Creatine is found in vertebrates, where it facilitates recycling of adenosine triphosphate (ATP), primarily in muscle and brain tissue.

Recycling is achieved by converting adenosine diphosphate (ADP) back to ATP via donation of phosphate groups.

[12] While creatine's influence on physical performance has been well documented since the early twentieth century, it came into public view following the 1992 Olympics in Barcelona.

95% of the human body's total creatine and phosphocreatine stores are found in skeletal muscle, while the remainder is distributed in the blood, brain, testes, and other tissues.

[25] During times of increased energy demands, the phosphagen (or ATP/PCr) system rapidly resynthesizes ATP from ADP with the use of phosphocreatine (PCr) through a reversible reaction catalysed by the enzyme creatine kinase (CK).

Studies have not established pharmacokinetic parameters for clinical usage of creatine such as volume of distribution, clearance, bioavailability, mean residence time, absorption rate, and half life.

However, higher doses for longer periods of time are being studied to offset creatine synthesis deficiencies and mitigating diseases.

A single 5 gram (5000 mg) oral dose in healthy adults results in a peak plasma creatine level of approximately 120 mg/L at 1–2 hours post-ingestion.

[40] Creatine supplementation for sporting performance enhancement is considered safe for short-term use but there is a lack of safety data for long term use, or for use in children and adolescents.

[42] A 2018 review article in the Journal of the International Society of Sports Nutrition said that creatine monohydrate might help with energy availability for high-intensity exercise.

[49] Creatine is sometimes reported to have a beneficial effect on brain function and cognitive processing, although the evidence is difficult to interpret systematically and the appropriate dosing is unknown.

[51][52] The greatest effect appears to be in individuals who are stressed (due, for instance, to sleep deprivation) or cognitively impaired.

[51][52][53] A 2018 systematic review found that "generally, there was evidence that short term memory and intelligence/reasoning may be improved by creatine administration", whereas for other cognitive domains "the results were conflicting".

It does, however, provide evidence to suggest that more research is required with stressed populations, as supplementation does appear to significantly affect brain content.

[57] A meta-analysis found that creatine treatment increased muscle strength in muscular dystrophies, and potentially improved functional performance.

[58] High doses of creatine lead to increased muscle pain and an impairment in activities of daily living when taken by people who have McArdle disease.

[58] According to a clinical study focusing on people with various muscular dystrophies, using a pure form of creatine monohydrate can be beneficial in rehabilitation after injuries and immobilization.

As of 2014, the evidence did not provide a reliable foundation for treatment decisions, due to risk of bias, small sample sizes, and the short duration of trials.

[68] A 2009 systematic review discredited concerns that creatine supplementation could affect hydration status and heat tolerance and lead to muscle cramping and diarrhea.

Studies have shown that creatine usage does not necessarily affect total body water relative to muscle mass in the long-term.

[71] A 2019 systematic review published by the National Kidney Foundation investigated whether creatine supplementation had adverse effects on renal function.

This situation is exacerbated by the fact that dialysis patients generally consume less meat and fish, the alimentary sources of creatine.

A 2011 survey of 33 supplements commercially available in Italy found that over 50% of them exceeded the European Food Safety Authority recommendations in at least one contaminant.

[87] When creatine is mixed with protein and sugar at high temperatures (above 148 °C), the resulting reaction produces carcinogenic heterocyclic amines (HCAs).