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.
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.


OBJECTIVE
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.


METHODS
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.
Research Group on Quality, Safety and Bioactivity of Plant Foods, Department Food Science and Technology, CEBAS-CSIC, 164, 30100, Espinardo (Murcia), Spain.
Begoña
B
Cerdá
Juan Carlos
JC
Espín
Soledad
S
Parra
Pedro
P
Martínez
Francisco A
FA
Tomás-Barberán
D000328:Adult; D000975:Antioxidants / Q000032:analysis / Q000493:pharmacokinetics*; D001421:Bacteria, Anaerobic / Q000378:metabolism*; D001628:Beverages / Q000032:analysis*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D003106:Colon / Q000382:microbiology*; D005260:Female; D005285:Fermentation; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D047348:Hydrolyzable Tannins / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D007408:Intestinal Absorption; D029561:Lythraceae / Q000737:chemistry*; D008297:Male; D009753:Nutritive Value
D000975:Antioxidants; D047348:Hydrolyzable Tannins; C013515:ellagitannin; C115642:punicalagin