Exploring the urinary selenometabolome following a multi-phase selenite administration regimen in humans

To gain more insight into the human metabolism of the essential trace element selenium, we investigate the response of the urinary selenium metabolites to changing selenium intake by applying a stepwise selenium administration regimen based on repeated dosaging. Sodium selenite was administered orally to healthy volunteers at an incrementally increasing dosage. The supplementation regimen extended over 20 days for each volunteer, and daily morning urine samples were collected prior to, during, and following the supplementation phases. A total of 160 urine samples were analyzed for total urinary selenium and a panel of selenometabolites by using ICPMS and HPLC/ICPMS. Selenosugar 1 gave the strongest response followed by TMSe and then selenosugar 3. Se-methylselenoneine excretion was not stimulated by increased selenium intake, suggesting that it is not in equilibrium with selenium body pools. Selenate was detected in all urine samples; it showed a clear and consistent response to supplementation and an abrupt return to baseline levels upon cessation of supplementation, indicating that it arose from the oxidation of the administered selenite rather than from the oxidation of endogenous hydrogen selenide. The gap between total urinary selenium and the sum of Se species markedly increased in response to selenium administration, which highlights the presence of unknown Se species that respond to selenite supplementation. The characterization of these unknown species and their possible biological activities might be essential before considering selenium supplementation in clinical trials. We discuss the implications of the responses of the selenium metabolites and their inter-relationships for selenium metabolism.