Soy Isoflavone Metabolite Equol--Formation and Fate

大豆异黄酮代谢物雌马酚——形成与归宿

• 批准号: 7455117
• 负责人: KENNETH DAVID SETCHELL
• 金额: $ 37.41万
• 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 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7455117
• 关键词: Accounting; Address; Adherence; Adult; Affinity; Aftercare; Age; Age-Months; Age-Years; Androgen Antagonists; Androgens; Antibiotic Therapy; Antibiotics; Appearance; Area; Awareness; Bacteria; Behavior; Binding; Biological Availability; Blood; Bolus Infusion; Bottle feeding; Breast Feeding; Carbohydrates; Cardiovascular system; Caspase-1; Cattle; Characteristics; Chromans; Class; Clinical; Clinical effectiveness; Complement; Computer software; Condition; Conflict (Psychology); Daily; Data; Development; Diet; Diet Habits; Diet Records; Dietary Factors; Dietary Fiber; Dietary Intervention; Dietary intake; Dose; Drug Kinetics; Enrollment; Estrogen Receptor beta; Estrogen Receptors; Exclusion; Failure; Feces; Fermentation; Fiber; Food; Frequencies; Future; Gastrointestinal tract structure; Genetic Crossing Over; Hand; Health; Health Benefit; Human; In Vitro; Individual; Infant; Intake; Intervention Studies; Intestines; Isoflavones; Knowledge; Label; Lead; Life; Lignans; Longitudinal Studies; Macronutrients Nutrition; Malignant neoplasm of prostate; Measures; Menopause; Metabolic; Metabolism; Metronidazole; Milk; Minnesota; Monitor; Mono-S; Non-Starch Polysaccharide; Non-Steroidal Estrogens; Numbers; Nutritional; Observational Study; Oral; Osteoporosis prevention; Outcome; Pathway interactions; Phytoestrogens; Plasma; Play; Population; Prevalence; Principal Investigator; Production; Productivity; Property; Questionnaires; Randomized; Rate; Reaction; Recruitment Activity; Relative (related person); Research; Research Design; Research Personnel; Role; Series; Serum; Soy Foods; Soy Proteins; Specificity; Stanolone; Sterility; Study Subject; Thumb structure; Time; Treatment Protocols; Universities; Urine; Variant; Vegetarian diet; Visit; Weaning; Work; absorption; base; clinically relevant; daidzein; daidzin; day; enantiomer; equol; feeding; human ESR1 protein; human data; human study; imprint; in vivo; infancy; infant nutrition; insight; insoluble fiber; interest; named group; nutrition; prebiotics; programs; response; saturated fat; soy; soy protein isolate; time interval; uptake; urinary

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）：雌马酚是异黄酮类的非甾体雌激素，是摄入大豆异黄酮的最重要代谢物。它是由肠道细菌产生的，在4个月前的婴儿的尿液和血液中找不到。由于未知的原因，只有三分之一的成年人食用大豆食品产生雌马酚。最近关于骨质疏松症预防、心血管健康和更年期的研究表明，大豆食品对“雌马酚产生者”的有益作用明显大于不能产生雌马酚的人，现在人们认识到，这两种不同的人群需要在饮食干预研究中加以界定。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 -雌马酚，它对雌激素受体er - β有很高的亲和力，与er - α的结合可以忽略不计。另一方面，r-雌马酚具有有效的抗雄激素特性，可拮抗双氢睾酮的作用，使其具有药理意义。首次测定了S-和r -雌马酚的药代动力学。我们的目的是证明s -雌马酚在人体血浆和尿液中的存在不是由于两种对映体的吸收差异，而是由于其细菌对映体的特异性形成。既然马酚生产有很多优势，那么了解马酚生产的控制因素就很重要了。我们将确定何时马雌酚首次出现在生命早期，以及是否是早期婴儿营养类型的差异，或者断奶后饮食的组成倾向于马雌酚的产生。与奶瓶喂养相比，母乳喂养会导致肠道细菌定植的差异和较低的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，摄入一些有利于结肠发酵的益生元常量营养素有利于马酚的形成。这将通过比较健康成年人的马酚产生量与其饮食中大量营养素的摄入量来确定，使用从食物频率问卷和3天饮食记录中确定的纤维摄入量来对各组进行分层。我们将确定成人马酚生成的长期稳定性及其对抗生素使用的反应。鉴于马雌酚的临床相关性，更好地了解控制其生产的因素将有助于未来控制马雌酚生产的策略，并提高大豆食品的整体临床有效性。

项目成果

Cross-border use of food databases: equivalence of US and Australian databases for macronutrients.

• DOI: 10.1016/j.jand.2013.05.021
• 发表时间: 2013-10
• 期刊: JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS
• 影响因子: 4.8
• 作者: Summer, Suzanne S.;Ollberding, Nicholas J.;Guy, Trish;Setchell, Kenneth D. R.;Brown, Nadine;Kalkwarf, Heidi J.
• 通讯作者: Kalkwarf, Heidi J.

Assessing risks and benefits of genistein and soy.

评估金雀异黄酮和大豆的风险和益处。

• DOI: 10.1289/ehp.114-a332
• 发表时间: 2006
• 期刊: Environmental health perspectives
• 影响因子: 10.4
• 作者: Setchell,KennethDR