A systems-based investigation into vitamin D and skeletal muscle repair, regeneration, and hypertrophy

Skeletal muscle is a direct target for vitamin D. Observational studies suggest that low 25[OH] D correlates with functional recovery of skeletal muscle following eccentric contractions in humans and crush injury in rats. However, a definitive association is yet to be established. To address this gap in knowledge in relation to damage repair, a randomised, placebo-controlled trial was performed in 20 males with insufficient concentrations of serum 25(OH) D (45 +/- 25 nmol/l). Prior to and following 6 wk of supplemental vitamin D-3 (4,000 IU/day) or placebo (50 mg of cellulose), participants performed 20 x10 damaging eccentric contractions of the knee extensors, with peak torque measured over the following 7 days of recovery. Parallel experimentation using isolated human skeletal muscle-derived myoblast cells from biopsies of 14 males with low serum 25(OH) D (37 +/- 11 nmol/l) were subjected to mechanical wound injury, which enabled corresponding in vitro studies of muscle repair, regeneration, and hypertrophy in the presence and absence of 10 or 100 nmol 1 alpha,25(OH)(2)D-3. Supplemental vitamin D-3 increased serum 25(OH) D and improved recovery of peak torque at 48 h and 7 days postexercise. In vitro, 10 nmol 1 alpha,25(OH)(2)D-3 improved muscle cell migration dynamics and resulted in improvedmyotube fusion/differentiation at the biochemical, morphological, and molecular level together with increased myotube hypertrophy at 7 and 10 days postdamage. Together, these preliminary data are the first to characterize a role for vitamin D in human skeletal muscle regeneration and suggest that maintaining serum 25(OH) D may be beneficial for enhancing reparative processes and potentially for facilitating subsequent hypertrophy.