SOY ISOFLAVONE METABOLITE EQUOL

大豆异黄酮代谢物雌马酚

• 批准号: 7374563
• 负责人: KENNETH DAVID SETCHELL
• 金额: $ 2.13万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7374563
• 关键词: SOY; ISOFLAVONE; METABOLITE; EQUOL

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Equol, a non-steroidal estrogen of the isoflavone class, is the most important metabolite of ingested soy isoflavones. It is made by intestinal bacteria from the isoflavone daidzein, and not found in the urine and blood of infants before 4-months of age. For unknown reasons daidzein's conversion to equol is variable in adults consuming soy foods and seems diet related. Recent studies of osteoporosis prevention, cardiovascular health, and menopause have shown that beneficial effects from soy foods are significantly greater in people who are 'equol-producers' compared with those unable to make equol, and it is now realized that these two distinct populations need defining in dietary intervention studies. Equol exists in two enantiomeric forms, R-equol and S-equol, and we have shown that S-equol has a high affinity for estrogen receptor ER-beta and shows negligible binding to ER-alpha. R-equol on the other-hand has potent anti-androgen properties, antagonizing the actions of dihydrotestosterone, making it of pharmacological interest. For the first time, the pharmacokinetics of S- and R-equol will be determined. Our aim is to prove that S-equol occurs in human plasma and urine not because of differences in the absorption of the two enantiomers, but due to bacterial enantiomeric-specific formation. Since there are advantages to being an equol-producer it is important to understand the factors governing equol production. We will determine when equol first appears in early life and whether it is differences in the type of early infant nutrition, or the composition of the post-weaning diet that predispose to the production of equol (Aim 1). Breast-feeding leads to differences in intestinal bacterial colonization and a lower pH compared with bottle-feeding, and this is expected to facilitate equol formation. Preliminary in vitro and human data suggest higher intakes of certain prebiotic macronutrients conducive to colonic fermentation favor equol formation. This will be determined by comparing equol-production in healthy adults relative to their dietary intakes of macronutrients using fiber intake determined from food frequency questionnaire and 3-day diet records to stratify groups (Aim 2). We will determine the long-term stability of equol-production in adults and its response to antibiotic use (Aim 3). Also, we will determine the metabolism and pharmacokinetics of R-equol and S-equol in subjects taking a single oral bolus dose (Aim 4). Given the clinical relevance of equol, a greater understanding of factors governing its production will facilitate future strategies to manipulate equol production and enhance the overall clinical effectiveness of soy foods.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。 Equol是异黄酮类的非甾体雌激素，是摄入的大豆异黄酮的最重要代谢产物。它是由异黄酮大麦素的肠道细菌制成的，在4个月之前的婴儿的尿液和血液中未发现。由于未知的原因，大豆食用大豆食品的成年人的转化为,、 Equol是可变的，并且似乎与饮食有关。最近关于预防骨质疏松症，心血管健康和更年期的研究表明，与无法制造,、的人相比，大豆食品的有益效应显着更大，而“雌性产生者”的人更大，现在已经意识到，这两个不同的人群在饮食干预研究中需要定义。 Equol以两种对映体形式R-Equol和S-Equol存在，我们已经表明S-Equol对雌激素受体ER-BETA具有很高的亲和力，并且与ER-Alpha的结合可忽略不计。另一方面的R-Equol具有有效的抗雄激素特性，使二氢睾丸激素的作用拮抗了药理学的兴趣。首次将确定S-和R-Equol的药代动力学。我们的目的是证明S-Equol发生在人血浆和尿液中，这并不是因为两个对映异构体的吸收差异，而是由于细菌对映体特异性的形成。由于成为雌性产生者有优势，因此了解有关雌雄同体生产的因素很重要。 我们将确定Equol何时首次出现在早期生活中，以及它的早期婴儿营养类型的差异，还是易于产生Equol的断奶后饮食的组成（AIM 1）。母乳喂养会导致肠道细菌定殖的差异和与奶瓶喂养相比较低的pH值，这有望促进雌激素的形成。初步的体外和人类数据表明，某些有利于结肠发酵的某些益生元大营养素的摄入量更高。这将通过比较健康成年人的雌性产生与他们的饮食摄入大量摄入大量摄入的纤维摄入量，从食物频率问卷和为期3天的饮食记录进行分层（AIM 2）来确定（AIM 2）。我们将确定成年人中股产阶级产生的长期稳定性及其对抗生素使用的反应（AIM 3）。此外，我们还将确定接受单个口服剂量的受试者中R-Equol和S-Equol的代谢和药代动力学（AIM 4）。鉴于Equol的临床相关性，对管理其生产的因素有更深入的了解将有助于未来操纵雌激素生产并提高大豆食品的整体临床有效性。