METABOLIC FATE PLASMA KINETICS OF DIETARY SOY ISOFLAVONE

描述：(申请人的描述)意识到饮食对健康的影响 在西方人群的许多常见疾病中发挥重要作用，已导致 对食品中多种生物活性非营养素的认识。其中 这些，植物雌激素在植物中相对丰富，并存在于 在远东消费的食品中浓度较高，那里的流行率 癌症和激素依赖型疾病的发病率明显低于 西方人。大豆是一种丰富的皂苷来源 异氟酮、大豆苷元和染料木素，它们是雌激素的模拟物，具有 无数强大的生物学特性可以解释他们的 明显的抗癌作用。现在很明显，一种富含 植物雌激素可能使人类在疾病中受益匪浅 预防。虽然已知大豆异黄酮的代谢途径是 肠道细菌被吸收，在肝脏中结合，在体内循环 血浆，并在尿液中排泄，这些信息大多是定性的 大自然。这项申请旨在提高我们对这些因素的理解 决定血浆水平、生物利用度和动力学的药物 女性和男性中的异黄酮类，这些如何受类型和 母体的数量和化学成分，无论是性别还是 与年龄相关的代谢和肠道生物利用度的差异 运输会影响新陈代谢。血浆和尿液中异黄酮浓度 将通过质谱仪进行测量，这是唯一符合要求的方法 异黄酮类成分检测的灵敏度、精密度和特异度 大动态范围内的生物流体。我们建议建立 大豆异黄酮药动学的剂量-反应关系 对于大豆食物，营养正常的摄入量范围，并比较 用三种不同的方法测定血浆和尿中异黄酮浓度 大豆食品含有先前发现的一定水平的异黄酮类 对人类和动物的生物效应。肠道转运将是 测量以检查停留时间对新陈代谢和 异黄酮类的吸收。尿液与血浆的相关性 浓度将允许评估最合适的方法 评估对大豆食品的遵从性。这些研究将改善我们的 对大豆食品在生理上提供的程度的理解 相关水平的异黄酮类，有助于设计的信息 未来的饮食研究。

DESCRIPTION: (Applicant's Description) The awareness that diet plays an important role in many common diseases of Western populations, has led to the recognition of many classes of bioactive non-nutrients in foods. Among these, the phytoestrogens are relatively abundant in plants, and occur in high concentrations in foods consumed in the Far-East, where the prevalence of cancers and hormone-dependent diseases is significantly lower than in Western populations. The soybean is a rich source of glycosides of the isoflaones, daidzein and genistein, which are estrogen mimics, and possess a myriad of potent biological properties that can account for their demonstrable anticancer actions. It is now apparent that a diet rich in phytoestrogens may confer significant benefit to humans in disease prevention. While it is known that soy isoflavones are metabolized by intestinal bacteria, absorbed, conjugated in the liver, circulated in plasma, and excreted in urine, much of this information is of a qualitative nature. This application seeks to improve our understanding of the factors that determine the plasma levels, bioavailability, and kinetics of isoflavones in women and men, how these are influenced by the type and amount of the matrix, and chemical composition, whether there are gender or age-related differences in metabolism and bioavailabilly and if intestinal transit influences metabolism. Plasma and urinary isoflavone concentrations will be measured by mass spectrometry, the only method with the required sensitivity, precision and specificity for the detection of isoflavones in biological fluids over a large dynamic range. We propose to establish dose-response relationships for the pharmacokinetics of soy isoflavones in a nutritionally normal range of intake, for a soy food, and to compare the plasma and urinary isoflavone concentrations attained with three different soy foods containing a level of isoflavones previously found to have biological effects in humans and animals. Intestinal transit will be measured to examine the effect of residence time on metabolism and absorption of isoflavones. Correlation between urinary and plasma concentrations will permit an evaluation of the most appropriate means of assessing compliance to soy foods. These studies will improve our understanding of the extent to which soy-foods deliver physiologically relevant levels of isoflavones, information that will facilitate the design of future dietary studies.