MON-834 - 25(OH)D and Not 1,25(OH)D Is Responsible for High-Dose Dietary Vitamin D Benefits in Muscle.

Background: In our recent publication we describe that high-dose dietary vitamin D improves grip strength, lean mass and muscle oxidative phosphorylation and decreases adiposity in mice. When we measured vitamin D metabolites in these mice we found that 25(OH)D was high and 1,25(OH)D was undetectable. The dominant paradigm to explain how dietary vitamin D would mediate this effect is that 1,25(OH)D is generated locally at the muscle.

Objective: We aimed to examine the novel and controversial hypothesis that 25(OH)D and not 1,25(OH)D, improves grip strength, lean mass and muscle oxidative phosphorylation and decreases adiposity.

Design/Methods: To examine the possibility that 25(OH)D, and not 1,25(OH)D, improves grip strength, lean mass and muscle oxidative phosphorylation and decreases adiposity we used both in vivo and in vitro approaches. To interrogate high-dose dietary vitamin D benefits in vivo we measured the change in grip strength in 1-hydroxylase knockout mice as compared with wild type mice in response to high-dose dietary vitamin D. To examine high-dose dietary vitamin D benefits in vitro we assessed the effect of different vitamin D metabolites (25(OH)D and 1,25(OH)D) on oxidative phosphorylation in differentiated C2C12 myocytes in cell culture.

Results: In vivo, high dose vitamin D improves the grip strength of both KO and WT mice (***=p < 0.001 by 2 way ANOVA for effects of diet with post-tests significant in both KO mice (**=p < 0.01) and WT mice (*=p < 0.05)). In vitro, 25(OH)D improves oxidative phosphorylation in C2C12 myocytes (**=p < 0.01 by one way ANOVA), while 1,25(OH)D has no significant effect (p>0.5). This effect of 25(OH)D is abrogated by knockdown of the vitamin D receptor and unchanged by knockdown of the 1-hydroxylase.

Conclusion(s): This result supports the novel and controversial model that 25(OH)D rather than 1,25(OH)D mediates metabolic benefits of high-dose dietary vitamin D. These results thus support high-dose dietary vitamin D supplementation to improve muscle mass and function in the context of diseases with chronic inflammation or GLP-1 receptor agonist treatment for obesity.

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