COPENHAGEN, Denmark — Higher mean serum vitamin D levels early in the course of multiple sclerosis (MS) robustly predicted a lower degree of disease activity, MRI lesion load, brain atrophy, and clinical progression over 5 years of follow-up, according to new data from the BENEFIT study.

Presenting the results here at the 29th Congress of the European Committee for Research and Treatment in Multiple Sclerosis (ECTRIMS), Alberto Ascherio, MD, Harvard Medical School, Boston, Massachusetts, concluded that results of the study "support the importance of identifying and correcting vitamin D deficiency early in the course of MS."

Giancarlo Comi, MD, Università Vita-Salute San Raffaele, Italy, who was not part of the research, called it "a very important study."

Commenting for Medscape Medical News, session chair, Eva Havrdova, MD, Charles University, Prague, Czech Republic, said she believed universal supplementation of vitamin D is the right way to go.

"Vitamin D is not just a vitamin. It is a hormone," she said. "Most people have suboptimal levels, so supplementation is necessary to get everyone to the levels needed to protect against rickets, never mind about its immunomodulating properties. I believe if we gave it to everyone we would see a major improvement in general health status and in many disease conditions in all populations."

The current analysis was a longitudinal follow-up of patients in the BENEFIT study, which investigated early vs delayed treatment with interferon β-1b. Clinical and MRI assessments were conducted at baseline and regularly throughout the 5-year follow-up.

For this analysis, vitamin D level was taken as the average of the levels at baseline, 6 months, and 12 months, early in the disease course, Dr. Ascherio noted.

Outcome data were those of the original trial, adjusted for sex, age, and initial randomization group.

He pointed out that most patients in the study had vitamin D levels below the 50 nmol/L mark, which is considered the deficiency threshold, a finding he called "striking."

Results showed that higher levels of vitamin D in the first year were associated with reduced rates of clinical relapse and reduced numbers of new active lesions both early on in the study and out to 5 years of follow-up.

Table 1. Rate Ratios (95% Confidence Intervals) for Clinical Relapse and New Active Lesions for Each 50-nmol/L Difference in Serum 25(OH)D

Endpoint 0 to 60 Months 12 to 60 Months 24 to 60 Months
Clinical relapse 0.73 (0.46 - 1.16) 0.43 (0.20 - 0.92) 0.41 (0.16 - 1.06)
New active lesions 0.61 (0.44 - 0.83) 0.54 (0.37 - 0.78) 0.37 (0.21 - 0.63)


When looking at results by quintile of vitamin D level, significant reductions in new active lesions were seen in groups with levels of 25(OH)D over 53 nmol/L, and T2 lesion volume increased by less in the higher quintiles.

In addition, disability, as measured by the Expanded Disability Status Scale (EDSS), increased less in the higher quintile groups. Dr. Ascherio noted that the power for this observation was low because the median change in disability was zero. "Most patients did not progress but nevertheless there was still an association with vitamin D level."

Table 2. Results by Quintile of Vitamin D Levels

Quintile Vitamin D Range (nmol/L) Risk Ratio for New Active Lesions Up to 5 Years Relative Annual Change in T2 Lesion Volume, Years 1 to 5 (%) Annualized Change in EDSS Score (6 Months to 5 Years)
1 22-36 1.00 0.00 0.00
2 36-45 1.00 0.45 –0.10
3 45-52 0.94 –6.00 –0.19
4 53-61 0.67 –10.47 –0.29
5 62-98 0.63 –17.30 –0.23


There was also a significant reduction in the percentage change of brain volume in patients with 25(OH)D levels above 50 nmol/L vs those with values below this level (P = .005).

Noting that the study was conducted mainly in white patients, Dr. Ascherio said further investigations are needed to determine whether the results apply to patients of different races.

Also, most patients were treated with interferon β in this study, so it is not known whether this is an additive effect with interferon β or whether a similar effect would be seen with other MS drugs as well, he commented. It is also not known whether this effect would be seen in patients at a later disease stage and those with progressive MS, he added.

29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Abstract #96. Presented October 3, 2013.


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