset or diarrhoea if you take large single doses — split loading doses (e.g. 4 x 5 g) and standard 3-5 g maintenance doses are well tolerated.
In a 28-day double-blind trial of 59 elite footballers, 2 x 5 g/day caused no more gastrointestinal complaints than placebo, but a single 10 g dose increased diarrhoea incidence (55.6% vs 35.0% placebo, p < 0.05). Loading protocols reliably add body mass — the Branch meta-analysis found the largest body-composition effect sizes after loading (ES 0.26) — largely as intracellular water in the first days; the ISSN position stand notes short-term gains of about 1-2 kg and identifies weight gain as the only consistently reported side effect.
Dosage & how to take it
- Creatine monohydrate: 3–5 g/day, any time of day, with or without food. 3-5 g daily is the maintenance dose used in most trials; muscle stores saturate in about 4 weeks without loading. Optional loading phase: 20 g/day split as 4 x 5 g for 5-7 days saturates stores in under a week — this is what most classic trials used (e.g. 20 g/day for 5-7 days, then 3-5 g/day). Loading is a convenience, not a requirement. Taking it with a carbohydrate-containing meal may modestly aid muscle uptake; timing is otherwise unimportant. Drink normally — no special fluid protocol is needed.
- Micronised creatine monohydrate: 3–5 g/day, any time of day, with or without food. Dose exactly as creatine monohydrate — it is the same compound. The same optional 20 g/day (4 x 5 g) loading phase for 5-7 days applies.
- Buffered creatine (Kre-Alkalyn): 3–5 g/day, any time of day, with or without food. If you use it at all, dose it like monohydrate. The manufacturer's low recommended dose (1.5 g/day) tended to raise muscle creatine less than monohydrate loading in the head-to-head trial, so low-dose claims are not supported.
- Creatine hydrochloride (HCl): 2–5 g/day, any time of day, with or without food. Labels often recommend 1.5-3 g/day on solubility grounds. The one head-to-head trial used about 0.03 g/kg body mass daily (roughly 2-2.5 g for most adults) and found no advantage over monohydrate; there is no evidence that doses below the monohydrate-equivalent saturate muscle stores as effectively.
Interactions
Metformin itself gets on well with creatine: in a randomised placebo-controlled trial in people with type 2 diabetes (most taking metformin), 5 g/day of creatine alongside exercise improved glycaemic control, and a systematic review of three trials found creatine lowered glucose and HbA1c with no major adverse events. The issue is monitoring. Metformin is renally cleared, and prescribers reduce or stop it when creatinine-based eGFR falls below set thresholds. Creatine raises serum creatinine — by roughly 0.1-0.2 mg/dL in trials — without any true change in kidney function, because supplemental creatine degrades to creatinine. In someone whose eGFR already sits near a metformin decision threshold, that artefact could prompt an unnecessary dose reduction, or complicate interpretation of a genuine decline. Tell your doctor you take creatine, establish a baseline creatinine before starting, and ask about cystatin C-based testing if an eGFR result looks unexpectedly low.
Creatine may help SSRIs work faster and better, at least in women with depression. In an 8-week randomised, double-blind, placebo-controlled trial, 52 women with major depressive disorder received escitalopram plus either 5 g/day of creatine monohydrate or placebo. The creatine group improved significantly more on the Hamilton Depression Rating Scale from as early as week 2, and the advantage held at weeks 4 and 8, with no difference in adverse events or dropout. The proposed mechanism is restoration of brain bioenergetics rather than anything serotonergic, so this is augmentation, not a safety interaction. Caveats: this is a single trial, in women only, with escitalopram specifically — evidence for sertraline and for men is indirect. If you take an SSRI, creatine at standard doses appears safe to combine and possibly helpful, but treat it as a complement to — never a replacement for — your prescribed treatment, and keep your doctor informed.
Tenofovir disoproxil can harm the kidneys, so clinicians monitor it with regular creatinine-based eGFR tests. Creatine does not add to that kidney risk in healthy users — controlled trials and a meta-analysis show no true decline in renal function — but it reliably raises serum creatinine, because supplemental creatine degrades to creatinine. In a 28-day trial, creatine raised serum creatinine by roughly 0.1-0.2 mg/dL, dose-dependently, in people with normal kidneys; a 3-month randomised trial found creatinine unchanged or elevated while cystatin C, a creatine-independent kidney marker, showed kidney function was actually fine. On tenofovir, that artificial creatinine bump can mimic early drug nephrotoxicity, triggering unnecessary investigations or treatment changes — or muddy the picture if real kidney injury develops. Tell your HIV clinician before starting creatine, get a baseline creatinine first, and ask whether cystatin C-based monitoring is appropriate. Do not start or stop creatine silently around monitoring visits.
Our medication coverage is not exhaustive. Absence of a warning here is not evidence of safety. Always confirm with your pharmacist.
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