The results of studies in mice suggest that vitamin D deficiency may impair muscle mitochondrial function, impacting on energy production in muscle cells and so potentially affecting muscle performance and recovery. While further research will be required, the newly reported studies, headed by Andrew Philp PhD, and his team at the Garvan Institute of Medical Research, suggest that preventing vitamin D deficiency in older adults could feasibly help to maintain better muscle strength and function, and reduce age related muscle deterioration.

“Our results show there is a clear link between vitamin D deficiency and oxidative capacity in skeletal muscle,” Philp commented. “They suggest that vitamin D deficiency decreases mitochondrial function, as opposed to reducing the number of mitochondria in skeletal muscle. We are particularly interested to examine whether this reduction in mitochondrial function may be a cause of age related loss in skeletal muscle mass and function.”

The Garvan Institute team and collaborators report on their findings in the Journal of Endocrinology, in a paper titled, “Diet-Induced Vitamin D Deficiency Reduces Skeletal Muscle Mitochondrial Respiration.”

Vitamin D is a hormone that is known to be important for maintaining bone health, and preventing rickets and osteoporosis. But it’s been estimated that the prevalence of vitamin D deficiency could be up to 40% among European populations, and reports suggest that reduced levels could be linked with an increased risk for conditions including COVID-19, cancer, and diabetes. Vitamin D deficiency is characterized by serum 25-hydroxyvitamin D (25(OH)D) levels of <50 nmol.L-1.

While the classical actions of vitamin D in the maintenance of bone health are well established, the authors wrote, “ … a number of non-classical associations have recently been identified, including the maintenance of skeletal muscle function. Multiple studies have also linked low vitamin D levels to poor muscle strength, particularly in older people. “Vitamin D deficiency is associated with symptoms of skeletal muscle myopathy including muscle weakness and fatigue,” the authors wrote. Prior research has suggested that reduced muscle strength in people with vitamin D deficiency may be linked with impaired muscle mitochondrial function. However, these types of studies have only been able to make associations, and not infer causality, the researchers continued.

Determining the role of vitamin D in muscle performance of older people is difficult, as individuals may suffer from a number of pre-existing health conditions that can also affect vitamin D status. This means that previous studies have been unable to determine how vitamin D may directly affect muscle performance.

Philp and colleagues turned to a mouse model to investigate the effects of diet-induced vitamin D deficiency on skeletal muscle mitochondrial function in young, male animals. The mice were fed a diet with either normal quantities of vitamin D, or with no vitamin D to induce deficiency, for a period of three months. A typical vitamin D level for humans is 40-50 nmol.L-1, and acute vitamin D deficiency is diagnosed when levels drop below 12 nmol.L-1. On average, the mice in this study had vitamin D levels of 30 nmol.L-1, with diet-induced vitamin D deficiency leading to levels of just 3 nmol.L-1. While this level was more extreme than typically observed in people, it is still within the clinically recognized range.

Tissue and blood samples were collected from the animals monthly to quantify vitamin D and calcium concentrations and to assess markers of muscle mitochondrial function and number. The results showed that after three months of diet-induced vitamin D deficiency, skeletal muscle mitochondrial function was impaired by up to 37%. This was not due to a reduced number of mitochondria or to reduced muscle mass. “Interestingly, despite the functional changes, we observed no differences in mitochondrial protein content following the induction of diet-induced vitamin D deficiency,” the team added.

The findings suggested that vitamin D deficiency may impair mitochondrial function and reduce the amount of energy produced in the muscles, which could lead to poor muscle function. Preventing vitamin D deficiency in older people might then help to maintain muscle performance and reduce the risk of muscle related diseases, such as sarcopenia. “ … our data provides evidence that vitamin D status is an important determinant of skeletal muscle mitochondrial function in vivo thereby supporting previous in vitro observations,” the investigators concluded. “Our data, when combined with previous in vitro observations, suggests that vitamin D mediated regulation of mitochondrial function may underlie the exacerbated muscle fatigue and performance deficits observed during vitamin D deficiency.”

They acknowledged that further studies designed to investigate the direct effect of vitamin D deficiency on muscle function and strength will be needed. While the reported work indicates that vitamin D deficiency can alter mitochondrial function in skeletal muscle, Philp and colleagues were unable to determine precisely how this process occurred.

Their future work aims to establish how vitamin D deficiency alters mitochondrial control and function in skeletal muscle. As the authors commented, “The further examination of mitochondrial function in such mouse models would help to determine whether the effects of vitamin D deficiency upon skeletal muscle mitochondrial function are a direct result of vitamin D-related signaling.”

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