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

Abstract

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 micromol/L (means +/- SD) for naringenin from orange juice and 6.0 +/- 5.4 micromol/L for naringenin from grapefruit juice. The corresponding value for hesperetin from orange juice was 2.2 +/- 1.6 micromol/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.

Bioavailability in humans of the flavanones hesperidin and narirutin after the ingestion of two doses of orange juice

“…The relative urinary excretion measured in this work for hesperetin and naringenin was similar to that reported in some previous studies, ranging from 1 to 5.3% (Ameer et al, 1996;Ishii et al, 2000;Erlund et al, 2001). Interestingly, the relative urinary excretion of naringenin from grapefruit juice seems higher than that of hesperetin from orange juice: 8.9% (Fuhr & Kummert, 1995), Bioavailability of flavanones in humans C Manach et al 14% (Lee & Reidenberg, 1998), 30% (Erlund et al, 2001). Only a few data have been published for flavonols and flavanols, but their relative urinary excretion seems slightly lower than that of flavanones: 2% for tea catechins (Lee et al, 1995) and 0.3 -1.4% for quercetin (Hollman et al, 1997;Aziz et al, 1998).…”

“…The inter-individual variability was fairly low, maybe because the five subjects were students with very close age, weight and BMI and had similar food habits. A previous study dealing with flavanone bioavailability reported higher plasma values ranging from 0.5 to 5 mmol=l hesperetin after the ingestion of orange juice providing 126 mg hesperetin (Erlund et al, 2001). However in that study, orange juice was given alone to fasted volunteers, whereas in our study, orange juice was administered with a meal.…”

Absorption and pharmacokinetics of grapefruit flavanones in beagles

“…Previous studies of naringin (naringenin-7-O-rhamnoglucoside) metabolism have suggested that sugar moiety cleavage, by gut microflora a-rhamonosidases, is the first step of this pathway, leading to the formation of naringenin, which undergoes rapid glucuronidation or sulphatation in the intestine or liver (Fuhr & Kummert, 1995;Felgines et al 2000;Scalbert & Williamson, 2000). Most studies have applied enzymatic hydrolysis with sulphatase and glucuronidase in order to identify the aglycone naringenin, and thus the individual metabolic profiles are lost during the hydrolysis procedure (Fuhr & Kummert, 1995;Ishii et al 1996Ishii et al , 1997Hollman et al 1999;Erlund et al 2001;Bugianesi et al 2002;Manach et al 2003;Zhang & Brodbelt, 2004).…”

Plasma concentrations of the flavonoids hesperetin, naringenin and quercetin in human subjects following their habitual diets, and diets high or low in fruit and vegetables

“…It has been shown that quercetin is bioavailable from foods such as onions, tea and apples (Hollman et al, 1997), which are its main dietary sources (Hertog et al, 1995). It has also been shown that hesperetin and naringenin are bioavailable from citrus (Ameer et al, 1996;Erlund et al, 2001). It is evident that the bioavailability of quercetin, and most likely of other flavonoids as well, is greatly affected by the type and binding site of the sugar moieties (Hollman et al, 1999).…”