High-dose vitamin D in multiple sclerosis

Background

Previous studies suggested that a deficiency of vitamin D is a risk factor for developing multiple sclerosis (MS) and is also associated with increased disease activity in patients with MS. However, there is uncertainty as to the therapeutic benefits of vitamin D. This study evaluated the efficacy of high-dose vitamin D therapy in reducing disease activity in patients with clinically isolated syndrome (CIS) that is typical for MS.

Methods

The D-Lay MS trial was a randomized, double-blind, placebo-controlled clinical trial involving adult patients (age, 18-55 years) with the following:

• CIS <90 days’ duration;
• Serum vitamin D levels <100 nmol/L;
• Diagnostic magnetic resonance imaging (MRI) 2010 criteria for dissemination in space or ≥2 lesions;
• Positive oligoclonal bands.

Patients received vitamin D₃ (cholecalciferol) 100,000 IU orally or matching placebo every 2 weeks for 24 months. The primary outcome was MS disease activity, which was defined as occurrence of a relapse, MRI activity (new and/or contrast-enhancing lesions), or both. These outcomes were analyzed separately as secondary outcomes.

Results

Of a total of 316 participants randomized, with a median (interquartile range) age of 34 (28-42) years and 70% female, the primary analysis included 303 (95.9%) patients who received ≥1 dose of the study drug and 288 (91.1%) patients who completed the 24-month trial.

Disease activity was observed in 60.3% of patients in the vitamin D group and 74.1% of patients in the placebo group (hazard ratio [HR], 0.66; 95% CI, 0.50-0.87; P = .004). The median time to disease activity was longer in the vitamin D group, with 432 versus 224 days (P = .003).

All 3 secondary MRI outcomes showed significant differences favoring the vitamin D group over the placebo group. All 10 secondary clinical outcomes showed no significant difference, including disease relapse, which occurred in 17.9% of patients in the vitamin D group and in 21.8% of those in the placebo group (HR, 0.69; 95% CI, 0.42-1.16; P =.16). The results were similar in a subgroup of 247 patients who met the updated 2017 diagnostic criteria for relapsing-remitting MS.

There were no serious adverse effects related to cholecalciferol.

Conclusions

The authors concluded that oral vitamin D₃ (cholecalciferol) at a dose of 100,000 IU received every 2 weeks significantly reduced disease activity in patients with CIS and early relapsing-remitting MS.

McMaster editors’ commentary

In middle-aged to elderly people vitamin D supplementation, typically at a dose of 800 IU daily, is widely used to maintain overall bone health and for the potential anticancer and immunity-enhancing benefits. It has few adverse effects, but excessive vitamin D intake, especially when combined with calcium supplementation, may lead to hypercalcemia, hypercalciuria, and nephrolithiasis.

In patients with MS it is suggested that vitamin D therapy is administered to attain serum 25-hydroxyvitamin D (25[OH]D) levels of 100 to 200 nmol/L. Many patients might attain this target with higher daily doses of vitamin D, in the range of 2000 to 5000 IU/d.

Overall, the results of this trial support the use of vitamin D in patients with MS but uncertainty remains as to the optimal dosing regimen, including the timing of dosing, and whether adding pulsed dosing enhances benefits.