Urolith
Conditions
Keywords
urolithin A, microflora
Brief summary
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.
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.
Interventions
DIETARY_SUPPLEMENTPomX
1000 mg POMx daily for 4 weeks
Sponsors
University of California, Los Angeles
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 50 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Percentage of Total Microflora Between Urolithin Excretors and Non-excretors | 4 weeks | Difference of percentage of total microflora between urolithin excretors and non-excretors after consumption of pomegranate extract for 4 weeks |
Participant flow
Recruitment details
The enrollment period was 10/31/2012 - 7/2/2013. Enrollment took place in a private setting in the clinic located at the site.
Pre-assignment details
Twenty-six healthy participants were enrolled in the study. There were two study phases including a 2-week run-in period and a 4-week intervention period. Six subjects who did not complete the study were excluded.
Participants by arm
| Arm | Count |
|---|---|
| Urolithin Excretors The excretor status was determined by analysis of urolithin A glucuronide in 24 hour urine after one dose of POMx. A blood sample and stool sample were obtained before administering the extract.
PomX: 1000 mg POMx daily for 4 weeks | 14 |
| Non Excretors The excretor status was determined by the analysis of urolithin A glucuronide in 24 hour urine after one dose of POMx. A blood sample and stool sample were obtained before administering the extract.
PomX: 1000 mg POMx daily for 4 weeks | 6 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | dropped study | 4 | 2 |
Baseline characteristics
| Characteristic | Total | Non Excretors | Urolithin Excretors |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 6 Participants | 14 Participants |
| Body Mass Index (BMI) | 23 kg/m^2 STANDARD_DEVIATION 3 | 23 kg/m^2 STANDARD_DEVIATION 3 | 23 kg/m^2 STANDARD_DEVIATION 3 |
| Race/Ethnicity, Customized Asian | 4 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Black | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized white | 14 Participants | 2 Participants | 12 Participants |
| Sex: Female, Male Female | 9 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 11 Participants | 3 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 14 | 1 / 6 |
| serious Total, serious adverse events | 0 / 14 | 0 / 6 |
Outcome results
Primary
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
Time frame: 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Microbial Phylum Abundance in Urolithin Excretors | Change in Percentage of Total Microflora Between Urolithin Excretors and Non-excretors | Percentage of phylum Firmecutes at baseline | 60 percentage of total microflora | Standard Deviation 10.1 |
| Microbial Phylum Abundance in Urolithin Excretors | Change in Percentage of Total Microflora Between Urolithin Excretors and Non-excretors | Percentage of phylum Firmecutes at week 4 | 56 percentage of total microflora | Standard Deviation 10.5 |
| Microbial Phylum Abundance in Urolithin Excretors | Change in Percentage of Total Microflora Between Urolithin Excretors and Non-excretors | Percentage of phylum Proteobacteria at baseline | 3.4 percentage of total microflora | Standard Deviation 2.5 |
| Microbial Phylum Abundance in Urolithin Excretors | Change in Percentage of Total Microflora Between Urolithin Excretors and Non-excretors | Percentage of phylum Proteobacteria at week 4 | 6 percentage of total microflora | Standard Deviation 5.4 |
| Microbial Phylum Abundance in Non Excretors | Change in Percentage of Total Microflora Between Urolithin Excretors and Non-excretors | Percentage of phylum Proteobacteria at week 4 | 1.8 percentage of total microflora | Standard Deviation 0.5 |
| Microbial Phylum Abundance in Non Excretors | Change in Percentage of Total Microflora Between Urolithin Excretors and Non-excretors | Percentage of phylum Firmecutes at baseline | 68 percentage of total microflora | Standard Deviation 17.2 |
| Microbial Phylum Abundance in Non Excretors | Change in Percentage of Total Microflora Between Urolithin Excretors and Non-excretors | Percentage of phylum Proteobacteria at baseline | 2.5 percentage of total microflora | Standard Deviation 1.4 |
| Microbial Phylum Abundance in Non Excretors | Change in Percentage of Total Microflora Between Urolithin Excretors and Non-excretors | Percentage of phylum Firmecutes at week 4 | 70 percentage of total microflora | Standard Deviation 9.3 |
Comparison: Comparison was made to week 4 minus baseline change of phylum Firmicutes abundance between urolithin excretors and non excretorsp-value: 0.012Wilcoxon (Mann-Whitney)
Comparison: Comparison was made to week 4 minus baseline change of phylum Proteobacteria abundance between urolithin excretors and non excretorsp-value: 0.009Wilcoxon (Mann-Whitney)