Hydroxytyrosol disposition in humans.
BACKGROUND
Animal and in vitro studies suggest that phenolic compounds in virgin olive oil are effective antioxidants. In animal and in vitro studies, hydroxytyrosol and its metabolites have been shown to be strong antioxidants. One of the prerequisites to assess their in vivo physiologic significance is to determine their presence in human plasma.


METHODS
We developed an analytical method for both hydroxytyrosol and 3-O-methyl-hydroxytyrosol in plasma. The administered dose of phenolic compounds was estimated from methanolic extracts of virgin olive oil after subjecting them to different hydrolytic treatments. Plasma and urine samples were collected from 0 to 12 h before and after 25 mL of virgin olive oil intake, a dose close to that used as daily intake in Mediterranean countries. Samples were analyzed by capillary gas chromatography-mass spectrometry before and after being subjected to acidic and enzymatic hydrolytic treatments.


RESULTS
Calibration curves were linear (r >0.99). Analytical recoveries were 42-60%. Limits of quantification were <1.5 mg/L. Plasma hydroxytyrosol and 3-O-methyl-hydroxytyrosol increased as a response to virgin olive oil administration, reaching maximum concentrations at 32 and 53 min, respectively (P <0.001 for quadratic trend). The estimated hydroxytyrosol elimination half-life was 2.43 h. Free forms of these phenolic compounds were not detected in plasma samples.


CONCLUSIONS
The proposed analytical method permits quantification of hydroxytyrosol and 3-O-methyl-hydroxytyrosol in plasma after real-life doses of virgin olive oil. From our results, approximately 98% of hydroxytyrosol appears to be present in plasma and urine in conjugated forms, mainly glucuronoconjugates, suggesting extensive first-pass intestinal/hepatic metabolism of the ingested hydroxytyrosol.
Miro-Casas
Elisabet
E
Unitat de Farmacologia de l'Institut Municipal d'Investigació Mèdica (URAF-IMIM), Doctor Aiguader No. 80, 08003 Barcelona, Spain.
Covas
Maria-Isabel
MI
Farre
Magi
M
Fito
Montserrat
M
Ortuño
Jordi
J
Weinbrenner
Tanja
T
Roset
Pere
P
de la Torre
Rafael
R
D000328:Adult; D000975:Antioxidants / Q000493:pharmacokinetics*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D057888:Iridoid Glucosides; D039823:Iridoids; D008297:Male; D008875:Middle Aged; D000069463:Olive Oil; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine; D010938:Plant Oils / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D011714:Pyrans / Q000737:chemistry
C475000:3-O-methylhydroxytyrosol; D000975:Antioxidants; D057888:Iridoid Glucosides; D039823:Iridoids; D000069463:Olive Oil; D010938:Plant Oils; D011714:Pyrans; C005975:3,4-dihydroxyphenylethanol; C002769:oleuropein; D010626:Phenylethyl Alcohol