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 .
Safety and T Cell Modulating Effects of High Dose Vitamin D3 Supplementation in Multiple Sclerosis
Background A poor vitamin D status has been associated with a high disease activity of multiple sclerosis ( MS ) . Recently , we described associations between vitamin D status and peripheral T cell characteristics in relapsing remitting MS ( RRMS ) patients . In the present study , we studied the effects of high dose vitamin D3 supplementation on safety and T cell related outcome measures . Methodology /Principal Findings Fifteen RRMS patients were supplemented with 20 000 IU/d vitamin D3 for 12 weeks . Vitamin D and calcium metabolism were carefully monitored , and T cell characteristics were studied by flowcytometry . All patients finished the protocol without side-effects , hypercalcaemia , or hypercalciuria . The median vitamin D status increased from 50 nmol/L ( 31–175 ) at week 0 to 380 nmol/L ( 151–535 ) at week 12 ( P<0.001 ) . During the study , 1 patient experienced an exacerbation of MS and was censored from the T cell analysis . The proportions of ( naïve and memory ) CD4 + Tregs remained unaffected . Although Treg suppressive function improved in several subjects , this effect was not significant in the total cohort ( P = 0.143 ) . An increased proportion of IL-10 + CD4 + T cells was found after supplementation ( P = 0.021 ) . Additionally , a decrease of the ratio between IFN-γ+ and IL-4 + CD4 + T cells was observed ( P = 0.035 ) . Conclusion / Significance Twelve week supplementation of high  dose vitamin D3 in RRMS patients was well tolerated and did not induce decompensation of calcium metabolism . The skewing towards an anti-inflammatory cytokine profile supports the evidence on vitamin D as an immune-modulator , and may be used as outcome measure for upcoming r and omized placebo-controlled trials . Trial Registration Clinical trials.gov
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 .