Selenium neurotoxicity in humans: Bridging laboratory and epidemiologic studies

•Acute overexposure to the metalloid selenium (Se) is neurotoxic in the human.•Neurotoxicity of chronic Se overexposure needs to be better characterized.•Chronic Se overexposure might induce lethargy and amyotrophic lateral sclerosis.•The different Se chemical species strongly vary in their neurotoxic effects.•Peripheral biomarkers of Se exposure may not reflect Se central nervous system levels.

Selenium is a metalloid of considerable interest in the human from both a toxicological and a nutritional perspective, with a very narrow safe range of intake. Acute selenium intoxication is followed by adverse effects on the nervous system with special clinical relevance, while the neurotoxicity of long-term overexposure is less characterized and recognized. We aimed to address this issue from a public health perspective, focusing on both laboratory studies and the few epidemiologic human studies available, with emphasis on their methodological strengths and limitations. The frequently overlooked differences in toxicity and biological activity of selenium compounds are also outlined. In addition to lethargy, dizziness, motor weakness and paresthesias, an excess risk of amyotrophic lateral sclerosis is the effect on the nervous system which has been more consistently associated with chronic low-level selenium overexposure, particularly to its inorganic compounds. Additional research efforts are needed to better elucidate the neurotoxic effects exerted by selenium overexposure.