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

1. We investigated the effect of oral creatine supplementation during leg i mmobilization and rehabilitation on muscle volume and function, and on myog enic 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 su bjects participated in a knee-extension rehabilitation programme (3 session s 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; ma ltodextrin). 3. Before and after immobilization, and after 3 and 10 weeks of rehabilitat ion training, the cross-sectional area (CSA) of the quadriceps muscle was a ssessed by NMR imaging. In addition, an isokinetic dynamometer was used to measure maximal knee-extension Power (W-max), and needle biopsy samples tak en from the vastus lateralis muscle were examined to asses expression of th e myogenic transcription factors MyoD, myogenin, Myf5, and MRF4, and muscle fibre diameters. 4. Immobilization decreased quadriceps muscle CSA (similar to 10%) and W-ma x (similar to 25%) by the same magnitude in both groups. During rehabilitat ion, CSA and W-max recovered at a faster rate in CR than in P (P < 0.05 for both parameters). Immobilization changed myogenic factor protein expressio n in neither P nor CR. However, after rehabilitation myogenin protein expre ssion was increased in P but not in CR (P < 0.05), whilst MRF4 protein expr ession 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 dia meter (r = 0.73, P < 0.05). 5. It is concluded that oral creatine supplementation stimulates muscle hyp ertrophy during rehabilitative strength training. This effect may be mediat ed by a creatine-induced change in MRF4 and myogenin expression.