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

Phase 1CompletedNCT02056496

National Research Council, Spain20 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

Conditions

Healthy

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 35 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

24-hour pharmacokinetics of ellagic acid in plasma

Determination of pharmacokinetic parameters (Cmax, Tmax, AUC, etc.) for ellagic acid and derived metabolites.

Time frame: Outcome measures at 0.5, 1, 2, 3, 4, 5, 6, and 24 hours post-dose.

Secondary Outcomes

72-h accumulation of urolithins in urine

Production of urolithins depending on the punicalagin:free ellagic acid ratio.

Time frame: Changes from baseline at 24, 48 and 72 hours