Amyotrophic lateral sclerosis incidence following exposure to inorganic selenium in drinking water

Background and aim. Some laboratory and epidemiologic studies have documented an association between high intake of the trace element selenium and risk of amyotrophic lateral sclerosis (ALS), a degenerative disease of the motor neurons. There have been few epidemiologic studies of the association. Methods. From 1986 through 2015, we followed a community cohort in northern Italy that had been inadvertently exposed in the 1974-86 period to drinking water with unusually high levels of selenium, around 8 µg/ml, in its inorganic hexavalent form (selenate). In this cohort, we previously identified a high incidence of ALS during 1986-94. Here we report extended follow-up of this exposed cohort, as well as of an unexposed cohort including over 95,000 municipal residents, for an additional 21 years. We identified incident cases through administrative sources and a specialized registry. Results. During follow-up, 7 and 112 ALS cases were newly diagnosed in the exposed and unexposed cohorts, respectively, yielding incidence rates of 14 and 5 per 100,000 person-years. A Poisson regression analysis adjusting for age, sex, and calendar year produced an overall rate ratio (RR) for ALS of 2.8 (95% confidence interval (CI) 1.3 - 6) in the entire period of follow-up. The association was stronger earlier than later in follow-up (1986-1994 vs. 1994-2015), and among women than men. All exposed cases were of the sporadic, non-familial form for the disease. Conclusion. Overall, results from this ‘natural experiment’ indicate a positive association between chronic exposure to inorganic selenium and ALS incidence, with rates in the exposed cohort declining over time after cessation of exposure. Also taking into account the recognized neurotoxicity of selenium, particularly its selective toxicity on motor neurons observed in animal studies, the present study provides additional support for the hypothesis that selenium in its inorganic form increases ALS risk.