Selenium Neurotoxicity and Amyotrophic Lateral Sclerosis: An Epidemiologic Perspective

.Selenium exposure has been proposed as possible risk factor for amyotrophic lateral sclerosis (ALS), due to the selective toxicity of the trace element, especially in its inorganic forms, toward motor neurons. The epidemiological evidence, in association with laboratory and veterinary findings, linking selenium exposure and ALS risk was originally suggested by the increased ALS mortality in an area characterized by high selenium content in soil, and subsequently confirmed in an Italian community. The latter was unintentionally exposed to high levels of inorganic hexavalent selenium through drinking water, and subsequently showed an increased incidence for neurodegenerative diseases, including ALS and Parkinson’s disease. Review of the epidemiological studies addressing the association between selenium exposure and ALS risk points out important lessons that should be considered in future research, in order to avoid misleading and biased evaluations of selenium’s effects. These include the use of central nervous system indicator of exposure such as cerebrospinal fluid, and the implementation of speciation analysis, due to the different toxic and nutritional properties of the various selenium compounds.