SOY ISOFLAVONE METABOLITE EQUOL

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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.