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Vitamin D and the higher incidence of autoimmune diseases in women
It has long been observed that autoimmune diseases like lupus and multiple sclerosis are more common in women than in men. Other related chronic conditions such as osteoporosis, osteoarthritis and chronic fatigue syndrome are also much more common in women as well. Two research papers published in the upcoming September, 2009 special issue of the Annals of the New York Academy of Sciences, titled Contemporary Challenges in Autoimmunity, show a possible connection that involves vitamin D and how it is metabolized in the body.
Vitamin D (also called cholecalciferol) is important in both men and women, and at first glance it would seem that it should behave the same way in both sexes. It has no role in sex-specific hormonal regulation like some of the sex hormones, but it has recently been discovered that a special molecule, called a receptor, that binds to one of the forms of vitamin D is more abundant in women than men. The receptor to which vitamin D binds is important in the activation of the innate immune response.
The vitamin D receptor (VDR) is found in the nucleus of certain cells throughout the body. Recently it was discovered that women have more of these receptors, because in addition to all the same kinds of cells shared with men, they also have VDRs in endometrial cells. Endometrial cells, which comprise the lining of the uterus, are cyclical. Therefore, the number of VDRs fluctuates in sync with the menstrual cycle.
1,25-D, also called calcitriol. This is the form of vitamin D that binds to vitamin D receptors (VDRs). Source: Wikipedia.
to how vitamin D plays its part is to understand what the VDR does. When the correct form of vitamin D (a form known as 1,25-D or calcitriol) binds to VDR, VDR then directly causes the expression of over 900 genes to occur. Two of the genes that are turned on produce proteins that are directly responsible for kicking the immune response into active mode. The reason for VDR in the endometrium is that it provides protection against infection for the developing fetus.
Another key to the puzzle has been the growing evidence that bacteria may play a role in the development of autoimmune disease. If so, why wouldn’t women, who have more VDRs, be better off than men? The problem is that bacteria of various kinds can interfere with VDRs and prevent vitamin D from binding. If vitamin is unable to bind, then the immune response is disrupted. Not only is the immune system affected, but thyroid hormone problems can result too.
Although these results do not provide a clear path to treatment, “the potential role of persistent pathogens in autoimmune disease mandates reconsideration of the use of corticosteroids as a first-line treatment for many autoimmune diseases. Corticosteroids effectively reduce the ability of the immune system to respond to pathogens, including persistent microbiota, which is counterproductive to recovery.”
As a result of the dysregulation of VDRs blood levels of the 1,25-D form of vitamin D increase, because less 1,25-D is binding. “Given the potential benefits of serum 1,25-D as a clinical marker both in the diagnosis and monitoring of treatment response, further research is warranted. If elevated levels of 1,25-D continue to be associated with an inflammatory disease state, 1,25-D could be used as a reliable marker of the autoimmune disease process.”
Amy D. Proal, Paul J. Albert, and Trevor G. Marshall. 2009. Dysregulation of the Vitamin D Nuclear Receptor May Contribute to the Higher Prevalence of Some Autoimmune Diseases in Women, In Contemporary Challenges in Autoimmunity. Annals of the New York Academy of Sciences 1173: 252–259.
Greg P. Blaney, Paul J. Albert, and Amy D. Proal. 2009. Vitamin D Metabolites as Clinical Markers in Autoimmune and Chronic Disease, In Contemporary Challenges in Autoimmunity. Annals of the New York Academy of Sciences 1173: 384–390