Identifying the limits for ellagic acid bioavailability: A crossover pharmacokinetic study in healthy volunteers after consumption of pomegranate extracts

Antonio González-Sarrías and colleagues from CEBAS-CSIC and the Catholic University of San Antonio(ES) have examined factors contributing to ellagic acid bioavailability in order to evaluate whether this can be improved.

Like other polyphenols, ellagic acid has been reported to have antioxidant, anti-adipogenic and chemo preventative effects inhuman health. A limited number of human pharmacokinetic studies have reported the bioavailability of ellagic acid following intake of pomegranate (juice and extracts), and indicate that free ellagic acid ranged from 12 to 25 mg.

In this study, the impact of much higher concentrations of ellagic acid on bioavailability was explored.

Ellagic acid must be released from ellagitannins in pomegranates, walnuts or strawberries in order to be absorbed. The in vivo–in vitro study identified that human ellagic acid bioavailability is highly variable between individuals, due to: i) low solubility of free ellagic acid under gastric conditions; ii) type of ellagitannin consumed; and iii) limited intestinal ellagic acid absorption.

Furthermore, higher free EA intake does not enhance EA bioavailability. However, the biological activity in the gastrointestinal tract might be greater and, importantly, promote the production of urolithins, which contribute to the health benefits associated with pomegranate consumption.

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Highlights:

  1. Targeted metabolomics (UPLC-ESI-qTOF-MS/MS) identified plasma free ellagic acid but not phase-II conjugates.
  2. Ellagic acid pharmacokinetics showed high inter-individual variability.
  3. Ellagic acid bioavailability is limited by ellagitannin content, pH and the protein environment.