Isoflavone pharmacokinetics and metabolism after consumption of a standardized soy and soy-almond bread in men with asymptomatic prostate cancer.
Epidemiologic associations suggest that populations consuming substantial amounts of dietary soy exhibit a lower risk of prostate cancer. A 20-week randomized, phase II, crossover trial was conducted in 32 men with asymptomatic prostate cancer. The crossover involved 8 weeks each of soy bread (SB) and soy-almond bread (SAB). 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 SBs were formulated to deliver approximately 60 mg aglycone equivalents of isoflavones per day. The isoflavones were present as aglycones (∼78% as aglycones) in the SAB whereas in the standard 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 1 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 h of dihydrodaidzein and O-desmethylangolensin was significantly greater after an 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 SB used for future large-scale randomized clinical trials to affect human prostate carcinogenesis is feasible.
Department of Food Science and Technology, College of Food, Agricultural, and Environmental Sciences, The Ohio State University, Columbus, Ohio.
Jennifer H
JH
Ahn-Jarvis
Division of Medical Oncology, Department of Internal Medicine, The Arthur G. James and Richard Solove Research Institute, The Ohio State University, Columbus, Ohio. The Ohio State University Comprehensive Cancer Center, Columbus, Ohio. steven.clinton@osumc.edu.
Steven K
SK
Clinton
The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
Elizabeth M
EM
Grainger
Department of Food Science and Technology, College of Food, Agricultural, and Environmental Sciences, The Ohio State University, Columbus, Ohio. The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
Kenneth M
KM
Riedl
Department of Food Science and Technology, College of Food, Agricultural, and Environmental Sciences, The Ohio State University, Columbus, Ohio. The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
Steven J
SJ
Schwartz
Department of Epidemiology and Biostatistics at the University of Maryland, College Park, Maryland.
Mei-Ling T
ML
Lee
Department of Epidemiology and Biostatistics at the University of Maryland, College Park, Maryland.
Raul
R
Cruz-Cano
Center for Biostatistics at The Ohio State University College of Medicine, Columbus, Ohio.
Gregory S
GS
Young
Division of Medical Oncology, Department of Internal Medicine, The Arthur G. James and Richard Solove Research Institute, The Ohio State University, Columbus, Ohio. The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
Gregory B
GB
Lesinski
Department of Food Science and Technology, College of Food, Agricultural, and Environmental Sciences, The Ohio State University, Columbus, Ohio. The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
Yael
Y
Vodovotz
D019540:Area Under Curve; D001682:Biological Availability; D001939:Bread; D016000:Cluster Analysis; D018592:Cross-Over Studies; D004032:Diet; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000737:chemistry; D005960:Glucosides / Q000737:chemistry; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D007529:Isoflavones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D009754:Nuts / Q000737:chemistry*; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000628:therapy*; D000068181:Prunus dulcis / Q000737:chemistry; D013002:Somatomedins / Q000378:metabolism; D013025:Glycine max / Q000737:chemistry*
D005960:Glucosides; D018969:Insulin-Like Growth Factor Binding Proteins; D007529:Isoflavones; D013002:Somatomedins; C433163:dihydrodaidzein; C074869:7-deoxy-13-dihydroadriamycinone; D004317:Doxorubicin; C050052:O-desmethylangolensin