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

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

Abstract

The aim of this study was to evaluate the effect of virgin olive oils (VOOs) enriched with phenolic compounds and triterpenes on metabolic syndrome and endothelial function biomarkers in healthy adults. The trial was a three-week randomized, crossover, controlled, double-blind, intervention study involving 58 subjects supplemented with a daily dose (30 mL) of three oils: (1) a VOO (124 ppm of phenolic compounds and 86 ppm of triterpenes); (2) an optimized VOO (OVOO) (490 ppm of phenolic compounds and 86 ppm of triterpenes); and (3) a functional olive oil (FOO) high in phenolic compounds (487 ppm) and enriched with triterpenes (389 ppm). Metabolic syndrome and endothelial function biomarkers were determined in vivo and ex vivo. Plasma high density lipoprotein cholesterol (HDLc) increased after the OVOO intake. Plasma endothelin-1 levels decreased after the intake of the three olive oils, and in blood cell cultures challenged. Daily intake of VOO enriched in phenolic compounds improved plasma HDLc, although no differences were found at the end of the three interventions, while VOO with at least 124 ppm of phenolic compounds, regardless of the triterpenes content improved the systemic endothelin-1 levels in vivo and ex vivo. No effect of triterpenes was observed after three weeks of interventions. Results need to be confirmed in subjects with metabolic syndrome and impaired endothelial function (Clinical Trials number NCT02520739).

Keywords: cardiovascular diseases; endothelial function; maslinic acid; metabolic syndrome; oleanolic acid; olive oil; olive oil polyphenols; 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
CONSORT Based Flow Diagram of the recruitment, enrollment and randomization process.
Figure 2
Figure 2
Plasma endothelin-1 ex vivo changes (post-intervention minus pre-intervention data) when stimulated with PHA, LPS or PMA + IO in whole blood cultures from healthy adults. Values are expressed as the means ± SEMs. ANOVA was used to compare differences between interventions and induction treatments. The Tukey post-hoc test was used for multiple comparisons among groups. p < 0.05 was considered significant. FOO, functional olive oil; IO, ionomycin; OVOO, optimized virgin olive oil; PHA, phytohemagglutinin; PMA, phorbol 12-myristate 13-acetate; VOO, virgin olive oil.
Figure 3
Figure 3
In vivo urinary triterpenes changes (post-intervention minus pre-intervention data) for each olive oil intervention in healthy adults. Values are expressed as the means ± SEMs. ANOVA was used to compare differences between the three interventions. Different superscript letters indicate significant differences between the interventions for oleanolic acid (a,b) and for maslinic acid (c,d). p < 0.05 was considered significant. FOO, functional olive oil; OVOO, optimized virgin olive oil; VOO, virgin olive oil.

References

    1. Sarafidis P.A., Nilsson P.M. The metabolic syndrome: A glance at its history. J. Hypertens. 2006;24:621–626. doi: 10.1097/01.hjh.0000217840.26971.b6.
    1. Alberti K.G., Zimmet P., Shaw J. The metabolic syndrome—A new worldwide definition. Lancet. 2005;366:1059–1062. doi: 10.1016/S0140-6736(05)67402-8.
    1. Freitas Lima L.C., Braga V.A., do Socorro de França Silva M., Cruz J.C., Sousa Santos S.H., de Oliveira Monteiro M.M., Balarini C.M. Adipokines, diabetes and atherosclerosis: An inflammatory association. Front. Physiol. 2015;6:1–15. doi: 10.3389/fphys.2015.00304.
    1. Gardener H., Wright C.B., Gu Y., Demmer R.T., Boden-Albala B., Elkind M.S., Sacco R.L., Scarmeas N. Mediterranean-style diet and risk of ischemic stroke, myocardial infarction, and vascular death: The Northern Manhattan Study. Am. J. Clin. Nutr. 2011;94:1458–1464. doi: 10.3945/ajcn.111.012799.
    1. Mayneris-Perxachs J., Sala-Vila A., Chisaguano M., Castellote A.I., Estruch R., Covas M.I., Fitó M., Salas-Salvadó J., Martínez-González M.A., Lamuela-Raventós R., et al. Effects of 1-Year Intervention with a Mediterranean Diet on Plasma Fatty Acid Composition and Metabolic Syndrome in a Population at High Cardiovascular Risk. PLoS ONE. 2014;9:e85202. doi: 10.1371/journal.pone.0085202.
    1. Estruch R., Ros E., Salas-Salvadó J., Covas M., Corella D., Arós F., Gómez-Gracia E., Ruiz-Gutiérrez V., Fiol M., Lapetra J., et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N. Engl. J. Med. 2013;368:1279–1290. doi: 10.1056/NEJMoa1200303.
    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. 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. Tresserra-Rimbau A., Medina-Remón A., Pérez-Jiménez J., Martínez-González M.A., Covas M.I., Corella D., Salas-Salvadó J., Gómez-Gracia E., Lapetra J., Arós F., et al. Dietary intake and major food sources of polyphenols in a Spanish population at high cardiovascular risk: The PREDIMED study. Nutr. Metab. Cardiovasc. Dis. 2013;23:953–959. doi: 10.1016/j.numecd.2012.10.008.
    1. Storniolo C.E., Roselló-Catafau J., Pintó X., Mitjavila M.T., Moreno J.J. Polyphenol fraction of extra virgin olive oil protects against endothelial dysfunction induced by high glucose and free fatty acids through modulation of nitric oxide and endothelin-1. Redox Biol. 2014;2:971–977. doi: 10.1016/j.redox.2014.07.001.
    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. Rodríguez-Rodríguez 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. EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA) General guidance for stakeholders on the evaluation of Article 13.1, 13.5 and 14 health claims. EFSA J. 2011;9:1–24.
    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.D., 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. FDA U.S. Food and Drug Administration. [(accessed on 28 March 2018)]; Available online: .
    1. Covas M.-I., Nyyssönen K., Poulsen H.E., Kaikkonen J., Zunft H.-J.F., Kiesewetter H., Gaddi A., de la Torre R., Mursu J., Bäumler H., et al. The Effect of Polyphenols in Olive Oil on Heart Disease Risk Factors. Ann. Intern. Med. 2006;145:333–341. doi: 10.7326/0003-4819-145-5-200609050-00006.
    1. Fielding C.J., Havel R.J., Todd K.M., Yeo K.E., Schloetter M.C., Weinberg V., Frost P.H. Effects of dietary cholesterol and fat saturation on plasma lipoproteins in an ethnically diverse population of healthy young men. J. Clin. Investig. 1995;95:611–618. doi: 10.1172/JCI117705.
    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;4:142–148. doi: 10.4162/nrp.2010.4.2.142.
    1. Base de Datos de Composición de Alimentos (BEDCA) [(accessed on 28 March 2018)]; Available online:
    1. Huisman H.W., Schutte A.E., van Rooyen J.M., Schutte R., Malan L., Fourie C.M.T., Malan N.T. The Association of Red Blood Cell Counts with Endothelin-1 in African and Caucasian Women. Clin. Exp. Hypertens. 2009;31:1–10. doi: 10.1080/10641960802409838.
    1. Walter R., Mark M., Gaudenz R., Harris L.G., Reinhart W.H. Influence of nitrovasodilators and endothelin-1 on rheology of human blood in vitro. Br. J. Pharmacol. 1999;128:744–750. doi: 10.1038/sj.bjp.0702817.
    1. Pozo O.J., Pujadas M., Gleeson S.B., Mesa-García M.D., Pastor A., Kotronoulas A., Fitó M., Covas M.I., Navarro J.R.F., Espejo J.A., et al. Liquid chromatography tandem mass spectrometric determination of triterpenes in human fluids: Evaluation of markers of dietary intake of olive oil and metabolic disposition of oleanolic acid and maslinic acid in humans. Anal. Chim. Acta. 2017;990:84–95. doi: 10.1016/j.aca.2017.07.041.
    1. Senn S. Cross-over Trials in Clinical Research. 2nd ed. John Wiley & Sons, Ltd.; Chichester, UK: 2002. pp. 35–53.
    1. Liu G.F., Lu K., Mogg R., Mallich M., Mehrotra D.V. Should baseline be a covariate or dependent variable in analyses of change from baseline in clinical trials? Stat. Med. 2009;28:2509–2530. doi: 10.1002/sim.3639.
    1. Estruch R., Salas-Salvadó J. Towards an even healthier mediterranean diet. Nutr. Metab. Cardiovasc. Dis. 2013;23:1163–1166. doi: 10.1016/j.numecd.2013.09.003.
    1. Babio N., Toledo E., Estruch R., Ros E., Martínez-González M.A., Castañer O., Bulló M., Corella D., Arós F., Gómez-Gracia E., et al. Mediterranean diets and metabolic syndrome status in the PREDIMED randomized trial. CMAJ. 2014;186:E649–E657. doi: 10.1503/cmaj.140764.
    1. Salas-Salvadó J., Bulló M., Estruch R., Ros E., Covas M.-I., Ibarrola-Jurado N., Corella D., Arós F., Gómez-Gracia E., Ruiz-Gutiérrez V., et al. Prevention of Diabetes with Mediterranean Diets. Ann. Intern. Med. 2014;160:1–10. doi: 10.7326/M13-1725.
    1. Peyrol J., Riva C., Amiot M. Hydroxytyrosol in the Prevention of the Metabolic Syndrome and Related Disorders. Nutrients. 2017;9:306. doi: 10.3390/nu9030306.
    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. Rondanelli M., Giacosa A., Morazzoni P., Guido D., Grassi M., Morandi G., Bologna C., Riva A., Allegrini P., Perna S. MediterrAsian Diet Products that Could Raise HDL-Cholesterol: A Systematic Review. BioMed. Res. Int. 2016;2016:1–15. doi: 10.1155/2016/2025687.
    1. Farràs M., Castañer O., Martín-Peláez S., Hernáez Á., Schröder H., Subirana I., Muñoz-Aguayo D., Gaixas S., de la Torre R., Farré M., et al. 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. 2015;59:1758–1770. doi: 10.1002/mnfr.201500030.
    1. Hernaez A., Fernandez-Castillejo S., Farras M., Catalan U., Subirana I., Montes R., Sola R., Munoz-Aguayo D., Gelabert-Gorgues A., Diaz-Gil O., et al. Olive Oil Polyphenols Enhance High-Density Lipoprotein Function in Humans: A Randomized Controlled Trial. Arterioscler. Thromb. Vasc. Biol. 2014;34:2115–2119. doi: 10.1161/ATVBAHA.114.303374.
    1. Fernández-Castillejo S., Valls R.-M., Castañer O., Rubió L., Catalán Ú., Pedret A., Macià A., Sampson M.L., Covas M.-I., Fitó M., et al. Polyphenol rich olive oils improve lipoprotein particle atherogenic ratios and subclasses profile: A randomized, crossover, controlled trial. Mol. Nutr. Food Res. 2016;60:1544–1554. doi: 10.1002/mnfr.201501068.
    1. Hernáez Á., Castañer O., Goday A., Ros E., Pintó X., Estruch R., Salas-Salvadó J., Corella D., Arós F., Serra-Majem L., et al. The Mediterranean Diet decreases LDL atherogenicity in high cardiovascular risk individuals: A randomized controlled trial. Mol. Nutr. Food Res. 2017;61:1601015. doi: 10.1002/mnfr.201601015.
    1. Nordestgaard B.G., Langsted A., Mora S., Kolovou G., Baum H., Bruckert E., Watts G.F., Sypniewska G., Wiklund O., Borén J., et al. Fasting is not routinely required for determination of a lipid profile: Clinical and laboratory implications including flagging at desirable concentration cut-points—A joint consensus statement from the European Atherosclerosis Society and European Federation of Clinical Chemistry and Laboratory Medicine. Eur. Heart J. 2016;37:1944–1958.
    1. Saibandith B., Spencer J., Rowland I., Commane D. Olive Polyphenols and the Metabolic Syndrome. Molecules. 2017;22:1082. doi: 10.3390/molecules22071082.
    1. Luo H., Liu J., Ouyang Q., Xuan C., Wang L., Li T., Liu J. The effects of oleanolic acid on atherosclerosis in different animal models. Acta Biochim. Biophys. Sin. 2017;49:349–354. doi: 10.1093/abbs/gmx013.
    1. Ross R. The pathogenesis of atherosclerosis: A perspective for the 1990s. Nature. 1993;362:801–809. doi: 10.1038/362801a0.
    1. Gkaliagkousi E., Gavriilaki E., Triantafyllou A., Douma S. Clinical Significance of Endothelial Dysfunction in Essential Hypertension. Curr. Hypertens. Rep. 2015;17:85. doi: 10.1007/s11906-015-0596-3.
    1. Cambiaggi C., Mencarelli M., Muscettola M., Grasso G. Gene expression of endothelin-1 (ET-1) and release of mature peptide by activated human neutrophils. Cytokine. 2001;14:230–233. doi: 10.1006/cyto.2001.0865.
    1. Shinagawa S., Okazaki T., Ikeda M., Yudoh K., Kisanuki Y.Y., Yanagisawa M., Kawahata K., Ozaki S. T cells upon activation promote endothelin 1 production in monocytes via IFN-γ and TNF-α. Sci. Rep. 2017;7:14500. doi: 10.1038/s41598-017-14202-5.
    1. Massai L., Carbotti P., Cambiaggi C., Mencarelli M., Migliaccio P., Muscettola M., Grasso G. Prepro-endothelin-1 mRNA and its mature peptide in human appendix. Gastrointest. Liver Physiol. 2003;284:G340–G348. doi: 10.1152/ajpgi.00262.2002.
    1. Mencarelli M., Pecorelli A., Carbotti P., Valacchi G., Grasso G., Muscettola M. Endothelin receptor A expression in human inflammatory cells. Regul. Pept. 2009;158:1–5. doi: 10.1016/j.regpep.2009.06.004.
    1. Achmad T.H., Rao G.S. Chemotaxis of human boold monocytes toward endothelin-1 and the influence of calcium channel blockers. Biochem. Biophys. Res. Commun. 1992;189:994–1000. doi: 10.1016/0006-291X(92)92302-E.
    1. Ruetten H., Thiemermann C. Endothelin-1 stimulates the biosynthesis of tumour necrosis factor in macrophages: ET-receptors, signal transduction and inhibitionby dexamethasone. J. Physiol. Pharmacol. 1997;48:675–688.
    1. Zouki C., Baron C., Fournie A., Filep J.G. Endothelin-1 enhances neutrophil adhesion to human coronary artery endothelial cells: Role of ETA receptors and platelet activating factor. Br. J. Pharmacol. 1999;127:969–979. doi: 10.1038/sj.bjp.0702593.
    1. Zern T.L., Fernandez M.L. Cardioprotective effects of dietary polyphenols. J. Nutr. 2005;135:2291–2294. doi: 10.1093/jn/135.10.2291.
    1. Musini V.M., Wright J.M. Factors affecting blood pressure variability: Lessons learned from two systematic reviews of randomized controlled trials. PLoS ONE. 2009;4:e5673. doi: 10.1371/journal.pone.0005673.
    1. Handler J. The Importance of Accurate Blood Pressure Measurement. Perm. J. 2009;13:51–54. doi: 10.7812/TPP/09-054.
    1. Rodriguez-Rodriguez R., Herrera M.D., de Sotomayor M.A., Ruiz-Gutierrez V. Pomace Olive Oil Improves Endothelial Function in Spontaneously Hypertensive Rats by Increasing Endothelial Nitric Oxide Synthase Expression. Am. J. Hypertens. 2007;20:728–734. doi: 10.1016/j.amjhyper.2007.01.012.
    1. Valero-Muñoz M., Martín-Fernández B., Ballesteros S., de la Fuente E., Quintela J.C., Lahera V., de las Heras N. Protective effect of a pomace olive oil concentrated in triterpenic acids in alterations related to hypertension in rats: Mechanisms involved. Mol. Nutr. Food Res. 2014;58:376–383. doi: 10.1002/mnfr.201300256.
    1. Dell’Agli M., Fagnani R., Mitro N., Scurati S., Masciadri M., Mussoni L., Galli G.V., Bosisio E., Crestani M., De Fabiani E., et al. Minor Components of Olive Oil Modulate Proatherogenic Adhesion Molecules Involved in Endothelial Activation. J. Agric. Food Chem. 2006;54:3259–3264. doi: 10.1021/jf0529161.
    1. Fitó M., Cladellas M., de la Torre R., Martí J., Muñoz D., Schröder H., Alcántara M., Pujadas-Bastardes M., Marrugat J., López-Sabater M.C., et al. Anti-inflammatory effect of virgin olive oil in stable coronary disease patients: A randomized, crossover, controlled trial. Eur. J. Clin. Nutr. 2007;62:570–574. doi: 10.1038/sj.ejcn.1602724.
    1. Papageorgiou N., Tousoulis D., Psaltopoulou T., Giolis A., Antoniades C., Tsiamis E., Miliou A., Toutouzas K., Siasos G., Stefanadis C. Divergent anti-inflammatory effects of different oil acute consumption on healthy individuals. Eur. J. Clin. Nutr. 2011;65:514–519. doi: 10.1038/ejcn.2011.8.
    1. Martín-Peláez S., Castañer O., Konstantinidou V., Subirana I., Muñoz-Aguayo D., Blanchart G., Gaixas S., de la Torre R., Farré M., Sáez G.T., et al. Effect of olive oil phenolic compounds on the expression of blood pressure-related genes in healthy individuals. Eur. J. Nutr. 2017;56:663–670. doi: 10.1007/s00394-015-1110-z.

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