Isoflavone Pharmacokinetics and Metabolism after Consumption of a Standardized Soy and Soy–Almond Bread in Men with Asymptomatic Prostate Cancer

Abstract

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.

Phytotherapeutics in cancer invasion and metastasis

“…Isoflavones have been also suggested as active anticancer agents (Ahn-Jarvis et al, 2015). Particularly, genistein is an angiogenesis inhibitor and a phytoestrogen found in legumes, especially soybeans (Glycine Noteworthy, its in vitro and in vivo activities have been confirmed by clinical trials.…”

“…Isoflavones have been also suggested as active anticancer agents (Ahn‐Jarvis et al, ). Particularly, genistein is an angiogenesis inhibitor and a phytoestrogen found in legumes, especially soybeans ( Glycine max ), with well‐known tyrosine kinase receptor and DNA topoisomerase inhibitory activities (Figure ; Zaheer & Humayoun Akhtar, ).…”

Food-based natural products for cancer management: Is the whole greater than the sum of the parts?

“…A recent trial using soy bread slices in recurrent PCA patients highlighted an immuno-modulatory function of soy isoflavones by decreasing T-helper cells and myeloid derived suppressor cells-associated cytokines [67]. Supporting this observation, a 20-week crossover randomized trial of soy bread in asymptomatic PCA patients established its safety and caused a three-fold prolongation in PSADT [68]. In contrast, a double-blind, randomized trial of soy isoflavones administered six weeks prior to radical prostatectomy showed no change in serum hormone levels or PSA [69].…”

Nutraceuticals in prostate cancer therapeutic strategies and their neo-adjuvant use in diverse populations

“…Medical Center, Columbus, Ohio 32 cases Ethnicity: N/A •Decreased plasma levels of pro-inflammatory cytokines, Th1, T regulatory (CD4 + CD25 + FoxP3 + ), and monocytic (CD33 + HLADR neg CD14 + ) myeloid-derived suppressor cells (MDSC) •Increased CD56 + Natural Killer (NK) cells Lesinski et al 32 Soy •Phase II •Randomized trial •Cross-over design •Daily consumption of soy bread [2 slices (34 mg soy isoflavones/slice)] or soy-almond bread [2 slices (60 mg aglycone equivalents/day] •Patients diagnosed with asymptomatic biochemically recurrent PCa •Time: For 20 weeks (8 weeks intervention with one type of bread with 2 weeks of legume-free wash-out period) Ohio State Univ. Medical Center, Columbus, Ohio 32 cases Ethnicity: N/A •Increased blood levels of IGFBP-3 •Increased (3-fold) serum PSA doubling time •Decrease in LDL cholesterol and triglyceride levels in PCa patients with hypercholesterolemia Anh Jarvis et al 31 Soy •Randomized double-blind, placebo-controlled •Open-label trial •Daily administration of GCP [genistein (450 mg), daidzein (300 mg), and other isoflavones)] •Patients with histologically confirmed PCa and two consecutive increases in PSA readings •Time: For 12 months Univ. of California, Davis Medical Center 66 cases Ethnicity: GCP group EAs [ n = 20] AAs [ n = 3] •High serum concentrations of genistein and daidzein but no significant difference in serum PSA levels after 6 and 12 months De Vere et al 111 Soy •Phase II •Randomized, double-blind placebo-controlled trial •Daily administration of synthetic genistein (30 mg) •Patients diagnosed with localized PCa (aged ≥18 years) •Time: For 3–6 weeks prior to prostatectomy Oslo Univ.…”

“…In a 20-week phase II trial in asymptomatic PCa patients, consumption of soy-almond bread and standard soy bread contributed to a significant increase in IGFBP-3 and decrease in pro-inflammatory cytokines blood levels. 31 Unfortunately, dietary soy intervention increased serum PSA levels and its doubling time after 126 days with a slight decrease in PSA velocity in PCa patients. Similar to the previous report, isoflavones have exhibited some immunomodulatory properties in the plasma of asymptomatic biochemically recurrent PCa patients.…”