Vitamin D Status Does Not Affect Disability Progression of Patients with Multiple Sclerosis over Three Year Follow-Up

Abstract

Background and ObjectiveThe risk of developing multiple sclerosis (MS) as well as MS disease activity is associated with vitamin D (25(OH)D) status. The relationship between the main functional disability hallmark of MS, disability progression, and 25(OH)D status is less well established though, especially not in MS patients with progressive disease.MethodsThis retrospective follow-up study included 554 MS patients with a serum baseline 25(OH)D level and Expanded Disability Status Scale (EDSS) with a minimum follow-up of three years. Logistic regressions were performed to assess the effect of baseline 25(OH)D status on relapse rate. Repeated measures linear regression analyses were performed to assess the effect on disability and disability progression.ResultsBaseline deseasonalized 25(OH)D status was associated with subsequent relapse risk (yes/no), but only in the younger MS patients (≤ 37.5 years; OR = 0.872, per 10 nmol/L 25(OH)D, p = 0.041). Baseline 25(OH)D status was not significantly associated with either disability or disability progression, irrespective of MS phenotype.ConclusionWithin the physiological range, 25(OH)D status is just significantly associated with the occurrence of relapses in younger MS patients, but is not associated with disability or disability progression over three years follow-up. Whether high dose supplementation to supra physiological 25(OH)D levels prevents disability progression in MS should become clear from long term follow-up of supplementation studies.

Mapping the effects of vitamin D in multiple sclerosis

“…In a cross-sectional design, we found higher 25(OH)D levels in relapse-free patients with a disease duration shorter than 5 years [42] . In a longitudinal analysis, higher 25(OH)D levels predicted a reduced risk of relapses only in the younger RRMS patients in our cohort [61] . In the study by Simpson et al, higher 25(OH)D levels were associated with a lower hazard of relapses in an RRMS cohort with a mean disease duration of 6.8 years [41] .…”

“…Participants were randomized to receive either high-dose vitamin D 3 supplementation (cholecalciferol, Vigantol® Oil, Merck KGaA, Darmstadt, Germany; 14000 IU/day) or placebo during 48 weeks. This study design should expose participants to similar environmental supplies of vitamin D 3 prior to both time points and limit an effect of seasonal fluctuation of 25(OH)D. Moreover, seasonal fluctuation was negligible in our previous studies when compared to the elevation of serum 25(OH) D levels achieved with supplements [61] . For validation of our results on CD25 cell surface expression also data from a separate smaller randomized controlled study on vitamin D 3 supplementation (4000 IU/day during 16 weeks) available in 27 female RRMS patients was used (Table S2; NCT02096133).…”

“…Several studies have shown associations of serum 25(OH)D levels with MS disease activity. During relapses, serum 25(OH)D levels appeared to be lower [169] , and lower serum 25(OH)D levels have also been associated with an increased risk of relapses [61] and new lesions on MRI [41][42][43] . A 50 nmol/L increase in 25(OH)D level has been calculated to result in a decrease in the relapse rate of 41-55% [41,173] .…”

“…Furthermore, inverse correlations between 25(OH)D levels and the level of disability have been found [42,59] . The correlations were not observed for disability progression [59][60][61] , except for a study including only clinically isolated syndrome (CIS) patients [53] . Here a poor vitamin D status was associated with more cerebral lesion accumulation, more brain atrophy and more disability progression over time [53] .…”

“…Although negative correlations between disability and vitamin D status have been described in MS cohorts [42,59] , an effect of vitamin D status on disability progression was not found in longitudinal [60][61] and cross-sectional data [59] . Only at the start of disease, in clinically isolated syndrome (CIS) patients, a higher vitamin D status predicts less disability progression [53] .…”