The association between vitamin D deficiency and multiple sclerosis: an updated systematic review and meta-analysis.
Level 4 - case-series / case-control
Systematic review and meta-analysis of retrospective case-control studies
PubMed 39180838 · doi:10.1016/j.msard.2024.105804
What was done
A systematic review and meta-analysis of MEDLINE, EMBASE, and CINAHL databases was conducted to examine the association between vitamin D deficiency (defined in most studies as serum 25(OH)D < 50 nmol/L) and multiple sclerosis (MS). Random-effects models pooled odds ratios (ORs) across studies, with subgroup analysis based on participant vitamin D supplement use. Meta-regression evaluated the influence of age, latitude, ethnicity, vitamin D deficiency definition, and seasonality. Study quality was evaluated using the Newcastle-Ottawa Scale.
What was found
Across 14 case-control studies (4,130 cases and 4,604 controls) published between 2007 and 2021, individuals with vitamin D deficiency had a 54% higher risk of MS compared to those with sufficient levels (OR 1.54; 95% CI: 1.05 to 2.24). In the 7 studies that excluded participants taking vitamin D supplements, the association was stronger (OR 2.19; 95% CI: 1.44 to 3.35), whereas studies that did not exclude supplement users showed no statistically significant association (OR 0.82; 95% CI: 0.43 to 1.58). Inclusion/exclusion of supplement users (R² = 33.4%) and mean age (R² = 27.4%) accounted for the largest shares of effect-size variability.
Why it matters
This review clarifies the specific link between categorical vitamin D deficiency and MS risk, showing that failure to account for post-onset vitamin D supplementation substantially masks the underlying observational association.
Limits
All included evidence came from case-control studies, which are susceptible to reverse causation (e.g., reduced mobility or sun exposure after MS onset lowering vitamin D levels). Blood draw timing relative to disease onset and adjustments for confounders like sun exposure and physical activity varied across studies.
Cited by
- supports Vitamin D deficiency increases the risk of developing multiple sclerosis.