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 .
Effect of vitamin D3 supplementation on relapses, disease progression, and measures of function in persons with multiple sclerosis: exploratory outcomes from a double-blind randomised controlled trial
Background : High vitamin D levels may reduce the risk of relapses and disease progression in multiple sclerosis . Methods : This 96-week r and omised controlled trial was design ed to assess the effect of vitamin D3 supplementation on bone mineral density in persons with multiple sclerosis . Supplementation with 20,000 IU vitamin D3 weekly raised median serum 25-hydroxy vitamin D ( 25[OH]D ) to 121 nmol/L. The modified intention to treat analysis included 35 persons in the vitamin D3 group and 33 in the placebo group . Participants were age 21 to 50 years and fully ambulatory ( median Exp and ed Disability Status Scale ( EDSS ) 2.5 ) . We studied the effect of supplementing vitamin D3 on the exploratory outcomes annualised relapse rate ( ARR ) , EDSS , multiple sclerosis functional composite ( MSFC ) components , grip strength , and fatigue . Results : After 96 weeks , there was no significant difference between groups in ARR ( absolute difference 0.10 , 95 % CI -0.07 to 0.27 ; p = 0.25 ) , EDSS ( absolute difference -0.01 , 95 % CI -0.35 to 0.35 ; p = 0.97 ) , MSFC components , grip strength , or fatigue . Conclusion : Supplementation with 20,000 IU vitamin D3 weekly did not result in beneficial effects on the measured multiple sclerosis-related outcomes . This study was not powered to address clinical outcomes , but none of the results were suggestive of an effect in this unselected population of fully ambulatory persons 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 .