Bioavailability of pure isoflavones in healthy humans and analysis of commercial soy isoflavone supplements

The pharmacokinetic behavior of naturally occurring isoflavones has been de termined for the first time in healthy adults. We compared plasma kinetics of pure daidzein, genistein and their beta -glycosides administered as a si ngle-bolus dose to 19 healthy women. This study demonstrates differences in the pharmacokinetics of isoflavone glycosides compared with their respecti ve beta -glycosides. Although all isoflavones are efficiently absorbed from the intestinal tract, there are striking differences in the fate of aglyco nes and beta -glycosides. Mean time to attain peak plasma concentrations (t (max)) for the aglycones genistein and daidzein was 5.2 and 6.6 h, respecti vely, whereas for the corresponding beta -glycosides, the t(max) was delaye d to 9.3 and 9.0 h, respectively, consistent with the residence time needed for hydrolytic cleavage of the glycoside moiety for bioavailability. The a pparent volume of distribution of isoflavones confirms extensive tissue dis tribution after absorption. Plasma genistein concentrations are consistentl y higher than daidzein when equal amounts of the two isoflavones are admini stered, and this is accounted for by the more extensive distribution of dai dzein (236 L) compared with genistein (161 L). The systemic bioavailability of genistein [mean AUC = 4.54 mug/(mL . h)] is much greater than that of d aidzein [mean AUC = 2.94 mug/(mL . h)], and bioavailability of these isofla vones is greater when ingested as beta -glycosides rather than aglycones as measured from the area under the curve of the plasma appearance and disapp earance concentrations. The pharmacokinetics of methoxylated isoflavones sh ow distinct differences depending on the position of the methoxyl group in the molecule. Glycitin, found in two phytoestrogen supplements, underwent h ydrolysis of the beta -glycoside moiety and little further biotransformatio n, leading to high plasma glycitein concentrations. Biochanin A and formono netin, two isoflavones found in one phytoestrogen supplement, were rapidly and efficiently demethylated, resulting in high plasma genistein and daidze in concentrations typically observed after the ingestion of soy-containing foods. These differences in pharmacokinetics and metabolism have implicatio ns for clinical studies because it cannot be assumed that all isoflavones a re comparable in their pharmacokinetics and bioavailability. An analysis of 33 phytoestrogen supplements and extracts revealed considerable difference s in the isoflavone content from that claimed by the manufacturers. Plasma concentrations of isoflavones show marked qualitative and quantitative diff erences depending on the type of supplement ingested. These studies indicat e a need for improvement in quality assurance and standardization of such p roducts.