Muscles starve/waste in the absence of vitamin D

As turns out, yet again, vitamin D is far from being the simple “bone vitamin” as most TV/online commercials would have us believe. It is actually a (seco)steroid and has already been implicated in a host of metabolic and immune process affecting virtually every disease. Recently, I posted a few studies demonstrating that vitamin D has an anti-catabolic effect on muscles, as well as protective effects on liver against the harm caused by excess cortisol. The study below now demonstrated that vitamin D has an even more basic metabolic function when it comes to muscle health – i.e. allowing the muscles to utilize the glycogen stored inside them. As the study shows, without sufficient vitamin D, the muscles synthesize a lot of glycogen but cannot use it, and this creates a state of “glucose deficiency”, which triggers cortisol release and subsequent muscle breakdown/wasting despite plenty of energy being stored in the actual muscle. I wonder if this is one of the mechanisms implicated in type II diabetes – i.e. plenty of glycogen in the muscles yet very low levels of muscle protein synthesis and, often, even sarcopenia.

https://pubmed.ncbi.nlm.nih.gov/34877816/

https://www.thehindu.com/sci-tech/science/muscles-starve-in-the-absence-of-vitamin-d-study-of-mice-finds/article38275243.ece

“…Initially, scientists suspected that the absence of VDR is preventing the synthesis of glycogen from the food. “We checked whether the energy deprivation in skeletal muscles is associated with differences in glycogen levels,” says Dr. Aneeshkumar. To their surprise, VDR knockout mice had higher glycogen levels than the control ones. “We found that the glycogen synthase, the key enzyme that converts glucose into glycogen, was having a field day without the inhibitory enzymes active”. More and more glycogen was being produced and stored in the skeletal muscle. Nevertheless, the glycogen phosphorylase, an enzyme that converts glycogen to glucose when energy is needed, was significantly lower. “As a result, while muscle continued to make glycogen, none of it could be converted back to glucose resulting in energy deficiency,” explains Dr. Aneeshkumar. Even with abundant glycogen present, the skeletal muscle could not extract the energy in the absence of vitamin D. “From this research, we think we have found the molecular mechanism by which the vitamin D deficiency leads to muscle wasting. Without vitamin D, glycogen storage cannot be utilised for glucose production. When the glycogen storage does not give energy, particularly in a post-absorb state, the skeletal muscle draws more glucose from the blood. This leads to a systemic energy shortage. When there is systemic lack of energy, like during hunger, the protein degradation in muscle is triggered leading to muscle wasting,” explains Dr. Aneeshkumar.”