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1 Unitat de Farmacologia de l’Institut Municipal d’Investigació Mèdica (URAF-IMIM) and
2 Unitat de Lípids i Epidemiologia Cardiovascular de l’Institut Municipal d’Investigació Mèdica (ULEC-IMIM), Doctor Aiguader No. 80, 08003 Barcelona, Spain.
3 Universitat Autónoma de Barcelona (UAB), 08003 Barcelona, Spain.
4 Universitat Pompeu Fabra (CEXS-UPF), 08003 Barcelona, Spain.
aAddress correspondence to this author at: Unitat de Farmacologia Institut Municipal d’Investigació Mèdica (IMIM), Carrer Doctor Aiguader, 80, 08003 Barcelona, Spain. Fax 34-932213237; e-mail rtorre{at}imim.es.
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, 
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.
The following articles in journals at HighWire Press have cited this article:
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  H. Schroder, R. de la Torre, R. Estruch, D. Corella, M. A. Martinez-Gonzalez, J. Salas-Salvado, E. Ros, F. Aros, G. Flores, E. Civit, et al. Alcohol consumption is associated with high concentrations of urinary hydroxytyrosol Am. J. Clinical Nutrition, November 1, 2009; 90(5): 1329 - 1335. [Abstract] [Full Text] [PDF]
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 G Corona, J. Spencer, and M. Dessi Extra virgin olive oil phenolics: absorption, metabolism, and biological activities in the GI tract Toxicology and Industrial Health, May 1, 2009; 25(4-5): 285 - 293. [Abstract] [PDF]
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 M. A. Carluccio, M. A. Ancora, M. Massaro, M. Carluccio, E. Scoditti, A. Distante, C. Storelli, and R. De Caterina Homocysteine induces VCAM-1 gene expression through NF-{kappa}B and NAD(P)H oxidase activation: protective role of Mediterranean diet polyphenolic antioxidants Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2344 - H2354. [Abstract] [Full Text] [PDF]
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J. Ruano, J. Lopez-Miranda, R. de la Torre, J. Delgado-Lista, J. Fernandez, J. Caballero, M. I. Covas, Y. Jimenez, P. Perez-Martinez, C. Marin, et al. Intake of phenol-rich virgin olive oil improves the postprandial prothrombotic profile in hypercholesterolemic patients Am. J. Clinical Nutrition, August 1, 2007; 86(2): 341 - 346. [Abstract] [Full Text] [PDF]
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S. J. Rietjens, A. Bast, J. de Vente, and G. R. M. M. Haenen The olive oil antioxidant hydroxytyrosol efficiently protects against the oxidative stress-induced impairment of the NObullet response of isolated rat aorta Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1931 - H1936. [Abstract] [Full Text] [PDF]
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 S. Acin, M. A. Navarro, J. M. Arbones-Mainar, N. Guillen, A. J. Sarria, R. Carnicer, J. C. Surra, I. Orman, J. C. Segovia, R. d. l. Torre, et al. Hydroxytyrosol Administration Enhances Atherosclerotic Lesion Development in Apo E Deficient Mice J. Biochem., September 1, 2006; 140(3): 383 - 391. [Abstract] [Full Text] [PDF]
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 R. Zamora-Ros, M. Urpi-Sarda, R. M. Lamuela-Raventos, R. Estruch, M. Vazquez-Agell, M. Serrano-Martinez, W. Jaeger, and C. Andres-Lacueva Diagnostic Performance of Urinary Resveratrol Metabolites as a Biomarker of Moderate Wine Consumption Clin. Chem., July 1, 2006; 52(7): 1373 - 1380. [Abstract] [Full Text] [PDF]
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 R. Fabiani, A. De Bartolomeo, P. Rosignoli, M. Servili, R. Selvaggini, G. F. Montedoro, C. Di Saverio, and G. Morozzi Virgin Olive Oil Phenols Inhibit Proliferation of Human Promyelocytic Leukemia Cells (HL60) by Inducing Apoptosis and Differentiation J. Nutr., March 1, 2006; 136(3): 614 - 619. [Abstract] [Full Text] [PDF]
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 P. M. Furneri, A. Piperno, A. Sajia, and G. Bisignano Antimycoplasmal Activity of Hydroxytyrosol Antimicrob. Agents Chemother., December 1, 2004; 48(12): 4892 - 4894. [Abstract] [Full Text] [PDF]
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T. Weinbrenner, M. Fito, R. d. l. Torre, G. T. Saez, P. Rijken, C. Tormos, S. Coolen, M. F. Albaladejo, S. Abanades, H. Schroder, et al. Olive Oils High in Phenolic Compounds Modulate Oxidative/Antioxidative Status in Men J. Nutr., September 1, 2004; 134(9): 2314 - 2321. [Abstract] [Full Text] [PDF]
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