Bioavailability of pure isoflavones in healthy humans and analysis of commercial soy isoflavone supplements
Bioavailability of pure isoflavones in healthy humans and analysis of commercial soy isoflavone supplements
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DOI：
10.1093/jn/131.4.1362s
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发表时间：
2001-04-01
影响因子：
4.2
通讯作者：
Heubi, JE
中科院分区：
文献类型：
--
作者：
Setchell, KDR;Brown, NM;Heubi, JE
首次在健康成人中确定了天然异黄酮的药代动力学行为。我们比较了以单次推注剂量向 19 名健康女性施用的纯大豆苷元、染料木黄酮及其 β-糖苷的血浆动力学。这项研究证明了异黄酮苷与其各自的β-苷相比，其药代动力学存在差异。尽管所有异黄酮都能有效地从肠道吸收，但苷元和β-糖苷的命运存在显着差异。苷元金雀异黄素和黄豆苷元达到峰值血浆浓度的平均时间 (t(max)) 分别为 5.2 和 6.6 小时，而对于相应的 β-糖苷，t(max) 分别延迟至 9.3 和 9.0 小时，与糖苷部分水解裂解以获得生物利用度所需的停留时间一致。异黄酮的表观分布体积证实了吸收后广泛的组织分布。当给予等量的两种异黄酮时，血浆染料木黄酮浓度始终高于大豆黄酮，这是由于与染料木黄酮（161 L）相比，黄豆黄酮（236 L）分布更广泛。金雀异黄酮的全身生物利用度[平均 AUC = 4.54 mug/(mL·h)] 远大于黄豆苷元 [平均 AUC = 2.94 mug/(mL·h)]，并且当以 β-糖苷而不是苷元形式摄入时，这些异黄酮的生物利用度更高（从血浆出现和消失浓度曲线下的面积测量）。甲氧基化异黄酮的药代动力学根据分子中甲氧基的位置而显示出明显的差异。两种植物雌激素补充剂中发现的黄豆黄素经历了β-糖苷部分的水解，并且几乎没有进一步的生物转化，导致血浆黄黄素浓度较高。生物鸡素 A 和芒柄花素（一种植物雌激素补充剂中发现的两种异黄酮）被快速有效地去甲基化，导致摄入含大豆食品后通常会观察到血浆染料木黄酮和大豆黄酮浓度较高。药代动力学和代谢的这些差异对临床研究具有影响，因为不能假设所有异黄酮的药代动力学和生物利用度都具有可比性。对 33 种植物雌激素补充剂和提取物的分析显示，异黄酮含量与制造商声称的含量存在很大差异。根据摄入的补充剂类型，异黄酮的血浆浓度显示出明显的定性和定量差异。这些研究表明需要改进此类产品的质量保证和标准化。
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 mug/(mL . h)] is much greater than that of daidzein [mean AUC = 2.94 mug/(mL . 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.