Although Vitamin D is best known as a modulator of calcium homeostasis, it also has immune modulating potential. A protective effect of Vitamin D on Multiple Sclerosis (MS) is supported by the reduced risk associated with sun exposure and use of Vitamin D supplements. Moreover, high circulating levels of Vitamin D have been associated with lower risk of MS. To gain more insight into putative regulatory mechanisms of Vitamin D in MS pathogenesis, we studied 132 Hispanic patients with clinically definite MS, 58 with relapsing remitting MS (RR MS) during remission, 34 RR MS patients during relapse, and 40 primary progressive MS cases (PP MS). Sixty healthy individuals matched with respect to place of residence, race/ethnicity, age and gender served as controls. Levels of 25(OH) Vitamin D and 1,25(OH)(2) Vitamin D, measured by ELISA were significantly lower in RR MS patients than in controls. In addition, levels in patients suffering relapses were lower than during remissions. By contrast, PP MS patients showed similar values to controls. Proliferation of both freshly isolated CD4+ T cells and MBP-specific T cells was significantly inhibited by 1,25(OH)(2) Vitamin D. Moreover, activated Vitamin D enhanced the development of IL-10 producing cells, and reduced the number of IL-6 and IL-17 secreting cells. Notably, VDR expression was induced by 1,25(OH)(2) Vitamin D in both activated and resting cells. Interestingly, T cells were able to metabolize 25(OH) Vitamin D into biologically active 1,25(OH)(2) Vitamin D, since T cells express 1α-hydroxylase constitutively. Finally, 1,25(OH)(2) Vitamin D also increased the expression and biological activity of IDO, triggering significant increase in the number of CD4+CD25+ T regulatory cells. Collectively, these findings suggest that 1,25(OH)(2) VitaminD plays an important role in T cell homeostasis during the course of MS, suggesting correction of its deficiency may be useful during treatment of the disease.
High exposure to vitamin D may protect against development and progression of multiple sclerosis (MS), possibly through the immunomodulatory properties of its biologically active metabolite 1,25-dihydroxyvitamin D. So far, most studies on the possible mechanisms for vitamin D involvement in MS have focused on immune modulation outside the central nervous system (CNS). However, vitamin D may also interfere with the pathophysiology of MS within the CNS. In this review, the potential presence and functions of vitamin D in the inflamed and healthy CNS are explored. We discuss that vitamin D, vitamin D binding protein (DBP), the vitamin D receptor (VDR) and enzymes needed for metabolism (CYP27B1) are present in the CNS. Both VDR and CYP27B1 are expressed on a variety of cells, including neurons, glial cells, and invading lymphocytes. Additionally, vitamin D has been postulated to play a modulating role in several key-processes in MS pathophysiology, including inflammation, demyelination, axonal damage, and remyelination. We conclude that a local role of vitamin D in the inflamed CNS is likely and potentially relevant to MS. Future studies should further characterize the impact of vitamin D on the local disease process of MS in the CNS.
Loumalone wrote:Thanks for that,
how do you get that much vitamin D per day? I take 4x1000iu (the strongest ones ive found), how do you get that much? For all the vit D findings that are coming up i can't find a simple recommended dosage, and I don't understand most of the science above, sorry!
In summary, the Christakos-Steinman team is the first to identify the molecular mechanisms by which vitamin D down-regulates autoimmune phenotypes characteristic of MS and EAE. They demonstrated that the active form of vitamin D represses IL17A transcription by blocking NFAT, recruiting HDAC, complexing with the VDR and sequestering RUNX1, and inducing FOXP3. Their work provides a much needed framework for initiating clinical trials to test the efficacy of vitamin D or its analogs in fighting MS and other autoimmune diseases.
These results demonstrate the safety of taking 5,000U or 10,0000U of vD3 per day and the importance of measuring blood levels of vD3 to ensure that the dose taken is adequate to achieve optimal blood levels.
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