title: Gut and microbial resveratrol metabolite profiling after moderate long-term consumption of red wine versus dealcoholized red wine in humans by an optimized ultra-high-pressure liquid chromatography tandem mass spectrometry method.
abstract: Resveratrol exerts a variety of biological and pharmacological activities, which are observed despite its extremely low bioavailability and rapid clearance from the circulation due to extensive sulfation and glucuronidation in the intestine and liver. In order to more accurately quantify all known resveratrol metabolites, a sensitive and optimized analytical assay was developed and validated by pure standards. Methodology improvements aimed to the chromatographic detection of disulfates and sulfoglucuronides, improving resolution of sulfates, by using a buffered solution, with recovery values of resveratrol and its metabolites, even of sulfates, of 99%. The adapted methodology was then applied to a clinical study with high cardiovascular risk subjects, after the moderate consumption of red wine (RW) or dealcoholized red wine (DRW) for 28 days. Up to 21 resveratrol metabolites, including those formed by gut and microbial metabolism, were identified in 24-h urine samples. Interestingly, after long-term consumption of RW and DRW, resveratrol metabolite concentration significantly increased in urine with no differences between the two interventions, indicating that bioavailability and biotransformation of resveratrol is not affected by the alcoholic matrix of wine. In summary, we established a sensitive analytical assay for the quantification of a wide resveratrol metabolic profile in human urine, also regarding gut microbial-derived metabolites, which may also be applied to blood and tissue samples. The resveratrol metabolic pattern might therefore act as an excellent marker for the efficacy of resveratrol in clinical and epidemiological studies for the study of the beneficial effects of grape product consumption. In this sense, having a more precise concentration value of all the resveratrol metabolites in target tissues would finally lead to a better interpretation of the obtained results.
authors.affiliation: Nutrition and Food Science Department, XaRTA-INSA, Pharmacy Faculty, University of Barcelona, Av Joan XXIII, s/n, 08028 Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Rotches-Ribalta
authors.forename: Mireia
authors.initials: M
authors.lastname: Urpi-Sarda
authors.forename: Rafa
authors.initials: R
authors.lastname: Llorach
authors.forename: Maria
authors.initials: M
authors.lastname: Boto-Ordoñez
authors.forename: Olga
authors.initials: O
authors.lastname: Jauregui
authors.forename: Gemma
authors.initials: G
authors.lastname: Chiva-Blanch
authors.forename: Lluïsa
authors.initials: L
authors.lastname: Perez-Garcia
authors.forename: Walter
authors.initials: W
authors.lastname: Jaeger
authors.forename: Marisa
authors.initials: M
authors.lastname: Guillen
authors.forename: Dolores
authors.initials: D
authors.lastname: Corella
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Tinahones
authors.forename: Ramon
authors.initials: R
authors.lastname: Estruch
authors.forename: Cristina
authors.initials: C
authors.lastname: Andres-Lacueva
mesh_terms: D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D000431:Ethanol / Q000302:isolation & purification*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000382:microbiology; D008875:Middle Aged; D012015:Reference Standards; D015203:Reproducibility of Results; D000077185:Resveratrol; D013267:Stilbenes / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014920:Wine
chemical_list: D013267:Stilbenes; D000431:Ethanol; D000077185:Resveratrol