High-Dose Vitamin D Shows Promising Effects in MS

January 07, 2016

Patients with multiple sclerosis (MS) who took high doses of cholecalciferol (vitamin D3) had increased blood levels of 25-hydroxyvitamin D levels [25(OH)D] to those proposed to be sufficient in MS and showed promising immunologic changes, in a new study.

The study, published online in Neurology on December 30, was conducted by a team led by Peter A. Calabresi, MD, Johns Hopkins University School of Medicine, Baltimore, Maryland.

"Future studies are warranted to further elucidate the molecular mechanisms of these effects and ongoing randomized controlled clinical trials will be instrumental to establish the clinical utility of cholecalciferol as a novel immunomodulatory therapy for MS," the authors conclude.

They note that low serum 25(OH)D levels are associated with an increased risk for MS and in established disease are associated with increased disability and disease activity. In addition, animal studies of vitamin D supplementation show treatment can prevent or ameliorate experimental autoimmune encephalitis, a murine model of MS.

They conducted the current study to investigate the immunologic effects of high-dose vitamin D in patients with MS.

For the study, 40 patients with relapsing-remitting MS were randomly assigned to receive high-dose (10,400 IU) or low-dose (800 IU) cholecalciferol daily for 6 months. Baseline levels of serum 25(OH)D were 27 ng/mL in both groups, but the high-dose group had a much greater increase (mean increase of 34.9 ng/mL) compared with the low-dose group (6.9 ng/mL).

The authors explain that optimal levels of serum 25(OH)D in MS are currently unclear, but it has been proposed that levels between 40 and 60 ng/mL may be the best target for this population, which such levels being achieved with the high dose of cholecalciferol given in this study, but not with the low dose.

In terms of immunologic effects, patients taking the high dose of cholecalciferol showed a reduction in the proportion of interleukin (IL)-17 CD4+ T cells, CD161 CD4+ T cells, and effector memory CD4+ T cells, which are believed to be major contributors to the immunopathogenesis of MS. The high-dose group also showed a concomitant increase in the proportion of central memory CD4+ T cells and naive CD4+ T cells. None of these effects were observed in the low-dose group.

The researchers write: "Our finding that high-dose cholecalciferol leads to a decrease in the proportion of CD4+ IL-17+ T cells in the peripheral blood of patients with MS suggests that this may be a major mechanism underlying the possible therapeutic role of vitamin D in MS."

In terms of adverse effects, the authors report that these did not differ between the two groups, and there was one MS relapse in each treatment group, leading them to conclude that the high dose was "safe and well-tolerated."

However, commenting on the findings for Medscape Medical News, Alberto Ascherio, MD, Harvard Medical School, Boston, Massachusetts, was more cautious.

Noting that 4 (21%) of the 19 patients allocated to high-dose vitamin D had to stop (n = 3) or reduce (n = 1) the treatment because of side effects, he said, "I would be cautious to conclude that the study provides conclusive evidence that supplementation with 10,400 IU/day is safe and well-tolerated, as this statement may induce some MS patients to take this relatively high dose without appropriate supervision."

Dr Ascherio added that he thought the study was "interesting" but "the results are at risk of being overinterpreted."

"The study identifies some potential mechanisms by which vitamin D could affect the course of MS, but it does not provide evidence on whether supplementation at this high dose is beneficial to patients with MS," he noted.

The study was supported by the Kenneth and Claudia Silverman Family Foundation, Montel Williams Foundation, and National Multiple Sclerosis Society.

Neurology. Published online December 30, 2015. Abstract


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