Vitamin D Deficiency In MS: What The Genetic Link Means
For nearly a decade researchers worldwide have been investigating a link between vitamin D deficiency and autoimmune diseases, particularly multiple sclerosis (MS). In patients with the autoimmune hyperthyroid disorder Graves' disease the link has been explored even further with evidence suggesting that genetic polymorphism of the vitamin D receptor sometimes seen in patients with Graves' disease prevents adequate absorption of the vitamin D hormone. Whether the problem in autoimmune diseases is one of poor vitamin D absorption or the fact that labs have difficulty measuring vitamin D effectively in general, a number of studies have shown that vitamin D levels are often deficient or inadequate in patients with multiple sclerosis and other autoimmune disorders. In 2008, after finding low levels of vitamin D in children with MS, the American Academy of Pediatrics raised the minimum amount of vitamin D recommended for children.
In the latest study reporting vitamin D deficiency in multiple sclerosis published in PLoS Genetics in February 2009, researchers from the University of Oxford and the University of British Columbia demonstrated a genetic link for this observed hormone deficiency. Previous studies have shown that the immune system gene HLA-DRB1 on chromosome 6 is commonly seen in patients with MS. Among Northern Europeans who have this gene, the most common variant, out of 400 possible variations, is HLA-DRB1*1501. Individuals with this allele have been reported to have a three-fold greater risk of developing MS.
University of Oxford researchers George Ebers and Julian Knight report in this study that HLA-DRB1*1501 contains a receptor or switch that is activated by one form of vitamin D. This switch or vitamin D response element is not seen in other variants or alleles of the HLA-DRB1 gene that are not associated with MS. The researchers hope that testing for this gene variant can help in showing risk for vitamin D deficiency associated with MS.
Like other immune system genes, HLA-DRB1 determines which protein antigens the immune system will react with, and it determines the severity of the immune system's response to a particular antigen. To further complicate matters, other HLA antigens can offer protection and prevent certain immune system reactions, particularly to the body's own proteins (the situation in autoimmune diseases), from occurring. If vitamin D deficiency in MS isn't a lab anomaly related to measuring the inactive hormone and it is truly related to disease development, the question still remains whether the problem is one of inadequate absorption of vitamin D or poor hormone conversion.
As a result of this study's release, sales of vitamin D supplements in Scotland, where the incidence of MS is the highest in the world, have skyrocketed. However, there's no data to show that supplements are the answer for vitamin D deficiency. In fact, in high doses supplements could make matters worse. In a study published in Science Daily in January 2008, Trevor Marshall, Ph.D. a professor at Australia's Murdoch School of Biological Medicine and Biotechnology reported that supplements of vitamin D3, the recommended form for supplements, can interfere with vitamin D's ability to react with the vitamin D receptor, altering the genetic expression of vitamin D. The Vitamin D receptor, a protein on cells that reacts with vitamin D molecules is involved in the repression or transcription of hundreds of genes associated with diseases ranging from cancers to multiple sclerosis. The Vitamin D receptor also regulates innate immunity particularly the body's natural antimicrobial peptides. By persistently activating the Vitamin D receptor with vitamin D3 supplements, other natural proteins are prevented from reacting with the vitamin D receptor. This ultimately suppresses the immune system. Marshall as well as other experts in the field suggest that a minimum daily exposure of 15 minutes to natural sunlight without the use of sunblock offers adequate protection against vitamin D deficiency.
The debate in clinical laboratories still continues over which form of vitamin D should be measured. Research suggests that tests for 25-OH Vitamin D3 may provide a better picture of vitamin D status. Roche introduced the first tests for 25-OH Vitamin D3 in the fall of 2008 and as this test becomes more popular, a different picture of vitamin D deficiency may emerge.