Brief Article
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World J Gastroenterol. Jul 21, 2013; 19(27): 4325-4333
Published online Jul 21, 2013. doi: 10.3748/wjg.v19.i27.4325
Phytoestrogens/insoluble fibers and colonic estrogen receptor β: Randomized, double-blind, placebo-controlled study
Mariabeatrice Principi, Alfredo Di Leo, Maria Pricci, Maria Principia Scavo, Raffaella Guido, Sabina Tanzi, Domenico Piscitelli, Antonio Pisani, Enzo Ierardi, Maria Cristina Comelli, Michele Barone
Mariabeatrice Principi, Alfredo Di Leo, Maria Pricci, Maria Principia Scavo, Raffaella Guido, Sabina Tanzi, Antonio Pisani, Michele Barone, Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy
Domenico Piscitelli, Pathology Unit, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy
Enzo Ierardi, Gastroenterology Unit, Department of Medical Sciences, University of Foggia, 71100 Foggia, Italy
Maria Cristina Comelli, R and D, CMD Pharma Limited, London SW1V4BJ, United Kingdom
Author contributions: Di Leo A and Comelli MC contributed formulation and invention of the active dietary intervention and designed research; Pricci M, Scavo MP, Guido R, Tanzi S, Piscitelli D and Pisani A performed research; Principi M, Ierardi E and Barone M analyzed data and wrote the paper.
Supported by Wholly granted from R and D, CMD Pharma Limited, United Kingdom
Correspondence to: Alfredo Di Leo, Professor, Chief of Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy. b.principi@gmail.com
Telephone: +39-80-5502577 Fax: +39-80-5593251
Received: February 8, 2013
Revised: April 18, 2013
Accepted: May 8, 2013
Published online: July 21, 2013
Processing time: 162 Days and 0.7 Hours
Abstract

AIM: To assess the safety and effect of the supplementation of a patented blend of dietary phytoestrogens and insoluble fibers on estrogen receptor (ER)-β and biological parameters in sporadic colonic adenomas.

METHODS: A randomized, double-blind placebo-controlled trial was performed. Patients scheduled to undergo surveillance colonoscopy for previous sporadic colonic adenomas were identified, and 60 eligible patients were randomized to placebo or active dietary intervention (ADI) twice a day, for 60 d before surveillance colonoscopy. ADI was a mixture of 175 mg milk thistle extract, 20 mg secoisolariciresinol and 750 mg oat fiber extract. ER-β and ER-α expression, apoptosis and proliferation (Ki-67 LI) were assessed in colon samples.

RESULTS: No adverse event related to ADI was recorded. ADI administration showed a significant increases in ER-β protein (0.822 ± 0.08 vs 0.768 ± 0.10, P = 0.04) and a general trend to an increase in ER-β LI (39.222 ± 2.69 vs 37.708 ± 5.31, P = 0.06), ER-β/ER-α LI ratio (6.564 ± 10.04 vs 2.437 ± 1.53, P = 0.06), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (35.592 ± 14.97 vs 31.541 ± 11.54, P = 0.07) and Ki-67 (53.923 ± 20.91 vs 44.833 ± 10.38, P = 0.07) approximating statistical significance. A significant increase of ER-β protein (0.805 ± 0.13 vs 0.773 ± 0.13, P = 0.04), mRNA (2.278 ± 1.19 vs 1.105 ± 1.07, P < 0.02) and LI (47.533 ± 15.47 vs 34.875 ± 16.67, P < 0.05) and a decrease of ER-α protein (0.423 ± 0.06 vs 0.532 ± 0.11, P < 0.02) as well as a trend to increase of ER-β/ER-α protein in ADI vs placebo group were observed in patients without polyps (1.734 ± 0.20 vs 1.571 ± 0.42, P = 0.07).

CONCLUSION: The role of ER-β on the control of apoptosis, and its amenability to dietary intervention, are supported in our study.

Keywords: Estrogen receptor-β; Estrogen receptor-α; Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling; Sporadic adenomatous polyposis; Phytoestrogens; Insoluble fibers

Core tip: Active dietary intervention, a mixture of phytoestrogens and insoluble fibers, was administered in patients with sporadic colonic adenomas in a randomized, double-blind placebo-controlled trial. Dietary supplementation induced an increase in estrogen receptor (ER)-β protein and the ER-β/ER-α ratio with a general trend towards an increase in epithelial proliferation and apoptosis. These results, even if limited by the small number of subjects and short period of dietary supplementation, suggest the possibility of an interaction with epithelial apoptosis by means of mediating ER-β levels.