The Association of Vitamin D Levels and MS

  • Published Mar 30, 2018

Original Article

The Association of Vitamin D Levels and Multiple Sclerosis

Munger KL, Levin LI, Hollis BW, et al. JAMA. 2006;296:2832–2838

Neurology Evidence

The global distribution of MS increases with distance from the equator in both Northern and Southern hemispheres. A possible explanation for this interesting observation is that sunlight exposure and vitamin D levels also decrease with distance from the equator. Prior to this study, some epidemiologic and experimental evidence suggested that high levels of vitamin D may decrease the risk of MS. This was the first prospective study to address this hypothesis.

To examine whether levels of 25-hydroxyvitamin D are associated with risk of MS.

Prospective nested case-control study among more than 7 million US military personnel.
Cases obtained were from databases from 1992 through 2004.

MS cases (n = 257) were identified through Army and Navy physical disability databases, and diagnoses were confirmed by medical record review. For each of the 257 cases, there were two controls that were matched by age, sex, race/ethnicity, and dates of blood collection.

Vitamin D status was estimated by averaging 25-hydroxyvitamin D levels of two or more serum samples collected before the date of initial MS symptoms.

The main outcome measure included the odds ratios (ORs) of MS associated with continuous or categorical levels of serum 25-hydroxyvitamin D within each racial/ethnic group.



  • The risk of MS significantly decreased with increasing levels of 25-hydroxy vitamin D among whites (148 cases, 296 controls) with an OR of 0.59 (95% CI = 0.36–0.97) for a 50-nmol/L increase in 25-hydroxyvitamin D.
  • Individuals were also classified under five predefined categories of 25-hydroxyvitamin showed significance (p = 0.02) across quintiles.D by 25-nmol/L increments. In the categorical analyses, the ORs for each category showed significance (p = 0.02) across quintiles.
  • There was a strong inverse relationship with MS risk and 25-hydroxyvitamin D levels measured before age 20 years.
  • There was no significant association between vitamin D and MS risk among blacks and Hispanics (109 cases, 218 controls), who had lower 25-hydroxyvitamin D levels than whites.

The results suggest that high circulating levels of vitamin D are associated with a lower risk of MS.

One potential environmental risk factor thought to be involved in increased susceptibility to MS is reduced levels of vitamin D. This large prospective study found that the risk of MS decreased with increasing serum levels of 25-hydroxyvitamin D. However, this association was not seen with blacks and Hispanics, but the authors suggest this could be because of the smaller sample size of this population. This study does not prove that decreased vitamin D levels actually causes MS. Rather, it suggests that high levels of vitamin D in the serum are associated with a lower risk of MS. Subsequent studies have confirmed this finding and extended it by revealing that patients diagnosed with MS who have higher vitamin D levels show less disease activity by relapses and MRI. Whether vitamin D supplementation may alter possibility or developing MS or may help attenuate disease after a diagnosis of MS requires further study.

Full Article

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