Two Swedish case-control studies have reported that the benefits of sun exposure in MS patients occur largely independently of vitamin D (Hedstrom et al. J Neurol 2020;267:1045-1052). The finding has particular relevance during the current COVID-19 pandemic as patients self-isolate indoors.
The study analysed data from two population-based case–control studies: the Genes and Environment in MS (GEMS) study (2009-2011), which included MS cases identified from the Swedish National MS registry (n=6156 cases, 5408 controls); and the Epidemiological Investigation of MS (EIMS) study (2005-2015), which included newly-diagnosed patients (n=2880 cases, 6122 controls). Patients identified in the EIMS study were not included in the GEMS sample. The median age at MS onset for both studies was 33 years. Participants completed questionnaires and provided blood samples for genotyping and to determine 25(OH)-D levels. GEMS used an index to classify subjects as having high or low sun exposure in the 10 years prior to MS onset. EIMS stratified sun exposure for the five years prior to study inclusion. Vitamin D deficiency was defined as < 50 nmol/L.
Low sun exposure was associated with a 20% (winter) to 30% (summer) increased risk of MS in GEMS, and a 40% increased risk in EIMS. The trend to increasing MS risk with decreasing sun exposure was statistically significant. MS risk was also increased with decreasing vitamin D levels but only in subjects with serum 25(OH)D levels < 50 nmol/L; once that threshold was reached, vitamin D levels had no impact on MS risk.
The overall odds ratio for low sun exposure on MS risk was 1.38; 70% of this effect was directly attributable to sun exposure (OR 1.26) and about 30% to vitamin D deficiency (OR 1.10). MS risk was higher in patients with the DRB1*15:01 haplotype and low sun exposure, with an odds ratio of 6.0 (vs. OR 3.8 for high sun exposure) in summer and OR 5.2 (vs. OR 3.7) in winter (adjusted for sex, smoking, BMI in adolescence, history of mononucleosis and other factors).
The study concluded that low sun exposure and vitamin D deficiency are different risk factors, although they may act synergistically to further increase MS risk. Previous studies have also suggested that sun exposure and vitamin D are independent MS risk factors (Baarnhielm et al. Eur J Neurol 2012;19:955-962. Lucas et al. Neurology 2011;76:540-548). It has been suggested that UV exposure activates regulatory T and B cells and alters cytokine and chemokine release via vitamin D-independent pathways (Lucas et al. Neurodegener Dis Manag 2015;5:413-424. Breuer et al. Ann Neurol 2014;75:739-758).