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Alan Crozier - One of the best experts on this subject based on the ideXlab platform.
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Absorption, metabolism, distribution and excretion of (−)-epicatechin: A review of recent findings
Molecular Aspects of Medicine, 2017Co-Authors: Gina Borges, Hagen Schroeter, Javier I Ottaviani, Justin J J Van Der Hooft, Alan CrozierAbstract:Abstract This paper reviews pioneering human studies, their limitations and recent investigations on the absorption, metabolism, distribution and excretion (aka bioavailability) of (–)-epicatechin. Progress has been made possible by improvements in mass spectrometric detection when coupled to high performance liquid chromatography and through the increasing availability of authentic reference compounds of in vivo metabolites of (–)-epicatechin. Studies have shown that [2-14C](–)-epicatechin is absorbed in the small intestine with the 12 structural-related (–)-epicatechin metabolites (SREMs), mainly in the form of (–)-epicatechin-3′-O-glucuronide, 3′-O-methyl-(–)-epicatechin-5-sulfate and (–)-epicatechin-3′-sulfate, attaining sub-μmol/L peak plasma concentrations (Cmax) ∼1 h after ingestion. SREMs were excreted in urine over a 24 h period in amounts corresponding to 20% of (–)-epicatechin intake. On reaching the colon the flavan-3-ol undergoes microbiota-mediated conversions yielding the 5C-ring fission metabolites (5C-RFMs) 5-(hydroxyphenyl)-γ-valerolactones and 5-(hydroxyphenyl)–γ-hydroxyvaleric Acids which appear in plasma as phase II metabolites with a Cmax of 5.8 h after intake and are excreted in quantities equivalent to 42% of the ingested (–)-epicatechin. Other catabolites excreted in 0–24 h urine in amounts equivalent to 28% of intake included 3-(3′-hydroxyphenyl)Hydracrylic Acid, hippuric Acid and 3′-hydroxyhippuric Acid. Overall (–)-epicatechin is highly bioavailable with urinary excretion indicating that 95% is absorbed and passes through the circulatory systems as a diversity of phase II metabolites. Rats produce a very different profile of SREMs than that of humans. These findings demonstrate that ex vivo studies investigating the mechanisms underlying the protective effects of (–)-epicatechin on human health should make use of physiological concentrations human of SREMs and 5C-RFMs, and not the parent (–)-epicatechin, with model systems derived from human cells. In epidemiological studies 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-sulfate and 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-O-glucuronide, the principal 5C-RFMs in both plasma and urine, could serve as key biomarkers of (–)-epicatechin intake.
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Absorption, metabolism, distribution and excretion of (−)-epicatechin: A review of recent findings
Molecular Aspects of Medicine, 2017Co-Authors: Gina Borges, Hagen Schroeter, Javier I Ottaviani, Justin J J Van Der Hooft, Alan CrozierAbstract:Abstract This paper reviews pioneering human studies, their limitations and recent investigations on the absorption, metabolism, distribution and excretion (aka bioavailability) of (–)-epicatechin. Progress has been made possible by improvements in mass spectrometric detection when coupled to high performance liquid chromatography and through the increasing availability of authentic reference compounds of in vivo metabolites of (–)-epicatechin. Studies have shown that [2-14C](–)-epicatechin is absorbed in the small intestine with the 12 structural-related (–)-epicatechin metabolites (SREMs), mainly in the form of (–)-epicatechin-3′-O-glucuronide, 3′-O-methyl-(–)-epicatechin-5-sulfate and (–)-epicatechin-3′-sulfate, attaining sub-μmol/L peak plasma concentrations (Cmax) ∼1 h after ingestion. SREMs were excreted in urine over a 24 h period in amounts corresponding to 20% of (–)-epicatechin intake. On reaching the colon the flavan-3-ol undergoes microbiota-mediated conversions yielding the 5C-ring fission metabolites (5C-RFMs) 5-(hydroxyphenyl)-γ-valerolactones and 5-(hydroxyphenyl)–γ-hydroxyvaleric Acids which appear in plasma as phase II metabolites with a Cmax of 5.8 h after intake and are excreted in quantities equivalent to 42% of the ingested (–)-epicatechin. Other catabolites excreted in 0–24 h urine in amounts equivalent to 28% of intake included 3-(3′-hydroxyphenyl)Hydracrylic Acid, hippuric Acid and 3′-hydroxyhippuric Acid. Overall (–)-epicatechin is highly bioavailable with urinary excretion indicating that 95% is absorbed and passes through the circulatory systems as a diversity of phase II metabolites. Rats produce a very different profile of SREMs than that of humans. These findings demonstrate that ex vivo studies investigating the mechanisms underlying the protective effects of (–)-epicatechin on human health should make use of physiological concentrations human of SREMs and 5C-RFMs, and not the parent (–)-epicatechin, with model systems derived from human cells. In epidemiological studies 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-sulfate and 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-O-glucuronide, the principal 5C-RFMs in both plasma and urine, could serve as key biomarkers of (–)-epicatechin intake.
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absorption metabolism distribution and excretion of epicatechin a review of recent findings
Molecular Aspects of Medicine, 2017Co-Authors: Gina Borges, Hagen Schroeter, Javier I Ottaviani, Justin J J Van Der Hooft, Alan CrozierAbstract:Abstract This paper reviews pioneering human studies, their limitations and recent investigations on the absorption, metabolism, distribution and excretion (aka bioavailability) of (–)-epicatechin. Progress has been made possible by improvements in mass spectrometric detection when coupled to high performance liquid chromatography and through the increasing availability of authentic reference compounds of in vivo metabolites of (–)-epicatechin. Studies have shown that [2-14C](–)-epicatechin is absorbed in the small intestine with the 12 structural-related (–)-epicatechin metabolites (SREMs), mainly in the form of (–)-epicatechin-3′-O-glucuronide, 3′-O-methyl-(–)-epicatechin-5-sulfate and (–)-epicatechin-3′-sulfate, attaining sub-μmol/L peak plasma concentrations (Cmax) ∼1 h after ingestion. SREMs were excreted in urine over a 24 h period in amounts corresponding to 20% of (–)-epicatechin intake. On reaching the colon the flavan-3-ol undergoes microbiota-mediated conversions yielding the 5C-ring fission metabolites (5C-RFMs) 5-(hydroxyphenyl)-γ-valerolactones and 5-(hydroxyphenyl)–γ-hydroxyvaleric Acids which appear in plasma as phase II metabolites with a Cmax of 5.8 h after intake and are excreted in quantities equivalent to 42% of the ingested (–)-epicatechin. Other catabolites excreted in 0–24 h urine in amounts equivalent to 28% of intake included 3-(3′-hydroxyphenyl)Hydracrylic Acid, hippuric Acid and 3′-hydroxyhippuric Acid. Overall (–)-epicatechin is highly bioavailable with urinary excretion indicating that 95% is absorbed and passes through the circulatory systems as a diversity of phase II metabolites. Rats produce a very different profile of SREMs than that of humans. These findings demonstrate that ex vivo studies investigating the mechanisms underlying the protective effects of (–)-epicatechin on human health should make use of physiological concentrations human of SREMs and 5C-RFMs, and not the parent (–)-epicatechin, with model systems derived from human cells. In epidemiological studies 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-sulfate and 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-O-glucuronide, the principal 5C-RFMs in both plasma and urine, could serve as key biomarkers of (–)-epicatechin intake.
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Bioavailability of orange juice (poly)phenols: the impact of short-term cessation of training by male endurance athletes.
The American journal of clinical nutrition, 2017Co-Authors: Gema Pereira-caro, Thelma Polyviou, Iziar A. Ludwig, Ana-maria Nastase, José Manuel Moreno-rojas, Ada L. Garcia, Dalia Malkova, Alan CrozierAbstract:Background: Physical exercise has been reported to increase the bioavailability of citrus flavanones.Objective: We investigated the bioavailability of orange juice (OJ) (poly)phenols in endurance-trained males before and after cessation of training for 7 d.Design: Ten fit, endurance-trained males, with a mean ± SD maximal oxygen consumption of 58.2 ± 5.3 mL · kg-1 · min-1, followed a low (poly)phenol diet for 2 d before drinking 500 mL of OJ containing 398 μmol of (poly)phenols, of which 330 μmol was flavanones. After the volunteers stopped training for 7 d the feeding study was repeated. Urine samples were collected 12 h pre- and 24 h post-OJ consumption. Bioavailability was assessed by the quantitative analysis of urinary flavanone metabolites and (poly)phenol catabolites with the use of high-pressure liquid chromatography-high resolution mass spectrometry.Results: During training, 0-24-h urinary excretion of flavanone metabolites, mainly hesperetin-3'-O-glucuronide, hesperetin-3'-sulfate, naringenin-4'-O-glucuronide, naringenin-7-O-glucuronide, was equivalent to 4.2% of OJ flavanone intake. This increased significantly to 5.2% when OJ was consumed after the volunteers stopped training for 7 d. Overall, this trend, although not significant, was also observed with OJ-derived colonic catabolites, which, after supplementation in the trained state, were excreted in amounts equivalent to 51% of intake compared with 59% after cessation of training. However, urinary excretion of 3 colonic catabolites of bacterial origin, most notably, 3-(3'-hydroxy-4'-methoxyphenyl)Hydracrylic Acid, did increase significantly when OJ was consumed postcessation compared with precessation of training. Data were also obtained on interindividual variations in flavanone bioavailability.Conclusions: A 7-d cessation of endurance training enhanced, rather than reduced, the bioavailability of OJ flavanones. The biological significance of these differences and whether they extend to the bioavailability of other dietary (poly)phenols remain to be determined. Hesperetin-3'-O-glucuronide and the colonic microbiota-derived catabolite 3-(3'-hydroxy-4'-methoxyphenyl)Hydracrylic Acid are key biomarkers of the consumption of hesperetin-O-glycoside-containing OJ and other citrus products. This trial was registered at clinicaltrials.gov as NCT02627547.
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In vitro colonic catabolism of orange juice (poly)phenols
Molecular nutrition & food research, 2015Co-Authors: Gema Pereira-caro, Gina Borges, M. N. Clifford, D. Del Rio, S. A. Roberts, Aleix Ribas, Luca Calani, Alan CrozierAbstract:cope The role of colonic microbiota in the breakdown of hesperetin, naringenin, and ferulic Acid, compounds found as glycosides in orange juice, was investigated using an in vitro fermentation model. Methods and results Test compounds were incubated with human fecal slurries cultured under anaerobic conditions, and the production of phenolic Acid catabolites were monitored by GC-MS and HPLC-MS2. Hesperetin was converted to 3-(3′-hydroxy-4′-methoxyphenyl)propionic Acid, 3-(3′,4′-dihydroxyphenyl)propionic Acid, and 3-(3′-hydroxyphenyl)propionic Acid while 3-(phenyl)propionic Acid was the major end product derived from naringenin. The data obtained are compared to our previously published data on urinary excretion of phenolic and aromatic Acids after acute orange juice consumption (Pereira-Caro et al. Am. J. Clin. Nutr. 2014, 100, 1385–1391). Catabolism pathways are proposed for events occurring in the colon and those taking place postabsorption into the circulatory system with particular reference to the excretion of 3-(3′-hydroxy-4′-methoxyphenyl)Hydracrylic Acid, which is not formed in fecal incubations. Ferulic Acid was also degraded by the colonic microflora being converted principally to 3-(3′-methoxy-4′-hydroxyphenyl)propionic Acid, a phenolic Acid that appears in urine after orange juice consumption. Conclusion The study provides novel information on the potential involvement of the colonic microbiota in the overall bioavailability of orange juice (poly)phenols through the production of phenylpropionic Acids and subsequent hepatic conversions that lead to hippuric Acid and its hydroxylated analogues.
Gina Borges - One of the best experts on this subject based on the ideXlab platform.
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Absorption, metabolism, distribution and excretion of (−)-epicatechin: A review of recent findings
Molecular Aspects of Medicine, 2017Co-Authors: Gina Borges, Hagen Schroeter, Javier I Ottaviani, Justin J J Van Der Hooft, Alan CrozierAbstract:Abstract This paper reviews pioneering human studies, their limitations and recent investigations on the absorption, metabolism, distribution and excretion (aka bioavailability) of (–)-epicatechin. Progress has been made possible by improvements in mass spectrometric detection when coupled to high performance liquid chromatography and through the increasing availability of authentic reference compounds of in vivo metabolites of (–)-epicatechin. Studies have shown that [2-14C](–)-epicatechin is absorbed in the small intestine with the 12 structural-related (–)-epicatechin metabolites (SREMs), mainly in the form of (–)-epicatechin-3′-O-glucuronide, 3′-O-methyl-(–)-epicatechin-5-sulfate and (–)-epicatechin-3′-sulfate, attaining sub-μmol/L peak plasma concentrations (Cmax) ∼1 h after ingestion. SREMs were excreted in urine over a 24 h period in amounts corresponding to 20% of (–)-epicatechin intake. On reaching the colon the flavan-3-ol undergoes microbiota-mediated conversions yielding the 5C-ring fission metabolites (5C-RFMs) 5-(hydroxyphenyl)-γ-valerolactones and 5-(hydroxyphenyl)–γ-hydroxyvaleric Acids which appear in plasma as phase II metabolites with a Cmax of 5.8 h after intake and are excreted in quantities equivalent to 42% of the ingested (–)-epicatechin. Other catabolites excreted in 0–24 h urine in amounts equivalent to 28% of intake included 3-(3′-hydroxyphenyl)Hydracrylic Acid, hippuric Acid and 3′-hydroxyhippuric Acid. Overall (–)-epicatechin is highly bioavailable with urinary excretion indicating that 95% is absorbed and passes through the circulatory systems as a diversity of phase II metabolites. Rats produce a very different profile of SREMs than that of humans. These findings demonstrate that ex vivo studies investigating the mechanisms underlying the protective effects of (–)-epicatechin on human health should make use of physiological concentrations human of SREMs and 5C-RFMs, and not the parent (–)-epicatechin, with model systems derived from human cells. In epidemiological studies 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-sulfate and 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-O-glucuronide, the principal 5C-RFMs in both plasma and urine, could serve as key biomarkers of (–)-epicatechin intake.
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Absorption, metabolism, distribution and excretion of (−)-epicatechin: A review of recent findings
Molecular Aspects of Medicine, 2017Co-Authors: Gina Borges, Hagen Schroeter, Javier I Ottaviani, Justin J J Van Der Hooft, Alan CrozierAbstract:Abstract This paper reviews pioneering human studies, their limitations and recent investigations on the absorption, metabolism, distribution and excretion (aka bioavailability) of (–)-epicatechin. Progress has been made possible by improvements in mass spectrometric detection when coupled to high performance liquid chromatography and through the increasing availability of authentic reference compounds of in vivo metabolites of (–)-epicatechin. Studies have shown that [2-14C](–)-epicatechin is absorbed in the small intestine with the 12 structural-related (–)-epicatechin metabolites (SREMs), mainly in the form of (–)-epicatechin-3′-O-glucuronide, 3′-O-methyl-(–)-epicatechin-5-sulfate and (–)-epicatechin-3′-sulfate, attaining sub-μmol/L peak plasma concentrations (Cmax) ∼1 h after ingestion. SREMs were excreted in urine over a 24 h period in amounts corresponding to 20% of (–)-epicatechin intake. On reaching the colon the flavan-3-ol undergoes microbiota-mediated conversions yielding the 5C-ring fission metabolites (5C-RFMs) 5-(hydroxyphenyl)-γ-valerolactones and 5-(hydroxyphenyl)–γ-hydroxyvaleric Acids which appear in plasma as phase II metabolites with a Cmax of 5.8 h after intake and are excreted in quantities equivalent to 42% of the ingested (–)-epicatechin. Other catabolites excreted in 0–24 h urine in amounts equivalent to 28% of intake included 3-(3′-hydroxyphenyl)Hydracrylic Acid, hippuric Acid and 3′-hydroxyhippuric Acid. Overall (–)-epicatechin is highly bioavailable with urinary excretion indicating that 95% is absorbed and passes through the circulatory systems as a diversity of phase II metabolites. Rats produce a very different profile of SREMs than that of humans. These findings demonstrate that ex vivo studies investigating the mechanisms underlying the protective effects of (–)-epicatechin on human health should make use of physiological concentrations human of SREMs and 5C-RFMs, and not the parent (–)-epicatechin, with model systems derived from human cells. In epidemiological studies 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-sulfate and 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-O-glucuronide, the principal 5C-RFMs in both plasma and urine, could serve as key biomarkers of (–)-epicatechin intake.
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absorption metabolism distribution and excretion of epicatechin a review of recent findings
Molecular Aspects of Medicine, 2017Co-Authors: Gina Borges, Hagen Schroeter, Javier I Ottaviani, Justin J J Van Der Hooft, Alan CrozierAbstract:Abstract This paper reviews pioneering human studies, their limitations and recent investigations on the absorption, metabolism, distribution and excretion (aka bioavailability) of (–)-epicatechin. Progress has been made possible by improvements in mass spectrometric detection when coupled to high performance liquid chromatography and through the increasing availability of authentic reference compounds of in vivo metabolites of (–)-epicatechin. Studies have shown that [2-14C](–)-epicatechin is absorbed in the small intestine with the 12 structural-related (–)-epicatechin metabolites (SREMs), mainly in the form of (–)-epicatechin-3′-O-glucuronide, 3′-O-methyl-(–)-epicatechin-5-sulfate and (–)-epicatechin-3′-sulfate, attaining sub-μmol/L peak plasma concentrations (Cmax) ∼1 h after ingestion. SREMs were excreted in urine over a 24 h period in amounts corresponding to 20% of (–)-epicatechin intake. On reaching the colon the flavan-3-ol undergoes microbiota-mediated conversions yielding the 5C-ring fission metabolites (5C-RFMs) 5-(hydroxyphenyl)-γ-valerolactones and 5-(hydroxyphenyl)–γ-hydroxyvaleric Acids which appear in plasma as phase II metabolites with a Cmax of 5.8 h after intake and are excreted in quantities equivalent to 42% of the ingested (–)-epicatechin. Other catabolites excreted in 0–24 h urine in amounts equivalent to 28% of intake included 3-(3′-hydroxyphenyl)Hydracrylic Acid, hippuric Acid and 3′-hydroxyhippuric Acid. Overall (–)-epicatechin is highly bioavailable with urinary excretion indicating that 95% is absorbed and passes through the circulatory systems as a diversity of phase II metabolites. Rats produce a very different profile of SREMs than that of humans. These findings demonstrate that ex vivo studies investigating the mechanisms underlying the protective effects of (–)-epicatechin on human health should make use of physiological concentrations human of SREMs and 5C-RFMs, and not the parent (–)-epicatechin, with model systems derived from human cells. In epidemiological studies 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-sulfate and 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-O-glucuronide, the principal 5C-RFMs in both plasma and urine, could serve as key biomarkers of (–)-epicatechin intake.
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In vitro colonic catabolism of orange juice (poly)phenols
Molecular nutrition & food research, 2015Co-Authors: Gema Pereira-caro, Gina Borges, M. N. Clifford, D. Del Rio, S. A. Roberts, Aleix Ribas, Luca Calani, Alan CrozierAbstract:cope The role of colonic microbiota in the breakdown of hesperetin, naringenin, and ferulic Acid, compounds found as glycosides in orange juice, was investigated using an in vitro fermentation model. Methods and results Test compounds were incubated with human fecal slurries cultured under anaerobic conditions, and the production of phenolic Acid catabolites were monitored by GC-MS and HPLC-MS2. Hesperetin was converted to 3-(3′-hydroxy-4′-methoxyphenyl)propionic Acid, 3-(3′,4′-dihydroxyphenyl)propionic Acid, and 3-(3′-hydroxyphenyl)propionic Acid while 3-(phenyl)propionic Acid was the major end product derived from naringenin. The data obtained are compared to our previously published data on urinary excretion of phenolic and aromatic Acids after acute orange juice consumption (Pereira-Caro et al. Am. J. Clin. Nutr. 2014, 100, 1385–1391). Catabolism pathways are proposed for events occurring in the colon and those taking place postabsorption into the circulatory system with particular reference to the excretion of 3-(3′-hydroxy-4′-methoxyphenyl)Hydracrylic Acid, which is not formed in fecal incubations. Ferulic Acid was also degraded by the colonic microflora being converted principally to 3-(3′-methoxy-4′-hydroxyphenyl)propionic Acid, a phenolic Acid that appears in urine after orange juice consumption. Conclusion The study provides novel information on the potential involvement of the colonic microbiota in the overall bioavailability of orange juice (poly)phenols through the production of phenylpropionic Acids and subsequent hepatic conversions that lead to hippuric Acid and its hydroxylated analogues.
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Orange juice (poly)phenols are highly bioavailable in humans
The American journal of clinical nutrition, 2014Co-Authors: Gema Pereira-caro, Gina Borges, J. Van Der Hooft, M. N. Clifford, D. Del Rio, M. E. Lean, S. A. Roberts, M. B. Kellerhals, Alan CrozierAbstract:Background: We assessed the bioavailability of orange juice (poly) phenols by monitoring urinary flavanone metabolites and ring fission catabolites produced by the action of the colonic microbiota. Objective: Our objective was to identify and quantify metabolites and catabolites excreted in urine 0‐24 h after the acute ingestion of a (poly)phenol-rich orange juice by 12 volunteers. Design: Twelve volunteers [6 men and 6 women; body mass index (in kg/m 2 ): 23.9‐37.2] consumed a low (poly)phenol diet for 2 d before first drinking 250 mL pulp-enriched orange juice, which contained 584 mmol (poly)phenols of which 537 mmol were flavanones, and after a 2-wk washout, the procedure was repeated, and a placebo drink was consumed. Urine collected for a 24-h period was analyzed qualitatively and quantitatively by using high-performance liquid chromatography‐mass spectrometry (HPLC-MS) and gas chromatography‐mass spectrometry (GC-MS). Results: A total of 14 metabolites were identified and quantified in urine by using HPLC-MS after orange juice intake. Hesperetin-Oglucuronides, naringenin-O-glucuronides, and hesperetin-3#-O-sulfate were the main metabolites. The overall urinary excretion of flavanone metabolites corresponded to 16% of the intake of 584 mmol (poly)phenols. The GC-MS analysis revealed that 8 urinary catabolites were also excreted in significantly higher quantities after orange juice consumption. These catabolites were 3-(3#-methoxy-4#-hydroxyphenyl)propionic Acid, 3-(3#-hydroxy-4#-methoxyphenyl)propionic Acid, 3-(3#-hydroxy-4#methoxyphenyl)Hydracrylic Acid, 3-(3#-hydroxyphenyl)Hydracrylic Acid, 3#-methoxy-4#-hydroxyphenylacetic Acid, hippuric Acid, 3#-hydroxyhippuric Acid, and 4#-hydroxyhippuric Acid. These aromatic Acids originated from the colonic microbiota-mediated breakdown of orange juice (poly) phenols and were excreted in amounts equivalent to 88% of (poly)phenol intake. When combined with the 16% excretion of metabolites, this percentage raised to overall urinary excretion tow100% intake. Conclusions: When colon-derived phenolic catabolites are included with flavanone glucuronide and sulfate metabolites, orange juice (poly)phenols are much-more bioavailable than previously envisaged. In vitro and ex vivo studies on mechanisms underlying the potential protective effects of orange juice consumption should use in vivo metabolites and catabolites detected in this investigation at physiologic concentrations. The trial was registered at BioMed Central Ltd (www.controlledtrials.com) as ISRCTN04271658. Am J Clin Nutr doi: 10.3945/ajcn.114.090282.
Gema Pereira-caro - One of the best experts on this subject based on the ideXlab platform.
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Bioavailability of orange juice (poly)phenols: the impact of short-term cessation of training by male endurance athletes.
The American journal of clinical nutrition, 2017Co-Authors: Gema Pereira-caro, Thelma Polyviou, Iziar A. Ludwig, Ana-maria Nastase, José Manuel Moreno-rojas, Ada L. Garcia, Dalia Malkova, Alan CrozierAbstract:Background: Physical exercise has been reported to increase the bioavailability of citrus flavanones.Objective: We investigated the bioavailability of orange juice (OJ) (poly)phenols in endurance-trained males before and after cessation of training for 7 d.Design: Ten fit, endurance-trained males, with a mean ± SD maximal oxygen consumption of 58.2 ± 5.3 mL · kg-1 · min-1, followed a low (poly)phenol diet for 2 d before drinking 500 mL of OJ containing 398 μmol of (poly)phenols, of which 330 μmol was flavanones. After the volunteers stopped training for 7 d the feeding study was repeated. Urine samples were collected 12 h pre- and 24 h post-OJ consumption. Bioavailability was assessed by the quantitative analysis of urinary flavanone metabolites and (poly)phenol catabolites with the use of high-pressure liquid chromatography-high resolution mass spectrometry.Results: During training, 0-24-h urinary excretion of flavanone metabolites, mainly hesperetin-3'-O-glucuronide, hesperetin-3'-sulfate, naringenin-4'-O-glucuronide, naringenin-7-O-glucuronide, was equivalent to 4.2% of OJ flavanone intake. This increased significantly to 5.2% when OJ was consumed after the volunteers stopped training for 7 d. Overall, this trend, although not significant, was also observed with OJ-derived colonic catabolites, which, after supplementation in the trained state, were excreted in amounts equivalent to 51% of intake compared with 59% after cessation of training. However, urinary excretion of 3 colonic catabolites of bacterial origin, most notably, 3-(3'-hydroxy-4'-methoxyphenyl)Hydracrylic Acid, did increase significantly when OJ was consumed postcessation compared with precessation of training. Data were also obtained on interindividual variations in flavanone bioavailability.Conclusions: A 7-d cessation of endurance training enhanced, rather than reduced, the bioavailability of OJ flavanones. The biological significance of these differences and whether they extend to the bioavailability of other dietary (poly)phenols remain to be determined. Hesperetin-3'-O-glucuronide and the colonic microbiota-derived catabolite 3-(3'-hydroxy-4'-methoxyphenyl)Hydracrylic Acid are key biomarkers of the consumption of hesperetin-O-glycoside-containing OJ and other citrus products. This trial was registered at clinicaltrials.gov as NCT02627547.
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In vitro colonic catabolism of orange juice (poly)phenols
Molecular nutrition & food research, 2015Co-Authors: Gema Pereira-caro, Gina Borges, M. N. Clifford, D. Del Rio, S. A. Roberts, Aleix Ribas, Luca Calani, Alan CrozierAbstract:cope The role of colonic microbiota in the breakdown of hesperetin, naringenin, and ferulic Acid, compounds found as glycosides in orange juice, was investigated using an in vitro fermentation model. Methods and results Test compounds were incubated with human fecal slurries cultured under anaerobic conditions, and the production of phenolic Acid catabolites were monitored by GC-MS and HPLC-MS2. Hesperetin was converted to 3-(3′-hydroxy-4′-methoxyphenyl)propionic Acid, 3-(3′,4′-dihydroxyphenyl)propionic Acid, and 3-(3′-hydroxyphenyl)propionic Acid while 3-(phenyl)propionic Acid was the major end product derived from naringenin. The data obtained are compared to our previously published data on urinary excretion of phenolic and aromatic Acids after acute orange juice consumption (Pereira-Caro et al. Am. J. Clin. Nutr. 2014, 100, 1385–1391). Catabolism pathways are proposed for events occurring in the colon and those taking place postabsorption into the circulatory system with particular reference to the excretion of 3-(3′-hydroxy-4′-methoxyphenyl)Hydracrylic Acid, which is not formed in fecal incubations. Ferulic Acid was also degraded by the colonic microflora being converted principally to 3-(3′-methoxy-4′-hydroxyphenyl)propionic Acid, a phenolic Acid that appears in urine after orange juice consumption. Conclusion The study provides novel information on the potential involvement of the colonic microbiota in the overall bioavailability of orange juice (poly)phenols through the production of phenylpropionic Acids and subsequent hepatic conversions that lead to hippuric Acid and its hydroxylated analogues.
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Orange juice (poly)phenols are highly bioavailable in humans
The American journal of clinical nutrition, 2014Co-Authors: Gema Pereira-caro, Gina Borges, J. Van Der Hooft, M. N. Clifford, D. Del Rio, M. E. Lean, S. A. Roberts, M. B. Kellerhals, Alan CrozierAbstract:Background: We assessed the bioavailability of orange juice (poly) phenols by monitoring urinary flavanone metabolites and ring fission catabolites produced by the action of the colonic microbiota. Objective: Our objective was to identify and quantify metabolites and catabolites excreted in urine 0‐24 h after the acute ingestion of a (poly)phenol-rich orange juice by 12 volunteers. Design: Twelve volunteers [6 men and 6 women; body mass index (in kg/m 2 ): 23.9‐37.2] consumed a low (poly)phenol diet for 2 d before first drinking 250 mL pulp-enriched orange juice, which contained 584 mmol (poly)phenols of which 537 mmol were flavanones, and after a 2-wk washout, the procedure was repeated, and a placebo drink was consumed. Urine collected for a 24-h period was analyzed qualitatively and quantitatively by using high-performance liquid chromatography‐mass spectrometry (HPLC-MS) and gas chromatography‐mass spectrometry (GC-MS). Results: A total of 14 metabolites were identified and quantified in urine by using HPLC-MS after orange juice intake. Hesperetin-Oglucuronides, naringenin-O-glucuronides, and hesperetin-3#-O-sulfate were the main metabolites. The overall urinary excretion of flavanone metabolites corresponded to 16% of the intake of 584 mmol (poly)phenols. The GC-MS analysis revealed that 8 urinary catabolites were also excreted in significantly higher quantities after orange juice consumption. These catabolites were 3-(3#-methoxy-4#-hydroxyphenyl)propionic Acid, 3-(3#-hydroxy-4#-methoxyphenyl)propionic Acid, 3-(3#-hydroxy-4#methoxyphenyl)Hydracrylic Acid, 3-(3#-hydroxyphenyl)Hydracrylic Acid, 3#-methoxy-4#-hydroxyphenylacetic Acid, hippuric Acid, 3#-hydroxyhippuric Acid, and 4#-hydroxyhippuric Acid. These aromatic Acids originated from the colonic microbiota-mediated breakdown of orange juice (poly) phenols and were excreted in amounts equivalent to 88% of (poly)phenol intake. When combined with the 16% excretion of metabolites, this percentage raised to overall urinary excretion tow100% intake. Conclusions: When colon-derived phenolic catabolites are included with flavanone glucuronide and sulfate metabolites, orange juice (poly)phenols are much-more bioavailable than previously envisaged. In vitro and ex vivo studies on mechanisms underlying the potential protective effects of orange juice consumption should use in vivo metabolites and catabolites detected in this investigation at physiologic concentrations. The trial was registered at BioMed Central Ltd (www.controlledtrials.com) as ISRCTN04271658. Am J Clin Nutr doi: 10.3945/ajcn.114.090282.
Hagen Schroeter - One of the best experts on this subject based on the ideXlab platform.
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Absorption, metabolism, distribution and excretion of (−)-epicatechin: A review of recent findings
Molecular Aspects of Medicine, 2017Co-Authors: Gina Borges, Hagen Schroeter, Javier I Ottaviani, Justin J J Van Der Hooft, Alan CrozierAbstract:Abstract This paper reviews pioneering human studies, their limitations and recent investigations on the absorption, metabolism, distribution and excretion (aka bioavailability) of (–)-epicatechin. Progress has been made possible by improvements in mass spectrometric detection when coupled to high performance liquid chromatography and through the increasing availability of authentic reference compounds of in vivo metabolites of (–)-epicatechin. Studies have shown that [2-14C](–)-epicatechin is absorbed in the small intestine with the 12 structural-related (–)-epicatechin metabolites (SREMs), mainly in the form of (–)-epicatechin-3′-O-glucuronide, 3′-O-methyl-(–)-epicatechin-5-sulfate and (–)-epicatechin-3′-sulfate, attaining sub-μmol/L peak plasma concentrations (Cmax) ∼1 h after ingestion. SREMs were excreted in urine over a 24 h period in amounts corresponding to 20% of (–)-epicatechin intake. On reaching the colon the flavan-3-ol undergoes microbiota-mediated conversions yielding the 5C-ring fission metabolites (5C-RFMs) 5-(hydroxyphenyl)-γ-valerolactones and 5-(hydroxyphenyl)–γ-hydroxyvaleric Acids which appear in plasma as phase II metabolites with a Cmax of 5.8 h after intake and are excreted in quantities equivalent to 42% of the ingested (–)-epicatechin. Other catabolites excreted in 0–24 h urine in amounts equivalent to 28% of intake included 3-(3′-hydroxyphenyl)Hydracrylic Acid, hippuric Acid and 3′-hydroxyhippuric Acid. Overall (–)-epicatechin is highly bioavailable with urinary excretion indicating that 95% is absorbed and passes through the circulatory systems as a diversity of phase II metabolites. Rats produce a very different profile of SREMs than that of humans. These findings demonstrate that ex vivo studies investigating the mechanisms underlying the protective effects of (–)-epicatechin on human health should make use of physiological concentrations human of SREMs and 5C-RFMs, and not the parent (–)-epicatechin, with model systems derived from human cells. In epidemiological studies 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-sulfate and 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-O-glucuronide, the principal 5C-RFMs in both plasma and urine, could serve as key biomarkers of (–)-epicatechin intake.
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Absorption, metabolism, distribution and excretion of (−)-epicatechin: A review of recent findings
Molecular Aspects of Medicine, 2017Co-Authors: Gina Borges, Hagen Schroeter, Javier I Ottaviani, Justin J J Van Der Hooft, Alan CrozierAbstract:Abstract This paper reviews pioneering human studies, their limitations and recent investigations on the absorption, metabolism, distribution and excretion (aka bioavailability) of (–)-epicatechin. Progress has been made possible by improvements in mass spectrometric detection when coupled to high performance liquid chromatography and through the increasing availability of authentic reference compounds of in vivo metabolites of (–)-epicatechin. Studies have shown that [2-14C](–)-epicatechin is absorbed in the small intestine with the 12 structural-related (–)-epicatechin metabolites (SREMs), mainly in the form of (–)-epicatechin-3′-O-glucuronide, 3′-O-methyl-(–)-epicatechin-5-sulfate and (–)-epicatechin-3′-sulfate, attaining sub-μmol/L peak plasma concentrations (Cmax) ∼1 h after ingestion. SREMs were excreted in urine over a 24 h period in amounts corresponding to 20% of (–)-epicatechin intake. On reaching the colon the flavan-3-ol undergoes microbiota-mediated conversions yielding the 5C-ring fission metabolites (5C-RFMs) 5-(hydroxyphenyl)-γ-valerolactones and 5-(hydroxyphenyl)–γ-hydroxyvaleric Acids which appear in plasma as phase II metabolites with a Cmax of 5.8 h after intake and are excreted in quantities equivalent to 42% of the ingested (–)-epicatechin. Other catabolites excreted in 0–24 h urine in amounts equivalent to 28% of intake included 3-(3′-hydroxyphenyl)Hydracrylic Acid, hippuric Acid and 3′-hydroxyhippuric Acid. Overall (–)-epicatechin is highly bioavailable with urinary excretion indicating that 95% is absorbed and passes through the circulatory systems as a diversity of phase II metabolites. Rats produce a very different profile of SREMs than that of humans. These findings demonstrate that ex vivo studies investigating the mechanisms underlying the protective effects of (–)-epicatechin on human health should make use of physiological concentrations human of SREMs and 5C-RFMs, and not the parent (–)-epicatechin, with model systems derived from human cells. In epidemiological studies 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-sulfate and 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-O-glucuronide, the principal 5C-RFMs in both plasma and urine, could serve as key biomarkers of (–)-epicatechin intake.
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absorption metabolism distribution and excretion of epicatechin a review of recent findings
Molecular Aspects of Medicine, 2017Co-Authors: Gina Borges, Hagen Schroeter, Javier I Ottaviani, Justin J J Van Der Hooft, Alan CrozierAbstract:Abstract This paper reviews pioneering human studies, their limitations and recent investigations on the absorption, metabolism, distribution and excretion (aka bioavailability) of (–)-epicatechin. Progress has been made possible by improvements in mass spectrometric detection when coupled to high performance liquid chromatography and through the increasing availability of authentic reference compounds of in vivo metabolites of (–)-epicatechin. Studies have shown that [2-14C](–)-epicatechin is absorbed in the small intestine with the 12 structural-related (–)-epicatechin metabolites (SREMs), mainly in the form of (–)-epicatechin-3′-O-glucuronide, 3′-O-methyl-(–)-epicatechin-5-sulfate and (–)-epicatechin-3′-sulfate, attaining sub-μmol/L peak plasma concentrations (Cmax) ∼1 h after ingestion. SREMs were excreted in urine over a 24 h period in amounts corresponding to 20% of (–)-epicatechin intake. On reaching the colon the flavan-3-ol undergoes microbiota-mediated conversions yielding the 5C-ring fission metabolites (5C-RFMs) 5-(hydroxyphenyl)-γ-valerolactones and 5-(hydroxyphenyl)–γ-hydroxyvaleric Acids which appear in plasma as phase II metabolites with a Cmax of 5.8 h after intake and are excreted in quantities equivalent to 42% of the ingested (–)-epicatechin. Other catabolites excreted in 0–24 h urine in amounts equivalent to 28% of intake included 3-(3′-hydroxyphenyl)Hydracrylic Acid, hippuric Acid and 3′-hydroxyhippuric Acid. Overall (–)-epicatechin is highly bioavailable with urinary excretion indicating that 95% is absorbed and passes through the circulatory systems as a diversity of phase II metabolites. Rats produce a very different profile of SREMs than that of humans. These findings demonstrate that ex vivo studies investigating the mechanisms underlying the protective effects of (–)-epicatechin on human health should make use of physiological concentrations human of SREMs and 5C-RFMs, and not the parent (–)-epicatechin, with model systems derived from human cells. In epidemiological studies 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-sulfate and 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-O-glucuronide, the principal 5C-RFMs in both plasma and urine, could serve as key biomarkers of (–)-epicatechin intake.
Justin J J Van Der Hooft - One of the best experts on this subject based on the ideXlab platform.
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Absorption, metabolism, distribution and excretion of (−)-epicatechin: A review of recent findings
Molecular Aspects of Medicine, 2017Co-Authors: Gina Borges, Hagen Schroeter, Javier I Ottaviani, Justin J J Van Der Hooft, Alan CrozierAbstract:Abstract This paper reviews pioneering human studies, their limitations and recent investigations on the absorption, metabolism, distribution and excretion (aka bioavailability) of (–)-epicatechin. Progress has been made possible by improvements in mass spectrometric detection when coupled to high performance liquid chromatography and through the increasing availability of authentic reference compounds of in vivo metabolites of (–)-epicatechin. Studies have shown that [2-14C](–)-epicatechin is absorbed in the small intestine with the 12 structural-related (–)-epicatechin metabolites (SREMs), mainly in the form of (–)-epicatechin-3′-O-glucuronide, 3′-O-methyl-(–)-epicatechin-5-sulfate and (–)-epicatechin-3′-sulfate, attaining sub-μmol/L peak plasma concentrations (Cmax) ∼1 h after ingestion. SREMs were excreted in urine over a 24 h period in amounts corresponding to 20% of (–)-epicatechin intake. On reaching the colon the flavan-3-ol undergoes microbiota-mediated conversions yielding the 5C-ring fission metabolites (5C-RFMs) 5-(hydroxyphenyl)-γ-valerolactones and 5-(hydroxyphenyl)–γ-hydroxyvaleric Acids which appear in plasma as phase II metabolites with a Cmax of 5.8 h after intake and are excreted in quantities equivalent to 42% of the ingested (–)-epicatechin. Other catabolites excreted in 0–24 h urine in amounts equivalent to 28% of intake included 3-(3′-hydroxyphenyl)Hydracrylic Acid, hippuric Acid and 3′-hydroxyhippuric Acid. Overall (–)-epicatechin is highly bioavailable with urinary excretion indicating that 95% is absorbed and passes through the circulatory systems as a diversity of phase II metabolites. Rats produce a very different profile of SREMs than that of humans. These findings demonstrate that ex vivo studies investigating the mechanisms underlying the protective effects of (–)-epicatechin on human health should make use of physiological concentrations human of SREMs and 5C-RFMs, and not the parent (–)-epicatechin, with model systems derived from human cells. In epidemiological studies 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-sulfate and 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-O-glucuronide, the principal 5C-RFMs in both plasma and urine, could serve as key biomarkers of (–)-epicatechin intake.
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Absorption, metabolism, distribution and excretion of (−)-epicatechin: A review of recent findings
Molecular Aspects of Medicine, 2017Co-Authors: Gina Borges, Hagen Schroeter, Javier I Ottaviani, Justin J J Van Der Hooft, Alan CrozierAbstract:Abstract This paper reviews pioneering human studies, their limitations and recent investigations on the absorption, metabolism, distribution and excretion (aka bioavailability) of (–)-epicatechin. Progress has been made possible by improvements in mass spectrometric detection when coupled to high performance liquid chromatography and through the increasing availability of authentic reference compounds of in vivo metabolites of (–)-epicatechin. Studies have shown that [2-14C](–)-epicatechin is absorbed in the small intestine with the 12 structural-related (–)-epicatechin metabolites (SREMs), mainly in the form of (–)-epicatechin-3′-O-glucuronide, 3′-O-methyl-(–)-epicatechin-5-sulfate and (–)-epicatechin-3′-sulfate, attaining sub-μmol/L peak plasma concentrations (Cmax) ∼1 h after ingestion. SREMs were excreted in urine over a 24 h period in amounts corresponding to 20% of (–)-epicatechin intake. On reaching the colon the flavan-3-ol undergoes microbiota-mediated conversions yielding the 5C-ring fission metabolites (5C-RFMs) 5-(hydroxyphenyl)-γ-valerolactones and 5-(hydroxyphenyl)–γ-hydroxyvaleric Acids which appear in plasma as phase II metabolites with a Cmax of 5.8 h after intake and are excreted in quantities equivalent to 42% of the ingested (–)-epicatechin. Other catabolites excreted in 0–24 h urine in amounts equivalent to 28% of intake included 3-(3′-hydroxyphenyl)Hydracrylic Acid, hippuric Acid and 3′-hydroxyhippuric Acid. Overall (–)-epicatechin is highly bioavailable with urinary excretion indicating that 95% is absorbed and passes through the circulatory systems as a diversity of phase II metabolites. Rats produce a very different profile of SREMs than that of humans. These findings demonstrate that ex vivo studies investigating the mechanisms underlying the protective effects of (–)-epicatechin on human health should make use of physiological concentrations human of SREMs and 5C-RFMs, and not the parent (–)-epicatechin, with model systems derived from human cells. In epidemiological studies 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-sulfate and 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-O-glucuronide, the principal 5C-RFMs in both plasma and urine, could serve as key biomarkers of (–)-epicatechin intake.
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absorption metabolism distribution and excretion of epicatechin a review of recent findings
Molecular Aspects of Medicine, 2017Co-Authors: Gina Borges, Hagen Schroeter, Javier I Ottaviani, Justin J J Van Der Hooft, Alan CrozierAbstract:Abstract This paper reviews pioneering human studies, their limitations and recent investigations on the absorption, metabolism, distribution and excretion (aka bioavailability) of (–)-epicatechin. Progress has been made possible by improvements in mass spectrometric detection when coupled to high performance liquid chromatography and through the increasing availability of authentic reference compounds of in vivo metabolites of (–)-epicatechin. Studies have shown that [2-14C](–)-epicatechin is absorbed in the small intestine with the 12 structural-related (–)-epicatechin metabolites (SREMs), mainly in the form of (–)-epicatechin-3′-O-glucuronide, 3′-O-methyl-(–)-epicatechin-5-sulfate and (–)-epicatechin-3′-sulfate, attaining sub-μmol/L peak plasma concentrations (Cmax) ∼1 h after ingestion. SREMs were excreted in urine over a 24 h period in amounts corresponding to 20% of (–)-epicatechin intake. On reaching the colon the flavan-3-ol undergoes microbiota-mediated conversions yielding the 5C-ring fission metabolites (5C-RFMs) 5-(hydroxyphenyl)-γ-valerolactones and 5-(hydroxyphenyl)–γ-hydroxyvaleric Acids which appear in plasma as phase II metabolites with a Cmax of 5.8 h after intake and are excreted in quantities equivalent to 42% of the ingested (–)-epicatechin. Other catabolites excreted in 0–24 h urine in amounts equivalent to 28% of intake included 3-(3′-hydroxyphenyl)Hydracrylic Acid, hippuric Acid and 3′-hydroxyhippuric Acid. Overall (–)-epicatechin is highly bioavailable with urinary excretion indicating that 95% is absorbed and passes through the circulatory systems as a diversity of phase II metabolites. Rats produce a very different profile of SREMs than that of humans. These findings demonstrate that ex vivo studies investigating the mechanisms underlying the protective effects of (–)-epicatechin on human health should make use of physiological concentrations human of SREMs and 5C-RFMs, and not the parent (–)-epicatechin, with model systems derived from human cells. In epidemiological studies 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-sulfate and 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-O-glucuronide, the principal 5C-RFMs in both plasma and urine, could serve as key biomarkers of (–)-epicatechin intake.
