Creatine
Creatine monohydrate — the most evidence-backed performance supplement in existence
Unregulated by FDA
for efficacy/purity
Version 2025-04 · Last Reviewed April 1, 2025
About this review (v2025-04, last reviewed April 1, 2025): This review was compiled from peer-reviewed clinical trials, independent laboratory analyses, and regulatory filings. Supplement manufacturers had no editorial input. Funding sources for cited studies are disclosed where available. Read our full methodology
This content is for educational purposes only. Supplements are not FDA-approved to treat, cure, or prevent any disease. Discuss supplementation with your healthcare provider before starting, especially if you take medications.
What it is
A naturally occurring nitrogenous compound synthesized in the liver and kidneys from arginine, glycine, and methionine. Also obtained from dietary meat and fish. In muscle cells, creatine is phosphorylated to phosphocreatine (PCr), which rapidly regenerates ATP during high-intensity exercise — the primary energy currency of muscular contraction. The brain also uses significant amounts of creatine.
Why form matters
This is one case where the cheapest form (monohydrate) is definitively the best. Creatine monohydrate has been used in virtually every positive clinical trial. More expensive forms — Kre-Alkalyn ('buffered'), creatine ethyl ester, and many others — have never outperformed monohydrate in direct comparison trials and some are actually inferior. Purity source matters more than form.
Molecular Forms — What the Research Actually Used
The form in the bottle determines how much actually reaches your bloodstream.
Absorption: ~99% — reference standard
The form used in virtually all positive clinical trials. Absorption is nearly complete with adequate water. The least expensive form and definitively the best-supported. Creapure® (from AlzChem, Germany) is the pharmaceutical-grade reference used in most trials.
Absorption: Comparable to monohydrate with adequate water
Higher water solubility than monohydrate — may cause less GI distress at high doses for sensitive individuals. Bioavailability is comparable. No long-term safety data beyond monohydrate. Not established as superior.
Absorption: No advantage over monohydrate
Marketed as pH-corrected to avoid stomach conversion to creatinine. Direct comparison trials (Jagim et al. 2012) found no performance advantage over monohydrate. Higher price, no benefit.
Absorption: Inferior — converts to creatinine rapidly
Clinical trials found CEE was inferior to monohydrate: faster conversion to creatinine, lower muscle creatine accumulation. Not recommended despite premium marketing.
Dosing — What the Research Used
Standard loading protocol (fastest saturation)
ISSN Position Stand; Harris et al.
Conservative (no loading)
Same final muscle saturation as loading in ~4 weeks — better tolerated, avoids temporary water retention
Older adults (muscle and cognitive support)
Rawson & Volek 2003; Avgerinos et al. 2018
High cognitive demand / sleep deprivation context
Rawson et al. 2008 (US Army Research Laboratory)
Note: Creatine monohydrate should be taken with water — 8+ oz per serving. No specific timing advantage (pre vs post workout) has been established. The 'loading phase' is optional — it saturates muscle stores faster but produces the same outcome at lower doses over 4 weeks.
Frequently Asked Questions About Creatine
- What is Creatine?
- A naturally occurring nitrogenous compound synthesized in the liver and kidneys from arginine, glycine, and methionine. Also obtained from dietary meat and fish. In muscle cells, creatine is phosphorylated to phosphocreatine (PCr), which rapidly regenerates ATP during high-intensity exercise — the primary energy currency of muscular contraction. The brain also uses significant amounts of creatine.
- What does Creatine do?
- Creatine monohydrate has more controlled trial evidence than any other dietary supplement — over 500 studies. Effects on muscular strength, power, and lean mass in resistance training are among the most robustly replicated findings in sports science. Emerging cognitive research is promising, particularly in sleep-deprived and older populations. The kidney damage concern, widely circulated, is not supported by clinical evidence in healthy individuals. The most expensive forms have never outperformed monohydrate.
- What is the typical dose of Creatine?
- Creatine monohydrate should be taken with water — 8+ oz per serving. No specific timing advantage (pre vs post workout) has been established. The 'loading phase' is optional — it saturates muscle stores faster but produces the same outcome at lower doses over 4 weeks.
- Does Creatine interact with any medications?
- Creatine has known interactions with: Caffeine (high doses) — Early research suggested caffeine may blunt creatine's ergogenic effect. More recent evidence does not support a significant negative interaction at normal caffeine intake.; NSAIDs (ibuprofen, naproxen) — Creatine increases serum creatinine, a marker used to estimate kidney function. NSAIDs also have renal effects. Combination in people with existing kidney risk is theoretically concerning, though no documented case series exists.; Diuretics — Creatine causes intramuscular water retention while diuretics promote water excretion. Opposing mechanisms — not typically clinically significant..
- Who should be cautious about taking Creatine?
- Exercise caution or consult a healthcare provider if you are: Pre-existing kidney disease (CKD) — creatine increases serum creatinine, which can confound kidney function tests. The kidney damage concern in healthy individuals is not supported by clinical evidence, but CKD patients should use under medical supervision; People with upcoming kidney function lab work — creatine will raise creatinine without indicating actual kidney damage; inform your physician.
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