COPENHAGEN—Serum vitamin D level early in the course of multiple sclerosis (MS) may predict a patient’s rate of long-term progression, according to research presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Vitamin D level appears to have an inverse correlation with the number of relapses, the amount of MRI activity, the number of new active lesions, and the amount of brain atrophy over five years.
The study results suggest that vitamin D supplementation may have a role in the early treatment of MS, particularly for patients who have vitamin D insufficiency or deficiency, said Alberto Ascherio, MD, Professor of Epidemiology and Nutrition at the Harvard School of Public Health in Boston. For the purposes of the study, a serum vitamin D level of 50 nmol/L or higher was considered sufficient.
The BENEFIT Trial
To determine whether serum vitamin D levels predict disease activity after clinically isolated syndrome (CIS), Dr. Ascherio and colleagues examined data from the BENEFIT study, a randomized trial that compared the effects of early and delayed treatment with interferon beta-1b in patients with CIS. A total of 468 patients were randomized. The BENEFIT investigators measured participants’ serum 25(OH)D concentrations at baseline, six months, 12 months, and 24 months and performed clinical and MRI assessments at established intervals. At 24 months, patients entered the trial’s open phase and were offered treatment with interferon beta. Clinical and MRI follow-up lasted for five years.
Dr. Ascherio and colleagues created Cox proportional hazard models or generalized mixed effects models to analyze the data. They adjusted the data analysis for sex, age, initial randomization group, and baseline T2 lesion scores to relate season-adjusted serum 25(OH)D levels to MS outcomes.
High Vitamin D Levels Predicted Reduced Disease Activity
Most patients had a vitamin D level lower than 50 nmol/L, said Dr. Ascherio. At baseline, the number of T2 lesions was higher in patients with vitamin D deficiency than in patients with sufficient vitamin D. Higher 25(OH)D levels were correlated with slower conversion from CIS to MS, reduced MS activity, and a slower rate of progression. The associations were stronger when the researchers used seasonally asynchronous blood samples to assess long-term average 25(OH)D levels.
A 50-nmol/L increment in average serum 25(OH)D levels at 12 months predicted a 57% lower rate of new active lesions, a 57% lower relapse rate, a 25% lower increase in T2 lesion volume, and a 0.41% lower annual loss of brain volume from 12 to 60 months. Compared with serum 25(OH)D levels lower than 50 nmol/L at 12 months, serum 25(OH)D levels of 50 nmol/L or more at 12 months predicted fewer active lesions on MRI, a lower increase in T2 lesion volume, a lower rate of brain loss, and lower disability, as measured by Expanded Disability Status Scale score, during the following four years.
Patient Population Was Ethnically Homogeneous
Dr. Ascherio identified several limitations to the study. Almost all of the patients were Caucasians of European ancestry, so the researchers did not draw conclusions about patients of other ethnicities. In addition, most patients eventually were treated with interferon beta, so it is unclear whether the association between disease activity and vitamin D results from an additive effect of interferon beta and vitamin D. It also is uncertain whether researchers would observe a similar beneficial effect of vitamin D in patients treated with other disease-modifying therapies.
Dr. Ascherio’s group did not see a ceiling effect of vitamin D, so it is unclear whether vitamin D supplementation would provide additional benefit to the patients. A prospective trial could give more definitive information about the therapeutic value of increasing vitamin D levels in patients with sufficient vitamin D. Neurologists should strongly consider the detection and treatment of vitamin D insufficiency and deficiency, Dr. Ascherio concluded.
—Erik Greb
Senior Associate Editor