Is It Time to Rethink Low Vitamin D as a Contributor to MS?

Bret S. Stetka, MD

Disclosures

May 08, 2017

The idea that vitamin D deficiency may contribute to multiple sclerosis (MS) has been well established in the literature and has, for the most part, been etched into recent neurology dogma. Yet, research by Annette Langer-Gould, MD, PhD—a clinical assistant professor at the University of Southern California's Keck School of Medicine in Los Angeles—suggests that the association might not be that simple. While on site at the 2017 American Academy of Neurology (AAN) Annual Meeting, Medscape interviewed Dr Langer-Gould about her research and about how vitamin D may or may not influence MS risk.

Annette Langer-Gould, MD

Medscape: Can you summarize the goals of the study[1] that you presented here at the AAN meeting?

Annette Langer-Gould, MD, PhD: The overarching goal of our study—the MS Sunshine study, it's called—was to determine whether hypovitaminosis D is a more important risk factor for MS in certain subgroups, particularly those with darker skin or those who are genetically predisposed either to MS or hypovitaminosis D.

Studying this question in people of varying ethnicities provides a natural experiment to test the hypothesis that low vitamin D causes MS. Black and Hispanic people have lower vitamin D levels than white people, and most black people express a different vitamin D binding protein than whites and Hispanics. If low vitamin D truly causes MS, then this should be true across all racial/ethnic groups.

Medscape: What previous associations between MS and vitamin D have been published?

Dr Langer-Gould: In white people, there are four[2,3,4,5] published studies that demonstrate an association between low vitamin D and increased risk for MS. In black people, only one study[6] besides our own study has examined this, and it found no association between serum vitamin D levels and MS risk. However, that study's numbers were small and discounted the significance of this finding, as the same study found an association in whites. As far as I know, no one has examined whether the type of vitamin D binding protein a person carries affects the association between vitamin D level or lifetime sun exposure on MS risk.

Medscape: Vitamin D deficiency is a commonly cited risk factor for MS, correct?

Dr Langer-Gould: Absolutely. The prevailing belief among neurologists is that causality has already been established. It is common to order serum vitamin D levels and to supplement MS patients, as well as recommend that they supplement their children to prevent MS.

As background, the vitamin D–MS hypothesis originated from the observation that the prevalence of MS increases with increasing distance from the Equator, as ultraviolet radiation (UVR) from the sun becomes less intense. But this is also where more white people live. Exposure to UVR is, in turn, the principal natural source of vitamin D by stimulating intradermal synthesis; thus, low UVR (further from the Equator) should lead to low vitamin D status and be a possible explanation for the geographic distribution of MS. This relationship between UVR exposure and 25(OH)D levels is very strong in light-skinned individuals. However, people with darker skin tones produce less 25(OH)D following the same amount of UVR exposure as whites.

 
Our findings further challenge the biological plausibility of vitamin D deficiency as causal for MS.
 

Medscape: What were the results of your study?

Dr Langer-Gould: The main result of our study is that vitamin D is not associated with MS risk in blacks or Hispanics, regardless of genotype. In contrast, sun exposure is protective in all three racial/ethnic groups. Even when we examined patients who carry the "white" version of the vitamin D binding protein (which most whites and Hispanics carry but only about 30% of blacks do), there is still no association between vitamin D levels and risk for MS. In contrast, sun exposure seems to be particularly protective in those who carry the "white" version of the vitamin D binding protein.

The protective effect of UVR regardless of race/ethnicity may be particularly important in those who carry a specific polymorphism within the vitamin D binding protein gene. Our findings further challenge the biological plausibility of vitamin D deficiency as causal for MS. Furthermore, if our findings (showing that the protective effect of sun exposure on MS risk is modified by the vitamin D binding protein gene) are replicated, it invalidates the Mendelian randomization studies of vitamin D linked to MS or other diseases; it violates the assumption that the gene only affects disease risk through vitamin D.

A highly plausible explanation is that vitamin D is an excellent surrogate measure of sun exposure in whites but not so much in blacks and Hispanics.

Medscape: So, what would you tell practicing clinicians about vitamin D supplementation in their MS patients?

Dr Langer-Gould: Vitamin D supplementation is not a substitute for sun exposure. Get your vitamin D from natural sources.

This study adds to the growing literature that there are no ill health consequences of low vitamin D levels other than rickets.

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