Submitted to: Calcified Tissue International
Publication Type: Review article
Publication Acceptance Date: 10/21/2012
Publication Date: 1/29/2013
Citation: Ceglia, L., Harris, S. 2013. The impact of vitamin D on skeletal muscle function. Calcified Tissue International. 192:151-62. Interpretive Summary:
Technical Abstract: 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. Many clinical trials of vitamin D supplementation in older adults with low vitamin D status found improvements in muscle performance and a reduction in falls. There is growing evidence that a main mechanism by which vitamin D acts on muscle is via a vitamin D receptor (VDR) on skeletal myocytes. Knockout mouse models of the VDR demonstrate significant alterations in myocyte differentiation markers and muscle fiber development and morphology independent of calcium and phosphate abnormalities. Activation of the VDR by the active form of vitamin D, 1,25-dihydroxyvitamin D [1,25(OH)2D], at the level of the genome, upregulates transcription of genes involved in muscle contraction and myocyte differentiation. More rapid actions of 1,25(OH)2D3 in muscle cell lines have been hypothesized to occur via a membrane-associated VDR activating intracellular signaling pathways involved in myocyte differentiation and growth. Additional evidence comes from polymorphisms of the VDR which are associated with differences in muscle strength. Despite large advances in recent decades, many questions remain. Further research is needed to fully characterize underlying molecular mechanisms of vitamin D action on muscle cells and to understand how these cellular actions affect muscle performance.