Creatine is a compound that is derived from the amino acids arginine, glycine, and methionine.¹ The body needs 1 to 3g of creatine per day to maintain normal stores, about half of which comes from the diet and half of which is synthesized in the body, mostly in the kidneys and liver.^2,3 Dietary sources of creatine include beef, salmon, and pork.¹ 

Creatine and exercise

About 95 percent of the body’s creatine is stored in the skeletal muscles.^2,3 Creatine aids in the re-synthesis of adenosine triphosphate (ATP), thereby maintaining ATP (and, therefore, energy) availability, especially during high intensity, anaerobic exercise.² 

When creatine is consumed in large amounts via supplementation, muscle creatine stores increase, which leads to improved physical performance and exercise capacity during high intensity and repetitive exercises.² However, creatine supplementation does not provide benefits to aerobic exercise longer than 2.5 minutes (as the metabolic pathway involved in this type of exercise does not involve creatine), and it has not been shown to benefit athletes participating in endurance sports.¹ 

To most effectively increase creatine stores, the International Society of Sports Nutrition recommends that individuals should consume 5g (or about 0.3g/kg of body weight) of creatine monohydrate (the most studied and used form of creatine¹) four times per day for 5 to 7 days. Individuals can also gradually increase creatine stores by consuming 3g per day for 28 days. After the loading phase, increased creatine stores can be maintained by consuming about 3 to 10g (depending on body size) of creatine monohydrate per day.² Vegetarians can experience a greater response to creatine supplementation, compared to nonvegetarians, due to having lower muscular creatine stores.^1–3

Research indicates that, in addition to improving athletic performance, creatine supplementation may improve muscle recovery after exercise,^2,3 reduce dehydration and muscle cramps,³ reduce the risk of injury and heat-related illness during exercise, and decrease muscle atrophy and enhance rehabilitation/recovery following injuries.² Among older individuals, creatine supplementation in combination with resistance training might have a protective effect against sarcopenia and bone loss.^2,4

Creatine and the brain

The brain can also synthesize creatine, but dietary creatine uptake is limited, potentially due to the lack of SLC6A8, a creatine transporter that is responsible for creatine uptake in skeletal muscles.⁵ Compared to the well-known effects on muscles and physical performance, less is known about the effects of creatine supplementation on the brain.

Creatine deficiency syndromes. Individuals with creatine deficiency syndromes either have a reduced ability or inability to synthesize creatine in the body or engage in transcellular transport of creatine. These syndromes can lead to developmental issues, movement disorders, and seizure disorders, among others. High-dose creatine supplementation (0.3–0.8g/kg/day) has been shown to improve clinical outcomes among children and adults with creatine synthesis deficiencies.²

Neurodegenerative diseases. Currently, there is insufficient evidence to support the use of creatine supplementation in multiple sclerosis, Huntington’s disease, and amyotrophic lateral sclerosis (ALS). While research has demonstrated the creatine supplementation might lead to an improved response to dopaminergic therapy and heightened muscle function and strength in Parkinson’s disease (PD), it does not slow disease progression, and more research must be done to determine if creatine can benefit patients with PD. Creatine supplementation appears to be more promising in the treatment of Duchenne muscular dystrophy (DMD), as it has been associated with improvements in functionality and strength, but further research is needed to fully understand the effects of creatine in DMD, as well as other muscular dystrophies.⁵

Traumatic brain injury. Creatine supplementation could potentially help mitigate the effects of mild traumatic brain injury, but current research is largely restricted to animal studies, and human studies must be conducted to fully elucidate the effects of creatine supplementation on this condition.^5,6

Cognitive function. The impact of creatine supplementation on cognitive function is unclear. In some studies, researchers observed benefits to cognitive function with creatine supplementation, whereas other studies have found no such effect.⁵ A review of randomized controlled trials showed that, in terms of cognitive function, creatine supplementation in healthy individuals might potentially improve short-term memory and reasoning; however, the included studies were highly heterogenous, with varying populations, creatine supplement protocols, and cognitive tasks, and included a small sample size of 281 people overall. Additionally, there was a high risk of bias for one study that concluded creatine benefited short-term memory.⁷ Some studies indicate that creatine supplementation might be most effective at improving cognition when under stressful conditions, such as sleep deprivation, but this needs to be studied further in order to make any firm conclusions.^5,6 Furthermore, conclusions on creatine’s effects on cognitive function are limited by the inability to directly compare studies due to differing study designs, as well as limitations of individual studies (e.g., excluding a control group, failing to assess brain creatine concentration).⁶

Depression. Animal studies and a limited number of small-scale human studies have demonstrated the potential for creatine supplementation as a treatment for depression, but larger, more involved human studies are necessary.⁵

Adverse effects

Creatine monohydrate supplementation in doses of 0.3 to 0.8g/kg per day for up to five years is safe, with no associated health risks.² Weight gain is the only consistent side effect of creatine supplementation.^1,2 Anecdotal side effects, such as musculoskeletal injuries, gastrointestinal issues, dehydration, muscle cramping, kidney damage/renal impairments, and hair loss have not been corroborated by evidence-based studies.^2,4

Bottom Line

Creatine supplementation is a safe, effective way to improve exercise performance. More research is needed to determine the potential effects of creatine supplementation in other areas. Consult with a healthcare professional to determine if creatine supplementation is right for you.

Sources

1. National Institutes of Health Office of Dietary Supplements. Dietary supplements for exercise and athletic performance: fact sheet for health professionals. Updated 2 Jun 2022. https://ods.od.nih.gov/factsheets/ExerciseAndAthleticPerformance-HealthProfessional/#creatine. Accessed 18 Jan 2024.
2. Kreider RB, Kalman DS, Antonio J, et al. International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. J Int Soc Sports Nutr. 2017;14:18. 
3. Cleveland Clinic. Creatine. Reviewed 26 Apr 2023. https://my.clevelandclinic.org/health/treatments/17674-creatine. Accessed 18 Jan 2024.
4. Antonio J, Candow DG, Forbes SC, et al. Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show? J Int Soc Sports Nutr. 2021;18(1):13. 
5. Forbes SC, Cordingley DM, Cornish SM, et al. Effects of creatine supplementation on brain function and health. Nutrients. 2022;14(5):921.
6. Roschel H, Gualano B, Ostojic SM, Rawson ES. Creatine supplementation and brain health. Nutrients. 2021;13(2):586. 
7. Avgerinos KI, Spyrou N, Bougioukas KI, Kapogiannis D. Effects of creatine supplementation on cognitive function of healthy individuals: a systematic review of randomized controlled trials. Exp Gerontol. 2018;108:166–173.