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Articles

Plasma Kinetics and Urinary Excretion of the Flavanones Naringenin and Hesperetin in Humans after Ingestion of Orange Juice and Grapefruit Juice¹

Iris Erlund^*2, Esa Meririnne, Georg Alfthan^* and Antti Aro^*

Departments of ^* Nutrition and Mental Health and Alcohol Research (Research Unit of Substance Abuse), National Public Health Institute (KTL), Mannerheimintie 166 F, FIN-00300 Helsinki, Finland

²To whom correspondence should be addressed. E-mail: iris.erlund{at}ktl.fi

The flavanones naringenin and hesperetin exhibit estrogenic, anticarcinogenic and antioxidative properties. Orange juice and grapefruit juice contain high amounts of these compounds, and therefore their intake from the diet can be relatively high. No data are available regarding plasma concentrations or plasma kinetics of flavanones. The objectives of this study were to develop methods allowing the analysis of naringenin and hesperetin from plasma and urine and to study their plasma kinetics and urinary excretion. We also wanted to assess whether plasma or urine flavanone concentrations can be used as biomarkers of intake. Healthy volunteers ingested orange juice (five 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 electrochemical detection. Naringenin and hesperetin were bioavailable from the studied juices, but interindividual variation in bioavailability was remarkable. The resulting plasma concentrations were comparatively high, and the peak plasma concentrations (C_max) were 0.6 ± 0.4 µmol/L (means ± SD) for naringenin from orange juice and 6.0 ± 5.4 µmol/L for naringenin from grapefruit juice. The corresponding value for hesperetin from orange juice was 2.2 ± 1.6 µmol/L. The elimination half-lives were between 1.3 and 2.2 h, and therefore plasma concentrations reflect short-term intake. The relative urinary excretion varied depending on the flavanone source and dose and was 30.2 ± 25.5% and 1.1 ± 0.8% for naringenin from grapefruit juice and orange juice, respectively, and 5.3 ± 3.1% for hesperetin from orange juice. The considerable difference in the relative urinary excretion of naringenin from the two juices was most likely caused by dose-dependent renal clearance rather than differences in bioavailability (as indicated by the similar C_max-to-dose ratios). The results indicate that urine flavanone concentrations are not good biomarkers of dietary intake. We conclude that because of the relatively high concentrations of flavanones in plasma after ingestion of orange juice or grapefruit juice, considerable health effects could ensue in individuals consuming them regularly.

KEY WORDS: • flavonoids • naringenin • hesperetin • kinetics • bioavailability • humans