The selenium intakes of populations vary from severely deficient in some regions of China, including Tibet, to high in Venezuela and in other regions of China. Intakes in the U.S. and Canada appear to be adequate. However, many other countries, including virtually all of Europe and Scandinavia, have intakes between the recommended intake levels of the only 2 studies carried out to determine the selenium requirement. Thus, there is uncertainty about the amount of selenium needed to prevent deficiency and such a value would be important for deciding on supplementation of populations that have intakes near the requirement. Studies are being planned to evaluate the prevention of cancer by administration of pharmacologic doses of selenium. Biomarkers of selenium are needed to control those studies and to monitor safety and compliance. In recent years a great deal has been learned about selenium metabolism. There is a non-specific metabolism, involving the selenium in selenomethionine, and a specific metabolism that recognizes selenium and incorporates it into specific selenoproteins and other metabolites. Thus, a rational basis for choosing separate biomarkers for studying selenium adequacy and pharmacologic amounts of selenium is available. We propose to carry out a study in a low-selenium area of China to determine the amount of selenium needed to maximize the plasma selenoproteins selenoprotein P and GSHPx-3 (biomarkers). We will work with Chinese investigators who have long experience in such work. The study will provide data that can be used for calculating a recommended dietary allowance of selenium that can be applied throughout the world. We propose a second clinical study to identify and characterize biomarkers for pharmacologic selenium intake. It will evaluate 3 forms of selenium and will provide guidance to investigators administering selenium of subjects above the dietary requirement. We will develop ELISAs for selenoprotein P and GSHPx-3 to facilitate the studies and we will attempt to identify a small-molecule form of selenium, A-Se, that appears to be a transport form of the element in plasma. A-Se will be evaluated as a biomarker for selenium body burden and intake. These studies are all designed to improve understanding of selenium metabolism in human beings. They should also provide tools for investigators who need to evaluate subjects for selenium deficiency and for intake of pharmacologic amounts of selenium.
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