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ARS Home » Southeast Area » Little Rock, Arkansas » Arkansas Children's Nutrition Center » Research » Publications at this Location » Publication #195480
Title: METABOLIC PHENOTYPE OF ISOFLAVONES DIFFER BETWEEN FEMALE RATS, PIGS, MONKEYS, AND HUMAN SUBJECTS

Author
item GU, LIWEI - ACNC/UAMS
item HOUSE, SUZANNE - ACNC/UAMS
item Prior, Ronald
item FANG, NIANBAI - ACNC/UAMS
item RONIS, MARTIN - ACNC/UAMS
item CLARKSON, TOM - WAKE FOREST UNIV
item WILSON, M - EMORY UNIVERSITY
item BADGER, THOMAS - ACNC/UAMS

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/27/2006
Publication Date: 5/15/2006
Citation: Gu, L., House, S.E., Prior, R.L., Fang, N., Ronis, M.J., Clarkson, T.B., Wilson, M.E., Badger, T.M. 2006. Metabolic phenotype of isoflavones differ between female rats, pigs, monkeys, and human subjects. Journal of Nutrition. 136(5):1215-1221.

Interpretive Summary: Isoflavones are natural components of soy. Their physiological effects are of great concern for the public, especially infants taking soy-based formula. Experimental results from animals and humans showed great discrepancy. We speculated such discrepancy was caused by the differences in isoflavone metabolism among animal species. Daidzein, one of isoflavones, can be metabolized into equol. Equol is more bioactive than daidzein. The free isoflavones in the blood are more bioactive than their conjugates. We found humans produced minute amount of equol; so did the pigs. In contrast, monkeys (including breast–fed 2- to 6-month-old monkey infants) and rats produced large amount of equol. Monkeys also have higher amount of free isoflavones than humans. We concluded there is a significant interspecies difference in isoflavone metabolism. Pigs have an overall metabolic profile closer to human subjects than rats or monkeys.

Technical Abstract: Various physiological effects have been attributed to soy foods and many of these are thought to be due to the isoflavones associated with soy protein. Little attention has been given to the interspecies differences in the metabolism of isoflavones and the resultant metabolic profiles in serum and urine. Therefore, we determined the serum and urine isoflavone concentration profiles in three animal species typically used as models to study health effects of soy and compared them with isoflavone profiles in human subjects. Female rats (age 70 days, n=9), pigs (age 30 days, n=5), cynomolgus monkeys (mean age 3 years, n=15), and human subjects (mean age 38 years, n=10) were fed diets containing soy protein isolate. Approximately 77% and 52% (molar ratio) of summed isoflavones (isoflavones plus metabolites) in the serum of young adult rats and cynomolgus monkeys, respectively, was equol. However, equol was undetectable in pig serum and human plasma. Daidzein and genistein contributed to 88% and 91% of summed serum isoflavones in pigs and human subjects, respectively. Isoflavone profiles in urine also showed prominent interspecies differences. Monkey and rat urine contained high levels of aglycones (>85% and >32%, respectively). Pigs and human subjects excreted isoflavone mainly in the form of glucuronides (>80%) with less than 10% being aglycones. Isoflavones in human plasma were predominantly glucuronides (75%) with 24% as sulfates and less then 1% as aglycones; whereas 64% of isoflavones in monkey serum were sulfates, 30% glucuronides and 6% aglycones. Equol was also a major metabolite in serum of infant (age 2-4 months) rhesus monkeys (50~80% of summed isoflavones). Thus, there is a significant interspecies difference in isoflavone metabolism, mainly on equol production and isoflavone conjugation. It appears that pigs have an overall metabolic profile closer to human subjects than rats or monkeys.