Soy isoflavonoid metabolism and effects on prostate protein expression

One of the purposes of this doctoral project was to evaluate the intra-individual stability in isoflavonoid absorption and metabolite production over time in post-menopausal women and men. Urinary isoflavonoid excretion was used as a measure of apparent isoflavonoid bioavailability. Free living post menopausal (n = 14) were randomly assigned to consume soy protein isolate containing 63 +/- 12 g protein/d and providing either 2 mg isoflavone/kg body wt (higher dose) or 1 mg isoflavone/kg body wt (lower dose) using a cross over design. Each period lasted for three months. 72-hour urine was collected at the end of each month and urinary isoflavone concentrations were determined. Urinary isoflavonoid excretion appeared to be generally stable within the same person with consistent isoflavone exposure. Stability over time was generally not altered by dose or by equol producer status. However, two of the 14 women had variable urinary equol excretion during the study, indicating that equol production may potentially be inducible in a sub-section of the population. Similarly, low intra-individual variability was noted in men (n = 15) consuming soy protein isolate providing 40 g protein and 107 +/- 5 mg of isoflavones/day for 6 months.;A related purpose of this thesis was to evaluate the effects of soy protein isolate on prostatic protein expression in men at high risk of developing prostate cancer. Twenty three men at high risk of developing prostate cancer or with low grade prostate cancer were randomly assigned to consume either (i) soy protein isolates providing 107 +/- 5 mg isoflavone/d, or (ii) soy protein isolate largely devoid of isoflavones (< 6 mg/d), or (iii) milk protein isolate for a period of six months. Prostate biopsy samples were obtained at the end of the intervention. Proteins were identified using two-dimensional liquid chromatography-matrix assisted laser desorption ionization mass spectrometry and they were relatively quantified using iTRAQRTM labels. Using methodology that was optimized for this study, we identified 20 proteins that were differentially expressed in the prostates of men consuming soy protein isolate with isoflavones and those consuming milk protein. Network mapping indicated that several of these proteins interacted with the nuclear-factor kappa B pathway, and the nature of the interaction largely suggested a suppression of this pathway. Also, several immune and inflammation related proteins were altered. However similar interactions were observed in men receiving soy protein largely devoid of isoflavones, indicating that other compounds in soy may also exert biological effects. The effects observed were modest with about a 2-fold change. The suppression of the nuclear-factor kappa B pathway provides insights on potential mechanisms via which soy may exert chemopreventive effects. To the best of our knowledge this is the first study to use a proteomics approach to elucidate the effects of soy on prostate protein expression.