Submitted to: American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 12, 2002
Publication Date: November 15, 2002
Citation: SHELNUTT, S.R., CIMINO, C.O., WIGGINS, P.A., RONIS, M., BADGER, T.M. PHARMACOKINETICS OF THE GLUCURONIDE AND SULFATE CONJUGATES OF GENISTEIN AND DAIDZEIN IN MEN AND WOMEN AFTER CONSUMPTION OF A SOY BEVERAGE. AMERICAN JOURNAL OF CLINICAL NUTRITION. 2002. v. 76. p. 588-594. Interpretive Summary: Foods containing soybeans or commercially available soy protein are generally high in isoflavones. Isoflavones have been shown to have many biological effects, both beneficial and adverse. Since these biological effects of isoflavones depend upon the concentration, we studied the levels of isolfavones in the plasma and urine of men and women after they consumed a soy protein-containing beverage to determine if time course the major forms of isolfavones. We found that isoflavone metabolites had individual concentration curves and remained in the circulation at relatively high concentrations for 4 to 12 hours, suggesting that their biological activities may also last for hours. This would suggest that infants who consume soy formula every 2 to 4 hours will always have high exposure to isoflavones. Future research is needed to determine what the biological effects of these isoflavones are and how long these effects last. This would then help us recommend how much soy would need to be eaten and how often to maintain a particular health effect.
Technical Abstract: Background: The soy isoflavones genistein and diadzein are found in blood and tissue as aglycones, glucuronides, and sulfates. Isoflavone conjugates may serve as sources of aglycones at specif target tissue and may have bioactivity. Yet, very little is known about the plasma pharmocokinetics aof isoflavone conujugates after soy ingestion. Objective: The objective of this study was to determine the plasma pharmocokinetics of glucuronide and sulfate conjugates of genistein and diandzein in humans after the consumption of a drink made with soy-protein isolate. Design: Six men and six women (x plus/minus SD age: 40.8 plus/minus 3 y) consumed a soy-protein-isolate drink. The pharmacokinets of isoflavone glucuronide and sulfate conjugates were studied with the use of beta-glucuronidase (EC 220.127.116.11) and sulfatase (EC 18.104.22.168) digestion and liquid chromatography-mass spectrometry. Results: Glucuronides of genistein and diandzein made up a significantly lower percentage (P < 0.05) of the total isoflavone concentration in plasma (48% and 33%, respectively) than in urine. The percentages of sulfates of genistein and dianzein in plasma *8% and 26%, respectively) were 2- to 6-fold those in urine (P < 0.05). Approcimately 30% of the total genistein or diadzein was comprised of mixed conjugates (one glucuronide and one sulfate). For diadzein sulfate, genistein sulfate, diadzein glucuronide, and genistein glucuronide, the time to peak (t max) was 4.5, 4.5, 4.5, and 6.0 h, respectively, and the apparent half-life (t 1/2 yz) was 3.1, 5.7, 3.2, and 8.4 h, respectively. Conclusions: These data suggest that there are significant differences in the pharmacokinetics of sulfate and glucurnikde conjugates of isoflavones. This may have important implications for the meal frequency and maintenance of target tissue bioactivity required to elicit potential health benefits.