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

Abstract

Objective: Flavanones are polyphenols specific of citrus fruits, where they are present in high amounts. Although citrus fruits and juices are widely consumed in the world, little information has been published on flavanone bioavailability in humans. The aim of the present study was to determine the nature of the circulating metabolites, the plasma kinetics and the urinary excretion patterns of the flavanones, hesperidin and narirutin. Design: After an overnight fast, five healthy volunteers ingested 0.5 or 1 l of a commercial orange juice providing 444 mg=l hesperidin and 96.4 mg=l narirutin, together with a polyphenol-free breakfast. Blood was sampled at 10 different timepoints over a 24 h period. Urine was collected for 48 h, in five fractions. Results: Flavanones metabolites appeared in plasma 3 h after the juice ingestion, reached a peak between 5 and 7 h, then returned to baseline at 24 h. The peak plasma concentration of hesperetin was 0.46 AE 0.07 mmol=l and 1.28 AE 0.13 mmol=l after the 0.5 and 1 l intake, respectively. It was lower for naringenin: 0.20 AE 0.04 mmol=l after the 1 l dose. The circulating forms of hesperetin were glucuronides (87%) and sulphoglucuronides (13%). For both flavanones, the urinary excretion was nearly complete 24 h after the orange juice ingestion. The relative urinary excretion was similar for hesperetin and naringenin and did not depend on the dose: values ranged from 4.1 AE 1.2 to 7.9 AE 1.7% of the intake. Conclusions: In case of a moderate or high consumption of orange juice, flavanones may represent an important part of the pool of total polyphenols present in plasma.

Relative bioavailability of the flavonoids quercetin, hesperetin and naringenin given simultaneously through diet

“…In the study design we assumed that the low and natural amounts of flavonoids in the 'juice mix' excluded any interference with respect to pharmacokinetics of the flavonoids investigated. Previous studies dealing with flavanone and flavonol bioavailability report AUC values in the same range (Hollman et al, 1997;Erlund et al, 2001;Manach et al, 2003Manach et al, , 2005 as observed in the current study. However, the lack of blood sampling between 8-24 h in the present study may have caused an overestimation of the AUCs, especially for the flavanones.…”

“…T max for quercetin in the literature is between 1-9 h, depending on sugar moiety composition (Manach et al, 2005), and the intermediate T max (3.6 ± 1.6 h) in the present study correlates with the mixed content of quercetin glycosides. The average T max in the literature for naringenin is between 2.0-4.6 h (Manach et al, 2003) and that for hesperetin between 5.4-5.8 h (Manach et al, 2003), and are thus also in the same range as observed here.…”

Greater Apparent Absorption of Flavonoids Is Associated with Lesser Human Fecal Flavonoid Disappearance Rates

“…Hesperetin bioavailability ranged from 3 to 6% (26,27), which roughly agrees with the mean hesperetin bioavailability of 7% ( Table 3). We observed a sex difference in hesperetin bioavailability in that hesperetin was not recovered in the urine or plasma of females, so hesperetin bioavailability was based on the five males ( Table 3).…”

“…Low naringenin bioavailability was found in previous studies reporting 4-5% apparent absorption (urinary excretion) from a single oral dose of 1837 μmol of pure naringin ingested by human subjects (26). However, a wide range of 5-57% naringenin bioavailability (as urinary excretion) was reported in six subjects ingesting 26 μmol of naringin/kg of body weight (27). Because our study was the first to compare the apparent absorption of these flavonoids, perhaps the far greater dose of naringenin than of the other flavonoids may have limited naringenin uptake.…”

Absorption and pharmacokinetics of grapefruit flavanones in beagles

“…Previous studies of naringin (naringenin-7-O-rhamnoglucoside) metabolism have suggested that sugar moiety cleavage, by gut microflora a-rhamonosidases, is the first step of this pathway, leading to the formation of naringenin, which undergoes rapid glucuronidation or sulphatation in the intestine or liver (Fuhr & Kummert, 1995;Felgines et al 2000;Scalbert & Williamson, 2000). Most studies have applied enzymatic hydrolysis with sulphatase and glucuronidase in order to identify the aglycone naringenin, and thus the individual metabolic profiles are lost during the hydrolysis procedure (Fuhr & Kummert, 1995;Ishii et al 1996Ishii et al , 1997Hollman et al 1999;Erlund et al 2001;Bugianesi et al 2002;Manach et al 2003;Zhang & Brodbelt, 2004).…”