Effects of Virgin Olive Oils Differing in Their Bioactive Compound Contents on Biomarkers of Oxidative Stress and Inflammation in Healthy Adults: A Randomized Double-Blind Controlled Trial

Estefania Sanchez-Rodriguez, Sara Biel-Glesson, Jose R Fernandez-Navarro, Miguel A Calleja, Juan A Espejo-Calvo, Blas Gil-Extremera, Rafael de la Torre, Montserrat Fito, Maria-Isabel Covas, Pedro Vilchez, Juan de Dios Alche, Emilio Martinez de Victoria, Angel Gil, Maria D Mesa, Estefania Sanchez-Rodriguez, Sara Biel-Glesson, Jose R Fernandez-Navarro, Miguel A Calleja, Juan A Espejo-Calvo, Blas Gil-Extremera, Rafael de la Torre, Montserrat Fito, Maria-Isabel Covas, Pedro Vilchez, Juan de Dios Alche, Emilio Martinez de Victoria, Angel Gil, Maria D Mesa

Abstract

A regular consumption of virgin olive oil (VOO) is associated with a reduced risk of cardiovascular disease. We aimed to assess whether the raw intake of an optimized VOO (OVOO, 490 ppm of phenolic compounds and 86 ppm of triterpenes), and a functional olive oil (FOO, 487 ppm of phenolic compounds and enriched with 389 ppm of triterpenes) supplementation (30 mL per day) during three weeks would provide additional health benefits to those produced by a standard VOO (124 ppm of phenolic compounds and 86 ppm of triterpenes) on oxidative and inflammatory biomarkers. Fifty-one healthy adults participated in a randomized, crossover, and controlled study. Urinary 8-hidroxy-2'-deoxyguanosine, plasma interleukin-8 (IL-8), and tumor necrosis factor α (TNF- α) concentrations were lower after the intervention with the FOO than after the OVOO (p = 0.033, p = 0.011 and p = 0.020, respectively). In addition, IL-8 was lower after the intervention with FOO than after VOO intervention (p = 0.002). This study provides a first level of evidence on the in vivo health benefits of olive oil triterpenes (oleanolic and maslinic acids) in healthy humans, decreasing DNA oxidation and plasma inflammatory biomarkers. The trial was registered in ClinicalTrials.gov ID: NCT02520739.

Keywords: 8-hidroxy-2′-deoxyguanosine; TNF-alpha; cardiovascular diseases; interleukin-8; maslinic acid; oleanolic acid; olive oil; oxidative stress; phenolic compounds; triterpenes; virgin olive oil.

Conflict of interest statement

The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Figures

Figure 1
Figure 1
Post-pre-intervention changes in urinary 8-OHdG in a randomized control trial evaluating the effects of virgin olive oils differing in their bioactive compound contents on oxidative stress and inflammation. * Indicates significant differences (p < 0.05). FOO, functional olive oil; 8-OHdG, 8-hidroxy-2′-deoxyguanosine; OVOO, optimized virgin olive oil; VOO, virgin olive oil.

References

    1. Panth N., Paudel K.R., Parajuli K. Reactive oxygen species: A key hallmark of cardiovascular disease. Adv. Med. 2016 doi: 10.1155/2016/9152732.
    1. Frostegard J. Immunity, atherosclerosis and cardiovascular disease. BMC Med. 2013;11:117. doi: 10.1186/1741-7015-11-117.
    1. Buckland G., Gonzalez C.A. The role of olive oil in disease prevention: A focus on the recent epidemiological evidence from cohort studies and dietary intervention trials. Br. J. Nutr. 2015;113:s94–s101. doi: 10.1017/S0007114514003936.
    1. Covas M.I., de la Torre R., Fitó M. Virgin olive oil: A key food for cardiovascular risk protection. Br. J. Nutr. 2015;113:s19–s28. doi: 10.1017/S0007114515000136.
    1. Schwingshackl L., Christoph M., Hoffmann G. Effects of olive oil on markers of inflammation and endothelial function—A systematic review and meta-analysis. Nutrients. 2015;7:7651–7675. doi: 10.3390/nu7095356.
    1. Alarcón de la Lastra C., Barranco M.D., Motilva V., Herrerías J.M. Mediterranean diet and health: Biological importance of olive oil. Curr. Pharm. Des. 2001;7:933–950. doi: 10.2174/1381612013397654.
    1. Serreli G., Deiana M. Biological relevance of extra virgin olive oil polyphenols metabolites. Antioxidants. 2018;7:170. doi: 10.3390/antiox7120170.
    1. Covas M.-I., Ruiz-Gutierrez V., de la Torre R., Kafatos A., Lamuela-Raventos R.M., Osada J., Owen R.W., Visioli F. Minor components of olive oil: Evidence to date of health benefits in humans. Nutr. Rev. 2006;64:s20–s30. doi: 10.1111/j.1753-4887.2006.tb00260.x.
    1. Fitó M., de la Torre R., Covas M.-I. Olive oil and oxidative stress. Mol. Nutr. Food Res. 2007:1215–1224. doi: 10.1002/mnfr.200600308.
    1. Hohmann C.D., Cramer H., Michalsen A., Kessler C., Steckhan N., Choi K., Dobos G. Effects of high phenolic olive oil on cardiovascular risk factors: A systematic review and meta-analysis. Phytomedicine. 2015;22:631–640. doi: 10.1016/j.phymed.2015.03.019.
    1. Efsa Panel On Dietetic Products, Nutrition And Allergies (NDA) Scientific opinion on the substantiation of health claims related to polyphenols in olive and protection of LDL particles from oxidative damage (Id 1333, 1638, 1639, 1696, 2865), maintenance of normal blood HDL cholesterol concentrations (Id 1639), maintenance of normal blood pressure (Id 3781), “anti-inflammatory properties” (id 1882), “contributes to the upper respiratory tract health” (Id 3467) pursuant to article 13(1) of regulation (ec) no 1924/2006. EFSA J. 2011;9 doi: 10.2903/j.efsa.2011.2033.
    1. Sánchez-Quesada C., López-Biedma A., Warleta F., Campos M., Beltrán G., Gaforio J.J. Bioactive properties of the main triterpenes found in olives, virgin olive oil, and leaves of Olea europaea. J. Agric. Food Chem. 2013;61:12173–12182. doi: 10.1021/jf403154e.
    1. Herrera M., Rodriguez-Rodriguez R., Ruiz-Gutierrez V. Functional properties of pentacyclic triterpenes contained in “orujo” olive oil. Curr. Nutr. Food Sci. 2006;2:45–49. doi: 10.2174/157340106775471976.
    1. Lou-Bonafonte J.M., Arnal C., Navarro M.A., Osada J. Efficacy of bioactive compounds from extra virgin olive oil to modulate atherosclerosis development. Mol. Nutr. Food Res. 2012;56:1043–1057. doi: 10.1002/mnfr.201100668.
    1. Sánchez-Tena S., Reyes-Zurita F.J., Díaz-Moralli S., Vinardell M.P., Reed M., García-García F., Dopazo J., Lupiáñez J.A., Günther U., Cascante M. Maslinic acid-enriched diet decreases intestinal tumorigenesis in apcmin/+ mice through transcriptomic and metabolomic reprogramming. PLoS ONE. 2013;8:e59392. doi: 10.1371/journal.pone.0059392.
    1. Márquez Martín A., De La Puerta Vázquez R., Fernández-Arche A., Ruiz-Gutiérrez V. Suppressive effect of maslinic acid from pomace olive oil on oxidative stress and cytokine production in stimulated murine macrophages. Free Radic. Res. 2006;40:295–302. doi: 10.1080/10715760500467935.
    1. Huang L., Guan T., Qian Y., Huang M., Tang X., Li Y., Sun H. Anti-inflammatory effects of maslinic acid, a natural triterpene, in cultured cortical astrocytes via suppression of nuclear factor-kappa B. Eur. J. Pharmacol. 2011;672:169–174. doi: 10.1016/j.ejphar.2011.09.175.
    1. Velasco J., Holgado F., Márquez-Ruiz G., Ruiz-Méndez M.V. Concentrates of triterpenic acids obtained from crude olive pomace oils: Characterization and evaluation of their potential antioxidant activity. J. Sci. Food Agric. 2018;98:4837–4844. doi: 10.1002/jsfa.9012.
    1. Sanchez-Rodriguez E., Lima-Cabello E., Biel-Glesson S., Fernandez-Navarro J.R., Calleja M.A., Roca M., Espejo-Calvo J.A., Gil-Extremera B., Soria-Florido M., de la Torre R., et al. Effects of virgin olive oils differing in their bioactive compound contents on metabolic syndrome and endothelial functional risk biomarkers in healthy adults: A randomized double-blind controlled trial. Nutrients. 2018;10:626. doi: 10.3390/nu10050626.
    1. Montilla M.P., Agil A., Navarro M.C., Jiménez M.I., García-Granados A., Parra A., Cabo M.M. Antioxidant activity of maslinic acid, a triterpene derivative obtained from Olea europaea. Planta Med. 2003;69:472–474. doi: 10.1055/s-2003-39698.
    1. Dzubak P., Hajduch M., Vydra D., Hustova A., Kvasnica M., Biedermann D., Markova L., Urban M., Sarek J. Pharmacological activities of natural triterpenoids and their therapeutic implications. Nat. Prod. Rep. 2006;23:394. doi: 10.1039/b515312n.
    1. Biel S., Mesa M.-D., de la Torre R., Espejo J.-A., Fernández-Navarro J.-R., Fitó M., Sánchez-Rodriguez E., Rosa C., Marchal R., Alche J., et al. The nutraoleoum study, a randomized controlled trial, for achieving nutritional added value for olive oils. BMC Complement. Altern. Med. 2016;16:404. doi: 10.1186/s12906-016-1376-6.
    1. Yang Y.J., Kim M.K., Hwang S.H., Ahn Y., Shim J.E., Kim D.H. Relative validities of 3-day food records and the food frequency questionnaire. Nutr. Res. Pract. 2010;4:142. doi: 10.4162/nrp.2010.4.2.142.
    1. Base de Datos De Composición De Alimentos (BEDCA) [(accessed on 25 July 2017)]; Available online:
    1. Rangel-Huerta O.D., Aguilera C.M., Martin M.V., Soto M.J., Rico M.C., Vallejo F., Tomas-Barberan F., Perez-de-la-Cruz A.J., Gil A., Mesa M.D. Normal or high polyphenol concentration in orange juice affects antioxidant activity, blood pressure, and body weight in obese or overweight adults. J. Nutr. 2015;145:1808–1816. doi: 10.3945/jn.115.213660.
    1. Olza J., Mesa M.D., Aguilera C.M., Moreno-Torres R., Jiménez Á., Pérez de la Cruz A., Gil Á. Influence of an eicosapentaenoic and docosahexaenoic acid-enriched enteral nutrition formula on plasma fatty acid composition and biomarkers of insulin resistance in the elderly. Clin. Nutr. 2010;29:31–37. doi: 10.1016/j.clnu.2009.06.003.
    1. Lepage G., Roy C.C. Direct transesterification of all classes of lipids in a one-step reaction. J. Lipid Res. 1986;27:114–120.
    1. Senn S. Cross-Over Trials in Clinical Research. 2nd ed. Johnwiley & Sons, Ltd.; Chichester, UK: 2002. pp. 35–53.
    1. Rodriguez-Rodriguez R. Oleanolic acid and related triterpenoids from olives on vascular function: Molecular mechanisms and therapeutic perspectives. Curr. Med. Chem. 2015;22:1414–1425. doi: 10.2174/0929867322666141212122921.
    1. Sharma H., Kumar P., Deshmukh R.R., Bishayee A., Kumar S. Pentacyclic triterpenes: New tools to fight metabolic syndrome. Phytomedicine. 2018;50:166–177. doi: 10.1016/j.phymed.2018.09.011.
    1. Raatz S.K., Bibus D., Thomas W., Kris-Etherton P. Total fat intake modifies plasma fatty acid composition in humans. J. Nutr. 2001;131:231–234. doi: 10.1093/jn/131.2.231.
    1. Poulsen H.E. Oxidative DNA modifications. Exp. Toxicol. Pathol. 2005;57:161–169. doi: 10.1016/j.etp.2005.05.015.
    1. Di Minno A., Turnu L., Porro B., Squellerio I., Cavalca V., Tremoli E., di Minno M.N.D. 8-hydroxy-2-deoxyguanosine levels and cardiovascular disease: A systematic review and meta-analysis of the literature. Antioxid. Redox Signal. 2016;24:548–555. doi: 10.1089/ars.2015.6508.
    1. Fabiani R., Rosignoli P., de Bartolomeo A., Fuccelli R., Servili M., Montedoro G.F., Morozzi G. Oxidative DNA damage is prevented by extracts of olive oil, hydroxytyrosol, and other olive phenolic compounds in human blood mononuclear cells and hl60 cells. J. Nutr. 2008;138:1411–1416. doi: 10.1093/jn/138.8.1411.
    1. Quiles J.L., Farquharson A.J., Simpson D.K., Grant I., Wahle K.W.J. Olive oil phenolics: Effects on DNA oxidation and redox enzyme mrna in prostate cells. Br. J. Nutr. 2002;88:225. doi: 10.1079/BJN2002620.
    1. Jacomelli M., Pitozzi V., Zaid M., Larrosa M., Tonini G., Martini A., Urbani S., Taticchi A., Servili M., Dolara P., et al. Dietary extra-virgin olive oil rich in phenolic antioxidants and the aging process: Long-term effects in the rat. J. Nutr. Biochem. 2010;21:290–296. doi: 10.1016/j.jnutbio.2008.12.014.
    1. Allouche Y., Warleta F., Campos M., Sánchez-Quesada C., Uceda M., Beltrán G., Gaforio J.J. Antioxidant, antiproliferative, and pro-apoptotic capacities of pentacyclic triterpenes found in the skin of olives on mcf-7 human breast cancer cells and their effects on DNA damage. J. Agric. Food Chem. 2011;59:121–130. doi: 10.1021/jf102319y.
    1. Machowetz A., Poulsen H.E., Gruendel S., Weimann A., Fitó M., Marrugat J., de la Torre R., Salonen J.T., Nyyssönen K., Mursu J., et al. Effect of olive oils on biomarkers of oxidative DNA stress in northern and southern europeans. FASEB J. 2007;21:45–52. doi: 10.1096/fj.06-6328com.
    1. Romeu M., Rubió L., Sánchez-Martos V., Castañer O., de la Torre R., Valls R.M., Ras R., Pedret A., Catalán Ú., López de las Hazas M., et al. Virgin olive oil enriched with its own phenols or complemented with thyme phenols improves DNA protection against oxidation and antioxidant enzyme activity in hyperlipidemic subjects. J. Agric. Food Chem. 2016;64:1879–1888. doi: 10.1021/acs.jafc.5b04915.
    1. Salvini S., Sera F., Caruso D., Giovannelli L., Visioli F., Saieva C., Masala G., Ceroti M., Giovacchini V., Pitozzi V., et al. Daily consumption of a high-phenol extra-virgin olive oil reduces oxidative DNA damage in postmenopausal women. Br. J. Nutr. 2006;95:742–751. doi: 10.1079/BJN20051674.
    1. Weinbrenner T., Fitó M., De la Torre R., Saez G.T., Rijken P., Tormos C., Coolen S., Albaladejo M.F., Abanades S., Schroder H., et al. Olive oils high in phenolic compounds modulate oxidative/antioxidative status in men. J. Nutr. 2004;134:2314–2321. doi: 10.1093/jn/134.9.2314.
    1. Basu S. Isoprostanes: Novel bioactive products of lipid peroxidation. Free Radic. Res. 2004;38:105–122. doi: 10.1080/10715760310001646895.
    1. Basu S., Helmersson J. Factors regulating isoprostane formation in vivo. Antioxid. Redox Signal. 2005;7:221–235. doi: 10.1089/ars.2005.7.221.
    1. Visioli F., Caruso D., Grande S., Bosisio R., Villa M., Galli G., Sirtori C., Galli C. Virgin olive oil study (volos): Vasoprotective potential of extra virgin olive oil in mildly dyslipidemic patients. Eur. J. Nutr. 2005;44:121–127. doi: 10.1007/s00394-004-0504-0.
    1. Covas M.I., de la Torre K., Farré-Albaladejo M., Kaikkonen J., Fitó M., López-Sabater C., Pujadas-Bastardes M.A., Joglar J., Weinbrenner T., Lamuela-Raventós R.M., et al. Postprandial LDL phenolic content and LDL oxidation are modulated by olive oil phenolic compounds in humans. Free Radic. Biol. Med. 2006;40:608–616. doi: 10.1016/j.freeradbiomed.2005.09.027.
    1. Allouche Y., Beltrán G., Gaforio J.J., Uceda M., Mesa M.D.D. Antioxidant and antiatherogenic activities of pentacyclic triterpenic diols and acids. Food Chem. Toxicol. 2010;48:2885–2890. doi: 10.1016/j.fct.2010.07.022.
    1. Somova L.O., Nadar A., Rammanan P., Shode F.O. Cardiovascular, antihyperlipidemic and antioxidant effects of oleanolic and ursolic acids in experimental hypertension. Phytomedicine. 2003;10:115–121. doi: 10.1078/094471103321659807.
    1. Balanehru S., Nagarajan B. Protective effect of oleanolic acid and ursolic acid against lipid peroxidation. Biochem. Int. 1991;24:981–990.
    1. Rong Z.-T., Gong X.-J., Sun H.-B., Li Y.-M., Ji H. Protective effects of oleanolic acid on cerebral ischemic damage in vivo and h2o2-induced injury in vitro. Pharm. Biol. 2011;49:78–85. doi: 10.3109/13880209.2010.499130.
    1. Varela-López A., Ochoa J.J., Llamas-Elvira J.M., López-Frías M., Planells E., Speranza L., Battino M., Quiles J.L. Loss of bone mineral density associated with age in male rats fed on sunflower oil is avoided by virgin olive oil intake or coenzyme Q supplementation. Int. J. Mol. Sci. 2017;18:1397. doi: 10.3390/ijms18071397.
    1. Visioli F., Caruso D., Galli C., Viappiani S., Galli G., Sala A. Olive oils rich in natural catecholic phenols decrease isoprostane excretion in humans. Biochem. Biophys. Res. Commun. 2000;278:797–799. doi: 10.1006/bbrc.2000.3879.
    1. Yarla N.S., Polito A., Peluso I. Effects of olive oil on tnf-α and il-6 in humans: Implication in obesity and frailty. Endocr. Metab. Immune Disord. Drug Targets. 2017;18:63–74. doi: 10.2174/1871530317666171120150329.
    1. Casas R., Urpi-Sardà M., Sacanella E., Arranz S., Corella D., Castañer O., Lamuela-Raventós R.-M., Salas-Salvadó J., Lapetra J., Portillo M.P., et al. Anti-inflammatory effects of the Mediterranean diet in the early and late stages of atheroma plaque development. Mediat. Inflamm. 2017:1–12. doi: 10.1155/2017/3674390.
    1. Rigacci S., Stefani M. Nutraceutical properties of olive oil polyphenols. An itinerary from cultured cells through animal models to humans. Int. J. Mol. Sci. 2016;17:843. doi: 10.3390/ijms17060843.
    1. Richard N., Arnold S., Hoeller U., Kilpert C., Wertz K., Schwager J. Hydroxytyrosol is the major anti-inflammatory compound in aqueous olive extracts and impairs cytokine and chemokine production in macrophages. Planta Med. 2011;77:1890–1897. doi: 10.1055/s-0031-1280022.
    1. Lockyer S., Rowland I., Spencer J.P.E., Yaqoob P., Stonehouse W. Impact of phenolic-rich olive leaf extract on blood pressure, plasma lipids and inflammatory markers: A randomised controlled trial. Eur. J. Nutr. 2017;56:1421–1432. doi: 10.1007/s00394-016-1188-y.
    1. Liu Z., Dou W., Ni Z., Wen Q., Zhang R., Qin M., Wang X., Tang H., Cao Y., Wang J., et al. Deletion of nrf2 leads to hepatic insulin resistance via the activation of NF-κB in mice fed a high-fat diet. Mol. Med. Rep. 2016;14:1323–1331. doi: 10.3892/mmr.2016.5393.
    1. Fukumitsu S., Villareal M.O., Fujitsuka T., Aida K., Isoda H. Anti-inflammatory and anti-arthritic effects of pentacyclic triterpenoids maslinic acid through NF-κB inactivation. Mol. Nutr. Food Res. 2016;60:399–409. doi: 10.1002/mnfr.201500465.

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