In a prospective nested case-control study, an increase in serum 25-hydroxyvitamin D (25[OH]D) of 50 nmol/L) was associated with a 39% reduction in risk of MS after adjusting for sample year, number of pregnancies and births, and the matching factors (relative risk 0.61, 95% CI 0.44–0.85, P=0.003), reported Kassandra Munger, ScD, of the Harvard T.H. Chan School of Public Health in Boston, and colleagues.

Compared with women with adequate levels of vitamin D, the risk of developing MS about 9 years later was 43% greater for women with vitamin D deficiency (RR 1.43, 95% CI 1.02–1.99), and 27% greater for those with vitamin D insufficiency (RR 1.27, 95% CI 1.07–1.50), they wrote online in Neurology.

Among the women with two or more serum samples (511 with MS and 831 matched controls), providing data less affected by random variations, MS risk was twofold higher in women with vitamin D deficiency versus those with adequate levels of at least 50 nmol/L (RR 2.02, 95% CI 1.18–3.45, P=0.01).

“There have only been a few small studies suggesting that levels of vitamin D in the blood can predict risk,” Munger noted in a statement. “Our study, involving a large number of women, suggests that correcting vitamin D deficiency in young and middle-age women may reduce their future risk of MS.”

Using stored blood samples taken as part of prenatal testing of more than 800,000 women in the Finnish Maternity Cohort, the researchers identified 1,092 women diagnosed with MS from 1983 to 2009 with at least one serum sample collected before their MS diagnosis. They matched each of these cases with up to three controls (2,123 women) without MS, based on birth date within 2 years and region of residence.

Overall, slightly more than one in two women with and without MS had deficient vitamin D levels of less than 30 nmol/L, and one in three had insufficient levels between 30 and 50 nmol/L.

Munger’s group noted that they had selected a cohort with historically low vitamin D levels to examine the possible effect on MS risk.

The women who developed MS had vitamin D levels averaging 1.3 nmol/L lower than controls more than 9 years before their MS diagnosis, researchers reported. Also, 58% had deficient levels of vitamin D compared with 52% of those who did not develop the disease.

Additional analyses of those with at least two serum samples found that women with extreme vitamin D deficiency (less than 26.8 nmol/L) had a 53%-66% increased risk of MS as compared to women with the highest levels (41 nmol/L or more), and the overall trend of increasing MS risk with decreasing vitamin D levels was statistically significant (P=0.0001).

“Our results complement and expand those of 2 prior similarly designed studies of similar design, one in US and one in northern Sweden, which found that elevated levels of 25(OH)D (above 75 or 100 nmol/L) were associated with a 60% reduced risk of MS but did not report the effects of vitamin D insufficiency or deficiency,” researchers wrote.

In an accompanying editorial, Ruth Ann Marrie, MD, PhD, of the University of Manitoba in Canada, and Christopher Beck, PhD, the University of Rochester Medical Center in N.Y., noted that the research adds to the biologic data and epidemiologic body of evidence supporting a causal role for vitamin D in MS.

Studies in people from a broader range of racial groups and regions, and information regarding optimal timing and duration of vitamin D supplementation are needed, they commented. Nevertheless, they suggested that supplementation is simple, cost-effective, and unlikely to be harmful in adolescents and adults, noting that doses of up to 4,000 IU/day are safe for adults even in pregnancy.

“It is time to take an active approach to preventing MS, at a minimum targeting those individuals with an elevated risk of MS, including smokers, the obese, and those with a family history of MS,” Marrie and Beck wrote.

Study limitations include the use of a female and largely Caucasian study population which reduced generalizability; inability to adjust for other MS risk factors such as BMI in early life; Epstein-Barr virus infection; smoking; and human leukocyte antigen status; Also, the collection of the serum samples may not have preceded disease onset in some cases of women with pre-clinical disease.

• Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner