Sun Exposure across the Life Course Significantly Modulates Early Multiple Sclerosis Clinical Course.

Steve Simpson,Simon Broadley,Leigh Blizzard,Robyn M. Lucas,Bruce Taylor,Ingrid van der Mei,Anne-Louise Ponsonby

doi:10.3389/fneur.2018.00016

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https://doi.org/10.3389/fneur.2018.00016

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Abstract

Low vitamin D and/or sun exposure have been associated with increased risk of multiple sclerosis (MS) onset. However, comparatively, few studies have prospectively examined associations between these factors and clinical course. To evaluate the association of sun exposure parameters and vitamin D levels with conversion to MS and relapse risk in a prospectively monitored cohort of 145 participants followed after a first demyelinating event up to 5-year review (AusLong Study). Sun exposure prior to and after onset measured by annual questionnaire; ultraviolet radiation (UVR) "load" estimated by location of residence over the life course and ambient UVR levels. Serum 25-hydroxyvitamin D [25(OH)D] concentrations measured at baseline, 2/3-year, and 5-year review. MS conversion and relapse assessed by neurologist assessment and medical record review. Over two-thirds (69%) of those followed to 5-year review (100/145) converted to MS, with a total of 252 relapses. Higher pre-MS onset sun exposure was associated with reduced risk of MS conversion, with internal consistency between measures and dose-response relationships. Analogous associations were also seen with risk of relapse, albeit less strong. No consistent associations were observed between postonset sun exposure and clinical course, however. Notably, those who increased their sun exposure during follow-up had significantly reduced hazards of MS conversion and relapse. Serum 25(OH)D levels and vitamin D supplementation were not associated with conversion to MS or relapse hazard. We found that preonset sun exposure was protective against subsequent conversion to MS and relapses. While consistent associations between postonset sun exposure or serum 25(OH)D level and clinical course were not evident, possibly masked by behavior change, those participants who markedly increased their sun exposure demonstrated a reduced MS conversion and relapse hazard, suggesting beneficial effects of sun exposure on clinical course.

Highlights

Of the various environmental and behavioral—and poten tially modifiable—risk factors implicated in the onset and pro gression of multiple sclerosis (MS), evidence for a role for vitamin D and ultraviolet radiation (UVR) exposure has been among the most consistent, on a par with smoking and Epstein-Barr virus exposure
There were no material differences between the total cohort and those complet ing the 5-year review, except for the proportion converting to MS and the number of recorded relapses, which were higher among those with follow-up to 5 years
There was no consistent evidence that conversion to MS was a time point where patients changed their behavior to a large extent. In this prospective cohort study of classic first demyelinating event (FDE) cases followed for five years after FDE, we have shown that preonset sun exposure, during childhood and adolescence, significantly predicts a reduced hazard of subsequent disease activity in early MS, including hazards of conversion to MS and of relapse

Summary

Introduction

Of the various environmental and behavioral—and poten tially modifiable—risk factors implicated in the onset and pro gression of multiple sclerosis (MS), evidence for a role for vitamin D and ultraviolet radiation (UVR) exposure has been among the most consistent, on a par with smoking and Epstein-Barr virus exposure. Additional evidence comes from genetic studies that have detected significant associations with polymorphisms within or near vitamin D-associated genes [28], as well as by recent Mendelian randomization studies that implicated genetic differences in 25(OH)D levels in the develop ment of MS [29, 30]. All this taken together has led us to wait with anticipation for the results of UV treatment and vitamin D supplementation as interventions against MS outcomes in randomized trials [31]. Few studies have prospectively examined associations between these factors and clinical course

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