title: Hydroxytyrosol disposition in humans.
abstract: 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.
authors.affiliation: Unitat de Farmacologia de l'Institut Municipal d'Investigació Mèdica (URAF-IMIM), Doctor Aiguader No. 80, 08003 Barcelona, Spain.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Miro-Casas
authors.forename: Maria-Isabel
authors.initials: MI
authors.lastname: Covas
authors.forename: Magi
authors.initials: M
authors.lastname: Farre
authors.forename: Montserrat
authors.initials: M
authors.lastname: Fito
authors.forename: Jordi
authors.initials: J
authors.lastname: Ortuño
authors.forename: Tanja
authors.initials: T
authors.lastname: Weinbrenner
authors.forename: Pere
authors.initials: P
authors.lastname: Roset
authors.forename: Rafael
authors.initials: R
authors.lastname: de la Torre
mesh_terms: 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
chemical_list: 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