Parise · Journal of applied physiology (Bethesda, Md. : 1985) 2001 · randomized controlled trial · n=27

Effects of acute creatine monohydrate supplementation on leucine kinetics and mixed-muscle protein synthesis.

Cited 234 times in the scientific literature.

Level 2 - randomized trial

Individual randomized controlled trial

PubMed 11509496 · doi:10.1152/jappl.2001.91.3.1041 · record verified 2026-08-26

What was done

Healthy young men (n = 13) and women (n = 14) were randomly assigned to creatine monohydrate (20 g/day for 5 days, then 5 g/day for 3–4 days) or a glucose polymer placebo under standardized dietary and exercise controls. Muscle total creatine and phosphocreatine were assessed before and after supplementation. Mixed-muscle protein fractional synthetic rate and whole-body leucine kinetics were measured using a primed-continuous intravenous infusion of L-[1-13C]leucine and mass spectrometry.

What was found

Creatine supplementation increased muscle total creatine (+13.1%, P < 0.05) with a trend toward increased phosphocreatine (+8.8%, P = 0.09). Creatine did not alter mixed-muscle fractional synthetic rate, total body mass, or fat-free mass. In men, creatine reduced leucine oxidation (-19.6%) and plasma leucine rate of appearance (-7.5%, P < 0.05), but these kinetic changes were not observed in women.

Why it matters

Short-term creatine monohydrate loading does not stimulate muscle protein synthesis directly; observed early body composition changes may be driven by fluid retention or reduced protein breakdown rather than increased synthesis.

Limits

The total sample size was small (n = 27), resulting in small sex-stratified subgroups. Supplementation was acute (8–9 days total), and protein synthesis was evaluated under resting conditions rather than post-exercise.

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