American Journal of Clinical Nutrition, 2011, 94(5):1284-94.

Soy isoflavone phase II metabolism differs between rodents and humans: implications for the effect on breast cancer risk

Xueheng Zhao, et al

Division of Pathology and Laboratory Medicine, Cincinnati Children’s Hospital Medical Center, OH 45229, USA; et al

BACKGROUND: Human and animal studies have produced conflicting results with regard to the effect of soy isoflavones on breast cancer risk. This may be due to differences in isoflavone metabolism.

OBJECTIVE: The objective of this study was to determine whether soy isoflavone phase II metabolism differs between humans and rodents.

DESIGN: Circulating total and unconjugated isoflavone concentrations were determined by mass spectrometry in plasma samples from 7 separate studies: 1) in Sprague-Dawley rats and in 3 strains of mice fed commercial soy-containing diets; 2) in Sprague-Dawley rats gavaged with genistein; 3) in healthy adults who consumed single servings of soy nuts, soy milk, and tempeh; 4) in healthy adults subchronically given soy milk; 5) in healthy women orally administered 50 mg genistein; 6) in healthy women orally administered 20 mg pure S-(-)equol; and 7) in 6-mo-old infants fed soy infant formula and later, at age 3 y, a soy germ isoflavone supplement.

RESULTS: The proportion of unconjugated genistein in plasma from adults and infants who consumed different soy foods, pure genistein, or an isoflavone supplement was <1% in steady state and <2% at peak concentrations. By contrast, rodents fed soy-containing diets conjugate isoflavones less efficiently. The plasma percentages of unconjugated genistein concentrations in Sprague-Dawley rats and C57BL/6, nude, and transgenic AngptL4B6 mice were 4.0 ± 0.6%, 4.6 ± 0.6%, 11.6 ± 0%, and 30.1 ± 4.3%, respectively, which represent 20, 23, 58, and 150 times that in humans.

CONCLUSION: The markedly higher circulating concentrations of biologically active (unconjugated) genistein in certain strains of mice cast doubt on the value of the use of these rodents for gaining insight into the effects of isoflavones in humans, especially with regard to the effects on breast tissue.

美国《美国临床营养学杂志》，2011年11月

大豆异黄酮 II 期代谢在啮齿类动物和人类之间有所区别︰ 对患乳腺癌风险的影响

赵学恒等

美国辛辛那提儿童医院医学中心病理学和实验室医学科

背景︰ 人体和动物研究发现大豆异黄酮对患乳腺癌风险的影响结果互相矛盾。这可能是由于异黄酮代谢的差异。

目的︰ 本研究的目的是确定大豆异黄酮 II 相代谢在人体和啮齿类动物之间是否有区别。

设计︰通过质量分光光度法测定下列7 项单独研究血浆样品中全部和游离异黄酮的循环浓度︰ 1) 给大鼠和 3 种小鼠喂食商业含大豆的饮食；2） 给大鼠管饲染料木黄酮；3） 健康成年人消耗单份装的大豆坚果、 大豆牛奶和豆豉；4） 健康成年人慢性给予豆浆；5) 健康妇女口服给药 50 mg染料木黄酮；6) 在健康妇女口服给药20 mg纯雌马酚；和 7） 给 6 月大婴幼儿喂食大豆婴儿配方奶粉，并且在 3 岁 时，喂食大豆胚芽异黄酮补充剂。

结果︰消耗了不同大豆食品、 纯净的金雀异黄素或一种异黄酮补充剂的成人和婴儿等血浆中游离金雀异黄素的比例在稳态小于 1%并且峰值浓度<小于2%。相比之下，喂食含有大豆食品的啮齿类动物结合异黄酮的效率较低。游离染料木黄酮在大鼠和 C57BL/6、 裸体、 及转基因 AngptL4B6 小鼠中的血浆百分比分别为 4.0 ± 0.6%、 4.6 ± 0.6%、 11.6 ± 0%和 30.1 ± 4.3%，在人体中分别代表 20、 23、 58 和 150 倍。

结论︰ 生物活性 （游离） 染料木黄酮在某些小鼠中显著较高的循环浓度引起了人们对使用啮齿类动物来考察异黄酮对人体作用的怀疑，尤其是对乳腺组织的影响。