vitamin d3 and the stress-axis in ms

Conditions: Multiple Sclerosis

Summary: patients with multiple sclerosis (ms) have an increased risk of developing a major depression. the investigators observed a protective effect of high vitamin d levels on the risk of depression in ms. this might be driven by the effect of vitamin d on the stress-axis. therefore, the main goal of the present study is to assess whether high dose vitamin d supplementation results in a suppression of the stress-axis, as measured by decreased levels of cortisol.

the lifetime incidence of a major depression in multiple sclerosis (ms) is 50%. (patten et al. neurology 2003; 61(11):1524-7) our group reported a negative correlation between vitamin d status and depression score of the hospital anxiety and depression scale (hads) in a cross-sectional dataset of dutch ms patients. (knippenberg et al. acta neurol scand 2011; 124(3):171-5) this suggests an interaction between vitamin d and biological mechanisms affecting susceptibility to depression. currently, we have two main hypotheses: 1) vitamin d regulates the hypothalamic stress axis in ms. based on our findings that cortisol releasing hormone (crh)-positive hypothalamic neurons in the brains of ms patients stained positive for the vitamin d receptor (vdr) and 1,25(oh)2d-24-hydroxylase (24-ohase). (smolders et al. j neuropathol exp neurol 2013;72(2):91-105) 2) vitamin d affects t cell cytokine profile and hereby the odds of developing depression. also in non-ms depressed patients increased levels of pro-inflammatory cytokines are detected (maes et al. metab brain dis 2009; 24: 27-53). vitamin d3 has shown to be a potent promotor of t cell regulation both in vitro and in vivo. (smolders et al. j neuroimmunol 2008;194:7-17 and smolders et al. plos one 2010;5:e15235) the main goal of this study is to assess whether supplementation of high doses vitamin d3 results in a suppression of saliva cortisol day-curves in subjects with multiple sclerosis, and we will explore whether the pro-inflammatory cytokine profile of t lymphocytes is regulated.

Eligibility criteria:
inclusion criteria: * female * relapsing remitting ms * at start of study \> 6 weeks in clinical remission of disease * age \> 18 years. * premenopausal * treated with either no immune-modulating treatment, or the currently registered ms modulating treatments: interferon beta 1a (rebif®), interferon beta 1b (betaferon® or avonex®), glatiramer acetate (copaxone®), dimethylfumarate (tecfidera®), teriflunomide (aubagio®)) or fingolimod (gilenya®). exclusion criteria: * any contraindication to vitamin d according to summary of product characteristics: hypercalcaemia, hypervitaminosis d, nephrolithiasis, diseases or conditions resulting in hypercalcaemia and/or hypercalciuria (incl. primary hyperparathyroidism), severe renal impairment . * use of dexamethasone or other systemic glucocorticosteroids \<2 months prior to first study visit * supplementation of \>=1000 iu/d (25µg) vitamin d2 or d3 * medical history of disturbed vitamin d/ calcium metabolism other than low intake * present clinical (major)depression * present treatment with anti-depressants, benzodiazepines, or neuroleptics. * treatment with high-dose dexamethasone for ms exacerbation during study. * pregnancy or the intention to become pregnant during the study period.

Keywords: multiple sclerosis, vitamin d, hpa-axis, cortisol