Effects of Pomegranate Extract on Intestinal Flora (PomX)

Variations in Urolithin Production by the Microbiome After Pomegranate Extract Administration: Understanding Metabolism and Responsiveness to Pomegranate Ellagitannins

A total of 20 individuals, 10 urolithin excretors and 10 nonexcretors will be enrolled. The excretor status will be determined by analysis for urolithin A glucuronide in 24 hour urine after one dose of POMx. A blood sample and stool sample will be obtained before administering the extract. Subjects will be asked to consume one capsule of 1000 mg POMx daily for 4 weeks. At day 28, a blood sample, 24 hour urine sample will be obtained, and the stool collected by the participant in the prior 24 hours will be returned to the Center. Blood and urine urolithin, ellagic acid levels and stool bacteria enumeration and identification (including pyrosequencing) will be measured with the samples collected. A stool DNA sample will be preserved and frozen for potential future measurement of gene-nutrient interaction in pomegranate metabolism.

Throughout the study participants will be instructed not to consume pomegranate products, walnuts, or polyphenol-rich fruits ((strawberry, raspberry etc) or juices drawn from a list used in prior studies. The study will be carried out in accordance with the guidelines of the Human Subjects Protection Committee of the University of California, Los Angeles. All subjects will give written informed consent before the study begins. Participants will be recruited by advertisement in the local newspaper in the Los Angeles Area close to UCLA.

Study Overview

• Status: Completed
• Conditions: Urolith
• Intervention / Treatment: Dietary supplement: PomX

Detailed Description

At screening, informed consent and health insurance portability and assurance (HIPAA) authorization will be reviewed and signed. A medical history will be obtained. If criteria for enrollment are satisfied, a fasting blood sample will be collected for a comprehensive metabolic panel, and blood count. Results will be reviewed by the study physician for compliance to inclusion and exclusion criteria. The screening visit will also include a review of foods to avoid during run-in and study participation. Once lab results from the screening visit come back and are determined to be satisfactory for inclusion, the subject will be called and instructed to start dietary restrictions. The first stool collection (Day -1) will occur after two weeks of dietary compliance.

Day -1: Subjects will be asked to collect an entire stool and store it in a cooler filled with ice packs, along with a collection container until delivery to the lab within 24 hours.

Day 1: Subjects will take the 1st dose of POMx and be given a container for collecting their urine for 24 hours and asked to refrigerate this as the urine is collected. This urine will be used to determine the presence of urolithin A and whether they are "responder or non responder". Participants will be asked to consume 1 POMx capsule daily and to abstain from consuming pomegranates, walnuts, or polyphenol-rich foods or juices drawn from a list.

Day 27: Subjects will collect one entire stool and place in the provided cooler filled with ice packs for storage of the stool sample until delivery to the lab within 24 h. Urine collection will start at 8am after the morning dose of POMx and last until 8 am the day of clinic visit.

Day 28: Stool and urine sample will be collected. The stool sample collected at home (within the prior 24 hours) will be returned on this day. Blood sample will be collected. Compliance will be assessed by pill count. Safety and tolerance data will be collected.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 20-50 years of age at screen.
2. In good health
3. Subjects must read and sign the Institutional Review Board-approved written informed consent prior to the initiation of any study specific procedures or enrollment. A subject will be excluded for any condition that might compromise the ability to give truly informed consent.

Exclusion Criteria:

1. Any history of gastrointestinal disease except for appendectomy
2. Any use of antibiotics or laxatives during the 2 months prior to study enrollment.
3. Any subject with a history of diabetes mellitus, or other serious medical condition, such as chronic hepatic or renal disease, bleeding disorder, congestive heart disease, chronic diarrhea disorders, myocardial infarction, coronary artery bypass graft, angioplasty within 6 months prior to screening, current diagnosis of uncontrolled hypertension (defined as systolic BP>160mmHg, diastolic BP>95mmHg), active or chronic gastrointestinal disorders, bulimia, anorexia, or endocrine diseases (except thyroid disease requiring medication) as indicated by medical history or routine physical examination.
4. Any subject consuming pre- or probiotics
5. Any subject with a screening laboratory value outside of the laboratory normal range that is considered clinically significant for study participation by the investigator.
6. Any subject who currently uses tobacco products or has used tobacco products within the last year.
7. Any subject who is unable or unwilling to comply with the study protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: urolithin excretors; The excretor status will be determined by analysis for urolithin A glucuronide in 24 hour urine after one dose of POMx. A blood sample and stool sample will be obtained before administering the extract.	Dietary supplement: PomX; 1000 mg POMx daily for 4 weeks
Active Comparator: non excretors; The excretor status will be determined by analysis for urolithin A glucuronide in 24 hour urine after one dose of POMx. A blood sample and stool sample will be obtained before administering the extract.	Dietary supplement: PomX; 1000 mg POMx daily for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Percentage of Total Microflora Between Urolithin Excretors and Non-excretors	Difference of percentage of total microflora between urolithin excretors and non-excretors after consumption of pomegranate extract for 4 weeks	4 weeks

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Investigators: Principal Investigator: Zhaoping Li, M.D., Ph.D., UCLA Department of Medicine, Division of Clinical Nutrition

Publications and helpful links

General Publications

• Li Z, Henning SM, Lee RP, Lu QY, Summanen PH, Thames G, Corbett K, Downes J, Tseng CH, Finegold SM, Heber D. Pomegranate extract induces ellagitannin metabolite formation and changes stool microbiota in healthy volunteers. Food Funct. 2015 Aug;6(8):2487-95. doi: 10.1039/c5fo00669d. Epub 2015 Jul 20.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: February 18, 2015
• First Submitted That Met QC Criteria: February 24, 2015
• First Posted (Estimate): February 25, 2015

Study Record Updates

• Last Update Posted (Actual): October 2, 2019
• Last Update Submitted That Met QC Criteria: September 18, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: microflora; urolithin A
• Other Study ID Numbers: 12-000874

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan to share IPD with other researchers.