Human Se Nutritional Requirement and Biomarkers in Health and Disease

描述（由申请人提供）：硒缺乏导致硒酶浓度降低，从而导致硒酶功能降低。这在动物中的一些后果是对感染、某些药物和化学品的毒性以及其他营养缺乏的损害的易感性增加。有证据表明，在亚洲、欧洲和非洲的人群中存在不同程度的硒缺乏症。此外，美国的一些肝硬化患者似乎缺乏硒。该项目旨在获得必要的知识，以评估人口和个人对硒补充剂的需求，并制定具有成本效益的补充剂。在上一个赠款期内，完成了三项临床研究。一项在中国缺硒人群中进行的研究表明，作为血浆硒营养状况的指标，硒蛋白P浓度上级优于谷胱甘肽过氧化物酶活性。它指出，目前推荐的硒的膳食允许量太低，并表明常用形式的元素的生物利用度差异很大。美国一项针对健康受试者的研究表明，硒补充剂不会增加血浆硒蛋白，表明受试者硒充足。血浆硒增加，但增加与每一种形式的硒给予不同。并推导出硒蛋氨酸摄入量与血浆硒浓度的关系式。第三项研究表明，美国一些严重肝硬化患者缺硒，可能是因为他们无法代谢饮食中的硒代蛋氨酸。在即将到来的资助期内，我们建议在中国进行两项研究，那里有缺硒人群。一个将根据血浆硒蛋白P确定健康受试者的硒需要量，另一个将确定通常用作补充剂的硒形式的生物利用度。一项针对美国肝硬化患者的研究旨在评估疾病谱中硒缺乏的发生率，并确定修复硒缺乏所需的硒的形式和剂量。最后，将对血浆中硒的小分子转运形式进行表征，并开发一种测定方法，以期将其作为硒状态的上级指标。所有这些研究都旨在促进确定硒缺乏对健康的影响，并在需要时指导补充元素。

DESCRIPTION (provided by applicant): Selenium deficiency leads to decreased concentration and therefore functions of selenoenzymes. Some consequences of this in animals are increased susceptibility to infections, to toxicity of certain drugs and chemicals, and to damage by other nutritional deficiencies. There is evidence for selenium deficiency of varying severity in human populations in Asia, Europe, and Africa. In addition, some people in the U.S. with cirrhosis appear to be selenium deficient. This project aims to acquire the knowledge necessary to assess the need for selenium supplementation of populations and individuals and to formulate cost-effective supplements. In the previous grant period three clinical studies were completed. One, carried out in a selenium-deficient population in China, demonstrated that selenoprotein P concentration was superior to glutathione peroxidase activity as a plasma index of selenium nutritional status. It indicated that the present recommended dietary allowance for selenium is too low and showed that bioavailability of commonly used forms of the element vary widely. A study of healthy subjects in the U.S. demonstrated that selenium supplements did not increase either plasma selenoprotein, indicating that the subjects were selenium replete. Plasma selenium increased but the increase was different with each form of selenium given. An equation was derived that related increase in plasma selenium concentration to selenomethionine intake. The third study showed that some patients in the U.S. with severe cirrhosis are selenium deficient, presumably because they are unable to metabolize dietary selenomethionine. In the coming grant period we propose two studies in China, where a selenium-deficient population is available. One will determine the selenium requirement of healthy subjects based on plasma selenoprotein P and the other will determine the bioavailability of forms of selenium commonly used as supplements. A study of U.S. patients with cirrhosis is proposed to assess the occurrence of selenium deficiency over the disease spectrum and to determine the form and dose of selenium needed to repair it. Finally, characterization of the small-molecule transport form of selenium in plasma and development of an assay for it will be carried out with the expectation that it will serve as a superior index of selenium status. All these studies are aimed at facilitating efforts to determine the health effects of selenium deficiency and to guide supplementation of the element when that is needed.