A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis.
Stein et al, Neurology, October 25, 2011
OBJECTIVE: Higher latitude, lower ultraviolet exposure, and lower serum 25-hydroxyvitamin D (25OHD) correlate with higher multiple sclerosis (MS) prevalence, relapse rate, and mortality. We therefore evaluated the effects of high-dose vitamin D2 (D2) in MS.
METHODS: Adults with clinically active relapsing-remitting MS (RRMS) were randomized to 6 months’ double-blind placebo-controlled high-dose vitamin D2, 6,000 IU capsules, dose adjusted empirically aiming for a serum 25OHD 130-175 nM. All received daily low-dose (1,000 IU) D2 to prevent deficiency. Brain MRIs were performed at baseline, 4, 5, and 6 months. Primary endpoints were the cumulative number of new gadolinium-enhancing lesions and change in the total volume of T2 lesions. Secondary endpoints were Expanded Disability Status Scale (EDSS) score and relapses.
RESULTS: Twenty-three people were randomized, of whom 19 were on established interferon or glatiramer acetate (Copaxone) treatment. Median 25OHD rose from 54 to 69 nM (low-dose D2) vs 59 to 120 nM (high-dose D2) (p = 0.002). No significant treatment differences were detected in the primary MRI endpoints. Exit EDSS, after adjustment for entry EDSS, was higher following high-dose D2 than following low-dose D2 (p = 0.05). There were 4 relapses with high-dose D2 vs none with low-dose D2 (p = 0.04).
: We did not find a therapeutic advantage in RRMS for high-dose D2 over low-dose D2 supplementation. Classification of evidence: This study provides Class I evidence that high-dose vitamin D2 (targeting 25OHD 130-175 nM), compared to low-dose supplementation (1,000 IU/d), was not effective in reducing MRI lesions in patients with RRMS.
“This study is the first published randomised double blind controlled trial of vitamin D supplementation in MS. Disappointingly it did not show that taking higher doses of vitamin D can protect against MS disease activity. However, several features of this study mean that further work is still needed to test whether vitamin D is an effective treatment or not. This study was very small (20 patients- as compared to trials such as Alemtuzumab using 500- the more patients you have the more likely you are able to see whether a treatment works); both groups of patients were taking more vitamin D than the UK Government recommend per day (6000IU of vitamin D a day versus 1000IU) so the control group may have had some protection as well; the study was run for 6 months which is thought to be too short to really say whether there is a meaningful effect of treatment, and the investigators used vitamin D2 instead of the more active D3. All of this being said, the study raises the question of whether vitamin D deficiency is only involved in triggering MS and not in how the disease progresses; but we need to test this appropriately.”