The metabolic fate of red wine and grape juice polyphenols in humans assessed by metabolomics

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The metabolic impact of polyphenol-rich red wine and grape juice consumption in humans was studied using a metabolomics approach. Fifty-eight men and women participated in a placebo-controlled, double-crossover study in which they consumed during a period of 4 wk, either a polyphenol-rich 2:1 dry mix of red wine and red grape juice extracts (MIX) or only a grape juice extract (GJX). Twenty-four-hour urine samples were collected after each intervention. (1)H NMR spectroscopy was applied for global metabolite profiling, while GC-MS was used for focused profiling of urinary phenolic acids. Urine metabolic profiles after intake of both polyphenol-rich extracts were significantly differentiated from placebo using multilevel partial least squares discriminant analysis. A significant 35% increase in hippuric acid excretion (p<0.001) in urine was measured after the MIX consumption as) or only a red grape juice dry extract (GJX). 24-h urine samples were collected after each intervention. 1H-NMR spectroscopy was applied for global metabolite profiling, while gas chromatography-mass spectrometry (GC-MS) was used for focused profiling of urinary phenolic acids. Urine metabolic profiles after intake of both polyphenol-rich extracts were significantly differentiated from placebo using multilevel partial least squares discriminant analysis (ML-PLS-DA). A significant 35% increase in hippuric acid excretion (p<0.001) in urine was measured after the MIX consumption compared with placebo, whereas no change was found after GJX consumption. GC-MS-based metabolomics of urine allowed identification of 18 different phenolic acids, which were significantly elevated following intake of either extract. Syringic acid, 3- and 4-hydroxyhippuric acid and 4-hydroxymandelic acid were the strongest urinary markers for both extracts. MIX and GJX consumption had a slightly different effect on the excreted phenolic acid profile and on endogenous metabolite excretion, possibly reflecting their different polyphenol composition.