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 .
Interferon-β and serum 25-hydroxyvitamin D interact to modulate relapse risk in MS
Objective : To determine whether interferon-β ( IFN-β ) medication use is associated with vitamin D levels and whether the two interact in exerting effects on relapse risk . Methods : In a prospect i ve cohort of 178 persons with clinical ly definite multiple sclerosis ( MS ) living in southern Tasmania in 2002–2005 ,  serum 25-hydroxyvitamin D [ 25(OH)D ] was measured biannually , with assessment by question naire for relevant factors , including IFN-β treatment . Results : Subjects reporting IFN-β use had significantly higher mean 25(OH)D than persons who did not ( p < 0.001 ) . This was mediated by an interaction between personal sun exposure and IFN-β , with treated persons realizing nearly three times 25(OH)D per hour of sun exposure of persons not on therapy . The association between 25(OH)D and 1,25-dihydroxyvitamin D did not differ by IFN-β therapy ( p = 0.82 ) . 25(OH)D was associated with a reduced relapse risk only among persons on IFN-β ( p < 0.001 ) . Importantly , IFN-β was only protective against relapse among persons with higher 25(OH)D ( hazard ratio [ HR ] 0.58 [ 95 % confidence interval ( CI ) 0.35–0.98 ] ) , while among 25(OH)D-insufficient persons , IFN-β  increased relapse risk ( HR 2.01 [ 95 % CI 1.22–3.32 ] ) . Conclusion : In this study , we found that IFN-β therapy is associated with greater production of vitamin D from sun exposure , suggesting part of the therapeutic effects of IFN-β on relapse in MS may be through modulation of vitamin D metabolism . These findings suggest persons being treated with IFN-β should have vitamin D status monitored and maintained in the sufficiency range . Classification of evidence : This study provided Class III evidence that IFN-β is associated with reduced risk of relapse , and this effect may be modified by a positive effect of IFN-β on serum 25(OH)D levels
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 .