Absolute Bioavailability of Isoflavones from Soy Protein Isolate-Containing Food in Female Balb/c Mice

Soy isoflavones, genistein and daidzein, are widely consumed in soy-based foods and dietary supplements for their putative health benefits; however, evidence for potential adverse effects has been obtained from experimental animal studies. An important prerequisite for understanding the pharmacodynamics of isoflavones is better information about pharmacokinetics and bioavailability. This study determined the bioavailability of genistein and daidzein in a mouse model by comparing plasma pharmacokinetics of their aglycone and conjugated forms following administration of identical doses (1.2 mg/kg genistein and 0.55 mg/kg daidzein) by either an intravenous injection (IV) or gavage of the aglycones in 90% aqueous solution vs a bolus administration of equimolar doses delivered in a food pellet prepared using commercial soy protein isolate (SPI) as the isoflavone source. The bioavailability of genistein and daidzein was equivalent for the gavage and dietary routes of administration despite the use of isoflavone aglycones in the former and SPI-derived glucosides in the latter. While absorption of total isoflavones was nearly quantitative from both oral routes [>84% of areas under the curve (AUCs) for IV], presystemic and systemic phase II conjugation greatly attenuated internal exposures to the receptor-active aglycone isoflavones (9-14% for genistein and 29-34% for daidzein based on AUCs for IV). These results show that SPI is an efficient isoflavone delivery vehicle capable of providing significant proportions of the total dose into the circulation in the active aglycone form for distribution to receptor-bearing tissues and subsequent pharmacological effects that determine possible health benefits and/or risks.