Vitamin D as a protective factor in multiple sclerosis

Salzer et al. Vitamin D as a protective factor in multiple sclerosis. Neurology. 2012 Nov 20;79(21):2140-5. doi:10.1212/WNL. 0b013e3182752ea8.

OBJECTIVE: To examine the association between 25-hydroxyvitamin D (25[OH]D) levels and the risk of multiple sclerosis (MS) in blood samples collected prospectively and during gestation.

METHODS: In this nested case-control study, 2 population-based biobanks with 291,500 samples from 164,000 persons collected since 1975 in the northern half of Sweden were used. We identified prospectively collected blood samples from MS cases (n = 192, controls matched 2:1) and gestational samples from pregnant mothers where the offspring had later developed MS (n = 37, control mothers matched 5:1). 25(OH)D levels were measured using an ELISA, and the risk of MS was analyzed using matched logistic regression.

RESULTS: Levels of 25(OH)D ≥75 (vs. <75) nmol/L in prospectively collected blood samples were associated with a decreased risk of MS (odds ratio [OR] 0.39, 95% confidence interval [CI] 0.16-0.98). No decrease in MS risk was found in the offspring exposed to gestational 25(OH)D levels ≥75 (vs <75) nmol/L (OR 1.8, 95% CI 0.53-5.8). The prevalence of 25(OH)D levels ≥75 nmol/L in female controls decreased gradually during 1976-2005 (p trend = 0.005).

CONCLUSION: This study supports the presence of an association between high 25(OH)D levels during the years preceding disease onset and a decreased risk of MS. In the very limited material with samples drawn in early pregnancy, where month-of-birth effects were controlled for, we found no association between gestational 25(OH)D levels and MS risk in the offspring. Decreasing 25(OH)D levels in the population may contribute to explain the increasing MS incidence that is suggested from epidemiologic studies.

This study shows what can be done using routinely collected data and samples stored in Scandinavia. The authors looked at blood samples stored before MS onset in patients and compared to matched controls, individuals who went on to develop MS had lower levels of vitamin D, showing that vitamin D deficiency is a risk factor for MS.

This study confirms a landmark previous study, and these are the only two studies to assess vitamin D levels prior to disease onset. Measuring vitamin D levels post onset does not really address whether low vitamin D levels cause MS or a consequence of the inflammatory processes that are going on in MS (known as reverse causality). There is still the potential for reverse causality for both of the pre-onset studies as it is not known when the disease actually starts, it may be many years before clinical signs become apparent.
An additional aspect of this study was to look at vitamin D levels in pregnant mums who had children who went on to develop MS. However, this study found no association between pregnancy vitamin D levels and offspring risk of MS. This may be because they only had samples from 37 mothers, or that they only had vitamin D levels available in the first trimester or that there is actually no effect of vitamin D during pregnancy. This needs further work.

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