Quercetin is a strong antioxidant and a major dietary flavonoid. Epidemiological studies suggest that consumption of quercetin protects against cardiovascular disease, but its absorption in man is controversial. We fed nine subjects a single large dose of onions, which contain glucose conjugates of quercetin, apples, which contain both glucose and non-glucose quercetin glycosides, or pure quercetin-3-rutinoside, the major quercetin glycoside in tea. Plasma levels were then measured over 36 h. Bioavailability of quercetin from apples and of pure quercetin rutinoside was both 30% relative to onions. Peak levels were achieved less than 0.7 h after ingestion of onions, 2.5 h after apples and 9 h after the rutinoside. Half-lives of elimination were 28 h for onions and 23 h for apples. We conclude that conjugation with glucose enhances absorption from the small gut. Because of the long half-lives of elimination, repeated consumption of quercetin-containing foods will cause accumulation of quercetin in blood.© 1997 Federation of European Biochemical Societies.Key words: Flavonoid glycoside; Dietary quercetin; Bioavailability; Pharmacokinetics; Human pounds, which are called glycosides in general, or more specifically glucosides, rutinosides, or xylosides depending on their sugar moiety. The sugar-flavonol bond is a (3-glycosidic bond which is resistant to hydrolysis by pancreatic enzymes. It was thought that such glycosides cannot be absorbed [1]. However, when we measured faecal quercetin in ileostomy subjects we found that human absorption of quercetin-p-glucosides from onions was 52%, whereas absorption of quercetin without its sugar moiety, the so-called aglycone, and of quercetin-|3-rutinoside were both only about 20% [12]. These data suggest that the sugar moiety of quercetin glycosides affects their absorption. In the present study we determined the bioavailability and other pharmacokinetic parameters of various quercetin glycosides contained in foods. Subjects ingested onions, apples and pure quercetin rutinoside (rutin), the major quercetin compound found in tea [13]. Onions contain mainly glucose glycosides of quercetin [14,15]. Apples contain a variety of quercetin glycosides, including galactosides, arabinosides, rhamnosides, xylosides, and glucosides ( Fig. 1) [16][17][18]. Preliminary pharmacokinetic data on onions have been published [19].

Flavonols are antioxidants that may reduce the risk of heart disease. Two major flavonols in the diet are quercetin and kaempferol, and their main sources in The Netherlands are tea and onions. We investigated whether plasma concentrations and urinary excretion of quercetin and kaempferol in humans could be used as biomarkers of intake. We provided 15 subjects with strong black tea (1600 mL/d) or fried onions (129 g/d) for 3 d each in random order separated by a 4-d washout period. The tea provided 49 mg quercetin and 27 mg kaempferol daily and the onions provided 13 mg quercetin and no kaempferol. Flavonols from both foods were clearly absorbed. However, the excretion of unmodified quercetin was 0.5% of intake after tea and 1.1% after onions. Thus, the absorption of quercetin from tea was half of that from onions. The onion treatment was repeated 7-14 d later to estimate within-subject CVs as a measure of reproducibility when the same treatment is given twice. CVs for quercetin were 30% in plasma and 42% in urine. The magnitude of these variations relative to actual variations of approximately 60% between free-living subjects indicates that concentrations of quercetin in plasma and urine are applicable as biomarkers of its intake. We conclude that flavonols in plasma and urine reflect short-term flavonol intake and that they could be used as biomarkers to distinguish between high and low flavonol consumption in epidemiologic studies.

Flavonols are dietary antioxidants which may prevent coronary heart disease. To be able to study absorption of flavonols in humans, we developed a postcolumn derivatization with aluminum for HPLC with fluorescence detection. Variables governing postcolumn chelation, such as water content, buffer, organic modifier of the eluent, concentration of Al(3+), presence of acetic acid in the postcolumn reagent, and temperature, were studied and optimized. Of the flavonoids, only flavonols that contain a free 3-hydroxyl and 4-keto oxygen binding site form fluorescent complexes with Al(3+). The method has a detection limit of 0.15 ng/mL for quercetin, 0.05 ng/mL for kaempferol, 0.45 ng/mL for myricetin, and 0.05 mg/mL for isorhamnetin, thus improving detectability of quercetin 300-fold as compared to that possible with UV detection. The reproducibility relative standard deviation of the method is 1.4%. This extremely sensitive method enables, for the first time, determination of flavonols in body fluids after consumption of a normal diet.