title: Bioavailability is improved by enzymatic modification of the citrus flavonoid hesperidin in humans: a randomized, double-blind, crossover trial.
abstract: Hesperidin is the predominant polyphenol consumed from citrus fruits and juices. However, hesperidin is proposed to have limited bioavailability due to the rutinoside moiety attached to the flavonoid. The aim of this study was to demonstrate in human subjects that the removal of the rhamnose group to yield the corresponding flavonoid glucoside (i.e., hesperetin-7-glucoside) will improve the bioavailability of the aglycone hesperetin. Healthy volunteers (n=16) completed the double-blind, randomized, crossover study. Subjects randomly consumed hesperetin equivalents supplied as orange juice with natural hesperidin ("low dose"), orange juice treated with hesperidinase enzyme to yield hesperetin-7-glucoside, and orange juice fortified to obtain 3 times more hesperidin than naturally present ("high dose"). The area under the curve (AUC) for total plasma hesperetin of subjects consuming hesperetin-7-glucoside juice was 2-fold higher than that of subjects consuming the "low" dose hesperidin juice [3.45+/-1.27 vs. 1.16+/-0.52 mmol/(L.h), respectively, P>0.0001]. The AUC for hesperetin after consuming the hesperetin-7-glucoside juice was improved to the level of the "high" dose hesperidin juice [4.16+/-1.50 mmol/(L.h)]. The peak plasma concentrations (C(max)) of hesperetin were 4-fold higher (2.60+/-1.07 mmol/L, P<0.0001) after subjects consumed hesperetin-7-glucoside juice compared with those consuming "low" dose hesperidin juice (0.48 +/- 0.27 mmol/L), and 1.5-fold higher than those consuming "high" dose hesperidin juice (1.05+/-0.25 mmol/L). The corresponding T(max) was much faster (0.6+/-0.1 h, P<0.0001) after subjects consumed hesperetin-7-glucoside juice compared with "low" dose (7.0+/-3.0 h) and "high" dose (7.4+/-2.0 h) hesperidin juices. The results of this study demonstrated that the bioavailability of hesperidin was modulated by enzymatic conversion to hesperetin-7-glucoside, thus changing the absorption site from the colon to the small intestine. This may affect future interventions concerning the health benefits of citrus flavonoids.
authors.affiliation: Nestle Research Center, Vers-chez-les-Blanc, 1000 Lausanne 26, Switzerland.
authors.forename: Inge Lise F
authors.initials: IL
authors.lastname: Nielsen
authors.forename: Winnie S S
authors.initials: WS
authors.lastname: Chee
authors.forename: Lea
authors.initials: L
authors.lastname: Poulsen
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Offord-Cavin
authors.forename: Salka E
authors.initials: SE
authors.lastname: Rasmussen
authors.forename: Hanne
authors.initials: H
authors.lastname: Frederiksen
authors.forename: Marc
authors.initials: M
authors.lastname: Enslen
authors.forename: Denis
authors.initials: D
authors.lastname: Barron
authors.forename: Marie-Noelle
authors.initials: MN
authors.lastname: Horcajada
authors.forename: Gary
authors.initials: G
authors.lastname: Williamson
mesh_terms: D000328:Adult; D001682:Biological Availability; D002957:Citrus / Q000737:chemistry*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006569:Hesperidin / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D015394:Molecular Structure; D013997:Time Factors
chemical_list: D006569:Hesperidin