Creatine Monohydrate
Evidence Fact Sheet
Creatine monohydrate is the most extensively studied performance supplement, working primarily by replenishing the phosphocreatine reserve that regenerates ATP during short, high-intensity efforts. Meta-analyses support strength, power, anaerobic performance, lean mass in older adults, and modest memory gains; endurance and bone-density trials are honest negatives, and a kidney-function meta-analysis supports safety in healthy adults.
Also known as: α-methyl guanidinoacetic acid · Creatine monohydrate (Cr-H2O) · Creapure
Overview
Creatine monohydrate is the most extensively studied performance supplement, working primarily by replenishing the phosphocreatine reserve that rapidly regenerates ATP during short, high-intensity efforts, while also promoting muscle cell volumization, potentiating mTOR signaling, and augmenting the brain's creatine pool. Typical use is 3-5 g/day for maintenance, with an optional 20 g/day loading phase over 5-7 days. It carries an EFSA-authorized claim (3 g/day) for physical performance in repeated short-term high-intensity exercise and an over-55 resistance-training muscle-strength claim, plus an ANVISA functional claim in Brazil and self-affirmed GRAS status in the US. Beyond athletic performance, a growing body of research examines effects on cognition, aging muscle and bone, mood, and renal-function safety.
Mechanism of Action
Phosphocreatine system ATP regeneration · Muscle cell water retention (cell volumization) · mTOR signaling potentiation · Brain creatine pool augmentation
Body systems: Musculoskeletal · METABOLISM · CNS · Mitochondrial & Cellular Energy
Evidence-Based Benefits
Each benefit below is anchored to a specific PubMed-indexed study. Effect sizes, sample sizes, and p-values are reported as published; no values are inferred. Honest negatives and null results are kept alongside the positive findings, and disease-research populations are described as such — Creatine Monohydrate is not characterized as a treatment for any disease.
Muscle Strength and Power
Meta-analysis supported- +1.43 kgbench press · p=0.002
- +5.64 kgsquat · p=0.001
- 69 RCTsn = 1937 pooled
In adults, creatine combined with resistance training produced small but statistically significant gains in upper- and lower-body strength and power versus placebo across a large pooled dataset of 69 trials. Effects were modest in absolute terms (roughly 1-6 kg on key lifts) but consistent.
Reported effect: Bench/chest press WMD +1.43 kg (p=0.002); squat WMD +5.64 kg (p=0.001); vertical jump WMD +1.48 cm (p=0.01); Wingate peak power WMD +47.81 W (p=0.004); 69 studies, 1937 participants
“Creatine plus resistance training produced small but statistically significant improvements in bench and chest press strength [WMD = 1.43 kg, p = 0.002] ... squat strength [WMD = 5.64 kg, p = 0.001] ... vertical jump [WMD = 1.48 cm, p = 0.01] ... Wingate peak power [WMD = 47.81 Watts, p = 0.004]. A total of 69 studies with 1937 participants were included for analysis.”
Source: PMID 40944139 · Kazeminasab et al. 2025 · Nutrients
High-Intensity Sprint and Anaerobic Performance
Meta-analysis supported- SMD 1.23anaerobic · p<0.001
- SMD 2.26Wingate test · p<0.001
- 9 studiessoccer players
In soccer players, creatine supplementation showed a moderate-to-large benefit on anaerobic performance tests such as sprints and jumps, with the largest effect seen on the Wingate cycling test. This aligns with creatine's core phosphocreatine mechanism for short, explosive efforts.
Reported effect: Anaerobic performance SMD 1.23 (95% CI 0.55-1.91, p<0.001); Wingate test SMD 2.26 (95% CI 1.40-3.11, p<0.001); nine studies
“creatine supplementation showed beneficial effects on anaerobic performance tests (SMD, 1.23; 95% CI, 0.55-1.91; p <0.001) ... creatine demonstrated a large and significant effect on Wingate test performance (SMD, 2.26; 95% CI, 1.40-3.11; p <0.001)”
Source: PMID 30935142 · Mielgo-Ayuso et al. · Nutrients
Muscle Mass and Sarcopenia in Older Adults
Meta-analysis supported- P=0.004total body mass
- P<0.0001fat-free (lean) mass
- Cr + RTvs training alone
A meta-analysis of creatine added to resistance training in older adults found significantly greater gains in total body mass and fat-free (lean) mass versus resistance training alone, supporting its use against age-related muscle loss. The abstract reports significance levels but not a pooled effect-size magnitude.
Reported effect: Cr + RT increased total body mass (P=0.004) and fat-free mass (P<0.0001); pooled mean differences not stated in abstract
“Cr + RT increased total body mass (P = 0.004) and fat-free mass (P < 0.0001)”
Source: PMID 24576864 · Devries & Phillips · Med Sci Sports Exerc
Cognitive Function (Memory)
Meta-analysis supported- SMD 0.29memory · p=0.02
- 8 RCTshealthy individuals
- I² = 66%moderate heterogeneity
A meta-analysis of randomized controlled trials found creatine modestly improved memory performance in healthy individuals versus placebo. The effect was small and the analysis showed moderate heterogeneity, so the benefit is real but not large.
Reported effect: Memory SMD 0.29 (95% CI 0.04-0.53; I2=66%; p=0.02); 8 studies in the meta-analysis
“Overall, creatine supplementation improved measures of memory compared with placebo (standard mean difference [SMD] = 0.29, 95%CI, 0.04-0.53; I2 = 66%; P = 0.02).”
Source: PMID 35984306 · Prokopidis et al. · Nutrition Reviews
Depression (Adjunct to SSRI)
RCT supported- n = 52women with MDD
- 5 g/dayadded to escitalopram
- week 2earlier HAM-D gain
In a small RCT of women with major depressive disorder, adding 5 g/day creatine to the SSRI escitalopram produced significantly greater improvement on the Hamilton Depression Rating Scale than placebo, appearing as early as week 2. This is an investigational adjunctive finding in a studied patient population, not an established treatment, and the abstract does not report exact remission percentages.
Reported effect: n=52 (creatine 25, placebo 27); 5 g/day added to escitalopram; significantly greater HAM-D improvement at weeks 2, 4, and 8 (no numeric remission rates in abstract)
“In comparison to the placebo augmentation group, patients receiving creatine augmentation showed significantly greater improvements in HAM-D score, as early as week 2 of treatment.”
Source: PMID 22864465 · Lyoo, Renshaw et al. 2012 · Am J Psychiatry
Endurance Exercise Performance
Null / no benefit Meta-analysis supported- SMD −0.07trivial · non-significant
- p = 0.47no benefit
- 13 studiestrained populations
Honest negative: a meta-analysis in trained populations found creatine monohydrate did NOT improve endurance performance, with a trivial, non-significant negative pooled effect. Creatine's benefits are concentrated in short high-intensity work, not aerobic endurance.
Reported effect: Endurance SMD -0.07 (95% CI -0.32 to 0.18; I2=34.75%); non-significant (p=0.47); 13 studies
“The results for the pooled meta-analysis showed a non-significant change in endurance performance after creatine monohydrate supplementation in a trained population (p = 0.47), with a trivial negative effect (pooled standardized mean difference = - 0.07 [95% confidence interval - 0.32 to 0.18]; I2 = 34.75%).”
Source: PMID 36877404 · Fernandez-Landa et al. · Sports Med
Bone Density and Bone Health
Null / no benefit RCT supported- nullfemoral-neck BMD
- n = 237postmenopausal women
- 2 yearscreatine + exercise
Honest negative: in a 2-year RCT of 237 postmenopausal women combining creatine with exercise, creatine had no significant effect on bone mineral density at the femoral neck or any measured site versus placebo. Despite mechanistic interest, this well-powered long-term trial did not support a bone-density benefit.
Reported effect: n=237; no effect on femoral neck BMD (creatine 0.725 to 0.712 g/cm2; placebo 0.721 to 0.706 g/cm2); null at all sites
“Compared with placebo, creatine supplementation had no effect on BMD of the femoral neck (creatine: 0.725 +/- 0.110 to 0.712 +/- 0.100 g/cm2; placebo: 0.721 +/- 0.102 to 0.706 +/- 0.097 g/cm2)”
Source: PMID 37144634 · Chilibeck et al. 2023 · Med Sci Sports Exerc
Renal Function Safety
Meta-analysis supported- +0.07 µmol/Lserum creatinine · p=0.03
- GFR —no significant change
- 12 studies177 vs 263 control
A systematic review and meta-analysis found creatine causes only a small, transient rise in serum creatinine with no significant change in GFR, consistent with metabolic turnover rather than kidney injury. This supports the long-standing safety position for people with healthy kidneys.
Reported effect: Serum creatinine MD +0.07 µmol/L (95% CI 0.01 to 0.12; p=0.03); 12 studies, 177 creatine vs 263 control; no significant change in GFR
“Creatine supplementation was associated with a small but statistically significant increase in serum creatinine (MD: 0.07 µmol/L; 95% CI: 0.01 to 0.12; p = 0.03). ... The meta-analysis revealed a non-statistically significant differences in GFR following creatine supplementation compared to control.”
Source: PMID 41199218 · Kabiri Naeini et al. 2025 · BMC Nephrol
Dosage (research context · not a recommendation)
3-5 g/day maintenance; optional 20 g/day × 5-7 day loading (4 × 5 g); higher dose (10 g/day) explored for cognitive endpoints
Regulatory Status · 4 Markets
- US · FDA
- Self-affirmed GRAS (AlzChem Creapure · GRN 144 · 2003) · DSHEA dietary supplement framework
- EU · EFSA
- Authorized claim for creatine + increased physical performance in repeated short-term high-intensity exercise (3 g/day)
- CN · China
- Creatine: sports-nutrition food ingredient under GB 24154-2015 (mandatory in speed-strength category) and on the CBEC cross-border positive list; regulated conventional food, no SAMR health-function registration.
- BR · ANVISA
- RDC 243/2018 dietary supplement · IN 28/2018 Anexo V alegação funcional verbatim: "A creatina auxilia no aumento do desempenho físico durante exercícios repetidos de curta duração e alta intensidade." (Anexo III ≥ 3.000 mg/dia adultos ≥ 19 anos)
Authorized Claims
EFSA — “Creatine increases physical performance in successive bursts of short-term, high intensity exercise.” (Reg 432/2012)
EFSA — “Daily creatine consumption can enhance the effect of resistance training on muscle strength in adults over the age of 55.” (Reg 432/2012)
ANVISA — “A creatina auxilia no aumento do desempenho físico durante exercícios repetidos de curta duração e alta intensidade.” (IN 28/2018 Anexo V alegação funcional)
Safety
Most studied performance supplement; no harm in healthy kidneys (Kreider 2017 ISSN position); creatinine elevation is metabolite (not kidney injury marker in creatine users); hydration recommended
Related
Goals: athletic-performance · longevity-stack · cognitive-support
Lifestyles: athletic-performance · senior-60-plus · plant-based
References
PubMed-indexed citations anchoring the benefit findings above. Effect sizes are reported as published.
- PMID 40944139 · Kazeminasab et al. 2025 · Nutrients — Muscle Strength and Power
- PMID 30935142 · Mielgo-Ayuso et al. · Nutrients — High-Intensity Sprint and Anaerobic Performance
- PMID 24576864 · Devries & Phillips · Med Sci Sports Exerc — Muscle Mass and Sarcopenia in Older Adults
- PMID 35984306 · Prokopidis et al. · Nutrition Reviews — Cognitive Function (Memory)
- PMID 22864465 · Lyoo, Renshaw et al. 2012 · Am J Psychiatry — Depression (Adjunct to SSRI)
- PMID 36877404 · Fernandez-Landa et al. · Sports Med — Endurance Exercise Performance
- PMID 37144634 · Chilibeck et al. 2023 · Med Sci Sports Exerc — Bone Density and Bone Health
- PMID 41199218 · Kabiri Naeini et al. 2025 · BMC Nephrol — Renal Function Safety
Frequently Asked Questions
1. What is creatine best supported for?
The strongest, most consistent evidence is for short, high-intensity and resistance-training performance. A 69-trial meta-analysis (PMID 40944139) found significant strength and power gains when creatine is paired with resistance training, and a soccer-player meta-analysis (PMID 30935142) showed large benefits on anaerobic tests like the Wingate. This matches its core mechanism of regenerating ATP via the phosphocreatine system.
2. How much creatine should I take, and do I need to load?
The NutriCodex card lists 3-5 g/day as the maintenance dose, with an optional loading phase of about 20 g/day (4 x 5 g) for 5-7 days to fill muscle stores faster. Loading is optional - taking 3-5 g/day simply reaches the same saturation more gradually. Higher doses (around 10 g/day) have been explored for cognitive endpoints.
3. Does creatine help with brain or cognitive function?
A meta-analysis of RCTs (PMID 35984306) found a small but significant improvement in memory in healthy individuals (SMD 0.29). Benefits tend to be most noticeable under stress conditions or in people with lower baseline creatine, such as vegetarians. The effect is modest, not dramatic.
4. Is creatine safe for the kidneys?
In people with healthy kidneys, the evidence supports safety. A meta-analysis (PMID 41199218) found only a small, transient rise in serum creatinine with no significant change in GFR, consistent with metabolic turnover rather than kidney damage. Note that the creatinine increase can look like a lab change without being a kidney-injury signal. Staying hydrated is recommended, and anyone with existing kidney disease should consult a clinician.
5. Does creatine work for endurance or bone density?
Not strongly. A meta-analysis in trained athletes (PMID 36877404) found no benefit for endurance performance (a trivial, non-significant pooled effect of SMD -0.07). For bone, a 2-year RCT in 237 postmenopausal women (PMID 37144634) found no effect on bone mineral density. Creatine's value is concentrated in muscle performance and lean mass, not aerobic endurance or bone.
6. Can creatine help with mood or depression?
There is early, investigational evidence as an add-on therapy in studied patients, not a standalone treatment. A small RCT in women with major depressive disorder (PMID 22864465) found that adding 5 g/day creatine to an SSRI produced significantly greater improvement on a depression rating scale than placebo. This is a research finding in a clinical population and should be discussed with a healthcare provider rather than self-treated.
Last evidence review: 2026-05-31