Soy Isoflavone Metabolite Equol--Formation and Fate

大豆异黄酮代谢物雌马酚——形成与归宿

基本信息

批准号：
6983781
负责人：
KENNETH DAVID SETCHELL
金额：
$ 40.36万
依托单位：
CINCINNATI CHILDRENS HOSP MED CTR
依托单位国家：
美国
项目类别：
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

项目摘要

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）：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物。它由肠道细菌产生，4 个月前婴儿的尿液和血液中不存在。由于未知的原因，只有三分之一食用大豆食品的成年人会产生雌马酚。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。虽然雌马酚以两种对映体形式存在，但我们已经证明人类只产生 S-牛尿酚，并且它对雌激素受体 ER-β 具有高亲和力，与 ER-α 的结合可以忽略不计。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的吸收差异，而是因为其细菌对映体特异性形成。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。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常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。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。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。