A novel tomato-soy juice induces a dose-response increase in urinary and plasma phytochemical biomarkers in men with prostate cancer

Authors: GRAINGER, ELIZABETH - The Ohio State University; MORAN, NANCY - Children'S Nutrition Research Center (CNRC); FRANCIS, DAVID - The Ohio State University; SCHWARTZ, STEVEN - The Ohio State University; WAN, LEI - The Ohio State University; THOMAS-AHNER, JENNIFER - The Ohio State University; KOPEC, RACHEL - The Ohio State University; RIEDL, KEN - The Ohio State University; YOUNG, GREGORY - The Ohio State University; ABAZA, RONNEY - The Ohio State University; BAHNSON, ROBERT - The Ohio State University; CLINTON, STEVEN - The Ohio State University

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/1/2018
Publication Date: 1/1/2019
Citation: Grainger, E.M., Moran, N.E., Francis, D.F., Schwartz, S.J., Wan, L., Thomas-Ahner, J., Kopec, R.E., Riedl, K.M., Young, G.S., Abaza, R., Bahnson, R.R., Clinton, S.K. 2019. A novel tomato-soy juice induces a dose-response increase in urinary and plasma phytochemical biomarkers in men with prostate cancer. Journal of Nutrition. 149(1):26-35. https://doi.org/10.1093/jn/nxy232.
DOI: https://doi.org/10.1093/jn/nxy232

Interpretive Summary: Dietary consumption of tomato and soy have been associated with a reduced risk of prostate cancer. A standardized tomato-soy juice product was previously developed for clinical testing for prostate cancer prevention. In order to move toward cancer prevention trials, the dose-response effects of tomato soy juice on blood, urine, and prostate tissue biomarkers of phytochemical exposures were defined. Prostate cancer patients scheduled for prostate removal surgery were provided of 0, 1, or 2 cans (5.5 fluid ounces/can) of tomato soy juice while waiting for surgery (24 +/-4.6 d, mean +/- SD). Patients were compliant, consuming >90% of the targeted dose. Blood concentrations of tomato carotenoids and urinary concentrations of soy isoflavones significantly increased in a dose-response fashion. Prostate concentrations of isoflavones and carotenoids were variable and not directly related to the dose, but were correlated with respective blood and urine concentrations. These findings provide the foundation for evaluating a well-characterized tomato-soy juice in human clinical trials to define the impact on human prostate carcinogenesis.

Technical Abstract: Tomato and soy intake is associated with reduced prostate cancer risk or severity in epidemiologic and experimental studies. On the basis of the principle that multiple bioactives in tomato and soy may act on diverse anticancer pathways, we developed and characterized a tomato-soy juice for clinical trials. In this phase 2 dose-escalating study, we examined plasma, prostate, and urine biomarkers of carotenoid and isoflavone exposure. Men scheduled for prostatectomy were recruited to consume 0, 1, or 2 cans of tomato-soy juice/d before surgery (mean +/- SD duration:24 +/-4.6 d). The juice provided 20.6 mg lycopene and 66 mg isoflavone aglycone equivalents/177-mL can. Plasma carotenoids and urinary isoflavone metabolites were quantified by HPLC-photometric diode array and prostate carotenoids and isoflavones by HPLC-tandem mass spectrometry. We documented significant dose-response increases (P<0.05) in plasma concentrations of tomato carotenoids. Plasma concentrations were 1.86-, 1.69-, 1.73-, and 1.69-fold higher for lycopene, Beta-carotene, phytoene, and phytofluene, respectively, for the 1-can/d group and 2.34-, 3.43-, 2.54-, and 2.29-fold higher, respectively, for the 2-cans/d group compared with 0 cans/d. Urinary isoflavones daidzein, genistein, and glycitein increased in a dose-dependent manner. Prostate carotenoid and isoflavone concentrations were not dose-dependent in this short intervention; yet, correlations between plasma carotenoid and urinary isoflavones with respective prostate concentrations were documented (R2=0.78 for lycopene, P<0.001; R2=0.59 for dihydrodaidzein, P<0.001). Secondary clustering analyses showed urinary isoflavone metabolite phenotypes. To our knowledge, this is the first demonstration of the phytoene and phytofluene in prostate tissue after a dietary intervention. Secondary analysis showed that the 2-cans/d group experienced a nonsignificant decrease in prostate-specific antigen slope compared with 0 cans/d (P=0.078). These findings provide the foundation for evaluating a well-characterized tomato-soy juice in human clinical trials to define the impact on human prostate carcinogenesis.