Plasma kinetics and urinary excretion of the flavanones naringenin and hesperetin in humans after ingestion of orange juice and grapefruit juice

The flavanones naringenin and hesperetin exhibit estrogenic, anticarcinogen ic and antioxidative properties. Orange juice and grapefruit juice contain high amounts of these compounds, and therefore their intake from the diet c an be relatively high. No data are available regarding plasma concentration s or plasma kinetics of flavanones. The objectives of this study were to de velop methods allowing the analysis of naringenin and hesperetin from plasm a and urine and to study their plasma kinetics and urinary excretion. We al so wanted to assess whether plasma or urine flavanone concentrations can be used as biomarkers of intake. Healthy volunteers ingested orange juice (fi ve women and three men) or grapefruit juice (two women and three men) once (8 mL/kg). Eleven blood samples and urine were collected between 0 and 24 h after juice administration. Flavanones were analyzed by HPLC with electroc hemical detection. Naringenin and hesperetin were bioavailable from the stu died juices, but interindividual variation in bioavailability was remarkabl e. The resulting plasma concentrations were comparatively high, and the pea k plasma concentrations (C-max) were 0.6 +/- 0.4 mu mol/L (means +/- SD) fo r naringenin from orange juice and 6.0 +/- 5.4 mu mol/L for naringenin from grapefruit juice. The corresponding Value for hesperetin from orange juice was 2.2 +/- 1.6 mu mol/L. The elimination half-lives were between 1.3 and 2.2 h, and therefore plasma concentrations reflect short-term intake. The r elative urinary excretion varied depending on the flavanone source acid dos e and was 30.2 +/- 25.5% and 1.1 +/- 0.8% for naringenin from grapefruit ju ice and orange juice, respectively, and 5.3 +/- 3.1% for hesperetin from or ange juice. The considerable difference in the relative urinary excretion o f naringenin from the two juices was most likely caused by dose-dependent r enal clearance rather than differences in bioavailability (as indicated by the similar C-max-to-dose ratios). The results indicate that urine flavanon e concentrations are not good biomarkers of dietary intake. We conclude tha t because of the relatively high concentrations of flavanones in plasma aft er ingestion of orange juice or grapefruit juice, considerable health effec ts could ensue in individuals consuming them regularly.