RESULTS / DISCUSSION Both cross-sectional and longitudinal studies have fairly consistently demonstrated a strong positive correlation between  vitamin D deficiency and subsequent relapse and /or disability in patients with MS .
As well , there appears to be a negative correlation between vitamin D levels and inflammatory markers in MS patients , suggesting that vitamin D modifies serum cytokines to a more anti-inflammatory profile .
However , the criteria of temporality , dose-response , and experimental evidence are yet to be adequately met , although there is preliminary evidence from longitudinal studies and r and omized clinical trials ( RCTs ) of supplementation that vitamin D can attenuate the autoimmune response in patients , and potentially reduce relapse rates and burden of disease .
Ultimately , the current evidence does not permit inference of a causal relationship between vitamin D deficiency and disease activity in MS .
INTRODUCTION Given that vitamin D has a role in immunomodulation , and its levels appear to correlate with the development of Multiple Sclerosis ( MS ) , it is conceivable that vitamin D may also influence disease activity in MS patients .
In this regard , we conducted a systematic review investigating the evidence for : ( 1 ) the role of vitamin D in disease activity in MS , and ( 2 ) the therapeutic supplementation of vitamin D in MS .
Vitamin D-mediated immune regulation in Multiple Sclerosis
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 clinical ly 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
RESULTS / DISCUSSION Both cross-sectional and longitudinal studies have fairly consistently demonstrated a strong positive correlation between  vitamin D deficiency and subsequent relapse and /or disability in patients with MS .
As well , there appears to be a negative correlation between vitamin D levels and inflammatory markers in MS patients , suggesting that vitamin D modifies serum cytokines to a more anti-inflammatory profile .
However , the criteria of temporality , dose-response , and experimental evidence are yet to be adequately met , although there is preliminary evidence from longitudinal studies and r and omized clinical trials ( RCTs ) of supplementation that vitamin D can attenuate the autoimmune response in patients , and potentially reduce relapse rates and burden of disease .
Ultimately , the current evidence does not permit inference of a causal relationship between vitamin D deficiency and disease activity in MS .
INTRODUCTION Given that vitamin D has a role in immunomodulation , and its levels appear to correlate with the development of Multiple Sclerosis ( MS ) , it is conceivable that vitamin D may also influence disease activity in MS patients .
In this regard , we conducted a systematic review investigating the evidence for : ( 1 ) the role of vitamin D in disease activity in MS , and ( 2 ) the therapeutic supplementation of vitamin D in MS .