Bioavailability of Phytoestrogens and Prevalence of Adenomatous Polyps in Human Colon
Conditions: Intestinal Polyps
Sponsor: University of Bari

January 24, 2018 
Title of the study: 
BIOAVAILABILITY OF PHYTOESTROGENS AND PREVALENCE OF 
COLON POLYPS (FITOPOL) 
 
This document is relevant to the study in the record  
The NCT number is not yet available 
 
 
INTRODUCTION: Data obtained by in vitro and in vivo studies have demonstrated that 
phytoestrogens have an inhibitory effect on colorectal cancer (CRC). In humans, most  of  the 
studies on the influence of phytoestrogens in CRC, coming from population studies comparing the 
dietary intake of phytoestrogens, have produced contrasting results (1-5). The variability of these 
data may be essentially due to three different aspects: 1) phytoestrogens include several subclasses 
that differ for their preventative effects against CRC and colon adenomas; 2) the real absorption of 
phytoestrogens (by a serum or urinary determinations) is strongly influenced by the intestinal 
microbiota; 3) the production of equol, which is the most active phytoestrogen molecule, has not 
been determined. 
 
PURPOSE: To evaluate phytoestrogen absorption and equol production in individuals with and 
without colonoscopy-proved colonic adenoma. Moreover, the prominent genera of the human 
microbiome potentially involved in equol production was evaluated. 
 
STUDY DISEGN: 
Patients who underwent colonoscopy that demonstrated the presence of sporadic colorectal 
adenomas (Group I, case) or the absence of sporadic colorectal adenomas (Group II, control), 
matched for sex, age and BMI, will participate to the study. For the enrolment, they had to be 
undergone colonoscopy within the previous 1-3 months. In these patients we will evaluate: BMI, 
dietary history (for quantitative and qualitative analysis of dietary habits), quantitative analysis of 
phytoestrogens (by dietary questionnaires), home-based medications (aspirin), characteristics  
polyps (for calculating the risk of cancer), quantitative analysis of urinary excretion of 
phytoestrogens [by high pressure liquid chromatography (HPLC)] and intestinal flora [by mass 
spectrometry with Matrix Assisted Laser Desorption Ionization Time-of-Flight (MALDI-TOF) 
technology]. 

At the enrolment, patients will be invited to assume a standard quantitative of phytoestrogens at 
8:00 a.am. and collect both a fecal sample and the urine of the following 24 hrs. 
Inclusion criteria: 
• subjects of both sexes aged between 50 and 75 years. 
 
Exclusion criteria: 
 age < 50 and > 75 years 
 previous diagnosis of colon cancer or inflammatory bowel diseases (IBD) 
 Hereditary intestinal tumors (FAP, HNPCC, ...) 
 ongoing infections 
 intake, in the last 4 weeks, of drugs that could alter the intestinal microflora 
 creatinine clearance below 60 ml/min 
 liver failure 
 
 
 
REFERENCES: 
 
1) Jin H, Leng Q, Li C. Dietary flavonoid for preventing colorectal neoplasms. Cochrane 
Database Syst Rev. 2012;15:CD009350 
2) Kocic B, Kitic D, Brankovic S. Dietary flavonoid intake and colorectal cancer risk: evidence 
from human population studies. J BUON. 2013;18:34-43 
3) Xu X, Harris KS, Wang HJ, Murphy PA, Hendrich S. Bioavailability of soyben isoflavones 
depens upon gut microflora in women. J Nutr 1995;125:2307-2315 
4) Atkinson C, Frankenfeld CL, Lampe JW. Gut bacterial metabolism of the soy isoflavone 
daidzein: exploring the relevance to human health. Exp Biol Med (Maywood) 
2005;230:155-170. 
5) Setchell KD, Brown NM, Lydeking-Olsen E. The clinical importance of the metabolite 
equol-a clue to the effectiveness of soy and its isoflavones. J Nutr. 2002;132:3577-84 

STATISTICAL ANALYSIS PLAN 
 
 
Continuous variables will be expressed as means ± standard deviation. The t test for unpaired data (age and 
body mass index) will be used. The categorical variables (i.e. gender, proportion of specific bacterial genera in 
the feces, etc.) will be analyzed using the Chi-square or Fischer test (one- or two-tailed). For statistical analysis, 
SPSS software version 21.0 will be used. 

INFORMED CONSENT 
 
 
TITLE OF THE STUDY: Bioavailability of phytoestrogens and prevalence of colon polyps 
 
1. Introduction 
In this center a clinical trial is being carried out and you you are invited to take part of it. Before you 
decide, it is important that you understand why the trial is being conducted and what it will entail. 
Please take your time to read this information and consult your family doctor if you wish. 
Furthermore, as this form may contain words that are difficult to understand, ask the doctor 
responsible for the study or a doctor of your choice for any explanation or information that you deem 
appropriate. Take your time to decide if you want to participate. 
 
2. What is the aim of the study? 
- Primary objective: to evaluate whether patients with low urinary excretion of phytoestrogens (and 
therefore with reduced absorption of phytoestrogens) have a higher incidence of colon polyps. 
- Secondary objective: to identify the intestinal microbiota that best metabolizes the phytoestrogens. 
 
3. Why do you have been chosen? 
You were invited to participate in this study because you were considered suitable; in fact, you were 
chosen because you are on the list for performing a colonoscopy and you are between 50 and 75 years 
old. 
 
4. Am I bound to participate? 
Your participation in this study is completely voluntary. 
If you decide to participate, you will be asked to sign a consent form, and you will be given a copy of 
this document to keep. 
If you decide to participate, you are still free to stop your participation at any time without giving any 
explanation. 
The decision not to participate in the study or to stop participating will have no impact on the medical 
treatment you will receive. 
 
5. What will happen if I decide to participate? 
Fifteen days before the colonoscopy, you will be asked to provide a sample of your stool and urine 
after taking a specific amount of phytoestrogens. Moreover, you will be asked to answer a dietary 
questionnaire. 
 
6. What are the possible benefits of participating to the study? 
The results of this study could contribute to distinguish patients with low or high incidence of colon 
polyps on the basis on their ability to absorb phytoestrogens from the diet. 
 
7. Who reviewed the study? 
This study has been reviewed and approved by the "ETHICAL COMMITTEE OF THE 
POLYCLINIC HOSPITAL OF BARI".Thank you for reading this document and if you have any 
further doubt or questions, please contact the doctor responsible for the study. 
 
Your participation in this study is very useful for us and we thank you in advance if you decide to 
participate. 

The data will be processed in accordance with the Legislative Decree 196/03. 
At any time during the study, you can request further information to: 
the doctor responsible for the study 
 
Dr. …………………………………… 
 
Tel: ………………………………….. 
 
Date