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Exercise may ameliorate the detrimental side effects of high vitamin D supplementation on muscle function in mice

Debruin DA1,2, Timpani CA1,2, Lalunio H1,3, Rybalka E1,2, Goodman CA1,2,4, Hayes A1,2,3.

J Bone Miner Res. 2020 Feb 20. doi: 10.1002/jbmr.3985. [Epub ahead of print]

Vitamin D (VitD) is commonly prescribed to normalise deficiencies and to treat osteoporosis. However, the effect VitD supplements have on skeletal muscle health is equivocal. While VitD is known to play a role in the various processes that maintain muscle integrity and function, recent studies utilising high bolus dose VitD supplementation has demonstrated an increased risk of falls. Thus, the aim of this study was to investigate the effects of high VitD supplementation on skeletal muscle function with and without exercise enrichment. Four-week old C57BL/10 mice (n = 48) were separated into either normal VitD (1500 IU/kg diet; unsupplemented) or high VitD (20,000 IU/kg diet; supplemented) treatment groups. Each dietary group was further separated into interventional sub-groups where mice either remained sedentary or received exercise-enrichment for eight weeks in the form of voluntary running. Following the intervention period, whole body in vivo and ex vivo contractile analysis were performed. High VitD supplementation decreased force production in the slow-twitch soleus muscles of sedentary mice (p < 0.01), however exercise normalised this effect. Eight weeks of exercise did not improve fatigue resistance of the extensor digitorum longus (EDL) or soleus muscles in unsupplemented mice, likely due to low levels of activation in these muscles. In contrast, fatigability was improved in the EDL (p < 0.01) and even more so in the soleus (p < 0.001) in the supplemented exercise-enriched group. Our data highlights that increasing VitD levels above normal reduces postural muscle force as seen in the soleus. Thus, unnecessary VitD supplementation may contribute to the increased risk of falls observed in some studies. Interestingly, when VitD supplementation was combined with exercise, force production was effectively restored, and fatigue resistance improved, even in muscles lowly activated. Regular exercise may modulate the effects of VitD on skeletal muscle, and be recommended for individuals receiving VitD supplements.