Human Se Nutritional Requirement and Biomarkers in Health and Disease

说明(申请人提供)：缺硒会导致硒含量降低，从而导致硒酶的功能降低。这对动物的一些后果是增加了对感染、某些药物和化学品的毒性以及其他营养缺乏造成的损害的易感性。有证据表明，亚洲、欧洲和非洲的人口中存在不同程度的硒缺乏症。此外，美国一些肝硬变患者似乎缺乏硒。该项目旨在获得必要的知识，以评估人群和个人对补硒的需求，并制定具有成本效益的补充剂。在前一批赠款期间，完成了三项临床研究。在中国低硒人群中进行的一项研究表明，硒蛋白P浓度作为血浆硒营养状况的指标优于谷胱甘肽过氧化物酶活性。它表明，目前推荐的膳食硒摄入量太低，并表明常用形式的硒的生物利用度差别很大。一项对美国健康受试者的研究表明，补硒不会增加血浆中的硒蛋白，这表明受试者的硒是充足的。血浆硒含量升高，但不同形态的硒升高幅度不同。建立了血浆硒浓度升高与硒蛋氨酸摄入量之间的关系式。第三项研究表明，美国一些患有严重肝硬变的患者缺硒，可能是因为他们无法代谢饮食中的硒蛋氨酸。在接下来的资助期间，我们建议在中国进行两项研究，那里有硒缺乏的人群。一个将根据血浆硒蛋白P确定健康受试者的硒需求量，另一个将确定通常用作补充剂的各种形式的硒的生物利用度。一项针对美国肝硬变患者的研究被提出，以评估整个疾病谱中硒缺乏的发生，并确定修复它所需的硒的形式和剂量。最后，将对硒在血浆中的小分子转运形式进行表征，并建立一种检测方法，以期它将成为衡量硒状况的更好指标。所有这些研究的目的都是为了促进确定缺硒对健康的影响，并指导在需要时补充这种元素。

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.