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The aim of this study was to better understand the metabolic fate of dietary estrogenic isoflavones in humans. Twelve volunteers were challenged with soya flour and urinary levels of the isoflavones daidzein (Da), genistein (Gen), and glycitein (Gly), and the isoflavonoid metabolites equol (Eq) and O-desmethylangolensin (O-Dma) determined by GC and GC-MS. Prior to challenge, Da, Gen, and Gly were present in the urine of all participants at low levels and Eq and O-Dma were present in 9/12 and 10/12 participants, respectively. Urinary levels of all five diphenols were increased in each individual on the day following challenge, returning to approximately prechallenge levels on the second or third day post-challenge. Mean post-challenge peak levels of the five diphenols compared with pre-challenge levels were Da (4x), Gen (8x), Gly (5x), Eq (45x), and O-Dma (66x). However, there was considerable individual variation in this metabolic response with peak levels of Eq showing the highest variation (1527x). An inverse relationship between Eq and O-Dma excretion was also found post-challenge suggesting individual variability in the preferred metabolic pathways of dietary isoflavones.

BACKGROUND Previously, it was demonstrated that phenoxodiol induces apoptosis in epithelial ovarian carcinoma (EOC) cells and that it is capable of sensitizing these cells to Fas‐mediated apoptosis. The objectives of this study were to determine whether phenoxodiol can also act as chemosensitizer to chemotherapeutic agents and to characterize the molecular mechanism behind its sensitizing effect. METHODS Ten EOC cell lines were used in this study. The effect of phenoxodiol on the inhibitory concentration 50% (IC50) of carboplatin, paclitaxel, and gemcitabine was determined by the CellTiter 96 Assay. The in vivo effect of combination treatments with phenoxodiol and the above‐mentioned agents was determined in animal xenograft models. Apoptosis was measured using the Caspase‐Glo Assay and the apoptotic cascade was characterized by Western blot analyses. RESULTS The results showed that phenoxodiol is able to sensitize EOC cells to carboplatin, paclitaxel, and gemcitabine both in vitro and in vivo. In addition, it was demonstrated that phenoxodiol is capable of inducing apoptosis by: 1) the activation of the mitochondrial pathway through caspase‐2 and Bid signaling, and 2) the proteasomal degradation of the anti‐apoptotic protein XIAP. CONCLUSION Understanding the components of the apoptotic pathway activated by phenoxodiol, which allows it to sensitize EOC cells to chemotherapeutic agents, will provide valuable information on the characteristic mode of action of a chemosensitizer. This will help in the identification of novel drugs and in the design of better strategies for combination therapy in patients with recurrent ovarian carcinoma. Cancer 2006. © 2005 American Cancer Society.

These data do not indicate a therapeutic benefit from dietary supplementation with isoflavones in women experiencing menopausal symptoms, but do indicate that the apparent placebo effect in many studies of menopausal symptoms may be attributable to dietary sources of isoflavones. The study also demonstrates that 3 months of isoflavone supplementation did not cause adverse events or endometrial changes.