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 .
[Effects of alfacalcidol therapy on serum cytokine levels in patients with multiple sclerosis].
Multiple sclerosis ( MS ) is a consequence of genetic and environmental factors . Geographic , genetic , and biological evidence suggests that an important immunopathogenic factor might be the insufficiency of vitamin D. The aim of our study was to investigate the immunomodulatory effect of alfacalcidol , a vitamin D analogue , on cytokine levels in RRMS patients in relapse . We investigated 15 patients suffering from RRMS relapse ( an RRMS group ) and two control groups : one control group of healthy subjects ( n=10 ) and a NIND group , consisting of patients with non-inflammatory neurological diseases ( n=10 ) . All of the MS patients were treated with 5 microgr/day of oral alfacalcidol for a period of five days . The serum cytokine levels of TNF-alpha , IL-10 , IL-4 , and IL-12 were measured in all the MS patients one day prior to and one day after therapy , and in all the control subjects ( ELISA , Quantikine human immunoassay , R&D Systems , UK ) . Our results showed significantly lower IL-4 and IL-12 levels in the RRMS patients group compared to the N group and the NIND group ( p<0.001 Mann-Whitney U-test ) . No significant differences in TNF-alpha and IL-10 levels were found between the groups , and there was no influence of alfacalcidol on these cytokines in RRMS patients . High doses of oral alfacalcidol induced significant increases in IL-4 and IL-12 levels in RRMS patients ( p<0.001 , Wilcoxon rank signed test ) . Therefore , there were no differences in IL-4 and IL-12 levels compared to the N group and the NIND group . Alfacalcidol therapy in RRMS patients did not provoke any side effects .  Vitamin D and its analogues , such as alfacalcidol , act as immunomodulatory agents , with potential therapeutic effects for patients with multiple sclerosis
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 .