Vitamin D and its role in skeletal muscle.

This review discusses the clinical and laboratory studies that have examined a role of vitamin D in skeletal muscle. Many observational studies, mainly in older populations, indicate that vitamin D status is positively associated with muscle strength and physical performance and inversely associated with risk of falling. Clinical trials of vitamin D supplementation in older adults with low vitamin D status mostly report improvements in muscle performance and reductions in falls. The underlying mechanisms are probably both indirect via calcium and phosphate and direct via activation of the vitamin D receptor (VDR) on muscle cells by 1,25-dihydroxyvitamin D [1,25(OH)(2)D]. VDR activation at the genomic level regulates transcription of genes involved in calcium handling and muscle cell differentiation and proliferation. A putative membrane-associated VDR activates intracellular signaling pathways also involved in calcium handling and signaling and myogenesis. Additional evidence comes from VDR knockout mouse models with abnormal muscle morphology and physical function, and VDR polymorphisms which are associated with differences in muscle strength. Recent identification of CYP27B1 bioactivity in skeletal muscle cells and in regenerating adult mouse muscle lends support to the direct action of both 25-hydroxyvitamin D and 1,25(OH)(2)D in muscle. Despite these research advances, many questions remain. Further research is needed to fully characterize molecular mechanisms of vitamin D action on muscle cells downstream of the VDR, describe the effects on muscle morphology and contractility, and determine whether these molecular and cellular effects translate into clinical improvements in physical function.