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 i s 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.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Research Project (R01)
Project #
5R01AT002190-03
Application #
7272890
Study Section
Integrative Nutrition and Metabolic Processes Study Section (INMP)
Program Officer
Sorkin, Barbara C
Project Start
2005-09-30
Project End
2009-07-31
Budget Start
2007-08-01
Budget End
2008-07-31
Support Year
3
Fiscal Year
2007
Total Cost
$410,099
Indirect Cost
Name
Cincinnati Children's Hospital Medical Center
Department
Type
DUNS #
071284913
City
Cincinnati
State
OH
Country
United States
Zip Code
45229
Setchell, Kenneth D R; Brown, Nadine M; Zimmer-Nechemias, Linda et al. (2014) Metabolism of secoisolariciresinol-diglycoside the dietary precursor to the intestinally derived lignan enterolactone in humans. Food Funct 5:491-501
Brown, Nadine M; Galandi, Stephanie L; Summer, Suzanne S et al. (2014) S-(-)equol production is developmentally regulated and related to early diet composition. Nutr Res 34:401-9
Setchell, Kenneth D R; Brown, Nadine M; Summer, Suzanne et al. (2013) Dietary factors influence production of the soy isoflavone metabolite s-(-)equol in healthy adults. J Nutr 143:1950-8
Summer, Suzanne S; Ollberding, Nicholas J; Guy, Trish et al. (2013) Cross-border use of food databases: equivalence of US and Australian databases for macronutrients. J Acad Nutr Diet 113:1340-5
Setchell, Kenneth D R; Clerici, Carlo (2010) Equol: pharmacokinetics and biological actions. J Nutr 140:1363S-8S
Setchell, Kenneth D R; Clerici, Carlo (2010) Equol: history, chemistry, and formation. J Nutr 140:1355S-62S
Setchell, Kenneth Dr; Zhao, Xueheng; Jha, Pinky et al. (2009) The pharmacokinetic behavior of the soy isoflavone metabolite S-(-)equol and its diastereoisomer R-(+)equol in healthy adults determined by using stable-isotope-labeled tracers. Am J Clin Nutr 90:1029-37
Setchell, Kenneth D R (2006) Assessing risks and benefits of genistein and soy. Environ Health Perspect 114:A332-3
Setchell, Kenneth D R; Cole, Sidney J (2006) Method of defining equol-producer status and its frequency among vegetarians. J Nutr 136:2188-93