) 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.
