Creatine:
The most researched
supplement
in existence

Creatine is a naturally occurring compound synthesised from the amino acids arginine, glycine, and methionine. In muscle tissue, approximately two-thirds of creatine is stored as phosphocreatine (PCr), which is used to rapidly regenerate adenosine triphosphate (ATP), the immediate energy currency for muscular contraction. The primary mechanism of creatine supplementation is to increase intramuscular phosphocreatine stores, which extends the duration and capacity of high-intensity effort before the system depletes. This is why creatine benefits sprint-type activities, heavy compound lifts, and repeated high-intensity efforts more than steady-state endurance work. It does not make you fitter; it allows you to train harder, which over time produces greater adaptation.

Across the research literature, creatine supplementation combined with resistance training consistently outperforms resistance training alone on measures of strength, power output, and fat-free mass. A 2024 meta-analysis covering 23 studies found significant improvements in both upper-body and lower-body strength compared to placebo. A separate meta-analysis of 35 RCTs found that creatine increased lean body mass by an average of 0.68 kg across studies with and without exercise training (Delpino et al., 2022). The lean mass gain is partly explained by increased intramuscular water (creatine is osmotically active and draws water into muscle cells) and partly by genuine increases in muscle protein synthesis supported by the higher training capacity creatine enables.

Sarcopenia, progressive loss of muscle mass and strength with age, is one of the primary drivers of disability and loss of independence in later life. Multiple meta-analyses confirm that creatine combined with resistance training produces significantly greater gains in lean tissue and strength in older adults than resistance training alone. A 2021 meta-analysis by Forbes et al. found that creatine supplementation in older adults during resistance training increased fat-free mass by approximately 1.37 kg more than placebo over intervention periods of 7–52 weeks. Given that the absolute muscle mass most older adults can expect to gain from training alone is modest, this is a meaningful addition. Creatine also has emerging evidence for neuroprotective effects and cognitive function, though this is less established than the musculoskeletal data.

The maintenance dose supported across research is 3–5g of creatine monohydrate daily. A loading phase (20g/day in divided doses for 5–7 days) saturates stores faster but is not required; the same saturation is achieved with a maintenance dose in 3–4 weeks. Loading is not necessary for health or general training purposes and may cause transient gastrointestinal discomfort in some individuals. Timing is not a meaningful variable, take it when convenient. Taking it post-workout or with a meal containing carbohydrate and protein may marginally improve uptake due to insulin-mediated creatine transport, but the effect size is small and consistency of daily intake matters far more than timing precision.

The supplement industry has produced numerous creatine variants: creatine ethyl ester, buffered creatine (Kre-Alkalyn), creatine hydrochloride (HCl), liquid creatine, and others. None of these have demonstrated superiority to creatine monohydrate in head-to-head trials, and several have shown inferior performance. The International Society of Sports Nutrition (ISSN) position stand explicitly states that creatine monohydrate is the only form recommended based on current evidence. Premium-priced alternatives are marketing, not science. They exist because the patent on creatine monohydrate has long expired and the profit margin on a commodity product is low. Plain creatine monohydrate from a reputable third-party tested supplier is the correct choice.

The primary safety concern around creatine, that it damages kidneys, originates from one case report of a single patient with pre-existing kidney disease, and from the observation that creatine supplementation increases urinary creatinine (a kidney function marker), which was misinterpreted as damage rather than recognised as a direct consequence of increased creatine metabolism. Multiple long-term studies and systematic reviews in healthy adults find no adverse effects on kidney function at standard supplementation doses, even over extended periods. The ISSN position stand, the most comprehensive review of creatine safety data, concludes that creatine monohydrate is safe at recommended doses in healthy individuals. As with all supplementation, if you have a clinical history affecting kidney function, discuss with your GP first.

Creatine non-response, where supplementation does not meaningfully increase intramuscular creatine stores, exists and is estimated at roughly 25–30% of the population. Non-responders tend to have higher baseline intramuscular creatine stores, often associated with higher dietary intake of red meat and fish (both significant sources of dietary creatine). For non-responders, supplementation produces less measurable benefit because there is less room to increase stores. You cannot easily determine non-responder status without muscle biopsy, but if you have been supplementing consistently for 4–6 weeks and notice no change in training capacity or body composition, you may be in this category. It is not a meaningful health concern either way.

Beyond musculoskeletal benefits, creatine is being investigated for cognitive function and neuroprotection. The brain uses phosphocreatine for energy buffering in the same way as muscle, and preliminary research suggests that creatine supplementation may improve cognitive performance under conditions of sleep deprivation or mental fatigue, and may have neuroprotective effects relevant to neurodegenerative conditions. This is emerging evidence, not established fact. Several RCTs and reviews support a modest cognitive benefit, particularly in vegetarians (who have lower brain creatine stores) and in older adults. The mechanistic basis is sound. But the effect sizes are small and the literature is not yet at the same level of consistency as the musculoskeletal data. It is a reasonable additional reason to take creatine, not the primary one.