Low vitamin D, but not tobacco use or high BMI, is associated with long-term disability progression in multiple sclerosis

Kristin Wesnes,Kjell-Morten Myhr,Trond Riise,Silje Stokke Kvistad,Øivind Torkildsen,Stig Wergeland,Trygve Holmøy,Rune Midgard,Alla Bru,Astrid Edland,Randi Eikeland,Sonia Gosal,Hanne F Harbo,Grethe Kleveland,Yvonne S Sørenes,Nina Øksendal,Kjetil Bjørnevik

doi:10.1016/j.msard.2021.102801

Abstract

BackgroundLow vitamin D levels, tobacco use and high body mass index (BMI) have been linked to adverse disease outcomes in multiple sclerosis (MS), but their influence on long-term disability progression remains unclear. Therefore, we explored whether these modifiable lifestyle factors were associated with 10-year clinical disability progression in patients with MS. MethodsIn this prospective study, a cohort of 88 patients with relapsing-remitting MS completed a randomized controlled study on ω-3 fatty acids between 2004 and 2008. During 24 months, serum 25-hydroxyvitamin D (25(OH)D), serum cotinine (nicotine metabolite), and BMI were repeatedly measured. In 2017, a follow-up study was conducted among 80 of the participants, including disability assessment by the Expanded Disability Status Scale (EDSS). Linear regression was used to explore associations between the lifestyle factors and the EDSS change over 10 years. ResultsHigher seasonally adjusted 25(OH)D levels were associated with lower 10-year EDSS progression (change in EDSS per 1 SD increase in 25(OH)D in a model adjusted for sex, age and baseline EDSS: -0.45 point, 95% CI: -0.75 to -0.16, p=0.003). Further adjustments for potential confounders related to lifestyle and disease status gave similar results. The association was mainly driven by low 25(OH)D levels during spring, as well as seasonally adjusted levels below 80 nmol/L. No clear association was found for BMI and cotinine. ConclusionLower 25(OH)D levels, but apparently not tobacco use or higher BMI, were significantly associated with worse long-term disability progression in MS.

Highlights

Some studies indicate that higher body mass index (BMI) leads to more disease activity through weaker therapy response (Kvistad et al, 2015, Huppke et al, 2019), and may affect brain volume loss (Mowry et al, 2018), whereas other studies have failed to demonstrate any association between BMI and disease progression (Pilutti et al, 2012, Bove et al, 2016)
In subsequent analyses, lower 25(OH)D levels were associated with more inflammatory MRI-activity before initiation of subcutaneous interferon beta 1a (IFN-β) at study month 6 (Loke n-Amsrud et al, 2012), and higher BMI was associated with more dis ease activity after initiation of IFN-β (Kvistad et al, 2015)
At follow-up, 72.5% received any kind of disease-modifying treatment (DMT), including seven patients still on IFN-β and two patients on past autol ogous hematopoietic stem cell transplantation (aHSCT) treatment

Summary

Introduction

Established risk factors related to lifestyle such as vitamin D deficiency, tobacco smoking, and obesity may affect disease course (Waubant et al, 2019). Low vitamin D levels, tobacco use and high body mass index (BMI) have been linked to adverse disease outcomes in multiple sclerosis (MS), but their influence on long-term disability progression remains unclear. We explored whether these modifiable lifestyle factors were associated with 10-year clinical disability progression in patients with MS. Results: Higher seasonally adjusted 25(OH)D levels were associated with lower 10-year EDSS progression (change in EDSS per 1 SD increase in 25(OH)D in a model adjusted for sex, age and baseline EDSS: -0.45 point, 95% CI: -0.75 to -0.16, p=0.003). Conclusion: Lower 25(OH)D levels, but apparently not tobacco use or higher BMI, were significantly associated with worse long-term disability progression in MS

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Discussion

Conclusion