A phase I pilot study evaluating the beneficial effects of black raspberries in patients with Barrett’s esophagus

// Laura A. Kresty 1 , John J. Fromkes 2 , Wendy L. Frankel 3 , Cynthia D. Hammond 2 , Navindra P. Seeram 4 , Maureen Baird 3 , Gary D. Stoner 1 1 Division of Hematology & Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA 2 Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA 3 Department of Pathology, The Ohio State University, Columbus, Ohio, USA 4 Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, Rhode Island, USA Correspondence to: Laura A. Kresty, email: Lkresty@mcw.edu Keywords: Barrett’s esophagus, black raspberry, esophageal adenocarcinoma, chemoprevention, oxidative stress Received: February 18, 2016 Accepted: May 23, 2016 Published: July 7, 2016 ABSTRACT Black raspberries inhibit a broad range of cancers in preclinical models which has led to clinical evaluations targeting premalignant lesions of the colon, oral cavity and esophagus. A phase I pilot study was conducted in twenty Barrett’s esophagus (BE) patients to investigate the effect of lyophilized black raspberries (LBR) on urinary metabolites and markers of lipid peroxidation, DNA damage and tissue markers of cellular proliferation, detoxification, and inflammation. Surveys, biopsies, blood and urine samples were collected before and after 6 months of LBR treatment (32 or 45 g). LBR significantly reduced urinary excretion of 8-epi-prostaglandin F2α, a marker of lipid peroxidation linked to oxidative stress and free radical damage. Urinary levels of the ellagitannin metabolites, urolithin A-glucuronide, urolithin A-sulfate and dimethylellagic acid glucuronide were significantly increased following 12 and 26 weeks of LBR consumption and may prove useful as indicators of compliance in future clinical studies. Immunohistochemical staining of BE biopsies following LBR treatment showed significant increases in mean GST-pi levels, with 55.6% of subjects responding favorably. In summary, LBR significantly decreased urinary lipid peroxidation levels and significantly increased GST-pi, a marker of detoxification, in BE epithelium. Still, LBR may need to be formulated differently, administered at higher concentrations or multiple times a day to increase efficacy.