Abstract
Both selenium (Se) deficiency and excess are found in natural locations throughout the world, though Se excess can also be caused by supplementation with Se. Both have been associated with adverse health effects that have often been characterized by a U-shaped relationship. Some health effects, such as increased mortality, are associated with both low and high Se status. Certain people and populations are better able to tolerate low or high Se intake than others; there are a number of possible explanations for this fact. Firstly, it may relate to the presence of polymorphisms (SNPs) in genes that improve the ability to deal with a low or high Se intake. Secondly, high Se status, with apparent absence of toxicity and even beneficial effects, can be found in populations exposed to toxic elements that are known to interact with Se, forming complexes in some cases. Thirdly, beneficial and harmful effects of Se depend on Se dose and form (speciation); for instance, at a high dose, selenomethionine (SeMet) has toxic effects that are mediated by metabolism to selenols/selenolates that can redox-cycle, generate superoxide radicals, and react with thiols/diselenides to produce selenyl sulphides/disulphides. Finally, it is possible that exposure to a high Se intake from birth or from a very young age may alter the composition of the gut microbiota in such a way that excess Se is more readily excreted, thus reducing its toxicity.