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

Abstract

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.

Figure 1. Protein expression of the myogenic factors before and after leg immobilization and after rehabilitation training

A, myogenin; B, MRF4; C, MyoD; D, Myf5. Pre, before leg immobilixation; Post, 2 weeks after leg immobilization. R3, 3 weeks of rehabilitation training; R10, 10 weeks of rehabilitation training. Values are means ±s.e.m. of eight observations and are expressed relative to the baseline values (Pre). *Significant treatment effect compared with placebo.

Figure 2

Correlation between the individual changes (R10 minus Pre) in MRF4 protein expression (arbitrary units) and average muscle fibre size (μm²) from the start (Pre) to the end (R10) of the study