1. We investigated the effect of oral
creatine supplementation during leg immobilization and rehabilitation on muscle volume and function, and on myogenic
transcription factor expression in human subjects. 2. A double-blind trial was performed in young healthy volunteers (n = 22). A cast was used to immobilize the right leg for 2 weeks. Thereafter the subjects participated in a knee-extension rehabilitation programme (3 sessions x week(-1), 10 weeks). Half of the subjects received
creatine monohydrate (CR; from 20 g down to 5 g daily), whilst the others ingested placebo (P;
maltodextrin). 3. Before and after immobilization, and after 3 and 10 weeks of rehabilitation training, the cross-sectional area (CSA) of the quadriceps muscle was assessed by NMR imaging. In addition, an isokinetic dynamometer was used to measure maximal knee-extension power (Wmax), and needle biopsy samples taken from the vastus lateralis muscle were examined to asses expression of the myogenic
transcription factors MyoD,
myogenin, Myf5, and
MRF4, and muscle fibre diameters. 4. Immobilization decreased quadriceps muscle CSA (approximately 10 %) and Wmax (approximately 25 %) by the same magnitude in both groups. During rehabilitation, CSA and Wmax recovered at a faster rate in CR than in P (P < 0.05 for both parameters). Immobilization changed myogenic factor
protein expression in neither P nor CR. However, after rehabilitation
myogenin protein expression was increased in P but not in CR (P < 0.05), whilst
MRF4 protein expression was increased in CR but not in P (P < 0.05). In addition, the change in
MRF4 expression was correlated with the change in mean muscle fibre diameter (r = 0.73, P < 0.05). 5. It is concluded that oral
creatine supplementation stimulates muscle
hypertrophy during rehabilitative
strength training. This effect may be mediated by a
creatine-induced change in
MRF4 and
myogenin expression.