Deep Dive | The Science of Creatine
What the research actually says — without the fluff.
What is Creatine?
Creatine is a naturally occurring compound synthesized from the amino acids arginine, glycine, and methionine. It is stored mainly in skeletal muscle and used to regenerate adenosine triphosphate (ATP), the body's primary energy currency. Daily intake from diet and endogenous production approximates 1-2 grams, but studies show supplementation is the most efficient method to maximize intramuscular stores.¹
Proven Physical Benefits
Creatine monohydrate is one of the most rigorously studied ergogenic aids. Its use is associated with enhanced high-intensity exercise performance, increased strength and power, and greater fat-free mass when combined with resistance training.² ³ A 2021 systematic review concluded that creatine improves both upper and lower body strength across various populations.⁴
Cognitive and Neurological Effects
Beyond its muscular benefits, creatine supplementation may support cognitive performance. Emerging research suggests improvements in working memory, mental fatigue resistance, and neural protection, especially under stress conditions like sleep deprivation.⁵ ⁶ In older adults, creatine has shown potential in enhancing cognitive function and delaying neurodegeneration.⁷
Skeletal Health and Aging
Creatine may contribute to skeletal health by increasing muscle mass and function, which in turn supports balance and reduces fall risk. This is particularly relevant for aging populations at risk of sarcopenia and fractures.⁸ A 2015 review found that creatine, combined with resistance training, enhanced bone mineral density and muscular strength in older adults.⁹
Loading vs. Maintenance Dosing
A loading phase (e.g., 20g/day for 5–7 days) can accelerate intramuscular saturation but is not required. A standard maintenance dose of 3–5g/day is equally effective over a longer duration without increasing side effects.¹⁰
Safety and Tolerability
Creatine monohydrate has a robust safety profile. Long-term studies up to five years demonstrate no adverse effects on kidney or liver function in healthy individuals.¹¹ ¹² Concerns about hair loss stem from a single small study observing dihydrotestosterone (DHT) elevations, not clinically observed alopecia.¹³
Why Creatine Monohydrate?
Although numerous creatine formulations exist, monohydrate remains the gold standard. It is the form utilized in the vast majority of peer-reviewed studies and is consistently shown to be effective, stable, and cost-efficient.¹⁴
References
1. Persky AM, Brazeau GA. Clinical pharmacology of the dietary supplement creatine monohydrate. Pharmacological Reviews. 2001;53(2):161-76.
2. Kreider RB 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. Branch JD. Effect of creatine supplementation on body composition and performance: a meta-analysis. Int J Sport Nutr Exerc Metab. 2003;13(2):198–226.
4. Candow DG et al. Efficacy of creatine supplementation: systematic review. J Strength Cond Res. 2021.
5. Rae C et al. Oral creatine monohydrate supplementation improves brain performance: a double–blind, placebo–controlled, cross–over trial. Proc R Soc Lond B Biol Sci. 2003;270(1529):2147–2150.
6. McMorris T et al. Creatine supplementation and cognitive performance in elderly and sleep-deprived individuals. Psychopharmacology. 2007;185(1):93–99.
7. Avgerinos KI et al. Effects of creatine supplementation on cognitive function of healthy individuals: A systematic review of randomized controlled trials. Exp Gerontol. 2018;108:166-173.
8. Chilibeck PD et al. The effect of creatine supplementation combined with resistance training on bone mineral density in older adults. J Nutr Health Aging. 2015;19(5):547–552.
9. Candow DG et al. Creatine supplementation in aging populations: effects on skeletal muscle, bone and brain. J Cachexia Sarcopenia Muscle. 2011;2(4):191–198.
10. Buford TW et al. International Society of Sports Nutrition position stand: creatine supplementation and exercise. J Int Soc Sports Nutr. 2007;4:6.
11. Kreider RB et al. Long-term creatine supplementation does not significantly affect clinical markers of health in athletes. Mol Cell Biochem. 2003;244(1-2):95–104.
12. Poortmans JR, Francaux M. Long-term oral creatine supplementation does not impair renal function in healthy athletes. Med Sci Sports Exerc. 2000;32(5):1108–1110.
13. van der Merwe J et al. Three weeks of creatine monohydrate supplementation affects dihydrotestosterone to testosterone ratio in college-aged rugby players. Clin J Sport Med. 2009;19(5):399–404.
14. Jäger R et al. Analysis of the efficacy, safety, and regulatory status of novel forms of creatine. J Dietary Suppl. 2011;8(4):298–318.