calcitriol and Muscular-Atrophy

The objective of this review is to consider the mechanisms by which vitamin D affects muscle and the evidence that vitamin D status is important for muscle performance and fall prevention in older adults. Vitamin D receptors have been identified in human skeletal-muscle cells. Activation of these receptors by 1,25-dihydroxyvitamin D is involved in the action of vitamin D on the myocyte. Several studies have examined the effect of supplemental vitamin D on muscle strength, balance and falls. Among those examining muscle strength, results have been either positive for vitamin D or null. A recent meta-analysis of seventeen such trials revealed no significant effect of vitamin D overall, but a significant improvement in strength was observed in the trials in which the mean starting level of 25-hydroxyvitamin D was 25 nmol/l or below. Evidence for an effect of vitamin D on balance, measured as sway, is less abundant but more consistently positive. Many trials have evaluated the effect of supplemental vitamin D on falls. Overall, there is about a 20% lower risk of falling with supplementation. One meta-analysis considered the vitamin D dose administered and concluded that doses up through 15 μg (600 IU) were ineffective and doses of 17·5-25 μg/d (700-1000 IU/d) significantly lowered fall risk. The minimal 25-hydroxyvitamin D level needed for benefit was 60 nmol/l.

Topics: Accidental Falls; Aged; Dietary Supplements; Humans; Muscle Strength; Muscle, Skeletal; Muscular Atrophy; Postural Balance; Receptors, Calcitriol; Vitamin D; Vitamin D Deficiency

Loss of skeletal muscle is one of the main features of cancer cachexia. Vitamin D (VD) deficiency is associated with impairment of muscle mass and performance and is highly prevalent in cachectic patients; therefore, VD supplementation has been proposed to counteract cancer cachexia-associated muscle loss. However, in both cachectic cancer patients and tumour-bearing animals, VD supplementation led to disappointing results, urging the need for a better understanding of VD activity on skeletal muscle.. Cancer-associated muscle wasting was reproduced in vitro by treating C2C12 myotubes with cancer cell conditioned medium, a combination of TNF-α and IFNγ or IL-6 pro-cachectic cytokines. The biological effects and mechanisms of action of 1,25-dihydroxy VD (1,25 VD) and its precursor 25-hydroxy VD (25 VD) on myotubes were explored.. We demonstrated that only 25 VD was able to protect from atrophy by activating Akt signalling, inducing protein synthesis, and stimulating the autophagic flux, while 1,25 VD had an atrophic activity per se, increasing FoxO3 levels, inducing the expression of atrogenes, and blocking the autophagic flux. Furthermore, we showed that the contrasting activities of these VD metabolites on C2C12 myotubes depend on a differential induction of VD-24-hydroxylase and transformation of VD metabolites in pro-atrophic 24-hydroxylated products, as silencing of VD-24-hydroxylase reduced the atrophic activity of 1,25 VD.. Altogether these data might explain the lack of efficacy of VD treatment in vivo for the protection of muscle mass in cancer.

Topics: Cachexia; Cell Line, Tumor; Culture Media, Conditioned; Cytokines; Humans; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Atrophy; Vitamin D