Orally Administered Isoflavones Are Present as Glucuronides in the Human Prostate

Abstract

Better knowledge of the bioavailability and metabolism of isoflavones in prostate tissue is needed to further investigate their mechanisms of action in the context of prostate cancer prevention. A total of 12 men with benign prostatic hyperplasia received soy extract supplementation (3 Evestrel® capsules, providing a total of 112.5 mg isoflavones aglycone eq/day) for 3 days before prostate surgery. Blood and prostate tissues were sampled and metabolites were identified using electrospray ionization liquid chromatography tandem mass spectrometry (LC-ESI-MS/MS) and chemically synthesized standards of glucuronidated isoflavones. The main metabolites were the same in prostate tissue and in plasma, namely, 2 monoglucuronides of daidzein and 2 monoglucuronides of genistein. Concentrations of total isoflavones measured in prostate reached 1.05 ± 0.62 nmol/g tissue (range 0.30–2.23) at the time of sampling, 12 h after the last isoflavone supplementation. At that time point, prostate concentrations were lower than plasma concentrations in all volunteers: 0.47 nmol/g vs. 0.66 μ M for daidzein and 0.58 nmol/g vs. 0.78 μ M for genistein. Isoflavone mechanisms of action should thus be investigated in in vitro cell studies using physiological conditions, intracellular concentrations below 5 nmol/g and no intracellular deconjugation of the monoglucuronide metabolites.

ACKNOWLEDGMENTS

M. Urpi-Sarda thanks the FPI fellowship and AGL2004-08378-C02-01/02 project from Spanish Ministry of Education and Science. A. Gil-Izquierdo is grateful to the Spanish Ministry of Education and Science for his postdoctoral fellowship.

Notes

^a Abbreviations are as follows: MRM, multiple reaction monitoring; Nd, not detected; tr, trace; +/−, present in some but not all samples.