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Creatine Supplementation: Separating Fact from Fiction

By Sabeeka Malik

Graphic design by Sabrina Viloria

Walk into a gym, scroll through FitnessTok, or talk to a student athlete, and one supplement is almost guaranteed to come up: creatine. Creatine is one of the most widely used dietary supplements in the fitness world and is praised for its ability to enhance strength and performance.1 Some view it as an essential addition to any serious athlete’s routine, while others warn about its health risks. Research, however, shows that creatine is safe, and may even have benefits beyond athletic performance.

Creatine is an endogenous amino acid derivative that is synthesized in the liver, kidneys, and pancreas.2 Creatine can also be obtained through the diet, mainly from meat and fish.3 After uptake or synthesis, creatine travels through the bloodstream to tissues with high energy demands, including skeletal muscle, the brain, and the heart.2  

Short-duration energy production during high-intensity anaerobic activities such as weightlifting, sprinting, and football relies on creatine. At rest, creatine kinase (CK) facilitates the conversion of adenosine triphosphate (ATP) and creatine into phosphocreatine (PCr) and adenosine diphosphate (ADP).2,3 During periods of high energy demand, PCr acts as a phosphate reserve allowing the regeneration of ATP from ADP. This is achieved by CK, which transfers a phosphate from PCr back to ADP, restoring ATP and regenerating creatine.2,3 As resynthesis of ATP from PCr and ADP is quicker than the production of ATP from oxidative phosphorylation and other glycolytic processes, this process is critical during periods of brief, high-intensity energy demands.2 

Several studies have been conducted to determine the benefits of creatine supplementation for enhancing exercise and sports performance. A meta-analysis reviewing data from randomized controlled trials (RCTs) and biochemical and physiological studies found evidence to support the use of creatine for enhancing muscular strength and power, increasing capacity for high-intensity training, and improving recovery times.1 The performance-enhancing effects of creatine supplementation are attributable to increases in intracellular PCr.1

Importantly, while creatine supplementation can enhance high-intensity exercise performance, it is not a cure-all for athletes as it is less effective for improving endurance performance.1 Endurance training requires strenuous physical efforts for long intervals. As such, it relies heavily on aerobic energy, which requires higher sustained ATP yields over extended periods of time. Therefore, for aerobic activities requiring endurance, like long-distance running, cycling, or swimming, creatine supplementation does not have the same benefit.

Despite its advantages, there are common misconceptions about creatine supplementation, suggesting potential health risks associated with its usage. One such misconception is the effect of creatine supplementation on kidney function. These concerns are due to an observed increase in creatinine (the natural waste product of creatine and PCr) in the blood and urine, after creatine supplementation.4 Increased creatinine levels can be indicative of an underlying renal issue. However, increased levels alone are not a definitive sign of poor kidney function. For instance, increases are also observed in individuals with meat-rich diets.4 Currently, there is no evidence to suggest creatine supplementation negatively impacts renal function.5 

There are also controversies surrounding the effects of age and sex on the benefits of creatine supplementation. Most studies have been conducted in adult males, leading to skepticism about the reproducibility of results in females and adolescent populations. In the past several years, however, many studies have been conducted focusing on the effects of creatine supplementation in females. Despite sex differences, research shows creatine supplementation increases PCr stores in females as well, leading to comparable benefits to those observed in males.1,4 While research on the effects of creatine supplementation in adolescents is still limited, emerging studies indicate that creatine is not harmful and has similar benefits in children and adolescents.4 Overall, current evidence suggests that age and sex have little impact on the benefits of creatine.

There is also a misconception that when starting creatine supplementation, a “loading phase” is required before entering a “maintenance phase.” A “loading phase” is when individuals initially take a greater dosage (e.g., 20-25 grams/day, often broken down into four to five smaller doses throughout the day) for a short period of time. Then, in the “maintenance phase,” smaller doses are taken (e.g., 3-5 grams/day). For someone considering starting creatine supplementation, this can sound very intense. However, many studies demonstrate that a lower creatine dose, without a preliminary “loading phase,” is sufficient to increase cellular PCr stores.4 

Importantly, creatine is not only relevant to performance enhancement, but it is also fundamental to cellular energy homeostasis. The importance of creatine is demonstrated by the consequences of its deficiency, which can arise due to genetic defects. Creatine synthesis relies on two key enzymes: L-arginine-glycine amidinotransferase (AGAT) and guanidinoacetate N-methyltransferase (GAMT).2 Cellular uptake is mediated by the creatine transporter (CRT).2,3 Creatine deficiency disorders (CDDs)—a group of three rare genetic disorders (AGAT deficiency, GAMT deficiency, and CRT deficiency)—cause developmental delays and cognitive dysfunction.6 Because creatine supplementation has been shown to improve symptoms, it is part of standard treatment, extending creatine’s use beyond recreational contexts and into therapeutic ones.6 

Increasing evidence suggests that creatine may be relevant in health and disease. The brain, which accounts for nearly 20% of total resting energy expenditure, relies on continuous ATP supply to support neuronal function. Therefore, the ratio of PCr to creatine is critical for meeting energy demands.7 Recent studies suggest that creatine supplementation may improve cognition, especially memory, attention, and processing speed.2,8,9  

There are conflicting studies regarding creatine’s effect on cancer. Some studies have shown that creatine may enhance the activity of anti-tumour CD8+ T-cells and promote tumour apoptosis pathways.10 In contrast, others have shown that, due to its role in increasing ATP levels (which benefit proliferating cancerous cells), creatine may lead to cancer progression and metastasis.10 Some preliminary research shows that inhibiting the creatine transporter has promising therapeutic benefits in mitigating cancer progression.11 Taken together these studies suggest that creatine plays a complex role in cancer progression. 

Creatine is a well-studied compound with strong evidence supporting its efficacy in enhancing high-intensity exercise performance through increased PCr availability and faster ATP regeneration. Its benefits in strength, power, recovery, and even certain cognitive functions make it a valuable supplement for both athletes and the general population. Beyond the gym and CDDs, creatine research is evolving fast, and creatine is proving to be a promising compound with potential benefits across different fields. 

References

  1. Wax B, Kerksick CM, Jagim AR, et al. Creatine for exercise and sports performance, with recovery considerations for healthy populations. Nutrients. 2021;13(6):1915. doi:10.3390/nu13061915.
  2. Bonilla DA, Kreider RB, Stout JR, et al. Metabolic basis of creatine in health and disease: a bioinformatics-assisted review. Nutrients. 2021;13(4):1238. doi:10.3390/nu13041238.
  3. Kreider RB, Stout JR. Creatine in health and disease. Nutrients. 2021;13(2):447. doi:10.3390/nu13020447.
  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. doi:10.1186/s12970-021-00412-w.
  5. Naeini EK, Eskandari M, Mortazavi M, et al. Effect of creatine supplementation on kidney function: a systematic review and meta-analysis. BMC Nephrol. 2025;26:622. doi: 10.1186/s12882-025-04558-6
  6. Mercimek-Andrews S, Salomons GS. Creatine Deficiency Disorders. In: Adam MP, Bick S, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 2009 Jan 15 [updated 2025 Aug 7]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK3794/.
  7. Forbes SC, Cordingley DM, Cornish SM, et al. Effects of creatine supplementation on brain function and health. Nutrients. 2022;14(5):921. doi:10.3390/nu14050921.
  8. Marshall S, Kitzan A, Wright J, et al. Creatine and cognition in aging: a systematic review of evidence in older adults. Nutr Rev. 2026;84(2):333-344. doi:10.1093/nutrit/nuaf135. 
  9. Xu C, Liu P, Li Y, et al. The effects of creatine supplementation on cognitive function in adults: a systematic review and meta-analysis. Front Nutr. 2024;11:1453467. doi:10.3389/fnut.2024.1453467.
  10. Geng Y, DeLay SL, Chen X, et al. It is not just about storing energy: the multifaceted role of creatine metabolism on cancer biology and immunology.  Int J Mol Sci. 2024 Dec 11;25(24):13273. doi: 10.3390/ijms252413273.
  11. Abdollahzadeh M, Ghodsi R, Taherzadeh Z, et al. Targeting creatine and creatine kinase in cancer: exploring potential therapeutic strategies. Curr Drug Targets. 2025;26(11):739-756. doi: 10.2174/0113894501373936250609114913.