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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Dietary Supplement: Pomegranate extract

• Registration Number: NCT02056496
• Lead Sponsor: National Research Council, Spain

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-01
• Primary Completion: 2014-01
• Study Completion: 2014-02
• Study First Submitted: 2014-02-04
• Study First Submitted QC: 2014-02-04
• Study First Posted: 2014-02-06
• Status Verified: 2015-04
• Last Update Submitted: 2015-04-13
• Last Update Posted: 2015-04-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Pomegranate extract	Pomegranate extract	The same group will consume the two types of pomegranate extract (crossover study).

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

UCAM (San Antonio Catholic University from Murcia); 🇪🇸 Murcia, Spain