Abstract
BACKGROUND: Concerns about the neurotoxic potential of dental amalgam in multiple sclerosis (MS) persists but its impact on disease risk and progression remains unclear. METHODS: We used data from a Swedish population-based case-control study (2386 cases, 4849 controls) to investigate the association between dental amalgam exposure and MS risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated by using logistic regression and interaction with smoking was evaluated. Relapsing-onset MS cases born between 1965 and 1985 (n = 1191) were followed longitudinally by using clinical data from the Swedish MS registry. The time to confirmed disability worsening (CDW) and Expanded Disability Status Scale (EDSS) 3 and 4 were assessed by using Cox regression; EDSS trajectories were analysed by using linear mixed-effects models. RESULTS: Amalgam exposure was associated with increased MS risk in a dose-dependent manner (OR for trend 1.14, 95% CI 1.08-1.20). A significant interaction with smoking was observed (attributable proportion due to interaction 0.25, 95% CI 0.10-0.40). In the longitudinal cohort, those with at least six fillings had increased risk of CDW [hazard ratio (HR) 1.35, 95% CI 1.07-1.71] and progression to EDSS 3 (HR 1.48, 95% CI 1.07-2.05) and EDSS 4 (1.68, 95% CI 1.01-2.83). Associations were stronger among current smokers, those diagnosed after age 40 years, and individuals on low-efficacy therapies. The EDSS trajectories also showed faster progression in the high-exposure group (P = .044). CONCLUSION: Dental amalgam exposure may be associated with both increased risk of MS and faster disability progression. Findings support a potential synergistic effect with smoking and raise the hypothesis that mercury may contribute to MS-related neurodegeneration.