Dental-amalgam exposure and the risk and progression of multiple sclerosis.

backgroundConcerns about the neurotoxic potential of dental amalgam in multiple sclerosis (MS) persists but its impact on disease risk and progression remains unclear.

methodsWe 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.

resultsAmalgam 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).

conclusionDental 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.