Background: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS); it is the most common cause of neurological disability in young adults. The cause of MS is unknown but it is believed to be precipitated by both genetic and environmental risk factors. An association between vitamin D deficiency and increased risk of MS has been detected in several epidemiological and case-control studies and is further supported by immunological and genetic studies. It is still unclear whether there is any special age at which exposure to vitamin D deficiency increases the MS risk e.g. is in utero vitamin D deficiency particularly detrimental. Serum levels of vitamin D are associated with both clinical and magnetic resonance imaging (MRI)-assessed disease activity but there have been very few randomized placebo-controlled trials (RCTs) investigating the benefits of vitamin D supplementation in established MS patients. 

Aims of the study: This study initially investigated the association between vitamin D status during early pregnancy and the risk of MS in the offspring in the Finnish Maternity Cohort. Secondly, we performed the first RCT with vitamin D in MS, evaluating the safety and efficacy of 500 ug weekly dose of vitamin D supplementation or placebo in 68 MS patients receiving interferon beta-therapy. We also studied the mechanism of action of vitamin D supplementation in our study participants. Finally, we updated the MS prevalence and studied the fracture risk and the role of vitamin D in the risk of fractures in MS patients in Southwest Finland. 

Results: Maternal vitamin D deficiency during early pregnancy was associated with a nearly 2-fold increased risk of MS in their children in comparison with children born to mothers who were non-deficient for vitamin D. In the vitamin D supplementation study there was a statistically significant decrease in the total number of T1 Gadolinium (Gd) enhancing lesions in patients treated with vitamin D in comparison with placebo treated patients. Serum levels of transforming growth factor beta (TGF-β), an immunoregulating cytokine, indirectly measured by a latency-associated peptide (LAP) immunoassay, increased significantly in the vitamin D treated group but not in the placebo group. The prevalence of MS in southwest Finland was 212/105. The relative risk was 1.3 for all types of fractures and 1.5 for osteoporotic fractures in patients with MS compared with matched controls. 


Conclusions: Correcting vitamin D deficiency during pregnancy may exert a beneficial effect on the risk of the offspring developing MS. Vitamin D supplementation at 500 ug/week influenced the MRI-assessed activity in patients with MS. The immunoregulatory effects of TGF-β may play a role in the improved MRI outcomes observed in our vitamin D treated MS patients. At a mean serum level of 110 nmol/l of 25-hydroxyvitamin D (25(OH)D), its immunological effects can already be detected. We observed a statistically significantly elevated risk of osteoporotic fractures in patients with MS. Several conclusions emerge from our results. First, we recommend correcting vitamin D deficiency during pregnancy at the population level but especially in MS patients planning to become pregnant. Second, we recommend that vitamin D levels should be analyzed in all MS patients after the diagnosis of MS and vitamin D supplementation should be initiated at a dose of 50 to 100 ug/day, targeting serum levels above 100 nmol/l.