Isoflavone pharmacokinetics and metabolism after consumption of a standardized soy and soy-almond bread in men with asymptomatic prostate cancer

摘要

Epidemiological associations suggest populations consuming substantial amounts of dietary soy exhibit a lower risk of prostate cancer. A 20-week randomized, phase II, cross-over trial was conducted in 32 men with asymptomatic prostate cancer. The crossover involved 8 weeks each of soy-bread and soy-almond bread. The primary objective was to investigate isoflavone bioavailability and metabolite profile. Secondary objectives include safety, compliance and assessment of biomarkers linked to prostate carcinogenesis. Two distinct soy breads were formulated to deliver ~60 mg aglycone equivalents of isoflavones/day. The isoflavones were present as aglycones (~78% as aglycones,) in the soy-almond bread (SAB) while in the standard soy bread (SB) predominantly as glucosides (18% total isoflavones as aglycones). Compliance to SB (97% ± 4%) and SAB (92% ± 18%) was excellent, toxicity was rare and limited to grade I gastrointestinal complaints. Pharmacokinetic studies between SB and SAB showed modest differences. Peak serum concentration time (Tmax) was significantly faster with SAB meal compared with SB in some isoflavonoids and AUC0 to 24 hr of dihydrodaidzein and O- desmethylangolensin was significantly greater after a SB meal. An exploratory cluster analysis was used to identify four isoflavone metabolizing phenotypes. Insulin-like growth factor binding protein increased significantly by 41% (p=0.024) with soy intervention. Findings from this study provide the necessary framework to study isoflavone metabolizing phenotypes as a strategy for identification of individuals that might benefit or show resistance to cancer preventive strategies using dietary soy. A standardized soy bread used for future large-scale randomized clinical trials to impact human prostate carcinogenesis is feasible.