Pharmacokinetics and Bioavailability of Pomegranate Phenolics and Urolithins in Healthy Subjects.

Study Overview
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Brief Summary
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Pomegranate phenolics (such as the ellagitannin punicalagin and ellagic acid) are metabolized by the human gut microbiota to yield a number of metabolites called urolithins (mainly Uro-A). Both ellagic acid (EA) and urolithins can exert a number of biological activities. However, the bioavailability of ellagic acid has been reported to be very low and the existing studies are controversial so far. The investigators want to carry out a robust (cross-over, double-blind) pharmacokinetic assay in 20 healthy volunteers, using two types of pomegranate extracts (PEs). PEs with low (PE-1) and high (PE-2) punicalagin:EA ratio will be administered. The investigators will analyze blood and urine samples using UPLC-ESI-QTOF-MS/MS. The investigators will evaluate: The pharmacokinetics of EA. The effect of punicalagin:free EA ratio on the pharmacokinetics of EA and urolithins production.

Official Title
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Pharmacokinetics and Bioavailability of Pomegranate Phenolics and Gut Microbiota-derived Metabolites (Urolithins) in Overweight Subjects. Comparison Between Two Pomegranate Extracts

Conditions
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Healthy

Intervention / Treatment
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* Dietary Supplement: Pomegranate extract
* Dietary Supplement: Pomegranate extract


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-35 years. Healthy status (no illness in the previous 3-months). Exclusion Criteria: Smoking. Pregnancy/lactation. Severe medical illness/chronic disease/ or gastrointestinal pathology (ulcers, irritable bowel syndrome, ulcerative colitis, Crohn disease etc.). Previous gastrointestinal surgery Recent use of antibiotics (within 1-month prior to the study) Suspected hypersensitivity to pomegranate or any of its components Consumption of nutraceuticals, botanical extracts or other vitamin supplements or taking medication. Regular consumption of ellagitannin-containing foodstuffs (walnuts, pomegranate, strawberries, raspberries, oak-aged red wine) (after filling a food-frequency questionnaire). Intake of ellagitannins-containing foodstuffs the week before the pharmacokinetic intervention.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pomegranate extract<br>The same group will consume the two types of pomegranate extract (crossover study). | Dietary Supplement: Pomegranate extract<br>* Crossover study: The group will consume the pomegranate extract with low punicalagin:EA ratio (PE-1). After 2 weeks of washout, the same group will also consume the other extract with high punicalagin: EA ratio (PE-2).<br>* Other names: PE-1;Dietary Supplement: Pomegranate extract<br>* Crossover study: The group will consume the pomegranate extract with high punicalagin:EA ratio (PE-2) after 2 weeks of washout. The same group will also consume the other extract with low punicalagin: EA ratio (PE-1).<br>* Other names: PE-2;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24-hour pharmacokinetics of ellagic acid in plasma | Determination of pharmacokinetic parameters (Cmax, Tmax, AUC, etc.) for ellagic acid and derived metabolites. | Outcome measures at 0.5, 1, 2, 3, 4, 5, 6, and 24 hours post-dose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 72-h accumulation of urolithins in urine | Production of urolithins depending on the punicalagin:free ellagic acid ratio. | Changes from baseline at 24, 48 and 72 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pomegranate, Ellagic acid, Pharmacokinetics, Urolithins, Bioavailability