CINCINNATI—Providing some insights on why early research results on soy and breast cancer in mice have conflicted with later human research on the subject, researchers from Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine and Nutrition Matters Inc. have found differences in the way soy isoflavones are metabolized in rodents and humans. Their finding are published in the November issue of the American Journal Clinical Nutrition (2011 Nov;94(5):1284-94).
The researchers looked at phase II metabolism in Sprague-Dawley rats, three strains of mice and healthy adults. They determined circulating total and unconjugated isoflavone concentrations using mass spectrometry in plasma samples from seven separate studies: rats gavaged with genistein; mice fed commercial soy-containing diets; healthy adults who consumed single servings of soy nuts, soy milk, and tempeh; healthy adults subchronically given soy milk; healthy women orally administered 50 mg genistein; healthy women orally administered 20 mg pure S-(-)equol; and six-month-old infants fed soy infant formula, as well as a soy germ isoflavone supplement later, at age three.
The proportion of unconjugated genistein was less than one percent in steady state and less than two percent at peak concentrations in plasma from adults and infants who consumed different soy foods, pure genistein, or an isoflavone supplement. Conversely, rodents fed plasma percentages of unconjugated genistein concentrations in Sprague-Dawley rats and C57BL/6, nude, and transgenic AngptL4B6 mice were 4.0 ± 0.6 percent, 4.6 ± 0.6 percent, 11.6 ± 0 percent, and 30.1 ± 4.3percent, respectively, which represent 20-, 23-, 58- and 150-times that in humans.
The findings led researchers to conclude, “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.”