Pharmacokinetics and Bioavailability of Quercetin Glycosides in Humans

Abstract

Due to its potentially beneficial impact on human health, the polyphenol quercetin has come into the focus of medicinal interest. However, data on the bioavailability of quercetin after oral intake are scarce and contradictory. Previous investigations indicate that the disposition of quercetin may depend on the sugar moiety of the glycoside or the plant matrix. To determine the influence of the sugar moiety or matrix on the absorption of quercetin, two isolated quercetin glycosides and two plant extracts were administered to 12 healthy volunteers in a four-way crossover study. Each subject received an onion supplement or quercetin-4'-O-glucoside (both equivalent to 100 mg quercetin), as well as quercetin-3-O-rutinoside and buckwheat tea (both equivalent to 200 mg quercetin). Samples were analyzed by HPLC with a 12-channel coulometric array detector. In human plasma, only quercetin glucuronides, but no free quercetin, could be detected. There was no significant difference in the bioavailability and pharmacokinetic parameters between the onion supplement and quercetin-4'-O-glucoside. Peak plasma concentrations were 2.3 +/- 1.5 microg x mL(-1) and 2.1 +/- 1.6 microg x mL(-1) (mean +/- SD) and were reached after 0.7 +/- 0.2 hours and 0.7 +/- 0.3 hours, respectively. After administration of buckwheat tea and rutin, however, peak plasma levels were--despite the higher dose-only 0.6 +/- 0.7 microg x mL(-1) and 0.3 +/- 0.3 microg x mL(-1), respectively. Peak concentrations were reached 4.3 +/- 1.8 hours after administration of buckwheat tea and 7.0 +/- 2.9 hours after ingestion of rutin. The terminal elimination half-life was about 11 hours for all treatments. Thus, the disposition of quercetin in humans primarily depends on the sugar moiety. To a minor extent, the plant matrix influences both the rate and extent of absorption in the case of buckwheat tea administration compared with the isolated compound. The site of absorption seems to be different for quercetin-4'-O-glucoside and quercetin-3-O-rutinoside. The significance of specific carriers on the absorption of quercetin glycosides, as well as specific intestinal beta-glucosidases, needs to be further evaluated.

Absorption of kaempferol from endive, a source of kaempferol-3-glucuronide, in humans

“…Quercetin was excreted at an average of 1.1% of intake after onion consumption compared with 0.5% after tea, suggesting that quercetin from onions is more bioavailable than from tea. Recent studies have confirmed that the glycoside moiety is the major determinant of site of absorption of quercetin from the gastrointestinal tract, with quercetin rutinosides absorbed mainly from the colon and quercetin glucosides absorbed early in the small intestine (Morand et al, 2000;Olthof et al, 2000;Graefe et al, 2001). Kaempferol from endive was excreted at 1.9% of the amount ingested, which is comparable with the levels in urine shown by De Vries et al (1998), as their samples were taken after 7 days of an intervention study.…”

“…The intakes, plasma pharmacokinetics and urinary excretion of a few flavonoids and the soy isoflavones have been fairly extensively studied in man. For example, studies with quercetin have shown that various factors influence the amount absorbed, including the plant source and the type and linkage position of sugar(s) (Hollman et al, 1997(Hollman et al, , 1999Erlund et al, 2000;Graefe et al, 2001). Further, recent studies have shown that quercetin (and other flavonoids and isoflavones) are present in plasma and urine as a mixture of conjugated forms (methylated/glucuronidated/sulphated) Clark et al, 2002).…”

Bioavailability in humans of the flavanones hesperidin and narirutin after the ingestion of two doses of orange juice

“…Bioavailability of flavanones in humans C Manach et al Manach et al, 1997). In humans, some enzymatic activities or transport systems facilitate the absorption of glucosylated quercetin in the small intestine, but seem ineffective for flavonoids linked to a rutinose (Hollman et al, 1999;Erlund et al, 2000;Graëfe et al, 2001). Rutinosides such as narirutin and hesperidin are thus probably absorbed in the colon after hydrolysis by the microflora.…”

Nutritional flavonoids impact on nuclear and extranuclear estrogen receptor activities

“…They are on the order of 0.3-0.75 mmol/L after consumption of 80-100 mg quercetin equivalent administered in the form of apples, onions, or meals rich in plant products (Hollman et al, 1997;Graefe et al, 2001). Naringenin in grapefruit juice appears to be absorbed even better: a peak plasma concentration of 6 mmol/L is obtained after ingestion of 200 mg (Manach et al, 2004).…”