Soy Isoflavone Metabolite Equol - it's Formation and Fate

大豆异黄酮代谢物雌马酚 - 它的形成和命运

• 批准号: 7125181
• 负责人: KENNETH DAVID SETCHELL
• 金额: $ 40.15万
• 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: 2005-09-30 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7125181
• 关键词: adult human (21+); blood chemistry; clinical research; developmental nutrition; dietary carbohydrates; dietary constituent; dietary fiber; early experience; electrospray ionization mass spectrometry; enteric bacteria; flavones; gas chromatography mass spectrometry; gastrointestinal function; high performance liquid chromatography; human subject; infant human (0-1 year); liquid chromatography mass spectrometry; microorganism metabolism; nutrition related tag; pharmacokinetics; phytoestrogens; questionnaires; soybeans; statistics /biometry; steroid biosynthesis; urinalysis; adult human (21+); blood chemistry; clinical research; developmental nutrition; dietary carbohydrates; dietary constituent; dietary fiber; early experience; electrospray ionization mass spectrometry; enteric bacteria; flavones; gas chromatography mass spectrometry; gastrointestinal function; high performance liquid chromatography; human subject; infant human (0-1 year); liquid chromatography mass spectrometry; microorganism metabolism; nutrition related tag; pharmacokinetics; phytoestrogens; questionnaires; soybeans; statistics /biometry; steroid biosynthesis; urinalysis

DESCRIPTION (provided by applicant): Equol, a non-steroidal estrogen of the isoflavone class, is the most important metabolite of ingested soy isoflavones. It is made by intestinal bacteria and not found in the urine and blood of infants before 4-months of age. For unknown reasons only one-third of adults consuming soy foods make equol. 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. While equol exists in two enantiomeric forms, we have shown that humans make exclusively S-equol, and it has a high affinity for estrogen receptor ER-beta and shows negligible binding to ER-alpha. R-equol on the other-hand has potent antiandrogen 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 moreover due to its 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. Breastfeeding 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. We will determine the long-term stability of equol-production in adults and its response to antibiotic use. 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.

描述（由申请人提供）：Equol是异黄酮类的非甾体类雌激素，是最重要的摄入大豆异黄酮的代谢物。它是由肠道细菌制成的，在4个月之前婴儿的尿液和血液中未发现。由于未知原因，只有三分之一的食用大豆食品的成年人造就了雌雄同体。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。尽管Equol以两种对映体形式存在，但我们已经表明人类独家s-Equol，并且对雌激素受体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，而是由于其细菌对映体特异性的形成而引起的。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，以及它的早期营养类型的差异，还是易于产生Equol的断奶后饮食的组成。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。这将通过将健康成年人的雌性产生与使用食物频率问卷和3天饮食记录确定的纤维摄入量相对于其大量营养素的饮食摄入来确定。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。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。