Effects of Vitamin D Supplementation on Overload‐Induced Muscle Growth and Function in Mice

Muscle hypertrophy induced by functional overload (FO) provides an in vivo model to study muscle growth. Research suggests vitamin D supplementation may stimulate muscle growth and may be associated with increased growth factor levels, such as insulin-like growth factor-1 (IGF-1), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF). However, it is unclear if vitamin D impacts both muscle hypertrophy and contractile function. We hypothesized that vitamin D supplementation would positively impact the muscle response to a growth stimulus as evidenced by greater hypertrophy, increased IGF-1, FGF, and VEGF levels, and improved contractile function compared to placebo. Adult mice underwent functional overload (FO) of the plantaris or sham surgery. In vivo plantaris force and fatigue resistance (% of maximal force after 10 contractions) were measured 14d post-FO or sham in mice receiving daily vitamin D or placebo (n= 8-10/group). IGF-1, FGF, and VEGF were measured in the plantaris by ELISA. FO increased plantaris mass, independent of treatment (placebo: 22.8±1.7 vs. 13.4±1.3 and vitamin D: 20.3±3.3 vs. 13.2±0.7 mg, for FO and sham, respectively, p<0.05). Maximal force relative to body mass was unchanged with FO or vitamin D. Significant main effects of FO and vitamin D were found when maximal force was normalized to plantaris mass. With placebo, FO was associated with a significant decrease in force normalized to plantaris mass while vitamin D attenuated this decrease (placebo: 401±48 vs. 871±157 and vitamin D: 679±125 vs. 1062±120 g/g muscle, for FO and sham, respectively, p<0.05). Fatigue resistance was increased with FO, independent of treatment (placebo: 54±3% vs. 40±4% and vitamin D: 63±5% vs. 33±6%, for FO and sham, respectively, p<0.05). IGF-1 levels were increased in the overloaded plantaris, independent of treatment (placebo: 842±284 vs. 99±9 and vitamin D: 576±138 vs. 115±10 mg/mg, for FO and sham, respectively, p<0.05), but were unchanged in the unloaded tibialis anterior. FGF levels were increased in the overloaded plantaris, independent of treatment (placebo: 378±56 vs. 105±37 and vitamin D: 414±58 vs. 153±82 mg/mg, for FO and sham, respectively, p<0.05). VEGF levels were unchanged with FO and/or Vitamin D. Vitamin D treatment in combination with FO did not significantly improve the ability of skeletal muscle to hypertrophy or increase growth factor expression in response to a growth stimulus. However, vitamin D supplementation may positively impact muscle strength during periods of growth.