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| Date: 12-30-2016 | HC# 121661-559 |
Student V, Vidlar A, Bouchal J, et al. Cranberry intervention in patients with prostate cancer prior to radical prostatectomy. Clinical, pathological and laboratory findings. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2016;160(4):559-565.
Prostate cancer (PCa) impacts the lives of many men throughout the world. Cranberry (Vaccinium macrocarpon, Ericaceae) fruit extract and some of its constituents (flavonoid, proanthocyanidin, and triterpenoid fractions) have been shown to have anticancer bioactivity in vitro. This team's 2010 clinical trial showed that consumption of 1500 mg of cranberry fruit powder daily for 6 months decreased prostate-specific antigen (PSA, a marker for early detection of PCa) in men with lower urinary tract symptoms (chronic nonbacterial prostatitis and/or benign prostatic hyperplasia), a subpopulation with greater risk for the development of PCa. The primary objective of this randomized, double-blind, placebo-controlled study was to measure the impacts of cranberry fruit powder consumption on PSA concentrations and other biomarkers in patients with PCa scheduled for radical prostatectomy.
This study took place at the Department of Urology, University Hospital Olomouc, Czech Republic, from May 2012 to May 2013. Included (otherwise healthy) patients had a PCa diagnosis and a body mass index (BMI) of < 37. Those using antibiotics or who had undergone radiation or chemotherapy were excluded. In total, 64 patients were enrolled in the study and randomly assigned to receive 1500 mg/day of either cranberry powdered extract or placebo for at least 21 days prior to a prostatectomy surgery. Patients were told to avoid soy (Glycine max, Fabaceae) and foods rich in anthocyanins. The placebo was composed of maltodextrin, canola (Brassica napus, Brassicaceae) oil, Red 40 Lake, sodium aluminum silicate, and Blue 1 Lake. Cranberry fruit powder (Pacran®) was provided by NATUREX-DBS (Sagamore, Massachusetts); according to the manufacturer's website, Pacran is standardized to contain ˃ 1.5% proanthocyanidins. However, the authors' analysis found that total proanthocyanidins were 41 mg/100 mg and total anthocyanins/anthocyanidins were 234 mg/100 mg. The cranberry/placebo capsules were provided by Walmark, a.s. (Třinec, Czech Republic).
Blood and urine samples were collected at baseline and immediately before surgery, and prostatectomy specimens were collected during surgery for routine immunohistochemistry examination of prostate tissue markers. Basic biochemical and hematological parameters that were assessed included the following: total cholesterol, low-density lipoprotein, high-density lipoprotein, triacylglycerols, C-reactive protein, alanine aminotransferase, gamma-glutamyltranspeptidase (GGT), glycaemia, creatinine, blood urea nitrogen, interleukin-6, testosterone, PSA, insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein, and free testosterone. Markers of oxidative stress selected for evaluation included total sulphydryl groups, lipid peroxidation products such as malondialdehyde in plasma (PMDA) and erythrocytes (MDA), glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase in erythrocytes, paraoxonase 1 (PON1) activity, and plasma 8-hydroxydeoxyguanosine (8-OHdG). Urine samples were analyzed to determine levels of free phenolics, total phenolics, anthocyanins/anthocyanidins, proanthocyanidins, and 7 genetic markers for PCa. Protocol compliance was measured by counts of returned capsules.
From the total of 32 patients per group at the start of the trial, 1 patient in each group was withdrawn from the study due to a cancelled prostatectomy or early surgery date, leaving 31 patients in each group for final analysis. At baseline, there were no significant differences between groups in age, BMI, or blood concentrations of zinc or selenium; however, the cranberry group had a significantly elevated mean concentration of PSA as compared with placebo. Stage of cancer (mean Gleason score) was not significantly different between groups either before or following surgery.
In the cranberry group, the PSA concentrations were significantly decreased (22%) over the course of the study (8.83 ng/ml vs. 6.84 ng/ml, P<0.05); in the placebo group, PSA concentrations were significantly increased (5.38 ng/ml vs. 5.43 ng/ml, P<0.05). IGF-1 concentrations significantly increased over the course of the study in the cranberry group (P<0.01) but not in the placebo group (there is some evidence that elevated IGF-1 levels in patients with advanced cancer are associated with a longer survival time). GGT (a marker of liver function) significantly decreased in the cranberry group (P<0.01) but did not change in the placebo group.
MDA, PMDA, and total thiol concentrations were significantly elevated in both groups (P<0.05 for all). PON1 was significantly elevated only in the placebo group (P<0.01), while catalase was significantly elevated only in the cranberry group (P<0.05). There were no significant differences in immunohistochemical tissue markers or urinary total phenol concentrations between groups. No anthocyanins or proanthocyanidins were detected in the urine analyses. There was a trend for downregulation of beta-microseminoprotein (MSMB) after cranberry supplementation; in 6 out of 9 patients, this decrease was also associated with a downregulation of PSA.
This study found that 1500 mg/day of cranberry fruit powder for 21 days decreased PSA levels in patients with PCa, suggesting a potential use of this botanical in the treatment or prevention of PCa. The elevation of markers of oxidative stress suggests cranberry supplementation did not have an antioxidant effect in this study. Limitations of the study include the small sample size and short treatment duration; it should also be noted that all the P values reported were for the change from baseline, not the difference between groups. The authors conclude that "these data suggest that further studies to evaluate cranberry consumption as a prophylactic against the biochemical recurrence of prostate cancer in patients after surgery is warranted."
—Amy C. Keller, PhD
