British Journal of Nutrition

Research Article

Absorption, excretion and metabolite profiling of methyl-, glucuronyl-, glucosyl- and sulpho-conjugates of quercetin in human plasma and urine after ingestion of onions

William Mullena1 c1, Christine A. Edwardsa2 and Alan Croziera1

a1 Plant Products and Human Nutrition Group, Graham Kerr Building, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow Glasgow G12 8QQ, UK

a2 Human Nutrition Section, University of Glasgow Division of Developmental Medicine, Yorkhill Hospital, Glasgow G3 8SJ UK

Abstract

It is essential to have a thorough knowledge of the bioavailability and metabolism of dietary flavonols to understand their role in disease prevention. Lightly fried onions containing 275μmol flavonols, principally quercetin-4′-glucoside and quercetin-3,4′-diglucoside, were fed to healthy human volunteers and plasma and urine were collected over a 24h period. Samples were analysed by HPLC with diode array and tandem mass spectrometric detection. Five flavonol metabolites, quercetin-3′-sulphate, quercetin-3-glucuronide, isorhamnetin-3-glucuronide, a quercetin diglucuronide and a quercetin glucuronide sulphate, were detected in plasma in quantifiable amounts with trace quantities of six additional quercetin metabolites. Sub-micromolar peak plasma concentrations (cmax) of quercetin-3′-sulphate, quercetin-3-glucuronide, isorhamnetin-3-glucuronide and quercetin diglucuronide were observed 0.6–0.8h after ingestion. In contrast, the cmax of quercetin glucuronide sulphate was 2.5h. The elimination half-lives (t1/2) of quercetin-3′-sulphate, quercetin-3-glucuronide and quercetin diglucuronide were 1.71, 2.33 and 1.76h respectively, while the t1/2 of isorhamnetin-3-glucuronide was 5.34h and that of quercetin glucuronide sulphate was 4.54h. The profile of metabolites excreted in urine was markedly different to that of plasma with many of the major urinary components, including quercetin-3′-glucuronide, two quercetin glucoside sulphates and a methylquercetin diglucuronide, absent or present in only trace amounts in the bloodstream indicative of substantial phase II metabolism. Total urinary excretion of quercetin metabolites was 12·9μmol, corresponding to 4·7% of intake. If these samples had been subjected to hydrolysis, as in many previous studies, only quercetin and isorhamnetin would have been detected and quantified. The bioactivity of these metabolites should be considered.

(Received September 19 2005)

(Revised January 13 2006)

(Accepted February 21 2006)

Correspondence:

c1 *Corresponding author: Professor Alan Crozier, fax +44 (0)141 330 5364, email a.crozier@bio.gla.ac.uk

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