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.

A peer-reviewed open access journal published by the National Institute of Environmental Health Sciences

Summary: Diethyl phthalate (DEP), dibutyl phthalate (DBP) and butyl paraben (BP) are man‐made chemicals used in personal care products, such as lotions and creams. Exposure to these chemicals causes a variety of adverse reproductive outcomes in animal studies. Humans can be exposed to these chemicals through dermal absorption, but there are no published data on absorption, metabolism, and excretion after dermal application. This study investigates urinary concentrations of BP and metabolites of DEP and DBP after topical application. In a 2‐week single‐blinded study, 26 healthy Caucasian male subjects were given a whole body topical application of basic cream 2 mg/cm² (control week) and then a cream containing 2% (w/w) of DEP, DBP and BP each (treatment week) daily. Twenty‐four‐hour urine samples were collected. Urinary total, and unconjugated BP, monoethyl phthalate (MEP) and monobutyl phthalate (MBP) metabolites were analysed by Liquid Chromatography–Tandem Mass Spectroscopy (LC‐MS/MS). All 26 subjects showed increased excretion of MEP, MBP and BP following topical application. Total MEP, MBP and BP (mean ± SEM) excreted in urine in the treatment week were, respectively, 41 ± 1.9, 11.8 ± 0.6 and 2.6 ± 0.1 mg/24 h. On average 5.79, 1.82 and 0.32%, respectively, of the applied DEP, DBP and BP could be recovered in urine as MEP, MBP and BP. The concentration of the compounds peaked in urine 8–12 h after application. The fractions of unconjugated MEP, MBP, and BP were 78, 8.0 and 2.1%, respectively. Absorption of DEP, DBP and BP through skin could potentially contribute to adverse health effects. The three chemicals are systemically absorbed, metabolized and excreted in urine following application on the skin in a cream preparation. More DEP than DBP was absorbed, presumably because of a faster absorption rate for DEP.