This review covers current knowledge of selenium in the environment, dietary intakes, metabolism and status, functions in the body, thyroid hormone metabolism, antioxidant defense systems and oxidative metabolism, and the immune system. Selenium toxicity and links between deficiency and Keshan disease and Kashin-Beck disease are described. The relationships between selenium intake/status and various health outcomes, in particular gastrointestinal and prostate cancer, cardiovascular disease, diabetes, and male fertility, are reviewed, and recent developments in genetics of selenoproteins are outlined. The rationale behind current dietary reference intakes of selenium is explained, and examples of differences between countries and/or expert bodies are given. Throughout the review, gaps in knowledge and research requirements are identified. More research is needed to improve our understanding of selenium metabolism and requirements for optimal health. Functions of the majority of the selenoproteins await characterization, the mechanism of absorption has yet to be identified, measures of status need to be developed, and effects of genotype on metabolism require further investigation. The relationships between selenium intake/status and health, or risk of disease, are complex but require elucidation to inform clinical practice, to refine dietary recommendations, and to develop effective public health policies.

Information on selenium bioavailability is required to derive dietary recommendations and to evaluate and improve the quality of food products. The need for robust data is particularly important in light of recent suggestions of potential health benefits associated with different intakes of selenium. The issue is not straightforward, however, because of large variations in the selenium content of foods (determined by a combination of geologic/environmental factors and selenium supplementation of fertilizers and animal feedstuffs) and the chemical forms of the element, which are absorbed and metabolized differently. Although most dietary selenium is absorbed efficiently, the retention of organic forms is higher than that of inorganic forms. There are also complications in the assessment and quantification of selenium species within foodstuffs. Often, extraction is only partial, and the process can alter the form or forms present in the food. Efforts to improve, standardize, and make more widely available techniques for species quantification are required. Similarly, reliable and sensitive functional biomarkers of selenium status are required, together with improvements in current biomarker methods. This requirement is particularly important for the assessment of bioavailability, because some functional biomarkers respond differently to the various selenium species. The effect of genotype adds a potential further dimension to the process of deriving bioavailability estimates and underlines the need for further research to facilitate the process of deriving dietary recommendations in the future.Am J Clin Nutr 2010;91(suppl):1484S-91S.

Large variations were observed in mean nonheme-iron absorption (0.7-22.9%) between studies, which depended on iron status (diet had a greater effect at low serum and plasma ferritin concentrations) and dietary enhancers and inhibitors. Iron absorption was predicted from serum ferritin concentrations and dietary modifiers by using a regression equation. Extrapolation of these findings to developing countries and to men and women of different ages will require additional high-quality controlled trials.

Current reference values for selenium, an essential micronutrient, are based on the intake of selenium that is required to achieve maximal glutathione peroxidase activity in plasma or erythrocytes. In order to assess the evidence of relevance to setting dietary reference values for selenium, the EURRECA Network of Excellence focused on systematic searches, review, and evaluation of (i) selenium status biomarkers and evidence for relationships between intake and status biomarkers, (ii) selenium and health (including the effect of intake and/or status biomarkers on cancer risk, immune function, HIV, cognition, and fertility), (iii) bioavailability of selenium from the diet, and (iv) impact of genotype/single nucleotide polymorphisms on status or health outcomes associated with selenium. The main research outputs for selenium and future research priorities are discussed further in this review.

The relation between selenium status and decreased prostate cancer risk was examined over a relatively narrow range of selenium status; further studies in low-selenium populations are required.