The potent in vitro antioxidant ellagitannins from pomegranate juice are metabolised into bioavailable but poor antioxidant hydroxy-6H-dibenzopyran-6-one derivatives by the colonic microflora of healthy humans
Abstract
Background The antiatherogenic activity of pomegranate juice has been attributed to its antioxidant polyphenols. The most potent in vitro antioxidant polyphenol from this juice is the ellagitannin punicalagin. However, the bioavailability of ellagitannins, including punicalagin, has not been previously described in humans.Aim of the study The present work aims to evaluate, in healthy humans, the bioavailability and metabolism of pomegranate juice ellagitannins, to assess their effect on several blood parameters (including cardiovascular risk disease markers) and to compare the antioxidant activity of punicalagin with that of the in vivo generated metabolites.Design Six healthy subjects (four men and two women) consumed 1 L of pomegranate juice daily (5.58 g/L polyphenols, including 4.37 g/L punicalagin isomers) for 5 days. The polyphenols and the in vivo generated metabolites were measured by HPLC-DAD-MS-MS. Fourteen haematological and twenty serobiochemical parameters including LDL, HDL and VLDL as well as cholesterol and triglycerides in each lipoprotein were evaluated. In vitro antioxidant activity of plasma (ABTS and FRAP assays) and urine (ABTS and DPPH) were determined.Results Neither punicalagin nor ellagic acid present in the juice were detected in both plasma and urine. Three microbial ellagitannin-derived metabolites were detected: 3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one glucuronide, an unidentified aglycone (tentatively, trihydroxy-6H-dibenzo[b,d]pyran-6-one) and hydroxy-6-H-dibenzo[b,d]pyran-6-one glucuronide. These metabolites could reach up to 18.6 microM in plasma, although a large inter-individual variability was observed. In urine, the same metabolites and their corresponding aglycones became evident after 1 day of juice consumption. Total urine excretion of metabolites ranged from 0.7 to 52.7% regarding the ingested punicalagin. No relevant effect was observed on any blood parameter. The metabolites did not show significant antioxidant activity compared to punicalagin from pomegranate juice.Conclusions The potential systemic biological effects of pomegranate juice ingestion should be attributed to the colonic microflora metabolites rather than to the polyphenols present in the juice.
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UroA can only be detected in ∼40%-50% of human subjects upon consumption of EA/ET-containing diets.
“However, UroA can only be detected in ∼ 40%–50% of human subjects upon consumption of EA/ET-containing diets.131,136, 137, 138, 139, 140, 141, 142, 143”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [136]
Upon consumption of 1L of pomegranate juice daily for 5 days by healthy volunteers, urolithin levels ranged from 0.5 to 18.6 μM in the plasma.
“For example, upon consumption of 1L of pomegranate juice daily for 5 days by healthy volunteers, urolithin levels ranged from 0.5 to 18.6 μM in the plasma.136”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [136]
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- Authors
- Cerd�, B., Esp�n, J. C., Parra, S., Mart�nez, P., & Tom�s-Barber�n, F. A.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Hospital Universitario Virgen de la Arrixaca (ES)
- Venue
- European Journal of Nutrition
- Published
- 2004-01-06
- Volume
- 43
- Issue
- 4
- Pages
- 205-20
- ISSN
- 1436-6207 (ISSN-L)
- 1436-6215
- OpenAlex
- W1986371908
- Cited by
- 435
- References
- 26
- Citations by year
- 2026: 12 · 2025: 8 · 2024: 22 · 2023: 20 · 2022: 22 · 2021: 24 · 2020: 30 · 2019: 22 · 2018: 20 · 2017: 25 · 2016: 21 · 2015: 39 · 2014: 23 · 2013: 31 · 2012: 21
- FWCI
- 7.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- European Journal of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Pomegranate: compositions and health benefits
- Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Phytochemistry and Bioactivity Studies
- Keywords
- pomegranate juice, ellagitannins, punicalagin, ellagic acid, colonic microbiota, polyphenol metabolism, bioavailability, antioxidant activity, cardiovascular risk markers, LDL cholesterol, triglycerides, urinary excretion, glucuronide conjugates
- MeSH terms
- Adult, Antioxidants, Bacteria, Anaerobic, Beverages, Biological Availability, Chromatography, High Pressure Liquid, Colon, Female, Fermentation, Humans, Intestinal Absorption, Male, Gas Chromatography-Mass Spectrometry, Nutritive Value, Lythraceae, Hydrolyzable Tannins
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