Purpose This review provides a current perspective on the mechanism of vitamin D on skeletal muscle function with the emphasis on oxidative stress, muscle anabolic state and muscle energy metabolism. It focuses on several aspects related to cellular and molecular physiology such as VDR as the trigger point of vitamin D action, oxidative stress as a consequence of vitamin D deficiency. Method The interaction between vitamin D deficiency and mitochondrial function as well as skeletal muscle atrophy signalling pathways have been studied and clarified in the last years. To the best of our knowledge, we summarize key knowledge and knowledge gaps regarding the mechanism(s) of action of vitamin D in skeletal muscle. Result Vitamin D deficiency is associated with oxidative stress in skeletal muscle that influences the mitochondrial function and affects the development of skeletal muscle atrophy. Namely, vitamin D deficiency decreases oxygen consumption rate and induces disruption of mitochondrial function. These deleterious consequences on muscle may be associated through the vitamin D receptor (VDR) action. Moreover, vitamin D deficiency may contribute to the development of muscle atrophy. The possible signalling pathway triggering the expression of Atrogin-1 involves Src-ERK1/2-Akt- FOXO causing protein degradation. Conclusion Based on the current knowledge we propose that vitamin D deficiency results from the loss of VDR function and it could be partly responsible for the development of neurodegenerative diseases in human beings.

Recent studies show that vitamin D deficiency may be responsible for muscle atrophy. The purpose of this study was to investigate markers of muscle atrophy, signalling proteins, and mitochondrial capacity in patients with chronic low back pain with a focus on gender and serum vitamin D level. The study involved patients with chronic low back pain (LBP) qualified for posterior lumbar interbody fusion (PLIF). Patients were divided into three groups: supplemented (SUPL) with vitamin D (3200 IU/day for 5 weeks), placebo with normal levels of vitamin D (SUF), and the placebo group with vitamin D deficiency (DEF). The marker of muscle atrophy including atrogin-1 and protein content for IGF-1, Akt, FOXO3a, PGC-1α, and citrate synthase (CS) activity were determined in collected multifidus muscle. In the paraspinal muscle, IGF-1 levels were higher in the SUF group as compared to both the SUPL and DEF groups (p<0.05). In the SUPL group, we found significantly increased protein content for pAkt (p<0.05) and decreased level of FOXO3a (p<0.05). Atrogin-1 content was significantly different between men and women (p<0.05). The protein content of PGC-1α was significantly higher in the SUF group as compared to the DEF group (p<0.05). CS activity in the paraspinal muscle was higher in the SUPL group than in the DEF group (p<0.05). Our results suggest that vitamin D deficiency is associated with elevated oxidative stress, muscle atrophy, and reduced mitochondrial function in the multifidus muscle. Therefore, vitamin D-deficient LBP patients might have reduced possibilities on early and effective rehabilitation after PLIF surgery.

The aim of this experimental study was to assess whether five weeks preoperative supplementation with vitamin D will affect the intensity of pain and level of inflammatory markers in patients undergoing posterior lumbar interbody fusion (PLIF) followed by rehabilitation. 42 patients were divided by double-blind randomization into two groups: supplemented (SUPL) vitamin D (3200 IU dose of vitamin D/day for 5 weeks) and placebo group (PL) treated with vegetable oil. The 10-week program of early rehabilitation (3 times a week) was initiated 4 weeks following PLIF. Measurements of serum 25(OH)D3 and CRP, IL-6, TNF-α, and IL-10 were performed. Pain intensity was measured using VAS. After supplementation with vitamin D serum concentration of 25(OH)D3 significantly increased in the SUPL group (*p<0.005) and was significantly higher as compared to the PL group (*p<0.001). Significant reduction in pain intensity was observed 4 weeks after surgery and after rehabilitation in both groups. In the SUPL group serum CRP and IL-6 concentration significantly decreased after rehabilitation compared with postsurgical level (ap<0.04). The level of TNF-α was significantly lower after rehabilitation only in the supplemented group (*p<0.02). There were no significant changes in IL-10 level in both groups during the study. Our data indicate that supplementation with vitamin D may reduce systemic inflammation and combined with surgery and early postsurgical rehabilitation may decrease the intensity of pain in LBP patients undergoing PLIF. Data indicate that LBP patients undergoing spine surgery should use vitamin D perioperatively as a supplement.

Recently, in terms of amyotrophic lateral sclerosis (ALS), much attention has been paid to the cell structures formed by the mitochondria and the endoplasmic reticulum membranes (MAMs) that are involved in the regulation of Ca²⁺ signaling, mitochondrial bioenergetics, apoptosis, and oxidative stress. We assumed that remodeling of these structures via swim training may accompany the prolongation of the ALS lifespan. In the present study, we used transgenic mice with the G93A hmSOD1 gene mutation. We examined muscle energy metabolism, oxidative stress parameters, and markers of MAMs (Caveolin‐1 protein level and cholesterol content in crude mitochondrial fraction) in groups of mice divided according to disease progression and training status. The progression of ALS was related to the lowering of Caveolin‐1 protein levels and the accumulation of cholesterol in a crude mitochondrial fraction. These changes were associated with aerobic and anaerobic energy metabolism dysfunction and higher oxidative stress. Our data indicated that swim training prolonged the lifespan of ALS mice with accompanying changes in MAM components. Swim training also maintained mitochondrial function and lowered oxidative stress. These data suggest that modification of MAMs might play a crucial role in the exercise‐induced deceleration of ALS development.