Effects of vitamin D₃ in clinically isolated syndrome and healthy control participants: A double-blind randomised controlled trial

Abstract

BackgroundLowserum vitamin D levels are associated with susceptibility to, and severity of, multiple sclerosis. High dose vitamin D has been proposed as a potential immunomodulator in multiple sclerosis.ObjectivesWe performed a single centre, investigator-led, exploratory, double-blind, randomised, placebo controlled, trial of vitamin D3 in clinically isolated syndrome and healthy control participants to assess its immunological effects. Secondary end-points included clinical and magnetic resonance imaging outcomes and safety.MethodsClinically isolated syndrome patients and healthy control participants were randomised to: placebo, 5000 IU or 10,000 IU vitamin D3/day (Vigantol oil). Study duration was 24 weeks.ResultsThe trial did not meet its primary end point, with no difference in the frequency of pro-inflammatory CD4+ T cells (interleukin (IL)-17+/interferon (IFN)-γ+) seen. A higher level of disease freedom (67% versus 50%) was seen in those with serum 1,25 (OH) vitamin D levels>100 nmol/l but this did not reach significance. High dose vitamin D3 was well tolerated with no safety signal.ConclusionsHigh dose vitamin D3 over 24 weeks was well tolerated but without immunological, magnetic resonance imaging or clinical evidence of benefit. The hypothesised therapeutic effects in clinically isolated syndrome or multiple sclerosis patients may require longer periods of administration or may only be seen in patients treated with vitamin D3 as an adjunct to established disease modifying therapies.

High-Dose Vitamin D3 Intake Is Associated with Decreased Symptoms of Multiple Sclerosis

“…While the above studies reported encouraging results, four studies in this review showed results that were not as positive (O'Connell et al, 2017;Holmoy et al, 2017;Muris et al, 2016b;Rosjo et al, 20115). Holmoy et al (2017) and Rosjo et al (2015) examined bone health in RRMS patients who received 20,000 IU D3 weekly over 96 weeks.…”

“…Rosjo's group, however, did see the serum 25(OH)D levels more than doubled for the group receiving the supplements. O'Connell et al (2017) noted no difference in pro-inflammatory CD4+ T cells and while they observed a higher level of disease freedom, it was not at a significant level. This group admitted that further study is needed in this area.…”

“…All of these studies had a duration of three months but differed in sample size and study design. Three of the studies had a sample size of 94 patients with RRMS (Ashtari et al, 2015;Toghianifar et al, 2015), while one study examined 170 patients (O'Connell et al, 2017) and the other only 32.11 The studies conducted by Laursen et al (2016) and Gargari et al (2015) did not use a control group. The other three studies were double blind, randomized control trials.…”

“…Multiple Sclerosis (MS) has been defined as a chronic inflammatory demyelinating disease that affects the central nervous system (O'Connell et al, 2017). While researchers have not yet found a clear cause for developing MS, it is categorized as an autoimmune disease.…”

Vitamin D as an immune modulator in multiple sclerosis

“…No significant differences were observed in the concentrations of IL-10, IL-17 and IFN-gamma produced followed stimulation of peripheral blood mononuclear cells (PBMCs) in any treatment arm. Moreover, no significant reduction in the frequency of proinflammatory CD4 T cells was seen [34]. Only Ashtari et al showed that in RRMS patients IL-10 serum level increased significantly after taking high-dose vitamin D3 for three months [35].…”