Vitamin D and its role in skeletal muscle

Abstract

Purpose of review: Vitamin D is best known for its role in regulating calcium homeostasis and in strengthening bone. However, it has become increasingly clear that it also has important beneficial effects beyond the skeleton, including muscle. This review summarizes current knowledge about the role of vitamin D in skeletal muscle tissue and physical performance.

Recent findings: Molecular mechanisms of vitamin D action in muscle tissue include genomic and nongenomic effects via a receptor present in muscle cells. Knockout mouse models of the vitamin D receptor provide insight into understanding the direct effects of vitamin D on muscle tissue. Vitamin D status is positively associated with physical performance and inversely associated with risk of falling. Vitamin D supplementation has been shown to improve tests of muscle performance, reduce falls, and possibly impact on muscle fiber composition and morphology in vitamin D deficient older adults.

Summary: Further studies are needed to fully characterize the underlying mechanisms of vitamin D action in human muscle tissue, to understand how these actions translate into changes in muscle cell morphology and improvements in physical performance, and to define the 25-hydroxyvitamin D level at which to achieve these beneficial effects in muscle.

Figure 1

Synthesis of vitamin D₃ occurs in the skin where 7-dehydrocholesterol is converted to pre-vitamin D₃ in response to sunlight (ultraviolet B radiation) exposure. Vitamin D₃ is produced from the isomerization of pre-vitamin D₃ in the skin or intestinal absorption of natural and fortified foods and supplements. Vitamin D₃ (bound to vitamin D-binding protein) circulates in the bloodstream, and is transported to the liver where it is hydroxylated by liver 25-hydroxylases. The resultant 25-hydroxyvitamin D₃ is hydroxylated to the active secosteroid 1α,25(OH)₂D₃ in the kidney by 1α-hydroxylase. 1α,25(OH)₂D₃ acts on various target tissues via its receptor (VDR). 1α, 25(OH)₂D₃ appears to affect other nonclassical target tissues such as skeletal muscle possibly via the VDR.