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Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions

Metabolic Phenotype of Isoflavones Differ among Female Rats, Pigs, Monkeys, and Women¹

Liwei Gu^*,, Suzanne E. House^*, Ronald L. Prior^*, Nianbai Fang^**,*, Martin J. J. Ronis^*,, Thomas B. Clarkson, Mark E. Wilson and Thomas M. Badger^*,,2

^* Arkansas Children's Nutrition Center, Little Rock, AR 722 02; Departments of Physiology/Biophysics, ^** Pharmaceutical Sciences, and Pharmacology/Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72202; Comparative Medicine Clinical Research Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157; and Yerkes National Primate Center and Emory University, Atlanta, GA

² To whom correspondence should be addressed. E-mail: badgerthomasm{at}uams.edu.

Various physiologic effects of soy food consumption have been attributed to the estrogenic actions of isoflavones. The order of estrogen receptor binding potency of soy-derived isoflavone aglycones is equol > genistein > daidzein, and their conjugates are less potent. Because the metabolic profile may be an important determinant of bioactivity after soy intake, we studied the serum and urine isoflavone concentrations in 3 animal models and compared them with isoflavone profiles in women. Female Sprague-Dawley rats, Hampshire/Duroc Cross pigs, cynomolgus monkeys, and women were fed diets containing soy protein isolate. Isoflavones and their metabolites were measured by LC-MS or electrochemical detection. Equol represented 77 and 52% (molar ratio) of summed serum isoflavones (isoflavones plus metabolites) in rats and cynomolgus monkeys, respectively. Equol was undetectable in pig serum and human plasma, but daidzein and genistein contributed >88% of summed circulating isoflavones. Monkey and rat urine contained high levels of aglycones (>85% and >32%, respectively), whereas pigs and women excreted isoflavone mainly in the form of glucuronides (>80%), with <10% as aglycones. Isoflavones in human plasma were predominantly glucuronides (75%) with 24% as sulfates and <1% as aglycones; in monkey serum, however, 64% of isoflavones were sulfates, 30% glucuronides, and 6% aglycones. Equol was also a major serum metabolite of 6-mo-old rhesus monkeys (80% of summed isoflavones). Thus, there were significant interspecies differences in isoflavone metabolism, and the overall metabolic profile of pigs was closer to that of women than that of rats or monkeys.

KEY WORDS: • isoflavone • daidzein • genistein • equol • interspecies difference

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