ms and vitamin d

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Serum 25-Hydroxyvitamin D Levels and Risk of Multiple Sclerosis

Kassandra L. Munger, MSc; Lynn I. Levin, PhD, MPH; Bruce W. Hollis, PhD; Noel S.

, MD; Alberto Ascherio, MD, DrPH

JAMA. 2006;296:2832-2838.

Context Epidemiological and experimental evidence suggests that high levels of

vitamin D, a potent immunomodulator, may decrease the risk of multiple

sclerosis. There are no prospective studies addressing this hypothesis.

Objective To examine whether levels of 25-hydroxyvitamin D are associated with

risk of multiple sclerosis.

Design, Setting, and Participants Prospective, nested case-control study among

more than 7 million US military personnel who have serum samples stored in the

Department of Defense Serum Repository. Multiple sclerosis cases were identified

through Army and Navy physical disability databases for 1992 through 2004, and

diagnoses were confirmed by medical record review. Each case (n = 257) was

matched to 2 controls by age, sex, race/ethnicity, and dates of blood

collection. Vitamin D status was estimated by averaging 25-hydroxyvitamin D

levels of 2 or more serum samples collected before the date of initial multiple

sclerosis symptoms.

Main Outcome Measures Odds ratios of multiple sclerosis associated with

continuous or categorical levels (quantiles or a priori–defined categories) of

serum 25-hydroxyvitamin D within each racial/ethnic group.

Results Among whites (148 cases, 296 controls), the risk of multiple sclerosis

significantly decreased with increasing levels of 25-hydroxyvitamin D (odds

ratio [OR] for a 50-nmol/L increase in 25-hydroxyvitamin D, 0.59; 95% confidence

interval, 0.36-0.97). In categorical analyses using the lowest quintile (<63.3

nmol/L) as the reference, the ORs for each subsequent quintile were 0.57, 0.57,

0.74, and 0.38 (P = .02 for trend across quintiles). Only the OR for the highest

quintile, corresponding to 25-hydroxyvitamin D levels higher than 99.1 nmol/L,

was significantly different from 1.00 (OR, 0.38; 95% confidence interval,

0.19-0.75; P = .006). The inverse relation with multiple sclerosis risk was

particularly strong for 25-hydroxyvitamin D levels measured before age 20 years.

Among blacks and Hispanics (109 cases, 218 controls), who had lower

25-hydroxyvitamin D levels than whites, no significant associations between

vitamin D and multiple sclerosis risk were found.

Conclusion The results of our study suggest that high circulating levels of

vitamin D are associated with a lower risk of multiple sclerosis.

Author Affiliations: Departments of Nutrition (Ms Munger and Dr Ascherio) and

Epidemiology (Dr Ascherio), Harvard School of Public Health, and Channing

Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard

Medical School (Dr Ascherio), Boston, Mass; Division of Preventive Medicine,

Walter Army Institute of Research, Silver Spring, Md (Dr Levin);

Departments of Pediatrics, Biochemistry, and Molecular Biology, Medical

University of South Carolina, ton (Dr Hollis); and Department of the

Navy, Secretary of the Navy Council of Review Boards, Washington, DC (Dr

).

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