Selenium intake, status, and health: a complex relationship

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.

Keywords: Adverse health effects; Deficiency; Dose; Excess; Microbiota; Polymorphisms; Selenium; Speciation; Toxic elements.

Fig. 1

Cumulative mortality from all causes over time by treatment group. Non-parametric cumulative mortality curves (step functions) were estimated via the Kaplan-Meier method and compared with results generated by the generalized Wilcoxon test. Parametric cumulative mortality curves (smooth lines) were estimated from spline-based parametric survival models with treatment-specific log cumulative hazards parameterized as natural cubic splines of log time with knots at the 33th and 67th percentiles of the uncensored log-time distribution. Cumulative mortality estimates (95% CIs) at 5, 10 and 15 years of follow-up by treatment group were obtained from spline-based parametric survival models. Se denotes selenium [20] (published with permission of FRBM)

Fig. 2

U-shaped relationship between Se status and disease risk (for references, see [3])

Fig. 3

Beneficial and harmful effects of Se depending on dose and form (speciation). It is proposed that Se has hermetic effects, shown by the blue line [43]. Selenoproteins with beneficial health effects are shown as a green line, while selenoproteins with paradoxical roles that appear to have harmful effects are shown as a red line [–45]. As Se intake increases, particularly if the main source is SeMet, SeMet will increasingly replace methionine in body proteins, where its turnover is exceptionally slow; SeMet has toxic effects that are explained in the text (figure created with assistance from Wen-Hsing Cheng, Mississippi State University, Mississippi State, USA)