Vitamin D₃ supplementation in multiple sclerosis: Symptoms and biomarkers of depression

Depressive symptoms are common in multiple sclerosis (MS), and both depression and MS have been associated with a poor vitamin D status. As cytokine-mediated inflammatory processes play a role in the pathogenesis of both disorders, we hypothesized that vitamin D₃ supplementation reduces depressive symptoms in MS via its immunomodulatory properties. In this randomized pilot study relapsing remitting (RR) MS patients received either vitamin D₃ supplementation (n = 20; 14.000 IU/day) or placebo (n = 20) during 48 weeks. Pre- and post-supplementation depression scores, measured using the Hospital Anxiety Depression Scale (HADS) depression subscale (HADS-D), showed a significant decrease within the vitamin D₃ group (median HADS-D 4.0 to 3.0, p = 0.02), a trend towards a decrease within the placebo group (median HADS-D 3.0 to 2.0, p = 0.06), but no significantly different reductions between groups (p = 0.78). Furthermore, no reductions in pro- and anti-inflammatory cytokine balances, secreted by stimulated leukocytes and CD8⁺ T cells, were found in the vitamin D₃ compared to the placebo arm. Therefore, we found no evidence for a reduction of depressive symptoms or related biomarkers upon vitamin D₃ supplementation in RRMS patients in this exploratory study. Whether vitamin D₃ supplementation is of benefit in manifest depression in MS needs to be assessed by additional studies.