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 .
Efficacy of Vitamin D Supplementation in Multiple Sclerosis (EVIDIMS Trial): study protocol for a randomized controlled trial
Background Multiple sclerosis is the most common chronic inflammatory disease of the central nervous system in young adults . Despite the fact that numerous lines of evidence link both the risk of disease development and the disease course to the serum level of 25-hydroxyvitamin D it still remains elusive whether multiple sclerosis patients benefit from boosting the serum level of 25-hydroxyvitamin D , mainly because interventional clinical trials that directly address the therapeutic effects of vitamin D in multiple sclerosis are sparse . We here present the protocol of an interventional clinical phase II study to test the hypothesis , that high-dose vitamin D supplementation of multiple sclerosis patients is safe and superior to low-dose supplementation with respect to beneficial therapeutic effects . Methods / Design The EVIDIMS trial is a German multi-center , stratified , r and omized , controlled and double-blind clinical phase II pilot study . Eighty patients with the diagnosis of definite multiple sclerosis or clinical ly isolated syndrome who are on a stable immunomodulatory treatment with interferon-β1b will be r and omized to additionally receive either high-dose ( average daily dose 10.200 IU ) or low-dose ( average daily dose 200 IU ) cholecalciferol for a total period of 18 months . The primary outcome measure is the number of new lesions detected on T2-weighted cranial MRI at 3 tesla . Secondary endpoints include additional magnetic resonance imaging and optical coherence tomography parameters for neuroinflammation and -degeneration , clinical parameters for disease activity , as well as cognition , fatigue , depression , and quality of life . Safety and tolerability of high-dose vitamin D supplementation are further outcome parameters . Discussion In light of the discrepancy between existing epidemiological and pre clinical data on the one h and and available clinical data on the other the EVIDIMS trial will substantially contribute to the evaluation of the efficacy of high-dose vitamin D supplementation in MS patients . The study design presented here fulfills the criteria of a high- quality clinical phase II trial in MS.Trial Registration Clinical Trials.gov Identifier :
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 .