The association between vitamin D deficiency and multiple sclerosis: an updated systematic review and meta-analysis

Background: Although there is evidence of a link between vitamin D status and risk of multiple sclerosis (MS), there has been no systematic review where the exposure measure was vitamin D deficiency rather than 25 hydroxy vitamin D (25(OH)D) concentration. We conducted an updated systematic review and meta-analysis to estimate the association between vitamin D deficiency, defined in most studies as a serum 25(OH)D concentration of < 50 nmol L-1, and MS. Methods: We searched the MEDLINE, EMBASE, and CINAHL databases to identify relevant publications. We estimated the pooled odds ratio (OR) using a random effects model for the association between vitamin D deficiency and MS, overall and stratified by several factors, including whether or not studies included participants who were taking vitamin D supplements. We also analysed the association between mean 25(OH)D concentration and MS, and used meta-regression to assess the effects of vitamin D supplementation, latitude, age, ethnicity, vitamin D definition and seasonality on the OR estimates. The Newcastle-Ottawa Scale was used to assess study quality. Results: Results were pooled across 14 case-control studies published between 2007 and 2021 (n = 4130 cases, n = 4604 controls). Persons with vitamin D deficiency had a 54 % higher risk of multiple sclerosis than those with sufficient vitamin D status (OR 1.54; 95 % CI 1.05, 2.24). In studies that excluded participants taking vitamin D supplements (N = 7), the OR was 2.19 (95 % CI: 1.44, 3.35), whereas, in studies that did not exclude participants taking supplements, there was no increase in risk (OR 0.82; 95 % CI: 0.43, 1.58). Mean age (R-2 = 27.4 %) and inclusion/exclusion of participants taking supplements (R-2 = 33.4 %) contributed most to variability in the OR of vitamin D deficiency and MS. Conclusion: Vitamin D deficiency is associated with an increased likelihood of multiple sclerosis. Maintaining sufficient vitamin D may be an important modifiable risk factor for MS.