Kinetic profile and urinary excretion of phenyl-γ-valerolactones upon consumption of cranberry: a dose-response relationship
Cranberries are a rich source of poly(phenols), mainly monomeric and oligomeric flavan-3-ols. However, information on the appearance of their main circulating microbial metabolites, namely phenyl-γ-valerolactones and phenylvaleric acid, is lacking despite its relevance to understanding the health ef...
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| Published in | Food & function Vol. 11; no. 5; pp. 3975 - 3985 |
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| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
Royal Society of Chemistry
01.05.2020
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| Subjects | |
| Online Access | Get full text |
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| Summary: | Cranberries are a rich source of poly(phenols), mainly monomeric and oligomeric flavan-3-ols. However, information on the appearance of their main circulating microbial metabolites, namely phenyl-γ-valerolactones and phenylvaleric acid, is lacking despite its relevance to understanding the health effects attributed to cranberries. The aim of this study was to evaluate the absorption, metabolism and urinary excretion of cranberry flavan-3-ols through the targeted analysis of phenyl-γ-valerolactones and their related phenylvaleric acids, considering also their potential as biomarkers of flavan-3-ol intake and inter-individual variability in their appearance in plasma and urine. A six-arm acute crossover, randomized, double-blinded, controlled intervention trial was performed in ten healthy males who consumed a cranberry juice drink (375, 716, 1131, 1396, 1741 mg of total flavan-3-ols) or an isocaloric control drink with one-week washout. Plasma and urine were analyzed by UHPLC-ESI-QqQ-MS/MS and 22 compounds were identified. Glucuronide and sulfate conjugates of 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone were the main circulating and excreted metabolites after cranberry juice intake, with glucuronidation appearing to be the most favorable conjugation route. These compounds reached maximum plasma concentration at about 4-6 h. Plasma and urinary concentrations of the sum of the metabolites increased in relation to the amounts of cranberry flavan-3-ols provided by the drink, showing a clear and linear dose-dependent relationship and underscoring their potential as biomarkers of flavan-3-ol intake. A high inter-individual variability in circulating and urinary metabolite levels was observed and, interestingly, some subjects seemed to display a greater efficiency in metabolizing flavan-3-ols and producing phenyl-γ-valerolactones.
Cranberries are a rich source of poly(phenols), mainly monomeric and oligomeric flavan-3-ols. The metabolism of their main colonic compounds has been assessed. |
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| Bibliography: | 10.1039/d0fo00806k Electronic supplementary information (ESI) available: Supplementary Fig. 1e-n: Pharmacokinetic profile of 5-phenyl-γ-valerolactone-3′-sulfate (e), 5-phenyl-γ-valerolactone-4′-sulfate (f), 5-phenyl-γ-valerolactone-3′-glucuronide (g), 5-phenyl-γ-valerolactone-4′-glucuronide (h), 5-(5′-hydroxyphenyl)-γ-valerolactone-3′-sulfate (i), 5-(5′-hydroxyphenyl)-γ-valerolactone-3′-glucuronide (j), 5-phenyl-γ-valerolactone-methoxy-sulfate (3′,4′) isomer 1 (k), 5-phenyl-γ-valerolactone-methoxy-sulfate (3′,4′) isomer 2 (l), 5-phenyl-γ-valerolactone-methoxy-glucuronide isomer (3′,4′) (m) and 5-phenyl-γ-valerolactone-sulfate-glucuronide isomer (3′,4′) (n) for the different treatments. Supplementary Fig. 2a-n: Cumulative urinary excretion profile of 5-phenyl-γ-valerolactone-3′-sulfate (a), 5-phenyl-γ-valerolactone-3′-glucuronide (b), 5-phenyl-γ-valerolactone-4′-glucuronide (c), 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone (d), 5-(hydroxyphenyl)-γ-valerolactone-sulfate (3′,4′ isomers) (e), 5-(5′-hydroxyphenyl)-γ-valerolactone-3′-sulfate (f), 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-glucuronide (g), 5-(3′-hydroxyphenyl)-γ-valerolactone-4′-glucuronide (h), 5-(5′-hydroxyphenyl)-γ-valerolactone-3′-glucuronide (i), 5-phenyl-γ-valerolactone-methoxy-sulfate (3′,4′) isomer 1 (j), 5-phenyl-γ-valerolactone-methoxy-sulfate (3′,4′) isomer 2 (k), 5-phenyl-γ-valerolactone-methoxy-glucuronide isomer (3′,4′) (l), 5-phenyl-γ-valerolactone-sulfate-glucuronide isomer (3′,4′) (m) and of the sum of quantified PVLs (n) for the different treatments. Table S1: Individual dose-response relation between (a) total amount of ingested flavan-3-ols and Area under the curve (AUC) of the concentration in plasma of PVLs over 24 h and (b) total amount of ingested flavan-3-ols and cumulative quantity of excreted PVLs in urine. See DOI ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Undefined-3 |
| ISSN: | 2042-6496 2042-650X 2042-650X |
| DOI: | 10.1039/d0fo00806k |