Absorption, Conjugation and Excretion of the Flavanones, Naringenin and Hesperetin from Alpha-rhamnosidase-treated Orange Juice in Human Subjects

We have determined the absorption, conjugation and excretion of naringenin-7-O-rutinoside (narirutin) compared to the corresponding glucoside in an orange juice matrix in human subjects. Healthy volunteers (eight men and eight women), in a double blind, randomised, crossover study, consumed orange juice with (1) natural content of naringenin-7-O-rutinoside; (2) alpha-rhamnosidase-treated to yield naringenin-7-O-glucoside. Blood was sampled at twelve time points and three fractions of urine were collected over 24 h. The area under the plasma-time curve of naringenin from (2) alpha-rhamnosidase-treated orange juice was increased about 4-fold (P < 0.0001), peak plasma concentration (Cmax) was 5.4-fold higher (P < 0.0001) and Tmax was decreased from 311 to 92 min (P = 0.002) compared to untreated orange juice (1), indicating a change in absorption site from the colon to the small intestine. Furthermore, the amount in urine was increased from 7 to 47 % (P < 0.0001) of the dose after consumption of the alpha-rhamnosidase-treated orange juice (2). All urine samples contained both naringenin-7- and -4'-O-glucuronides. In addition, to examine the effect of dose and alpha-rhamnosidase treatment on hesperetin conjugate profiles, a further treatment where (3) orange juice fortified with three times the original content of hesperetin-7-O-rutinoside was used. Five hesperetin metabolites (3'-O-glucuronide; 7-O-glucuronide; 5,7-O-diglucuronide; 3',7-O-diglucuronide; 3'-O-sulphate) were present after all treatments (1-3), with the same profile of the conjugates. The present data show that bioavailability of naringenin is increased by conversion from rutinoside to glucoside, but the profile of the conjugates of flavanones formed and excreted in urine is neither affected by the absorption site nor by a 3-fold change in dose.