Stein et al.1 compared high- vs low-dose vitamin D2 treatment in MS without benefit in the high-dose treatment group. Sunlight exposure and reduced vitamin D3 levels independently contribute to MS risk. The effect of sunlight exposure is supported by decreased signs of actinic skin damage found in MS patients compared to controls.2 It is difficult to determine which of these 2 environmental factors is of primary importance as higher levels of sunlight exposure will enhance vitamin D levels.
The incidence of vitamin D–related rickets disease decreased in the United States and Europe during the last century following the discovery that vitamin D possessed antirachitic properties, whereas the incidence of MS seemed to increase in the same population. In the United States, most of the patients with rickets are African American, whereas the majority of patients with MS are of European ancestry.3 It seems improbable that the same environmental factor should be centrally involved in the etiology of both diseases, which differ clinically and occur in different populations living in the same geographic area.
These findings together with those of Stein et al. do not provide a reason for vitamin D supplementation in MS aside from correcting a proven vitamin D deficiency. Other factors associated with increased sunlight exposure may more effectively prevent MS.
The conclusion of Stein et al.1 that high-dose ineffective vs low-dose vitamin D2 supplementation in relapsing-remitting MS (RRMS) is not supported by data enabling level 1 evidence.
Randomization to interferon-β, glatiramer acetate, or no treatment results in very small treatment groups. Such MRI-based randomized placebo-controlled trials would need at least 85 patients per arm to reach statistical significance, assuming 50% treatment difference4 and, since vitamin D effects may appear after 12–24 weeks, an MRI follow-up period of at least 9—not 6—months.
In figure 2, only 4/11 subjects in the higher dose group exhibited 25(OH)D levels within the 130–175 nmol/L target range.1 Since dosages must have been adjusted continuously throughout the trial, likely fluctuations in serum 25(OH)D prevent firm conclusions.5
During the study, MKTVIF75HV (vitamin D2) was replaced by vitamin D3. As vitamin D2 and D3 are not equivalent,5 these results cannot be extended to all “vitamin D” subtypes.
To address these issues, an appropriately powered, randomized, double-blind, placebo-controlled, phase II study (SOLAR) of high-dose vitamin D3 (vigantol oil, 14,000 IU/d) add-on to interferon β–1a, 44 μg subcutaneously 3 times weekly (Rebif), for 96 weeks in 348 RRMS patients, is currently under way.6
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