Phenolic sulfates as new and highly abundant metabolites in human plasma after ingestion of a mixed berry fruit purée

Bioavailability studies are vital to assess the potential impact of bioactive compounds on human health. Although conjugated phenolic metabolites derived from colonic metabolism have been identified in the urine, the quantification and appearance of these compounds in plasma is less well studied. In this regard, it is important to further assess their potential biological activity in vivo. To address this gap, a cross-over intervention study with a mixed fruit purée (blueberry, blackberry, raspberry, strawberry tree fruit and Portuguese crowberry) and a standard polyphenol-free meal was conducted in thirteen volunteers (ten females and three males), who received each test meal once, and plasma metabolites were identified by HPLC–MS/MS. Sulfated compounds were chemically synthesised and used as standards to facilitate quantification. Gallic and caffeic acid conjugates were absorbed rapidly, reaching a maximum concentration between 1 and 2 h. The concentrations of sulfated metabolites resulting from the colonic degradation of more complex polyphenols increased in plasma from 4 h, and pyrogallol sulfate and catechol sulfate reached concentrations ranging from 5 to 20 μm at 6 h. In conclusion, phenolic sulfates reached high concentrations in plasma, as opposed to their undetected parent compounds. These compounds have potential use as biomarkers of polyphenol intake, and their biological activities need to be considered.

[1]  R. Ferreira,et al.  Daily polyphenol intake from fresh fruits in Portugal: contribution from berry fruits , 2013, International journal of food sciences and nutrition.

[2]  M. Ohmori,et al.  Urinary metabolites of gallic acid in rats and their radical-scavenging effects on 1,1-diphenyl-2-picrylhydrazyl radical. , 2000, Journal of natural products.

[3]  G. Williamson,et al.  Analysis of phenolic compounds in Portuguese wild and commercial berries after multienzyme hydrolysis. , 2013, Journal of agricultural and food chemistry.

[4]  C. Edwards,et al.  Colonic Catabolism of Ellagitannins, Ellagic Acid, and Raspberry Anthocyanins: In Vivo and In Vitro Studies , 2011, Drug Metabolism and Disposition.

[5]  S. Moco,et al.  Metabolomics view on gut microbiome modulation by polyphenol-rich foods. , 2012, Journal of proteome research.

[6]  T. Osawa,et al.  Absorption and metabolism of cyanidin 3‐O‐β‐D‐glucoside in rats , 1999 .

[7]  M. Clifford,et al.  Bioavailability of dietary flavonoids and phenolic compounds. , 2010, Molecular aspects of medicine.

[8]  A. Törrönen,et al.  Distribution and contents of phenolic compounds in eighteen Scandinavian berry species. , 2004, Journal of agricultural and food chemistry.

[9]  Gary Williamson,et al.  Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. , 2005, The American journal of clinical nutrition.

[10]  Mitchell R. McGill,et al.  Metabolism and Disposition of Acetaminophen: Recent Advances in Relation to Hepatotoxicity and Diagnosis , 2013, Pharmaceutical Research.

[11]  D. Barron,et al.  Dose-response plasma appearance of coffee chlorogenic and phenolic acids in adults. , 2014, Molecular nutrition & food research.

[12]  S. de Pascual-Teresa,et al.  Flavanols and Anthocyanins in Cardiovascular Health: A Review of Current Evidence , 2010, International journal of molecular sciences.

[13]  T. Sugahara,et al.  Concerted actions of the catechol O-methyltransferase and the cytosolic sulfotransferase SULT1A3 in the metabolism of catecholic drugs. , 2012, Biochemical pharmacology.

[14]  P. Kroon,et al.  The bioactivity of dietary anthocyanins is likely to be mediated by their degradation products. , 2009, Molecular nutrition & food research.

[15]  P. Curtis,et al.  Phenolic metabolites of anthocyanins following a dietary intervention study in post-menopausal women. , 2014, Molecular nutrition & food research.

[16]  S. Basu,et al.  Regioselective sulfation and glucuronidation of phenolics: insights into the structural basis. , 2011, Current drug metabolism.

[17]  C. Edwards,et al.  Gastrointestinal stability and bioavailability of (poly)phenolic compounds following ingestion of Concord grape juice by humans. , 2012, Molecular nutrition & food research.

[18]  O. Paredes-López,et al.  Berries: Improving Human Health and Healthy Aging, and Promoting Quality Life—A Review , 2010, Plant foods for human nutrition.

[19]  H. Glatt,et al.  In vitro and in vivo conjugation of dietary hydroxycinnamic acids by UDP-glucuronosyltransferases and sulfotransferases in humans. , 2010, The Journal of nutritional biochemistry.

[20]  G. Williamson,et al.  Colonic metabolites of berry polyphenols: the missing link to biological activity? , 2010, British Journal of Nutrition.

[21]  Liliana Jiménez,et al.  Polyphenols: food sources and bioavailability. , 2004, The American journal of clinical nutrition.

[22]  T. Preston,et al.  Human metabolism and elimination of the anthocyanin, cyanidin-3-glucoside: a (13)C-tracer study. , 2013, The American journal of clinical nutrition.

[23]  S. Shahrzad,et al.  Pharmacokinetics of gallic acid and its relative bioavailability from tea in healthy humans. , 2001, The Journal of nutrition.

[24]  G. Williamson,et al.  Urinary metabolite profiling identifies novel colonic metabolites and conjugates of phenolics in healthy volunteers. , 2014, Molecular nutrition & food research.

[25]  Ilja C W Arts,et al.  Polyphenols and disease risk in epidemiologic studies. , 2005, The American journal of clinical nutrition.

[26]  D. Barron,et al.  First synthesis, characterization, and evidence for the presence of hydroxycinnamic acid sulfate and glucuronide conjugates in human biological fluids as a result of coffee consumption. , 2010, Organic & biomolecular chemistry.

[27]  J. Magdalou,et al.  ASSESSMENT OF CATECHOL INDUCTION AND GLUCURONIDATION IN RAT LIVER MICROSOMES , 2004, Drug Metabolism and Disposition.

[28]  F. A. Muskiet,et al.  Urinary excretion of conjugated homovanillic acid, 3,4-dihydroxyphenylacetic acid, p-hydroxyphenylacetic acid, and vanillic acid by persons on their usual diet and patients with neuroblastoma. , 1979, Clinical chemistry.

[29]  B. Bartolomé,et al.  Insights into the metabolism and microbial biotransformation of dietary flavan-3-ols and the bioactivity of their metabolites. , 2010, Food & function.

[30]  Aleksandra Galetin,et al.  Prediction of Human Drug Clearance by Multiple Metabolic Pathways: Integration of Hepatic and Intestinal Microsomal and Cytosolic Data , 2011, Drug Metabolism and Disposition.

[31]  Jianghao Sun,et al.  Liquid chromatography-tandem mass spectrometry analysis of protocatechuic aldehyde and its phase I and II metabolites in rat. , 2007, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[32]  G. Williamson,et al.  Absorption of dimethoxycinnamic acid derivatives in vitro and pharmacokinetic profile in human plasma following coffee consumption. , 2012, Molecular nutrition & food research.

[33]  Jackie C Bloomer,et al.  Quantitative Evaluation of the Expression and Activity of Five Major Sulfotransferases (SULTs) in Human Tissues: The SULT “Pie” , 2009, Drug Metabolism and Disposition.

[34]  D. Barron,et al.  Metabolite Profiling of Hydroxycinnamate Derivatives in Plasma and Urine after the Ingestion of Coffee by Humans: Identification of Biomarkers of Coffee Consumption , 2009, Drug Metabolism and Disposition.

[35]  Alan Crozier,et al.  Colonic catabolism of dietary phenolic and polyphenolic compounds from Concord grape juice. , 2013, Food & function.