In a new animal model, researchers in France report on a detailed look at how and if vitamin D plays a role in nervous system:
In a past study, this same research group found that vitamin D improved nerve regeneration after injury and increased the diameter of nerve fibers in rats. While the results of this previous study were exciting, the researchers wanted to explore this animal model further before recommending that the same type of research be carried out in humans, too.
In particular, they wanted to know which form of vitamin D was most effective, how much and how safe different doses are, and which genes would be affected by vitamin D.
First, the researchers divided the rats into six groups:
- Low dose D2 (100 IU/kg/day)
- High dose D2 (500 IU/kg/day)
- Low dose D3 (100 IU/kg/day)
- High dose D3 (500 IU/kg/day)
Taking 500 IU of vitamin D per kilogram of body weight per day is equivalent to a 220 pound adult male taking 50,000 IU of vitamin D per day. While this is a lot, the authors noted that in a previous study, multiple sclerosis patients took similar doses of vitamin D per day for years at a time and did not show signs of toxicity.
At the start of the trial, the researchers injured the rats’ nerves and immediately put them on their respective vitamin D regimens. After three months of taking vitamin D, the researchers mimicked muscle fatigue in the rats by electrically stimulating their leg muscles.
The researchers investigated many parameters, but I will list the most exciting and clinically relevant results here.
Only the rats receiving high dose D3 had statistically and clinically significant improvements in their muscle recovery and their ability to move after their nerve injury. The results in the high dose D3 group were so dramatic the researchers noted that the recovered rats differed little from the rats in the control group.
After three months, the rats taking high dose D3 not only had more nerve fibers, their nerve fibers were larger and more myelinated than the nerves of rats in the other groups. The rats on the 500/IU/kg/day dose of D3 had an average 25(OH)D level of 120 ng/mL, which is higher than the normal range. However, it is not quite high enough to induce toxicity, and to no surprise, no evidence of toxicity at any of the vitamin D doses was observed.
In order to determine which genes were being affected by vitamin D treatment, the researchers cultured nerve cells with activated vitamin D to see if any changes in gene expression occurred. They found that the addition of vitamin D to the nerve cells up or down-regulated the expression of 40 genes involved in nerve cell generation and myelination. The researchers attributed the dramatic recovery of the rats in the D3 group to improved myelination and noted that vitamin D can be considered neuroprotective.
The authors of the study concluded that vitamin D3 was equally or more potent than D2 at the same dose for almost every parameter examined. While the results of their previous study indicated administration of D2 produced a modest recovery in nerve-injured rats, the authors noted substituting vitamin D3 for D2 produced a “dramatic improvement” in recovery from nerve injury, especially at the higher doses.
The interesting results of this study led the researchers to conclude,
“Altogether, our data pave the way for a randomised controlled trial in patients with a peripheral nerve injury.”
The potential of high dose vitamin D3 to improve the myelination of nerve cells has very important implications for patients with demyelinating diseases, such as multiple sclerosis (MS). Two large, high-quality trials of high dose D3 in MS patients are currently underway, and hopefully similar trials evaluating the role of D3 in patients with peripheral nerve injury will also be conducted.