Recent in vitro studies have demonstrated an anabolic role of vitamin D directly targeting skeletal muscle via vitamin D receptors (VDR) present in myotubes \[1,2,3\]. However, this has yet to be translated to in vivo human models.
25-hydroxyvitamin-D (25OHD) is the primary circulating metabolite and reference measurement for vitamin D status. This may then either be converted to 24,25-dihydroxyvitamin D3 (24,25OHD) to prevent intoxication \[4\] or be activated in the kidneys to 1,25-dihydroxyvitamin D (1,25OHD)\[5\].
Evidence support a biological role for 1,25OHD in skeletal muscle\[1-4,7\]. With focus on muscle hypertrophy, a study demonstrated that 25OHD can also be activated to 1,25OHD in myotubes\[8\] and promote cell proliferation, growth and differentiation of myocytes in in vitro skeletal muscle cells\[7,9-13\]. The mechanisms proposed include (i) gene expression of endocytic receptors for vitamin D binding protein (VDP) (megalin/cubulin) on the muscle cell surface membrane and (ii) high affinity for VDP to bind to actin inside the muscle cell. Furthermore, epidemiological studies support a positive role for vitamin D in human muscle function\[14-21\] and mechanistic studies implicate intracellular 25OHD in the regulation of protein metabolism. Cell culture and in vivo animal models demonstrate that 25OHD activates anabolic cell signalling proteins of the mTORC1 pathway in response to anabolic stimuli\[21,22\], which translates into an increased stimulation of muscle protein synthesis\[17\]. Despite these exciting results from cell culture and in vivo animal studies, no study has replicated these findings in in vivo human models.
The length of the intervention in studies investigating the effects of vitamin D supplementation on muscle health outcomes and MPS varies between studies; however, evidence supports improvements in fast-twitch muscle fibres in elderly women\[18\], muscle strength in humans and animals and an increased in MPS in rats and mice following a minimum of 12 weeks intervention \[22\]. Thus, this study plans to have 12 weeks of intervention to ensure there is sufficient time for a physiologically effect to take place. Seasonal variations in blood 25OHD concentrations have been evaluated in Caucasians residing in Northern Ireland\[4\]. Thirty-four percent were deficient (\<25nmol/L) in winter months\[4\]; however, despite insufficient sunlight in winter to synthesise vitamin D in skin, a significant proportion of a population resident in the same latitude, in Scotland, maintained blood 25OHD concentrations \>50nmol/L\[6\]. These data and a recent review\[8\] suggest that humans have evolved a storage mechanism, which allows 25OHD, produced in the summer, to be conserved and used more efficiently in winter.
