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 By Emma Hitt, PhD 

August 3, 2012 — Evidence suggests a role for vitamin D in the disease process of multiple sclerosis (MS).

One large study reports the novel finding that treatment with beta-interferon (IFN-ß) enhances the production of vitamin D from sun exposure in patients with multiple sclerosis (MS).

Two additional reports show that in people with MS, higher levels of circulating 25-hydroxyvitamin D (25[OH]D) may reduce the rate of clinical relapse and the number of new lesions.

The 3 new reports are published in the July 17 issue of Neurology.

Vitamin D Necessary for IFN-ß Effect

In the largest of the 3 studies, Niall Stewart, PhD, with the University of Tasmania, in Australia, and colleagues conducted a prospective analysis of 178 persons with clinically definite multiple MS living in southern Tasmania between 2002 and 2005. Patients were assessed for serum 25(OH)D and MS outcomes.

Investigators found that IFN-ß therapy was associated with greater production of vitamin D from sun exposure, "suggesting part of the therapeutic effects of IFN-ß on relapse in MS may be through modulation of vitamin D metabolism."

"Vitamin D and sun exposure are known to provide protection from developing MS, and high vitamin D levels are associated with reduced risk of relapse," Dr. Stewart told Medscape Medical News. "IFN-ß therapy is known to protect against relapse as well, but not all people respond to treatment," he added.

According to Dr. Stewart, these findings add to current knowledge by showing that adequate levels of vitamin D may be necessary for IFN-ß to be associated with reduced risk of relapse.

"This, in combination with the fact that IFN-ß therapy was associated with significantly higher levels of vitamin D mediated by an enhanced production of vitamin D from sun exposure, suggests that some of the protective effects of IFN-ß may be due to its effects on vitamin D," he added.

Disease Exacerbation Decreased With Higher Vitamin D

Another study, led by Rogier Q. Hintzen, MD, PhD, at the Erasmus Medical Centre, in Rotterdam, The Netherlands, included 72 patients with relapsing-remitting MS. Patients' blood levels were measured every 8 weeks for 25(OH)D, as were exacerbation rates.

Over a mean follow-up of 1.7 years, exacerbation risk decreased significantly with higher serum vitamin D levels (P value for trend = .007).

The association was linear, such that with each doubling of the serum 25(OH)D concentration, the exacerbation rate decreased by 27% (95% confidence interval, 8% - 42%; P = .008).

Although a strong seasonal fluctuation in vitamin D levels was noted, the association between clinical disease activity and season was not significant in this study. The association between vitamin D and relapse persisted through all seasons, the authors report.

Use of IFN-ß was infrequent in this study, which allowed researchers to study the effect of vitamin D alone, they note.

"Although some studies suggest an additional beneficial effect of vitamin D in [IFN-ß] users, we did not find an additional effect of [IFN-ß] in this study." The fact that the association persisted even in treated patients suggests that the effect of vitamin D may be additive to IFN-ß, they speculate, although they note that this study was not able to look at that question.

Still, they conclude, randomized studies of vitamin D supplementation in MS are needed. "Vitamin D has the advantage of being cheap, safe, and easy to administer, and could therefore be a valuable addition to the existing treatment opportunities in MS."

25-Hydroxyvitamin D Inversely Linked to Disease Activity

In a third study, led by Kristin I. Løken-Amsrud, MD, with the Innlandet Hospital Trust in Lillehammer, Norway, and colleagues, 88 patients with relapsing-remitting MS were followed for 6 months before treatment for 18 months with IFN-ß treatment.

Researchers found that increasing levels of 25-hydroxyvitamin D were inversely associated with radiologic disease activity irrespective of patients' HLA-DRB1*15 status. (Vitamin D has been shown to regulate expression of this MS-associated allele.)

Before IFN-ß treatment, each 10 nmol/L increase in 25-hydroxyvitamin D was associated with 12.7% (P = .037) reduced odds for new T1 gadolinium–enhancing lesions, 11.7% (P = .044) for new T2 lesions, and 14.1% (P = .024) for combined unique activity.

In contrast to the study by Dr. Stewart and colleagues, however, no association between 25-hydroxyvitamin D and disease activity was detected after initiation of IFN-ß.

According to a related editorial, "this discrepancy could perhaps be explained by differences in latitude…and thus UVR [ultraviolet B radiation] exposure, or differences in the timing of the 25(OH)D measurement relative to the outcome of interest."

Monitor Vitamin D Levels

In their editorial, Alberto Ascherio, MD, DrPH, with Harvard Medical School, in Boston, Massachusetts, and Ruth Ann Marrie, MD, PhD, FRCPC, with the University of Manitoba, in Winnipeg, Canada, conclude that it is "too soon to recommend the use of high-dose vitamin D in clinical practice."

However, they add that, "evidence is sufficient to recommend monitoring of vitamin D levels and supplementation as needed to achieve at least a year-round level of vitamin D sufficiency in persons with MS."

These studies were not commercially funded. The authors and the editorialists have disclosed no relevant financial relationships. Full disclosures are available at Neurology.org.

Neurology. 2012;79:208-210, 254-260, 261-266, 267-273. Abstract Abstract Abstract Editorial

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