Hespel · The Journal of physiology 2001 · double-blind randomized controlled trial · n=22

Oral creatine supplementation facilitates the rehabilitation of disuse atrophy and alters the expression of muscle myogenic factors in humans.

Cited 333 times in the scientific literature.

Level 2 - randomized trial

Individual double-blind randomized controlled trial

PubMed 11600695 · doi:10.1111/j.1469-7793.2001.0625c.xd · record verified 2026-08-29

What was done

A double-blind trial evaluated 22 young healthy volunteers whose right leg was cast-immobilized for 2 weeks, followed by a 10-week knee-extension rehabilitation program (3 sessions per week). Subjects received either oral creatine monohydrate (20 g daily tapering to 5 g daily) or placebo (maltodextrin). Quadriceps cross-sectional area (NMR imaging), maximal knee-extension power (Wmax), and vastus lateralis needle biopsies (fibre diameters and protein expression of MyoD, myogenin, Myf5, and MRF4) were measured before and after immobilization, and after 3 and 10 weeks of rehabilitation.

What was found

Immobilization decreased quadriceps cross-sectional area by approximately 10% and Wmax by approximately 25% identically in both groups, with no changes in myogenic factor protein expression. During rehabilitation, cross-sectional area and Wmax recovered significantly faster in the creatine group compared to placebo (P < 0.05 for both). Post-rehabilitation, myogenin protein expression increased in the placebo group but not in creatine (P < 0.05), whereas MRF4 protein expression increased in the creatine group but not in placebo (P < 0.05). Changes in MRF4 expression correlated with changes in mean muscle fibre diameter (r = 0.73, P < 0.05).

Why it matters

Oral creatine supplementation accelerates muscle mass and strength recovery following disuse atrophy, a response linked to differential expression of muscle regulatory factors such as MRF4.

Limits

The sample size was small (n = 22). The study was conducted in young, healthy volunteers with brief cast immobilization, which may not directly translate to elderly populations or clinical patients recovering from major injury or surgery.

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