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

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