Metabolic disposition and biological significance of simple phenols of dietary origin: hydroxytyrosol and tyrosol

Drug Metabolism Reviews

Volumn 48, Issue 2, 2016, Pages 218-236

  Rodríguez Morató, Jose ^a,b,c   Boronat, Anna ^a,b   Kotronoulas, Aristotelis ^a   Pujadas, Mitona ^a   Pastor, Antoni ^a,c   Olesti, Eulalia ^a,b   Pérez Mañá, Clara ^a,d   Khymenets, Olha ^a   Fitó, Montserrat ^a,c   Farré, Magí ^a,d,e   de la Torre, Rafael ^a,b,c  

^a HOSPITAL DEL MAR   (Spain)

^b UNIVERSITAT POMPEU FABRA   (Spain)

^c Instituto de Salud Carlos III   (Spain)

^d UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

^e HOSPITAL UNIVERSITARI GERMANS TRIAS I PUJOL   (Spain)

Author keywords

cardiovascular prevention; dopamine; ethanol; Hydroxytyrosol; Mediterranean Diet; phenolic compounds; red wine; tyramine; tyrosol; virgin olive oil

Indexed keywords

ALCOHOL; GLUCURONIDE; HYDROXYTYROSOL; SULFATE; TYRAMINE; TYROSOL; 3,4-DIHYDROXYPHENYLETHANOL; 4-HYDROXYPHENYLETHANOL; DOPAMINE; PHENETHYL ALCOHOL;

AEROBIC METABOLISM; ALCOHOL CONSUMPTION; ANALYTIC METHOD; BIOAVAILABILITY; BLOOD LEVEL; DIETARY INTAKE; EXCRETION; HUMAN; IN VITRO STUDY; IN VIVO STUDY; METABOLISM; METABOLITE; REVIEW; URINE LEVEL; ANALOGS AND DERIVATIVES; BLOOD; TISSUE DISTRIBUTION; URINE;

BIOLOGICAL AVAILABILITY; DOPAMINE; HUMANS; PHENYLETHYL ALCOHOL; TISSUE DISTRIBUTION; TYRAMINE;

EID: 84977579862     PISSN: 03602532     EISSN: 10979883     Source Type: Journal    
DOI: 10.1080/03602532.2016.1179754     Document Type: Review

References (127)

1. C.Almeida, I.F.Duarte, A.Barros,. (2006). Composition of beer by 1H NMR spectroscopy: Effects of brewing site and date of production. J Agric Food Chem 54:700–706.
2. A.Atzeri, R.Lucas, A.Incani,. (2016). Hydroxytyrosol and tyrosol sulfate metabolites protect against the oxidized cholesterol pro-oxidant effect in Caco-2 human enterocyte-like cells. Food Funct 7:337–346.
3. D.Auñon-Calles, L.Canut, F.Visioli (2013a). Toxicological evaluation of pure hydroxytyrosol. Food Chem Toxicol 55:498–504.
4. D.Auñon-Calles, E.Giordano, S.Bohnenberger, F.Visioli (2013b). Hydroxytyrosol is not genotoxic in vitro. Pharmacol Res 74:87–93.
5. C.Bai, X.Yan, M.Takenaka,. (1998). Determination of synthetic hydroxytyrosol in rat plasma by GC-MS. J Agric Food Chem 46:3998–4001.
6. R.Bartholomé, G.Haenen, P.C.H.Hollman,. (2010). Deconjugation kinetics of glucuronidated phase II flavonoid metabolites by beta-glucuronidase from neutrophils. Drug Metab Pharmacokinet 25:379–387.
7. B.Bayram, B.Ozcelik, G.Schultheiss,. (2013). A validated method for the determination of selected phenolics in olive oil using high-performance liquid chromatography with coulometric electrochemical detection and a fused-core column. Food Chem 138:1663–1669.
8. F.N.Bazoti, E.Gikas, A.Tsarbopoulos (2010). Simultaneous quantification of oleuropein and its metabolites in rat plasma by liquid chromatography electrospray ionization tandem mass spectrometry. Biomed Chromatogr 24:506–515.
9. A.Bendini, L.Cerretani, A.Carrasco-Pancorbo,. (2007). Phenolic molecules in virgin olive oils: A survey of their sensory properties, health effects, antioxidant activity and analytical methods. An overview of the last decade. Molecules 12:1679.
10. R.Bernini, N.Merendino, A.Romani, F.Velotti (2013). Naturally occurring hydroxytyrosol: Synthesis and anticancer potential. Curr Med Chem 20:655–670.
11. P.Bogani, C.Galli, M.Villa, F.Visioli (2007). Postprandial anti-inflammatory and antioxidant effects of extra virgin olive oil. Atherosclerosis 190:181–186.
12. M.Bordiga, C.Lorenzo, F.Pardo,. (2016). Factors influencing the formation of histaminol, hydroxytyrosol, tyrosol, and tryptophol in wine: Temperature, alcoholic degree, and amino acids concentration. Food Chem Part B 197:1038–1045.
13. R.Briante, F.Febbraio, R.Nucci (2003). Antioxidant properties of low molecular weight phenols present in the Mediterranean Diet. J Agric Food Chem 51:6975–6981.
14. S.Bulotta, M.Celano, S.M.Lepore,. (2014). Beneficial effects of the olive oil phenolic components oleuropein and hydroxytyrosol: Focus on protection against cardiovascular and metabolic diseases. J Transl Med 12:219.
15. I.Campesi, A.Romani, M.Marino, F.Franconi (2014). Phenolic compounds from a sex-gender perspective. In: Romani A, Lattanzio V, Quideau S, eds. Recent advances in polyphenol research. Chichester, UK: John Wiley & Sons, Ltd, 327–339.
16. A.Carrasco-Pancorbo, L.Cerretani, A.Bendini,. (2005). Evaluation of the antioxidant capacity of individual phenolic compounds in virgin olive oil. J Agric Food Chem 53:8918–8925.
17. D.Caruso, F.Visioli, R.Patelli,. (2001). Urinary excretion of olive oil phenols and their metabolites in humans. Metab Clin Exp 50:1426–1428.
18. Ú.Catalán, M.-C.López de las Hazas, L.Rubió,. (2015). Protective effect of hydroxytyrosol and its predominant plasmatic human metabolites against endothelial dysfunction in human aortic endothelial cells. Mol Nutr Food Res 59:2523–2536.
19. W.Chen, T.Becker, F.Qian, J.Ring (2014). Beer and beer compounds: Physiological effects on skin health. J Eur Acad Dermatol Venereol 28:142–150.
20. Z.Cheng, J.Ren, Y.Li,. (2002). Study on the multiple mechanisms underlying the reaction between hydroxyl radical and phenolic compounds by qualitative structure and activity relationship. Bioorg Med Chem 10:4067–4073.
21. G.Chiva-Blanch, S.Arranz, R.M.Lamuela-Raventos, R.Estruch (2013). Effects of wine, alcohol and polyphenols on cardiovascular disease risk factors: Evidences from human studies. Alcohol Alcoholism 48:270–277.
22. G.Chiva-Blanch, L.Badimon, R.Estruch (2014). Latest evidence of the effects of the Mediterranean Diet in prevention of cardiovascular disease. Curr Atheroscler Rep 16:1–7.
23. G.Corona, X.Tzounis, M.Assunta Dessì,. (2006). The fate of olive oil polyphenols in the gastrointestinal tract: Implications of gastric and colonic microflora-dependent biotransformation. Free Radic Res 40:647–658.
24. M.-I.Covas, K.de la Torre, M.Farré-Albaladejo,. (2006a). Postprandial LDL phenolic content and LDL oxidation are modulated by olive oil phenolic compounds in humans. Free Radic Biol Med 40:608–616.
25. M.-I.Covas, R.de la Torre, M.Fitó (2015). Virgin olive oil: A key food for cardiovascular risk protection. Br J Nutr 113:S19–S28.
26. M.-I.Covas, E.Miro-Casas, M.Fito,. (2003). Bioavailability of tyrosol, an antioxidant phenolic compound present in wine and olive oil, in humans. Drugs Exp Clin Res 29:203–206.
27. M.-I.Covas, K.Nyyssönen, H.E.Poulsen,. (2006b). The effect of polyphenols in olive oil on heart disease risk factors: A randomized trial. Ann Intern Med 145:333–341.
28. M.-I.Covas, V.Ruiz-Gutiérrez, R.de la Torre,. (2006c). Minor components of olive oil: Evidence to date of health benefits in humans. Nutr Rev 64:S20–S30.
29. M.C.Crespo, J.Tomé-Carneiro, E.Burgos-Ramos,. (2015). One-week administration of hydroxytyrosol to humans does not activate phase II enzymes. Pharmacol Res 95–96:132–137.
30. S.D'Angelo, C.Manna, V.Migliardi,. (2001). Pharmacokinetics and metabolism of hydroxytyrosol, a natural antioxidant from olive oil. Drug Metab Dispos 29:1492–1498.
31. V.E.Davis, H.Brown, J.A.Huff, J.L.Cashaw (1967). The alteration of serotonin metabolism to 5-hydroxytryptophol by ethanol ingestion in man. J Lab Clin Med 69:132–140.
32. V.E.Davis, M.J.Walsh (1970). Alcohol, amines, and alkaloids: A possible biochemical basis for alcohol addiction. Science 167:1005–1007.
33. V.E.Davis, M.J.Walsh, Y.Yamanaka (1970). Augmentation of alkaloid formation from dopamine by alcohol and acetaldehyde in vitro. J Pharmacol Exp Ther 174:401–412.
34. M.De Bock, J.G.Derraik, C.M.Brennan,. (2013a). Olive (Olea europaea L.) leaf polyphenols improve insulin sensitivity in middle-aged overweight men: A randomized, placebo-controlled, crossover trial. PLoS One 8:e57622.
35. M.De Bock, E.B.Thorstensen, J.G.B.Derraik,. (2013b). Human absorption and metabolism of oleuropein and hydroxytyrosol ingested as olive (Olea europaea L.) leaf extract. Mol Nutr Food Res 57:2079–2085.
36. M.De Graaf, E.Boven, H.W.Scheeren,. (2002). Beta-glucuronidase-mediated drug release. Curr Pharm Des 8:1391–1403.
37. R.de la Torre (2008). Bioavailability of olive oil phenolic compounds in humans. Inflammopharmacology 16:245–247.
38. R.C.M.de la Torre, M.A.Pujadas, M.Fitó, M.Farré (2006). Is dopamine behind the health benefits of red wine? Eur J Nutr 45:307–310.
39. K.de la Torre-Carbot, O.Jauregui, A.I.Castellote,. (2006). Rapid high-performance liquid chromatography-electrospray ionization tandem mass spectrometry method for qualitative and quantitative analysis of virgin olive oil phenolic metabolites in human low-density lipoproteins. J Chromatogr A 1116:69–75.
40. 2 induced lipid peroxidation in renal tubular epithelial cells. Food Chem Toxicol 46:2984–2990.
41. 2 induced oxidative damage. Chem-Biol Interact 193:232–239.
42. P.Del Boccio, A.Di Deo, A.De Curtis,. (2003). Liquid chromatography-tandem mass spectrometry analysis of oleuropein and its metabolite hydroxytyrosol in rat plasma and urine after oral administration. J Chromatogr B Analyt Technol Biomed Life Sci 785:47–56.
43. D.Di Tommaso, R.Calabrese, D.Rotilio (1998). Identification and quantitation of hydroxytyrosol in Italian wines. J High Res Chromatogr 21:549–553.
44. R.Domínguez-Perles, D.Auñón, F.Ferreres, A.Gil-Izquierdo (2015). Gender differences in plasma and urine metabolites from Sprague–Dawley rats after oral administration of normal and high doses of hydroxytyrosol, hydroxytyrosol acetate, and DOPAC. Eur J Nutr. [Epub ahead of print]. doi: 10.1007/s00394-015-1071-2.
45. S.Dragoni, J.Gee, R.Bennett,. (2006). Red wine alcohol promotes quercetin absorption and directs its metabolism towards isorhamnetin and tamarixetin in rat intestine in vitro. Br J Pharmacol 147:765–771.
46. EFSA. (2011) EFSA Panel on Dietetic Products, Nutrition and allergies (NDA) (2011) Scientific opinion on the substantiation of health claims related to polyphenols in olive oil and protection of LDL particles from oxidative damage. EFSA J 9, 2033. Available from: http://www.efsa.europa.eu/en/efsajournal/pub/2033 [last accessed August 2015].
47. R.Estruch, M.A.N.Martínez-González, D.Corella,. (2006). Effects of a Mediterranean-Style Diet on cardiovascular risk factors: A randomized trial. Ann Intern Med 145:1–11.
48. R.Estruch, E.Ros, J.Salas-Salvadó,. (2013). Primary prevention of cardiovascular disease with a Mediterranean Diet. N Engl J Med 368:1279–1290.
49. M.Farràs, O.Castañer, S.Martín-Peláez,. (2015). Complementary phenol-enriched olive oil improves HDL characteristics in hypercholesterolemic subjects. A randomized, double-blind, crossover, controlled trial. The VOHF study. Mol Nutr Food Res 59:1758–1770.
50. M.I.Fernández-Mar, R.Mateos, M.C.García-Parrilla,. (2012). Bioactive compounds in wine: Resveratrol, hydroxytyrosol and melatonin: A review. Food Chem 130:797–813.
51. M.Fitó, M.Cladellas, R.de la Torre,. (2005). Antioxidant effect of virgin olive oil in patients with stable coronary heart disease: A randomized, crossover, controlled, clinical trial. Atherosclerosis 181:149–158.
52. M.Fitó, E.Gimeno, M.I.Covas,. (2002). Postprandial and short-term effects of dietary virgin olive oil on oxidant/antioxidant status. Lipids 37:245–251.
53. H.J.Forman, K.J.A.Davies, F.Ursini (2014). How do nutritional antioxidants really work: Nucleophilic tone and para-hormesis versus free radical scavenging in vivo. Free Radic Biol Med 66:24–35.
54. R.García-Villalba, M.Larrosa, S.Possemiers,. (2014). Bioavailability of phenolics from an oleuropein-rich olive (Olea europaea) leaf extract and its acute effect on plasma antioxidant status: Comparison between pre- and postmenopausal women. Eur J Nutr 53:1015–1027.
55. E.Giordano, O.Dangles, N.Rakotomanomana,. (2015). 3-O-Hydroxytyrosol glucuronide and 4-O-hydroxytyrosol glucuronide reduce endoplasmic reticulum stress in vitro. Food Funct 6:3275–3281.
56. V.P.M.Gomes, C.Torres, J.E.Rodríguez-Borges, F.Paiva-Martins (2015). A convenient synthesis of hydroxytyrosol monosulfate metabolites. J Agric Food Chem 63:9565–9571.
57. M.González-Santiago, J.Fonollá, E.Lopez-Huertas (2010). Human absorption of a supplement containing purified hydroxytyrosol, a natural antioxidant from olive oil, and evidence for its transient association with low-density lipoproteins. Pharmacol Res 61:364–370.
58. S.Granados-Principal, J.L.Quiles, C.L.Ramirez-Tortosa,. (2010). Hydroxytyrosol: From laboratory investigations to future clinical trials. Nutr Rev 68:191–206.
59. D.Harman (1956). Aging: A theory based on free radical and radiation chemistry. J Gerontol 11:298–300.
60. T.Hashimoto, M.Ibi, K.Matsuno,. (2004). An endogenous metabolite of dopamine, 3,4-dihydroxyphenylethanol, acts as a unique cytoprotective agent against oxidative stress-induced injury. Free Radic Biol Med 36:555–564.
61. G.Holst B, Williamson (2008). Nutrients and phytochemicals: From bioavailability to bioefficacy beyond antioxidants. Curr Opin Biotechnol 19:73–82.
62. E.Karkoula, A.Skantzari, E.Melliou, P.Magiatis (2012). Direct measurement of oleocanthal and oleacein levels in olive oil by quantitative (1)H NMR. Establishment of a new index for the characterization of extra virgin olive oils. J Agric Food Chem 60:11696–11703.
63. F.C.Kauffman (1987). Conjugation-deconjugation reactions in drug metabolism and toxicity. Fed Proc 46:2434–2445.
64. O.Khymenets, M.Farré, M.Pujadas,. (2011). Direct analysis of glucuronidated metabolites of main olive oil phenols in human urine after dietary consumption of virgin olive oil. Food Chem 126:306–314.
65. O.Khymenets, M.Fitó, S.Touriño,. (2010). Antioxidant activities of hydroxytyrosol main metabolites do not contribute to beneficial health effects after olive oil ingestion. Drug Metab Dispos 38:1417–1421.
66. O.Khymenets, J.Joglar, P.Clapés,. (2006). Biocatalyzed synthesis and structural characterization of monoglucuronides of hydroxytyrosol, tyrosol, homovanillic alcohol, and 3-(4′-hydroxyphenyl)propanol. Adv Synth Cat 348:2155–2162.
67. V.Konstantinidou, M.-I.Covas, D.Munoz-Aguayo,. (2010). In vivo nutrigenomic effects of virgin olive oil polyphenols within the frame of the Mediterranean diet: a randomized controlled trial. FASEB J 24:2546–2557.
68. V.Konstantinidou, M.-I.Covas, R.Sola, M.Fitó (2013). Up-to date knowledge on the in vivo transcriptomic effect of the Mediterranean diet in humans. Mol Nutr Food Res 57:772–783.
69. A.Kotronoulas, N.Pizarro, A.Serra,. (2013). Dose-dependent metabolic disposition of hydroxytyrosol and formation of mercapturates in rats. Pharmacol Res 77:47–56.
70. P.Lin, W.Qian, X.Wang,. (2013). The biotransformation of oleuropein in rats. Biomed Chromatogr 27:1162–1167
71. S.Lockyer, G.Corona, P.Yaqoob,. (2015). Secoiridoids delivered as olive leaf extract induce acute improvements in human vascular function and reduction of an inflammatory cytokine: A randomised, double-blind, placebo-controlled, cross-over trial. Br J Nutr 114:75–83.
72. M.-C.López de las Hazas, L.Rubió, A.Kotronoulas,. (2015). Dose effect on the uptake and accumulation of hydroxytyrosol and its metabolites in target tissues in rats. Mol Nutr Food Res 59:1395–1399.
73. Q.-Y.Lu, L.Zhang, G.Eibl, V.L.W.Go (2014). Overestimation of flavonoid aglycones as a result of the ex vivo deconjugation of glucuronides by the tissue β-glucuronidase. J Pharm Biomed Anal 88:364–369.
74. R.Lucas, D.Alcantara, J.C.Morales (2009). A concise synthesis of glucuronide metabolites of urolithin-B, resveratrol, and hydroxytyrosol. Carbohydr Res 344:1340–1346.
75. C.Manna, P.Galletti, G.Maisto,. (2000). Transport mechanism and metabolism of olive oil hydroxytyrosol in Caco-2 cells. FEBS Lett 470:341–344.
76. E.Miró-Casas, M.-I.Covas, M.Farré,. (2003a). Hydroxytyrosol disposition in humans. Clin Chem 49:945–952.
77. E.Miró-Casas, M.-I.Covas, M.Fitó,. (2003b). Tyrosol and hydroxytyrosol are absorbed from moderate and sustained doses of virgin olive oil in humans. Eur J Clin Nutr 57:186–190.
78. J.Marrugat, M.-I.Covas, M.Fitó,. (2004). Effects of differing phenolic content in dietary olive oils on lipids and LDL oxidation. Eur J Nutr 43:140–147.
79. E.Miró-Casas, M.Farré Albadalejo, M.I.Covas Planells,. (2001a). Tyrosol bioavailability in humans after ingestion of virgin olive oil. Clin Chem 47:341–343.
80. E.Miró-Casas, M.Farré Albaladejo, M.-I.Covas,. (2001b). Capillary gas chromatography-mass spectrometry quantitative determination of hydroxytyrosol and tyrosol in human urine after olive oil intake. Anal Biochem 294:63–72.
81. J.I.Mosele, S.Martín-Peláez, A.Macià,. (2014). Faecal microbial metabolism of olive oil phenolic compounds: In vitro and in vivo approaches. Mol Nutr Food Res 58:1809–1819.
82. N.Nenadis, L.-F.Wang, M.Z.Tsimidou, H.-Y.Zhang (2005). Radical scavenging potential of phenolic compounds encountered in O. europaea products as indicated by calculation of bond dissociation enthalpy and ionization potential values. J Agric Food Chem 53:295–299.
83. K.A.O'Leary, A.J.Day, P.W.Needs,. (2001). Flavonoid glucuronides are substrates for human liver β-glucuronidase. FEBS Lett 503:103–106.
84. H.K.Obied, P.D.Prenzler, D.Ryan,. (2008). Biosynthesis and biotransformations of phenol-conjugated oleosidic secoiridoids from Olea europaea L. Nat Prod Rep 25:1167–1179.
85. M.I.Orozco-Solano, C.Ferreiro-Vera, F.Priego-Capote, M.D.Luque de Castro (2012). Automated method for determination of olive oil phenols and metabolites in human plasma and application in intervention studies. J Chromatogr A 1258:108–116.
86. F.Ortega-García, J.Peragón (2010). HPLC analysis of oleuropein, hydroxytyrosol, and tyrosol in stems and roots of Olea europaea L. cv. Picual during ripening. J Sci Food Agric 90:2295–2300.
87. F.Paiva-Martins, A.Silva, V.Almeida,. (2013). Protective activity of hydroxytyrosol metabolites on erythrocyte oxidative-induced hemolysis. J Agric Food Chem 61:6636–6642.
88. N.G.Panova, N.V.Veselovskaia, A.E.Medvedev (1997). [Involvement of monoamine oxidases in formation of 4-hydroxyphenylethanol, major component of tribulin A]. Vopr Med Khim 43:172–176.
89. A.Pastor, J.Rodríguez-Morató, E.Olesti,. (2016). Analysis of free hydroxytyrosol in human plasma following the administration of olive oil. J Chromatogr A 1437:183–190.
90. C.Pérez-Mañá, M.Farre, M.Pujadas,. (2015a). Ethanol induces hydroxytyrosol formation in humans. Pharmacol Res 95-96:27–33.
91. C.Pérez-Mañá, M.Farré, J.Rodríguez-Morató,. (2015b). Moderate consumption of wine, through both its phenolic compounds and alcohol content, promotes hydroxytyrosol endogenous generation in humans. A randomized controlled trial. Mol Nutr Food Res 59:1213–1216.
92. J.Pinto, F.Paiva-Martins, G.Corona,. (2011). Absorption and metabolism of olive oil secoiridoids in the small intestine. Br J Nutr 105:1607–1618.
93. Z.Piñeiro, E.Cantos-Villar, M.Palma, B.Puertas (2011). Direct liquid chromatography method for the simultaneous quantification of hydroxytyrosol and tyrosol in red wines. J Agric Food Chem 59:11683–11689.
94. K.Rahman (2007). Studies on free radicals, antioxidants, and co-factors. Clin Interv Aging 2:219–236.
95. M.Roche, C.Dufour, N.Mora, O.Dangles (2005). Antioxidant activity of olive phenols: Mechanistic investigation and characterization of oxidation products by mass spectrometry. Org Biomol Chem 3:423–430.
96. G.Rodríguez-Gutiérrez, S.Wood, J.Fernández-Bolaños Guzmán,. (2011). Determination of 3,4-dihydroxyphenylglycol, hydroxytyrosol and tyrosol purified from olive oil by-products with HPLC in animal plasma and tissues. Food Chem 126:1948–1952.
97. J.Rodríguez-Morató, L.Xicota, M.Fitó,. (2015). Potential role of olive oil phenolic compounds in the prevention of neurodegenerative diseases. Molecules 20:4655–4680.
98. L.Rubió, A.Macià, R.M.Valls,. (2012). A new hydroxytyrosol metabolite identified in human plasma: Hydroxytyrosol acetate sulphate. Food Chem 134:1132–1136.
99. L.Rubió, A.Serra, A.Macià,. (2014). In vivo distribution and deconjugation of hydroxytyrosol phase II metabolites in red blood cells: A potential new target for hydroxytyrosol. J Funct Foods 10:139–143.
100. V.Ruiz-Gutierrez, M.E.Juan, A.Cert, J.M.Planas (2000). Determination of hydroxytyrosol in plasma by HPLC. Anal Chem 72:4458–4461.
101. H.Schröder, R.de la Torre, R.Estruch,. (2009). Alcohol consumption is associated with high concentrations of urinary hydroxytyrosol. Am J Clin Nutr 90:1329–1335.
102. A.Serra, L.Rubió, X.Borràs,. (2012). Distribution of olive oil phenolic compounds in rat tissues after administration of a phenolic extract from olive cake. Mol Nutr Food Res 56:486–496.
103. A.Serra, L.Rubió, A.Macià,. (2013). Application of dried spot cards as a rapid sample treatment method for determining hydroxytyrosol metabolites in human urine samples. Comparison with microelution solid-phase extraction. Anal Bioanal Chem 405:9179–9192.
104. M.Servili, B.Sordini, S.Esposto,. (2014). Biological activities of phenolic compounds of extra virgin olive oil. Antioxidants 3:1–23.
105. D.Sharp (2003). Château resveratrol. Lancet 361:1404.
106. B.Sperker, J.T.Backman, H.K.Kroemer (1997). The role of beta-glucuronidase in drug disposition and drug targeting in humans. Clin Pharmacokinet 33:18–31.
107. M.Suárez, M.P.Romero, A.Macia,. (2009). Improved method for identifying and quantifying olive oil phenolic compounds and their metabolites in human plasma by microelution solid-phase extraction plate and liquid chromatography-tandem mass spectrometry. J Chromatogr B 877:4097–4106.
108. M.Tacker, P.J.Creaven, W.M.McIsaac (1970). Alteration in tyramine metabolism by ethanol. Biochem Pharmacol 19:604–607.
109. A.W.Tank, H.Weiner (1979). Ethanol-induced alteration of dopamine metabolism in rat liver. Biochem Pharmacol 28:3139–3147.
110. E.Tripoli, M.Giammanco, G.Tabacchi,. (2005). The phenolic compounds of olive oil: Structure, biological activity and beneficial effects on human health. Nutr Res Rev 18:98–112.
111. K.L.Tuck, M.P.Freeman, P.J.Hayball,. (2001). The in vivo fate of hydroxytyrosol and tyrosol, antioxidant phenolic constituents of olive oil, after intravenous and oral dosing of labeled compounds to rats. J Nutr 131:1993–1996.
112. K.L.Tuck, P.J.Hayball, I.Stupans (2002). Structural characterization of the metabolites of hydroxytyrosol, the principal phenolic component in olive oil, in rats. J Agric Food Chem 50:2404–2409.
113. R.Turner, N.Etienne, M.G.Alonso,. (2005). Antioxidant and anti-atherogenic activities of olive oil phenolics. Int J Vitam Nutr Res 75:61–70.
114. R.-M.Valls, M.Farràs, M.Suárez,. (2015). Effects of functional olive oil enriched with its own phenolic compounds on endothelial function in hypertensive patients. A randomised controlled trial. Food Chem 167:30–35.
115. S.Vasdev, V.Gill, P.K.Singal (2006). Beneficial effect of low ethanol intake on the cardiovascular system: possible biochemical mechanisms. Vasc Health Risk Manag 2:263–276.
116. C.Vilaplana-Pérez, D.Auñón, L.A.García-Flores, A.Gil-Izquierdo (2014). Hydroxytyrosol and potential uses in cardiovascular diseases, cancer and AIDS. Front Nutr 1::1–11.
117. F.Virgili, M.Marino (2008). Regulation of cellular signals from nutritional molecules: A specific role for phytochemicals, beyond antioxidant activity. Free Radic Biol Med 45:1205–1216.
118. F.Visioli, G.Bellomo, C.Galli (1998). Free radical-scavenging properties of olive oil polyphenols. Biochem Biophys Res Commun 247:60–64.
119. F.Visioli, E.Bernardini (2011). Extra virgin olive oils polyphenols: Biological activities. Curr Pharm Design 17:786–804.
120. F.Visioli, D.Caruso, E.Plasmati,. (2001). Hydroxytyrosol, as a component of olive mill waste water, is dose-dependently absorbed and increases the antioxidant capacity of rat plasma. Free Radic Res 34:301–305.
121. F.Visioli, C.Galli, F.Bornet,. (2000). Olive oil phenolics are dose-dependently absorbed in humans. FEBS Lett 468:159–160.
122. F.Visioli, C.Galli, S.Grande,. (2003). Hydroxytyrosol excretion differs between rats and humans and depends on the vehicle of administration. J Nutr 133:2612–2615.
123. F.Visioli, A.Poli, C.Gall (2002). Antioxidant and other biological activities of phenols from olives and olive oil. Med Res Rev 22:65–75.
124. M.N.Vissers, P.L.Zock, M.B.Katan (2004). Bioavailability and antioxidant effects of olive oil phenols in humans: A review. Eur J Clin Nutr 58:955–965.
125. M.N.Vissers, P.L.Zock, A.J.C.Roodenburg,. (2002). Olive oil phenols are absorbed in humans. J Nutr 132:409–417.
126. T.Weinbrenner, M.Fito, M.Farre Albaladejo,. (2004). Bioavailability of phenolic compounds from olive oil and oxidative/antioxidant status at postprandial state in healthy humans. Drugs Exp Clin Res 30:207–212.
127. J.L.Witztum (1994). The oxidation hypothesis of atherosclerosis. Lancet 344:793–795.