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 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。雌马酚是一种异黄酮类非甾体雌激素，是摄入大豆异黄酮最重要的代谢产物。它是由肠道细菌从异黄酮大豆黄酮中提取的，在 4 个月之前的婴儿的尿液和血液中不存在。由于未知的原因，大豆黄酮向雌马酚的转化在食用大豆食品的成年人中是可变的，并且似乎与饮食有关。最近有关骨质疏松症预防、心血管健康和更年期的研究表明，与无法产生雌马酚的人相比，大豆食品对“能产生雌马酚”的人的益处明显更大，而且现在人们认识到，这两种不同的人群需要饮食干预研究中的定义。雌马酚以两种对映体形式存在，R-牛尿酚和S-牛尿酚，我们已经证明S-牛尿酚对雌激素受体ER-β具有高亲和力，并且与ER-α的结合可忽略不计。另一方面，R-牛尿酚具有有效的抗雄激素特性，可以拮抗二氢睾酮的作用，使其具有药理学意义。首次测定 S-和 R-牛尿酚的药代动力学。我们的目的是证明S-牛尿酚出现在人血浆和尿液中并不是因为两种对映体吸收的差异，而是由于细菌对映体特异性的形成。由于成为雌马酚生产者有很多优势，因此了解控制雌马酚生产的因素非常重要。 我们将确定雌马酚在生命早期首次出现的时间，以及早期婴儿营养类型的差异或断奶后饮食的成分是否容易产生雌马酚（目标 1）。与奶瓶喂养相比，母乳喂养会导致肠道细菌定植差异和较低的 pH 值，这有望促进雌马酚的形成。初步的体外和人体数据表明，摄入较高的某些益生元常量营养素有利于结肠发酵，有利于雌马酚的形成。这将通过比较健康成年人的雌马酚产量与其膳食中大量营养素的摄入量来确定，使用食物频率调查问卷和 3 天饮食记录确定的纤维摄入量来分层（目标 2）。我们将确定成人雌马酚产生的长期稳定性及其对抗生素使用的反应（目标 3）。此外，我们将确定 R-牛尿酚和 S-牛尿酚在单次口服推注剂量受试者中的代谢和药代动力学（目标 4）。鉴于雌马酚的临床相关性，更好地了解控制其生产的因素将有助于未来控制雌马酚生产的策略并提高大豆食品的整体临床有效性。