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

Abstract

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 D3 (4,000 IU/day) or placebo (50 mg of cellulose), participants performed 20 × 10 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 1α,25(OH)2D3. Supplemental vitamin D3 increased serum 25(OH)D and improved recovery of peak torque at 48 h and 7 days postexercise. In vitro, 10 nmol 1α,25(OH)2D3 improved muscle cell migration dynamics and resulted in improved myotube 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.

Seasonal variation in vitamin D status, bone health and athletic performance in competitive university student athletes: a longitudinal study

“…One potential reason for this risk is that many highly active individuals and athletes spend large amounts of time indoors competing and training and therefore receive limited year-round sunlight exposure (13,14) . This is supported by evidence from studies conducted at different latitudes, including Australia (16) , the USA (17,18) , Europe (19,20) and the UK (21,22) . An Australian study (16) found that their elite indoor athletes had significantly lower vitamin D status when contrasted to their outdoor groups (90 v. 131 nmol/l, respectively), suggesting that indoor athletes may be at increased susceptibility to vitamin D deficiency in winter months due to a lack of subcutaneous exposure to sunlight.…”

Vitamin D Deficiency and Sarcopenia in Older Persons

“…Different biological mechanisms by which vitamin D might regulate skeletal muscle function have been evaluated in cellular models. There are genomic effects through the interaction between vitamin D, VDR and specific nuclear receptors that influence gene transcription, and non-genomic effects described by the interaction between vitamin D and its non-nuclear receptors, activating intracellular signal transduction by other complex pathways [22][23][24]. Functional in vitro studies have demonstrated the direct biological role of the active vitamin D form in the regulation of genes and signaling pathways affecting calcium and phosphate homeostasis, proliferation and differentiation of muscle cells [12,16].…”

Knockdown of the E3 Ubiquitin ligase UBR5 and its role in skeletal muscle anabolism

“…Following human biopsy procedures, muscle tissue was placed in sterile microfuge tubes (Ambion ® , Thermo Fisher Scientific Denmark) containing 1.5 ml of chilled (4˚C) transfer media composed of Ham's F-10 medium including 1 mM L-glutamine (LG; Thermo Fisher Scientific, Denmark), 0.1% heat inactivated fetal bovine serum (hiFBS; Gibco ™ , South America Origin, Fisher Scientific, UK), 0.1% heat inactivated new born calf serum (hiNBCS; Gibco, New Zealand Origin, Fisher Scientific, UK), 100 U/ml penicillin (Lonza, UK), 100 μg/ml streptomycin (Lonza, UK), 2.5 μg/ml amphotericin B (Sigma-Aldrich, UK) and transported on ice to a class II biological safety cabinet (Kojair Biowizard Silverline, Finland) to undergo subsequent cell isolations as described in previous work by our group (Crown et al, 2000;Owens et al, 2015;Turner et al, 2019a). Briefly, muscle tissue was minced in 5 ml trypsin (0.05%)/EDTA (0.02%) solution using 2 × sterile scalpels (No.…”