Creatine monohydrate

Muscle holds roughly 5 mmol/kg of ATP, which is enough for about two seconds of maximal contraction. The buffer that keeps that pool from collapsing is phosphocreatine at around 20 to 25 mmol/kg wet weight, and the creatine kinase reaction (PCr + ADP + H+ ⇌ Cr + ATP) is the fastest ATP-regenerating reaction in the cell. It sits near equilibrium, so it responds instantly. Capacity is not the point. Rate is.

Supplementation raises total muscle creatine by roughly 20 percent, from about 120 to 140 to 150 mmol/kg dry mass, against a ceiling near 160. Uptake runs through the sodium-dependent transporter SLC6A8, which is modestly insulin-sensitive, so taking it with a carbohydrate-containing meal helps a little. Loading with 20 g/day split into four doses for five or six days and taking 3 to 5 g/day for a month land at the same plateau. Loading is faster, not better.

The performance consequence is narrow and specific: faster phosphocreatine resynthesis between efforts. That means more quality reps in a set, more sets in a session, more sprints before the drop-off. Over weeks, that is a larger training stimulus. Creatine does not build tissue. It buys you more of the work that builds tissue.

Then the water. Creatine is osmotically active, so intracellular water rises with intracellular creatine. The typical 1 to 2 kg gain in the first week is water inside muscle cells, not under the skin, and it is the single most common reason athletes (female athletes especially) skip the one supplement with a mountain of evidence behind it. Cell swelling may itself be a mild anabolic signal, but that is a maybe, and maybes do not belong in a sales pitch.

Brain creatine also rises, but slowly and less: the blood-brain barrier expresses the transporter sparingly, so cerebral stores are far more stubborn than muscular ones. That asymmetry matters when reading the cognition studies.

The base is unusually deep: hundreds of randomised trials since Harris and Hultman's loading work in the early 1990s, plus an International Society of Sports Nutrition position stand that has survived two decades of scrutiny. Meta-analytic estimates put maximal strength gains at roughly 5 to 10 percent above placebo across training studies, with lean mass gains of about 1 to 2 kg over four to twelve weeks. The effect concentrates exactly where the mechanism predicts: repeated maximal efforts under 30 seconds with short rest.

Non-responders are real and predictable. Athletes with high habitual red meat intake start closer to the ceiling and gain less. Vegetarians and vegans start lowest and respond most, which is the most reliable subgroup finding in the whole literature.

Safety is where the gap between internet folklore and data is widest. Monitored trials run up to five years, and clinical populations have taken 20 to 30 g/day for months without a consistent renal signal in healthy kidneys. Serum creatinine does rise slightly, because creatinine is creatine's breakdown product. That is an assay artifact, not organ damage, and it is worth telling your physician before a routine panel. The cramping and dehydration claim runs the other way: controlled work finds no increase in cramping and, if anything, better thermoregulation.

The honest limits. Endurance performance: essentially nothing, and the added mass can be a net negative in weight-sensitive events. Cognition: the literature is far weaker than the performance literature. Samples are small and heterogeneous, effects cluster in sleep-deprived or vegetarian subjects, outcome batteries differ study to study, and recent short high-dose trials are not clean. The working-memory-under-sleep-deprivation signal is the most plausible piece of it.