Setchell K D, Brown N M, Desai P, Zimmer-Nechemias L, Wolfe B E, Brashear W T, Kirschner A S, Cassidy A, Heubi J E
Division of Clinical Mass Spectrometry, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.
J Nutr. 2001 Apr;131(4 Suppl):1362S-75S. doi: 10.1093/jn/131.4.1362S.
The pharmacokinetic behavior of naturally occurring isoflavones has been determined for the first time in healthy adults. We compared plasma kinetics of pure daidzein, genistein and their beta-glycosides administered as a single-bolus dose to 19 healthy women. This study demonstrates differences in the pharmacokinetics of isoflavone glycosides compared with their respective beta-glycosides. Although all isoflavones are efficiently absorbed from the intestinal tract, there are striking differences in the fate of aglycones 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, respectively, whereas for the corresponding beta-glycosides, the t(max) was delayed to 9.3 and 9.0 h, respectively, consistent with the residence time needed for hydrolytic cleavage of the glycoside moiety for bioavailability. The apparent volume of distribution of isoflavones confirms extensive tissue distribution after absorption. Plasma genistein concentrations are consistently higher than daidzein when equal amounts of the two isoflavones are administered, and this is accounted for by the more extensive distribution of daidzein (236 L) compared with genistein (161 L). The systemic bioavailability of genistein [mean AUC = 4.54 microg/(mL x h)] is much greater than that of daidzein [mean AUC = 2.94 microg/(mL x h)], and bioavailability of these isoflavones is greater when ingested as beta-glycosides rather than aglycones as measured from the area under the curve of the plasma appearance and disappearance concentrations. The pharmacokinetics of methoxylated isoflavones show distinct differences depending on the position of the methoxyl group in the molecule. Glycitin, found in two phytoestrogen supplements, underwent hydrolysis of the beta-glycoside moiety and little further biotransformation, leading to high plasma glycitein concentrations. Biochanin A and formononetin, two isoflavones found in one phytoestrogen supplement, were rapidly and efficiently demethylated, resulting in high plasma genistein and daidzein concentrations typically observed after the ingestion of soy-containing foods. These differences in pharmacokinetics and metabolism have implications for clinical studies because it cannot be assumed that all isoflavones are comparable in their pharmacokinetics and bioavailability. An analysis of 33 phytoestrogen supplements and extracts revealed considerable differences in the isoflavone content from that claimed by the manufacturers. Plasma concentrations of isoflavones show marked qualitative and quantitative differences depending on the type of supplement ingested. These studies indicate a need for improvement in quality assurance and standardization of such products.
首次在健康成年人中确定了天然存在的异黄酮的药代动力学行为。我们将纯黄豆苷元、染料木黄酮及其β-糖苷以单剂量推注的方式给予19名健康女性，比较了它们的血浆动力学。这项研究表明，异黄酮糖苷与其各自的β-糖苷在药代动力学上存在差异。尽管所有异黄酮都能从肠道有效吸收，但苷元和β-糖苷的命运存在显著差异。苷元染料木黄酮和黄豆苷元达到血浆峰值浓度（t(max)）的平均时间分别为5.2小时和6.6小时，而相应的β-糖苷的t(max)分别延迟至9.3小时和9.0小时，这与糖苷部分水解以实现生物利用度所需的停留时间一致。异黄酮的表观分布容积证实了吸收后在组织中的广泛分布。当给予等量的两种异黄酮时，血浆中染料木黄酮的浓度始终高于黄豆苷元，这是因为黄豆苷元（236升）的分布比染料木黄酮（161升）更广泛。染料木黄酮的全身生物利用度[平均AUC = 4.54微克/(毫升×小时)]远高于黄豆苷元[平均AUC = 2.94微克/(毫升×小时)]，并且从血浆出现和消失浓度曲线下面积测量，这些异黄酮以β-糖苷形式摄入时的生物利用度高于以苷元形式摄入时。甲氧基化异黄酮的药代动力学表现出明显差异，这取决于分子中甲氧基的位置。在两种植物雌激素补充剂中发现的大豆黄素经历了β-糖苷部分的水解，几乎没有进一步的生物转化，导致血浆中大豆黄素浓度较高。在一种植物雌激素补充剂中发现的两种异黄酮，即鹰嘴豆芽素A和芒柄花黄素，迅速且有效地脱甲基化，导致血浆中通常在摄入含大豆食品后观察到的染料木黄酮和黄豆苷元浓度较高。药代动力学和代谢的这些差异对临床研究具有重要意义，因为不能假定所有异黄酮在药代动力学和生物利用度方面都是可比的。对33种植物雌激素补充剂和提取物的分析表明，异黄酮含量与制造商声称的有相当大差异。根据摄入的补充剂类型，异黄酮的血浆浓度在定性和定量上都有显著差异。这些研究表明需要改进此类产品的质量保证和标准化。
