Creatine: what it is, how it works, and what the research really shows

What creatine is

Creatine is a molecule the body makes on its own and also gets from food, especially red meat and fish. It’s not a protein, not a hormone and not a steroid: it’s a simple nitrogen-containing compound that muscle uses as a ready reserve of energy.

About 95% of the body’s creatine sits in skeletal muscle, the rest in the brain and testes. Inside muscle, two-thirds exists as phosphocreatine and a third as free creatine. The total pool in a 70 kg person typically runs around 120 mmol per kg of dry muscle mass, with a physiological ceiling around 160 mmol/kg. People on a vegetarian diet start from lower stores, 90-110 mmol/kg, because their diet doesn’t supply the ready-made creatine found in meat and fish.

The mechanism: the phosphocreatine/ATP system

The energy muscles use to contract always comes from the same molecule, ATP. The catch is that the ATP reserves inside a muscle cell are tiny and run out within seconds of maximal effort. That’s where creatine comes in: bound to a phosphate group via the enzyme creatine kinase, it forms phosphocreatine (PCr).

When effort demands energy faster than ordinary metabolism can supply it, PCr hands off its phosphate and regenerates ATP almost instantly. The creatine kinase/phosphocreatine system works, in the words of the ISSN position stand, as an “energy shuttle”: a relay connecting the places where ATP is produced, glycolysis and the mitochondria, to the places where ATP gets used up by contracting fibres.

Practical example: in a 10-second sprint or a set of five heavy squats, the energy that arrives fastest is exactly the phosphocreatine system’s share. That’s why studies measure creatine’s effect mostly in short, repeated, very high-intensity efforts, not in long-distance endurance running.

The more phosphocreatine is available to start with, the longer the system can sustain that kind of effort before having to slow down: that’s the physiological rationale behind using creatine as a supplement.

Dosing: loading and maintenance

The literature describes two main strategies for raising muscle creatine stores, reaching the same endpoint on different timelines.

Protocol	Dose	Duration	Effect
Loading	5 g x 4 times a day (about 20 g/day, or 0.3 g/kg)	5-7 days	Muscle creatine content rises 20-40%
Maintenance (after loading)	3-5 g/day (up to 5-10 g/day in bigger individuals)	Ongoing	Keeps stores saturated
Slow protocol (no loading)	3 g/day	About 28 days	Similar saturation to loading, reached more gradually

Loading is the fastest way to saturate stores, not the only one. In clinical settings, much higher doses have been used too, 0.3-0.8 g/kg a day (21-56 g/day for a 70 kg person), sustained over long periods under medical supervision: a very different context from everyday sports use, and not one that anyone supplementing for training should take as a reference point.

What the research shows on performance and muscle mass

The 2017 ISSN position stand is direct: creatine monohydrate is “the most effective nutritional ergogenic supplement” available to athletes for increasing high-intensity exercise capacity and lean mass during training. On average, performance in repeated, intense exercise rises by 10-20%, with the size of the gain tied to how much muscle phosphocreatine increases.

A more recent review (Wax et al., 2021) breaks the effect down across disciplines, always comparing a creatine group with a placebo group:

Measure	Creatine	Placebo
Countermovement jump	+7.0%	+2.3%
Jump power	+6.8%	+3.1%
Cycling, peak power	+12.8%	+4.8%
Cycling, average power	+10.8%	+3.1%
Cycling, total work	+10.8%	+3.5%
Muscular endurance	+14% versus placebo	—

The same review reports relative strength gains (maximal strength tests) of about 8% more than training alone, and overall strength and power improvements between 5% and 15%. On a single isolated sprint, where the phosphocreatine system matters less than people expect, the gains shrink to 1-5%.

On longer-term effects, a meta-analysis cited in the ISSN position stand followed 357 participants aged 64 or older for an average of 12.6 weeks of resistance training: those taking creatine gained more muscle mass, strength and functional capacity than those training without supplementation. Consistent with that, EFSA recognised a specific causal link in 2016 between creatine (at least 3 g/day), resistance training three times a week, and improved muscle strength in adults over 55, provided the intake is daily and ongoing, not limited to training days alone.

A limit in the data: women appear to respond somewhat less than men in terms of strength and mass gains, for the same amount of training, according to the same position stand.

Safety: kidneys, hydration, side effects

The most common worry is about the kidneys. The ISSN position stand is blunt: “there is no compelling scientific evidence that creatine supplementation negatively affects kidney function” in healthy or clinical populations. Doses up to 20 g/day for 5 days, and up to 10 g/day for periods from 10 months to 5 years, showed no effect on creatinine clearance or glomerular filtration rate; a specific study on 5-10 g/day for 21 months found no significant changes.

A more recent meta-analysis (2025, covering 21 studies) does observe a modest rise in serum creatinine in supplemented groups (mean difference of 0.07 µmol/L, 95% CI 0.01-0.12, p = 0.03), but with two important caveats: the values stay within the normal range, and overall kidney function doesn’t differ between groups. The interpretation offered is that the rise simply reflects higher creatine turnover, since creatinine is creatine’s waste product, not organ damage. The one real caution concerns people who already have kidney disease: there, the advice is to check with a doctor before supplementing, out of clinical caution, not because there’s direct evidence of risk in that population.

On hydration and cramping, the literature runs opposite to the common fear. The one side effect reported consistently is an increase in body weight, tied to fluid retention: roughly 0.5-1.0 litres during loading, which shows up as 1-2 kg in the first week, mostly intracellular water. Studies on college football players found that creatine users had a lower, not higher, rate of muscle cramps, heat-related illness, stiffness and total injuries compared with non-users. In Wax et al.’s summary tables, the “adverse events” column reads “none reported” almost across the board, with only rare isolated exceptions (two cases of resting cramps in a 28-day study, one case of nausea in a 13-week study).

Practical example: someone who starts a creatine loading phase and gains 1-1.5 kg over three or four days isn’t putting on fat: they’re holding water inside muscle fibres, an effect that’s expected and well documented in the literature.

Creatine and cognitive function: two positions, not one certainty

On the possible cognitive benefit of creatine, the research holds two distinct positions that shouldn’t be collapsed into a single answer.

On one side, an independent systematic review (16 RCTs, 492 participants) finds statistically significant effects on some measures: memory (SMD 0.31), processing speed and attention time, while finding no effect on global cognitive function or executive function. The authors’ conclusion is cautious but positive: creatine “may confer beneficial effects on cognitive function in adults, particularly in memory, attention time, and processing speed.”

On the other side, EFSA, the European food safety authority, assessed the same question in 2024 to decide whether to authorise a commercial claim, and concluded the opposite: “a cause-and-effect relationship has not been established between creatine supplementation and an improvement in cognitive function in one or more of its domains.” The reasons for rejection are specific: the effects observed showed up mostly at very high doses (20 g/day for 5-7 days, the loading phase), in just one study out of ten for some measures, and weren’t consistent at the low maintenance doses (3 g/day) that most people actually use. The Panel also called the evidence for a biological mechanism “weak”.

The two assessments aren’t necessarily in conflict: they describe different thresholds of certainty. The scientific review registers promising signals in the available literature; EFSA applies the stricter standard required to authorise a commercial claim on a product label, and by that standard the data don’t yet add up. Treating the cognitive benefit as an established fact, on a par with the effect on physical performance, would overstate what those studies have shown.

Why not everyone responds the same way

A fact often overlooked is that creatine doesn’t do the exact same thing for everyone. A reference study (Syrotuik & Bell, 2004) used muscle biopsies to track how 11 healthy men responded to a classic 5-day loading protocol, finding three distinct profiles: 3 true “responders” (average +27.0% increase in stores), 5 “partial responders” (+13.6%) and 3 “non-responders” (+4.8%). Consistent with the classic threshold cited in the literature (Greenhaff et al.), about 20-30% of people fall into the non-responder category after a standard loading protocol.

The difference isn’t random: responders started with lower baseline intramuscular creatine (whoever has more room to begin with gains more) and had a higher share of type II muscle fibres, the ones geared toward explosive strength, along with a larger fibre cross-sectional area and more lean mass than non-responders. Only the true-responder group showed a measurable strength improvement in just 5 days (+25.8 kg on the leg press test), against minimal changes in the other two groups.

The practical takeaway from this line of research is that individual variability is real and documented: two people following the same protocol can end up with very different results, depending on each person’s starting physiology, regardless of how closely they follow the instructions.

Part of a broader training story, not just creatine

This all sits inside a bigger picture, of which creatine is just one piece: how muscle adapts to training. The mechanism by which muscle fibres grow in size in response to load, muscle hypertrophy, depends above all on mechanical tension and weekly training volume; creatine helps sustain that effort, without replacing it.