Creatine

ByLaura Shane-McWhorter, PharmD, University of Utah College of Pharmacy
Reviewed ByEva M. Vivian, PharmD, MS, PhD, University of Wisconsin School of Pharmacy
Reviewed/Revised Modified Jul 2025
v1126503
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Creatine refers to a variety of formulations; creatine monohydrate is one of the most common formulations available as a supplement. Creatine monohydrate undergoes phosphorylation after ingestion into phosphocreatine.

Phosphocreatine is a compound stored in muscle; it donates phosphate to adenosine diphosphate (ADP) and thereby rapidly replenishes ATP during anaerobic muscle contraction. It is synthesized endogenously in the liver from arginine, glycine, and methionine. Dietary sources are milk, steak, and some types of fish.Phosphocreatine is a compound stored in muscle; it donates phosphate to adenosine diphosphate (ADP) and thereby rapidly replenishes ATP during anaerobic muscle contraction. It is synthesized endogenously in the liver from arginine, glycine, and methionine. Dietary sources are milk, steak, and some types of fish.

Claims for Creatine

Creatine is said to improve physical and athletic performance and to reduce muscle fatigue. There is increasing interest in creatine supplementation, not only in healthy individuals, but in aging adults who wish to improve muscle strength and for postexercise recovery and injury prevention (1).

Evidence for Creatine

Some evidence suggests creatine is effective at increasing work done in a short duration with maximal effort (eg, sprinting, rowing, weightlifting). A small 6-week study in 22 physically active adults also showed creatine ingestion during resistance training sessions may improve muscle strength (2). Creatine has proven therapeutic use in muscle phosphorylase deficiency (glycogen storage disease type V [McArdle disease]) and gyrate atrophy of the choroid and retina; early data also suggest possible effects in Parkinson disease and amyotrophic lateral sclerosis.

Numerous clinical trials have demonstrated that creatine supplementation is well tolerated and may increase muscle mass. Improvements can be seen in several different patient populations (3–5):

  • Healthy people (improved strength and increased muscle mass)

  • Patients with muscle dystrophies (increased muscle strength)

  • Patients with osteoarthritis (improvements in physical function and quality of life)

Adverse Effects of Creatine

Creatine may cause weight gain (possibly because of an increase in muscle mass) and spurious increases in serum creatinine levels. Minor gastrointestinal symptoms, headache, dehydration, irritability and aggression, edema, electrolyte imbalance, and muscle cramps have been reported anecdotally.

Drug Interactions with Creatine

No drug interactions are well documented, but taking creatine may increase the risk from medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs), that affect kidney function. Also, caffeine may decrease the benefit of creatine by decreasing its energy production.No drug interactions are well documented, but taking creatine may increase the risk from medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs), that affect kidney function. Also, caffeine may decrease the benefit of creatine by decreasing its energy production.

References

  1. 1. Hall M, Manetta E, Tupper K. Creatine Supplementation: An Update. Curr Sports Med Rep. 2021 Jul 1;20(7):338-344. doi: 10.1249/JSR.0000000000000863

  2. 2. Mills S, Candow DG, Forbes SC, et al. Effects of creatine supplementation during resistance training sessions in physically active young adults. Nutrients. 12(6):1880, 2020. doi:10.3390/nu12061880

  3. 3. Kley RA, Tarnopolsky MA, Vorgerd M. Creatine for treating muscle disorders. Cochrane Database Syst Rev. (6):CD004760, 2013. doi: 10.1002/14651858.CD004760.pub4

  4. 4. Branch JD. Effect of creatine supplementation on body composition and performance: a meta-analysis. Int J Sport Nutr Exerc Metab. 13(2):198-226, 2003. doi:10.1123/ijsnem.13.2.198

  5. 5. Neves M Jr, Gualano B, Roschel H, et al. Beneficial effect of creatine supplementation in knee osteoarthritis. Med Sci Sports Exerc. 43(8):1538-1543, 2011. doi: 10.1249/MSS.0b013e3182118592

More Information

The following English-language resource may be useful. Please note that The Manual is not responsible for the content of this resource.

  1. National Institutes of Health (NIH), National Center for Complementary and Integrative Health: Dietary Supplements Marketed for Weight Loss, Bodybuilding, and Sexual Enhancement: What the Science Says

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