Metabolic and Vascular Effect of the Mediterranean Diet

Antonino Tuttolomondo, Irene Simonetta, Mario Daidone, Alba Mogavero, Antonella Ortello, Antonio Pinto, Antonino Tuttolomondo, Irene Simonetta, Mario Daidone, Alba Mogavero, Antonella Ortello, Antonio Pinto

Abstract

Several studies indicated how dietary patterns that were obtained from nutritional cluster analysis can predict disease risk or mortality. Low-grade chronic inflammation represents a background pathogenetic mechanism linking metabolic risk factors to increased risk of chronic degenerative diseases. A Mediterranean diet (MeDi) style has been reported as associated with a lower degree of inflammation biomarkers and with a protective role on cardiovascular and cerebrovascular events. There is heterogeneity in defining the MedDiet, and it can, owing to its complexity, be considered as an exposome with thousands of nutrients and phytochemicals. Recently, it has been reported a novel positive association between baseline plasma ceramide concentrations and cardiovascular events and how adherence to a Mediterranean Diet-style may influence the potential negative relationship between elevated plasma ceramide concentrations and cardiovascular diseases (CVD). Several randomized controlled trials (RCTs) showed the positive effects of the MeDi diet style on several cardiovascular risk factors, such as body mass index, waist circumference, blood lipids, blood pressure, inflammatory markers and adhesion molecules, and diabetes and how these advantages of the MeDi are maintained in comparison of a low-fat diet. Some studies reported a positive effect of adherence to a Mediterranean Diet and heart failure incidence, whereas some recent studies, such as the PREDIMED study, showed that the incidence of major cardiovascular events was lower among those assigned to MeDi supplemented with extra-virgin olive oil or nuts than among those assigned to a reduced-fat diet. New studies are needed to better understand the molecular mechanisms, whereby the MedDiet may exercise its effects. Here, we present recent advances in understanding the molecular basis of MedDiet effects, mainly focusing on cardiovascular diseases, but also discussing other related diseases. We review MedDiet composition and assessment as well as the latest advances in the genomic, epigenomic (DNA methylation, histone modifications, microRNAs, and other emerging regulators), transcriptomic (selected genes and whole transcriptome), and metabolomic and metagenomic aspects of the MedDiet effects (as a whole and for its most typical food components). We also present a review of the clinical effects of this dietary style underlying the biochemical and molecular effects of the Mediterranean diet. Our purpose is to review the main features of the Mediterranean diet in particular its benefits on human health, underling the anti-inflammatory, anti-oxidant and anti-atherosclerotic effects to which new knowledge about epigenetic and gut-microbiota relationship is recently added.

Keywords: cardiovascular risk; dietary pattern; mediterranean diet.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Mediterranean diet pyramid.
Figure 2
Figure 2
Some typical dishes of Mediterranean diet.
Figure 3
Figure 3
Beneficial effect of the Mediterranean diet.

References

    1. Keys A. Coronary heart disease in seven countries. 1970. Nutr. Burbank Los Angel. Cty. Calif. 1997;13:250–252.
    1. Buzina R., Keys A., Mohacek I., Marinkovic M., Hahn A., Blackburn H. Coronary Heart Disease in Seven Countries. V. Five-year follow-up in Dalmatia and Slavonia. [(accessed on 3 September 2019)]; Available online: .
    1. Fitó M., Konstantinidou V. Nutritional Genomics and the Mediterranean Diet’s Effects on Human Cardiovascular Health. Nutrients. 2016;8:218. doi: 10.3390/nu8040218.
    1. Keys A. Mediterranean diet and public health: Personal reflections. Am. J. Clin. Nutr. 1995;61:1321S–1323S. doi: 10.1093/ajcn/61.6.1321S.
    1. Keys A., Aravanis C., Blackburn H.W., Van Buchem F.S., Buzina R., Djordjević B.D., Dontas A.S., Fidanza F., Karvonen M.J., Kimura N., et al. Epidemiological studies related to coronary heart disease: Characteristics of men aged 40–59 in seven countries. Acta Med. Scand. 1966;460:1–392. doi: 10.1111/j.0954-6820.1966.tb04737.x.
    1. Menotti A., Keys A., Aravanis C., Blackburn H., Dontas A., Fidanza F., Karvonen M.J., Kromhout D., Nedeljkovic S., Nissinen A. Seven Countries Study. First 20-year mortality data in 12 cohorts of six countries. Ann. Med. 1989;21:175–179. doi: 10.3109/07853898909149929.
    1. Ahmad S., Moorthy M.V., Demler O.V., Hu F.B., Ridker P.M., Chasman D.I., Mora S. Assessment of Risk Factors and Biomarkers Associated with Risk of Cardiovascular Disease Among Women Consuming a Mediterranean Diet. JAMA Netw. Open. 2018;1 doi: 10.1001/jamanetworkopen.2018.5708.
    1. Dimitriou M.E., Dedoussis G.V.Z. Gene–Diet Interactions in Cardiovascular Disease. Curr. Nutr. Rep. 2012;1:153–160. doi: 10.1007/s13668-012-0020-4.
    1. Linseisen J., Kesse E., Slimani N., Bueno-De-Mesquita H.B., Ocké M.C., Skeie G., Kumle M., Dorronsoro Iraeta M., Morote Gómez P., Janzon L., et al. Meat consumption in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts: Results from 24-h dietary recalls. Public Health Nutr. 2002;5:1243–1258. doi: 10.1079/PHN2002402.
    1. La dieta mediterranea Come mangiare bene e stare bene - Ancel Keys - Margaret Keys - Libro - Slow Food - AsSaggi IBS. [(accessed on 3 September 2019)]; Available online: .
    1. Pereira-da-Silva L., Pinto E. Low Adherence to Mediterranean Diet in Portugal: Pregnant Women Nutrition in Portugal and its Repercussions. Acta Med. Port. 2016;29:658–666. doi: 10.20344/amp.7344.
    1. Benhammou S., Monteagudo C., Mariscal-Arcas M., Ortega V., Rivas A., Ortega E., Lorenzo M.L., Olea-Serrano F. Seguimiento de la dieta mediterránea e hidratación de la población española y marroquí. Nutr. Hosp. 2015;32:2749–2756.
    1. Balanza R., García-Lorda P., Pérez-Rodrigo C., Aranceta J., Bonet M.B., Salas-Salvadó J. Trends in food availability determined by the Food and Agriculture Organization’s food balance sheets in Mediterranean Europe in comparison with other European areas. Public Health Nutr. 2007;10:168–176. doi: 10.1017/S1368980007246592.
    1. Belahsen R., Rguibi M. Population health and Mediterranean diet in southern Mediterranean countries. Public Health Nutr. 2006;9:1130–1135. doi: 10.1017/S1368980007668517.
    1. Benhammou S., Heras-González L., Ibáñez-Peinado D., Barceló C., Hamdan M., Rivas A., Mariscal-Arcas M., Olea-Serrano F., Monteagudo C. Comparison of Mediterranean diet compliance between European and non-European populations in the Mediterranean basin. Appetite. 2016;107:521–526. doi: 10.1016/j.appet.2016.08.117.
    1. Hu F.B. Dietary pattern analysis: A new direction in nutritional epidemiology. Curr. Opin. Lipidol. 2002;13:3–9. doi: 10.1097/00041433-200202000-00002.
    1. Dedoussis G.V., Kanoni S., Mariani E., Cattini L., Herbein G., Fulop T., Varin A., Rink L., Jajte J., Monti D., et al. Mediterranean diet and plasma concentration of inflammatory markers in old and very old subjects in the ZINCAGE population study. Clin. Chem. Lab. Med. 2008;46:990–996. doi: 10.1515/CCLM.2008.191.
    1. Van Diepen S., Scholten A.M., Korobili C., Kyrli D., Tsigga M., Van Dieijen T., Kotzamanidis C., Grammatikopoulou M.G. Greater Mediterranean diet adherence is observed in Dutch compared with Greek university students. Nutr. Metab. Cardiovasc. Dis. NMCD. 2011;21:534–540. doi: 10.1016/j.numecd.2009.11.006.
    1. Kafatos A., Diacatou A., Voukiklaris G., Nikolakakis N., Vlachonikolis J., Kounali D., Mamalakis G., Dontas A.S. Heart disease risk-factor status and dietary changes in the Cretan population over the past 30 y: The Seven Countries Study. Am. J. Clin. Nutr. 1997;65:1882–1886. doi: 10.1093/ajcn/65.6.1882.
    1. Physical activity and health in Europe: Evidence for action. [(accessed on 3 September 2019)]; Available online: .
    1. Kyriacou A., Evans J.M.M., Economides N., Kyriacou A. Adherence to the Mediterranean diet by the Greek and Cypriot population: A systematic review. Eur. J. Public Health. 2015;25:1012–1018. doi: 10.1093/eurpub/ckv124.
    1. Sila S., Pavić A.M., Hojsak I., Ilić A., Pavić I., Kolaček S. Comparison of Obesity Prevalence and Dietary Intake in School-Aged Children Living in Rural and Urban Area of Croatia. Prev. Nutr. Food Sci. 2018;23:282–287.
    1. Cambien F., Poirier O., Lecerf L., Evans A., Cambou J.P., Arveiler D., Luc G., Bard J.M., Bara L., Ricard S. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature. 1992;359:641–644. doi: 10.1038/359641a0.
    1. Song Y., Stampfer M.J., Liu S. Meta-analysis: Apolipoprotein E genotypes and risk for coronary heart disease. Ann. Intern. Med. 2004;141:137–147. doi: 10.7326/0003-4819-141-2-200407200-00013.
    1. Pearson T.A., Manolio T.A. How to interpret a genome-wide association study. JAMA. 2008;299:1335–1344. doi: 10.1001/jama.299.11.1335.
    1. Corella D., Carrasco P., Sorlí J.V., Estruch R., Rico-Sanz J., MARTinez-GONZalez M.A., Salas-Salvadó J., Covas M.I., Coltell O., Arós F., et al. Mediterranean diet reduces the adverse effect of the TCF7L2-rs7903146 polymorphism on cardiovascular risk factors and stroke incidence: A randomize. [(accessed on 3 September 2019)];Diabetes Care. 2013 36:3803–3811. doi: 10.2337/dc13-0955. Available online: .
    1. Ortega-Azorín C., Sorlí J.V., Estruch R., Asensio E.M., Coltell O., González J.I., Martínez-González M.Á., Ros E., Salas-Salvadó J., Fitó M., et al. Amino acid change in the carbohydrate response element binding protein is associated with lower triglycerides and myocardial infarction incidence depending on level of adherence to the Mediterranean diet in the PREDIMED trial. Circ. Cardiovasc. Genet. 2014;7:49–58. doi: 10.1161/CIRCGENETICS.113.000301.
    1. García-Calzón S., Martínez-González M.A., Razquin C., Arós F., Lapetra J., Martínez J.A., Zalba G., Marti A. Mediterranean diet and telomere length in high cardiovascular risk subjects from the PREDIMED-NAVARRA study. Clin. Nutr. Edinb. Scotl. 2016;35:1399–1405. doi: 10.1016/j.clnu.2016.03.013.
    1. Boccardi V., Esposito A., Rizzo M.R., Marfella R., Barbieri M., Paolisso G. Mediterranean diet, telomere maintenance and health status among elderly. PLoS ONE. 2013;8:e62781. doi: 10.1371/journal.pone.0062781.
    1. Crous-Bou M., Fung T.T., Prescott J., Julin B., Du M., Sun Q., Rexrode K.M., Hu F.B., De Vivo I. Mediterranean diet and telomere length in Nurses’ Health Study: Population based cohort study. BMJ. 2014;349:g6674. doi: 10.1136/bmj.g6674.
    1. Marin C., Delgado-Lista J., Ramirez R., Carracedo J., Caballero J., Perez-Martinez P., Gutierrez-Mariscal F.M., Garcia-Rios A., Delgado-Casado N., Cruz-Teno C., et al. Mediterranean diet reduces senescence-associated stress in endothelial cells. Age Dordr. Neth. 2012;34:1309–1316. doi: 10.1007/s11357-011-9305-6.
    1. García-Calzón S., Martínez-González M.A., Razquin C., Corella D., Salas-Salvadó J., Martínez J.A., Zalba G., Marti A. Pro12Ala polymorphism of the PPARγ2 gene interacts with a mediterranean diet to prevent telomere shortening in the PREDIMED-NAVARRA randomized trial. Circ. Cardiovasc. Genet. 2015;8:91–99. doi: 10.1161/CIRCGENETICS.114.000635.
    1. Garcia-Rios A., Gomez-Delgado F.J., Garaulet M., Alcala-Diaz J.F., Delgado-Lista F.J., Marin C., Rangel-Zuñiga O.A., Rodriguez-Cantalejo F., Gomez-Luna P., Ordovas J.M., et al. Beneficial effect of CLOCK gene polymorphism rs1801260 in combination with low-fat diet on insulin metabolism in the patients with metabolic syndrome. Chronobiol. Int. 2014;31:401–408. doi: 10.3109/07420528.2013.864300.
    1. López-Guimerà G., Dashti H.S., Smith C.E., Sánchez-Carracedo D., Ordovas J.M., Garaulet M. CLOCK 3111 T/C SNP interacts with emotional eating behavior for weight-loss in a Mediterranean population. PLoS ONE. 2014;9:e99152. doi: 10.1371/journal.pone.0099152.
    1. Jackson A.A., Burdge G.C., Lillycrop K.A. Diet, Nutrition and Modulation of Genomic Expression in Fetal Origins of Adult Disease. J. Nutr. Nutr. 2011;3:192–208.
    1. Heijmans B.T., Tobi E.W., Stein A.D., Putter H., Blauw G.J., Susser E.S., Slagboom P.E., Lumey L.H. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc. Natl. Acad. Sci. USA. 2008;105:17046–17049. doi: 10.1073/pnas.0806560105.
    1. Alkemade F.E., van Vliet P., Henneman P., van Dijk K.W., Hierck B.P., van Munsteren J.C., Scheerman J.A., Goeman J.J., Havekes L.M., Gittenberger-de Groot A.C., et al. Prenatal exposure to apoE deficiency and postnatal hypercholesterolemia are associated with altered cell-specific lysine methyltransferase and histone methylation patterns in the vasculature. Am. J. Pathol. 2010;176:542–548. doi: 10.2353/ajpath.2010.090031.
    1. Lund G., Andersson L., Lauria M., Lindholm M., Fraga M.F., Villar-Garea A., Ballestar E., Esteller M., Zaina S. DNA methylation polymorphisms precede any histological sign of atherosclerosis in mice lacking apolipoprotein E. J. Biol. Chem. 2004;279:29147–29154. doi: 10.1074/jbc.M403618200.
    1. Roadmap E., Consortium K.A., Meuleman W., Ernst J., Bilenky M., Yen A., Heravi-Moussavi A., Kheradpour P., Zhang Z., Wang J., et al. Integrative analysis of 111 reference human epigenomes. Nature. 2015;518:317–330.
    1. Lillycrop K.A., Hoile S.P., Grenfell L., Burdge G.C. DNA methylation, ageing and the influence of early life nutrition. Proc. Nutr. Soc. 2014;73:413–421. doi: 10.1017/S0029665114000081.
    1. Gallach S., Calabuig-Fariñas S., Jantus-Lewintre E., Camps C. MicroRNAs: Promising new antiangiogenic targets in cancer. BioMed Res. Int. 2014;2014:878450. doi: 10.1155/2014/878450.
    1. Corella D., Ordovás J.M. How does the Mediterranean diet promote cardiovascular health? Current progress toward molecular mechanisms: Gene-diet interactions at the genomic, transcriptomic, and epigenomic levels provide novel insights into new mechanisms. BioEssays News Rev. Mol. Cell. Dev. Biol. 2014;36:526–537. doi: 10.1002/bies.201300180.
    1. Bünger M., Hooiveld G.J.E.J., Kersten S., Müller M. Exploration of PPAR functions by microarray technology--a paradigm for nutrigenomics. Biochim. Biophys. Acta. 2007;1771:1046–1064. doi: 10.1016/j.bbalip.2007.05.004.
    1. Konstantinidou V., Covas M.-I., Sola R., Fitó M. Up-to date knowledge on the in vivo transcriptomic effect of the Mediterranean diet in humans. Mol. Nutr. Food Res. 2013;57:772–783. doi: 10.1002/mnfr.201200613.
    1. Garcia-Aloy M., Llorach R., Urpi-Sarda M., Jáuregui O., Corella D., Ruiz-Canela M., Salas-Salvadó J., Fitó M., Ros E., Estruch R., et al. A metabolomics-driven approach to predict cocoa product consumption by designing a multimetabolite biomarker model in free-living subjects from the PREDIMED study. Mol. Nutr. Food Res. 2015;59:212–220. doi: 10.1002/mnfr.201400434.
    1. Zuker C.S. Food for the brain. Cell. 2015;161:9–11. doi: 10.1016/j.cell.2015.03.016.
    1. Lopez-Legarrea P., Fuller N.R., Zulet M.A., Martinez J.A., Caterson I.D. The influence of Mediterranean, carbohydrate and high protein diets on gut microbiota composition in the treatment of obesity and associated inflammatory state. Asia Pac. J. Clin. Nutr. 2014;23:360–368.
    1. Jin Q., Black A., Kales S.N., Vattem D., Ruiz-Canela M., Sotos-Prieto M. Metabolomics and Microbiomes as Potential Tools to Evaluate the Effects of the Mediterranean Diet. [(accessed on 3 September 2019)];Nutrients. 2019 11:207. doi: 10.3390/nu11010207. Available online: .
    1. González-Guardia L., Yubero-Serrano E.M., Delgado-Lista J., Perez-Martinez P., Garcia-Rios A., Marin C., Camargo A., Delgado-Casado N., Roche H.M., Perez-Jimenez F., et al. Effects of the Mediterranean diet supplemented with coenzyme q10 on metabolomic profiles in elderly men and women. J. Gerontol. A. Biol. Sci. Med. Sci. 2015;70:78–84. doi: 10.1093/gerona/glu098.
    1. Kakkoura M.G., Sokratous K., Demetriou C.A., Loizidou M.A., Loucaides G., Kakouri E., Hadjisavvas A., Kyriacou K. Mediterranean diet-gene interactions: A targeted metabolomics study in Greek-Cypriot women. Mol. Nutr. Food Res. 2017;61 doi: 10.1002/mnfr.201600558.
    1. Almanza-Aguilera E., Urpi-Sarda M., Llorach R., Vázquez-Fresno R., Garcia-Aloy M., Carmona F., Sanchez A., Madrid-Gambin F., Estruch R., Corella D., et al. Microbial metabolites are associated with a high adherence to a Mediterranean dietary pattern using a 1H-NMR-based untargeted metabolomics approach. J. Nutr. Biochem. 2017;48:36–43. doi: 10.1016/j.jnutbio.2017.06.001.
    1. Guasch-Ferré M., Zheng Y., Ruiz-Canela M., Hruby A., Martínez-González M.A., Clish C.B., Corella D., Estruch R., Ros E., Fitó M., et al. Plasma acylcarnitines and risk of cardiovascular disease: Effect of Mediterranean diet interventions. Am. J. Clin. Nutr. 2016;103:1408–1416. doi: 10.3945/ajcn.116.130492.
    1. Guasch-Ferré M., Hu F.B., Ruiz-Canela M., Bulló M., Toledo E., Wang D.D., Corella D., Gómez-Gracia E., Fiol M., Estruch R., et al. Plasma Metabolites from Choline Pathway and Risk of Cardiovascular Disease in the PREDIMED (Prevention with Mediterranean Diet) Study. J. Am. Heart Assoc. 2017;6 doi: 10.1161/JAHA.117.006524.
    1. Wang D.D., Toledo E., Hruby A., Rosner B.A., Willett W.C., Sun Q., Razquin C., Zheng Y., Ruiz-Canela M., Guasch-Ferré M., et al. Plasma Ceramides, Mediterranean Diet, and Incident Cardiovascular Disease in the PREDIMED Trial (Prevención con Dieta Mediterránea) Circulation. 2017;135:2028–2040. doi: 10.1161/CIRCULATIONAHA.116.024261.
    1. Zheng Y., Hu F.B., Ruiz-Canela M., Clish C.B., Dennis C., Salas-Salvado J., Hruby A., Liang L., Toledo E., Corella D., et al. Metabolites of Glutamate Metabolism Are Associated with Incident Cardiovascular Events in the PREDIMED PREvención con DIeta MEDiterránea (PREDIMED) Trial. J. Am. Heart Assoc. 2016;5 doi: 10.1161/JAHA.116.003755.
    1. Clemente J.C., Ursell L.K., Parfrey L.W., Knight R. The impact of the gut microbiota on human health: An integrative view. Cell. 2012;148:1258–1270. doi: 10.1016/j.cell.2012.01.035.
    1. Richards J.L., Yap Y.A., McLeod K.H., Mackay C.R., Mariño E. Dietary metabolites and the gut microbiota: An alternative approach to control inflammatory and autoimmune diseases. Clin. Transl. Immunol. 2016;5:e82. doi: 10.1038/cti.2016.29.
    1. Schugar R.C., Shih D.M., Warrier M., Helsley R.N., Burrows A., Ferguson D., Brown A.L., Gromovsky A.D., Heine M., Chatterjee A., et al. The TMAO-Producing Enzyme Flavin-Containing Monooxygenase 3 Regulates Obesity and the Beiging of White Adipose Tissue. Cell Rep. 2017;19:2451–2461. doi: 10.1016/j.celrep.2017.05.077.
    1. Tang W.H.W., Wang Z., Levison B.S., Koeth R.A., Britt E.B., Fu X., Wu Y., Hazen S.L. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N. Engl. J. Med. 2013;368:1575–1584. doi: 10.1056/NEJMoa1109400.
    1. Thorburn A.N., Macia L., Mackay C.R. Diet, metabolites, and “western-lifestyle” inflammatory diseases. Immunity. 2014;40:833–842. doi: 10.1016/j.immuni.2014.05.014.
    1. Haro C., García-Carpintero S., Rangel-Zúñiga O.A., Alcalá-Díaz J.F., Landa B.B., Clemente J.C., Pérez-Martínez P., López-Miranda J., Pérez-Jiménez F., Camargo A. Consumption of Two Healthy Dietary Patterns Restored Microbiota Dysbiosis in Obese Patients with Metabolic Dysfunction. Mol. Nutr. Food Res. 2017;61 doi: 10.1002/mnfr.201700300.
    1. Mazmanian S.K., Liu C.H., Tzianabos A.O., Kasper D.L. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell. 2005;122:107–118. doi: 10.1016/j.cell.2005.05.007.
    1. Sonnenburg E.D., Smits S.A., Tikhonov M., Higginbottom S.K., Wingreen N.S., Sonnenburg J.L. Diet-induced extinction in the gut microbiota compounds over generations. Nature. 2016;529:212–215. doi: 10.1038/nature16504.
    1. Dey N., Wagner V.E., Blanton L.V., Cheng J., Fontana L., Haque R., Ahmed T., Gordon J.I. Regulators of gut motility revealed by a gnotobiotic model of diet-microbiome interactions related to travel. Cell. 2015;163:95–107. doi: 10.1016/j.cell.2015.08.059.
    1. Griffin N.W., Ahern P.P., Cheng J., Heath A.C., Ilkayeva O., Newgard C.B., Fontana L., Gordon J.I. Prior Dietary Practices and Connections to a Human Gut Microbial Metacommunity Alter Responses to Diet Interventions. Cell Host Microbe. 2017;21:84–96. doi: 10.1016/j.chom.2016.12.006.
    1. Esposito K., Marfella R., Ciotola M., Di Palo C., Giugliano F., Giugliano G., D’Armiento M., D’Andrea F., Giugliano D. Effect of a mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: A randomized trial. JAMA. 2004;292:1440–1446. doi: 10.1001/jama.292.12.1440.
    1. Blankenberg S., Barbaux S., Tiret L. Adhesion molecules and atherosclerosis. Atherosclerosis. 2003;170:191–203. doi: 10.1016/S0021-9150(03)00097-2.
    1. Cortés B., Núñez I., Cofán M., Gilabert R., Pérez-Heras A., Casals E., Deulofeu R., Ros E. Acute effects of high-fat meals enriched with walnuts or olive oil on postprandial endothelial function. J. Am. Coll. Cardiol. 2006;48:1666–1671. doi: 10.1016/j.jacc.2006.06.057.
    1. Estruch R. Anti-inflammatory effects of the Mediterranean diet: The experience of the PREDIMED study. Proc. Nutr. Soc. 2010;69:333–340. doi: 10.1017/S0029665110001539.
    1. Carluccio M.A., Siculella L., Ancora M.A., Massaro M., Scoditti E., Storelli C., Visioli F., Distante A., De Caterina R. Olive oil and red wine antioxidant polyphenols inhibit endothelial activation: Antiatherogenic properties of Mediterranean diet phytochemicals. Arterioscler. Thromb. Vasc. Biol. 2003;23:622–629. doi: 10.1161/01.ATV.0000062884.69432.A0.
    1. Ros E., Núñez I., Pérez-Heras A., Serra M., Gilabert R., Casals E., Deulofeu R. A walnut diet improves endothelial function in hypercholesterolemic subjects: A randomized crossover trial. Circulation. 2004;109:1609–1614. doi: 10.1161/01.CIR.0000124477.91474.FF.
    1. Mena M.-P., Sacanella E., Vazquez-Agell M., Morales M., Fitó M., Escoda R., Serrano-Martínez M., Salas-Salvadó J., Benages N., Casas R., et al. Inhibition of circulating immune cell activation: A molecular antiinflammatory effect of the Mediterranean diet. Am. J. Clin. Nutr. 2009;89:248–256. doi: 10.3945/ajcn.2008.26094.
    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. Estruch R., Martínez-González M.A., Corella D., Salas-Salvadó J., Ruiz-Gutiérrez V., Covas M.I., Fiol M., Gómez-Gracia E., López-Sabater M.C., Vinyoles E., et al. Effects of a Mediterranean-style diet on cardiovascular risk factors: A randomized trial. Ann. Intern. Med. 2006;145:1–11. doi: 10.7326/0003-4819-145-1-200607040-00004.
    1. Elhayany A., Lustman A., Abel R., Attal-Singer J., Vinker S. A low carbohydrate Mediterranean diet improves cardiovascular risk factors and diabetes control among overweight patients with type 2 diabetes mellitus: A 1-year prospective randomized intervention study. Diabetes Obes. Metab. 2010;12:204–209. doi: 10.1111/j.1463-1326.2009.01151.x.
    1. Cani P.D., Delzenne N.M. The role of the gut microbiota in energy metabolism and metabolic disease. Curr. Pharm. Des. 2009;15:1546–1558. doi: 10.2174/138161209788168164.
    1. Ludwig D.S. The glycemic index: Physiological mechanisms relating to obesity, diabetes, and cardiovascular disease. JAMA. 2002;287:2414–2423. doi: 10.1001/jama.287.18.2414.
    1. Lovejoy J.C. Dietary fatty acids and insulin resistance. Curr. Atheroscler. Rep. 1999;1:215–220. doi: 10.1007/s11883-999-0035-5.
    1. Brown-Borg H.M., Buffenstein R. Cutting back on the essentials: Can manipulating intake of specific amino acids modulate health and lifespan? Ageing Res. Rev. 2017;39:87–95. doi: 10.1016/j.arr.2016.08.007.
    1. Schwingshackl L., Hoffmann G. Monounsaturated fatty acids and risk of cardiovascular disease: Synopsis of the evidence available from systematic reviews and meta-analyses. Nutrients. 2012;4:1989–2007. doi: 10.3390/nu4121989.
    1. Due A., Larsen T.M., Hermansen K., Stender S., Holst J.J., Toubro S., Martinussen T., Astrup A. Comparison of the effects on insulin resistance and glucose tolerance of 6-mo high-monounsaturated-fat, low-fat, and control diets. Am. J. Clin. Nutr. 2008;87:855–862. doi: 10.1093/ajcn/87.4.855.
    1. Paniagua J.A., de la Sacristana A.G., Sánchez E., Romero I., Vidal-Puig A., Berral F.J., Escribano A., Moyano M.J., Peréz-Martinez P., López-Miranda J., et al. A MUFA-rich diet improves posprandial glucose, lipid and GLP-1 responses in insulin-resistant subjects. J. Am. Coll. Nutr. 2007;26:434–444. doi: 10.1080/07315724.2007.10719633.
    1. Vessby B., Uusitupa M., Hermansen K., Riccardi G., Rivellese A.A., Tapsell L.C., Nälsén C., Berglund L., Louheranta A., Rasmussen B.M., et al. Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU Study. Diabetologia. 2001;44:312–319. doi: 10.1007/s001250051620.
    1. Vessby B. Dietary fat and insulin action in humans. Br. J. Nutr. 2000;83(Suppl. 1):S91–S96. doi: 10.1017/S000711450000101X.
    1. Wild S., Roglic G., Green A., Sicree R., King H. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030. Diabetes Care. 2004;27:1047–1053. doi: 10.2337/diacare.27.5.1047.
    1. Christiansen E., Schnider S., Palmvig B., Tauber-Lassen E., Pedersen O. Intake of a diet high in trans monounsaturated fatty acids or saturated fatty acids. Effects on postprandial insulinemia and glycemia in obese patients with NIDDM. Diabetes Care. 1997;20:881–887. doi: 10.2337/diacare.20.5.881.
    1. Garg A. High-monounsaturated-fat diets for patients with diabetes mellitus: A meta-analysis. Am. J. Clin. Nutr. 1998;67:577S–582S. doi: 10.1093/ajcn/67.3.577S.
    1. Ros E. Dietary cis-monounsaturated fatty acids and metabolic control in type 2 diabetes. Am. J. Clin. Nutr. 2003;78:617S–625S. doi: 10.1093/ajcn/78.3.617S.
    1. Brehm B.J., Lattin B.L., Summer S.S., Boback J.A., Gilchrist G.M., Jandacek R.J., D’Alessio D.A. One-year comparison of a high-monounsaturated fat diet with a high-carbohydrate diet in type 2 diabetes. Diabetes Care. 2009;32:215–220. doi: 10.2337/dc08-0687.
    1. Thomsen C., Rasmussen O., Christiansen C., Pedersen E., Vesterlund M., Storm H., Ingerslev J., Hermansen K. Comparison of the effects of a monounsaturated fat diet and a high carbohydrate diet on cardiovascular risk factors in first degree relatives to type-2 diabetic subjects. Eur. J. Clin. Nutr. 1999;53:818–823. doi: 10.1038/sj.ejcn.1600855.
    1. Shah M., Adams-Huet B., Linda B., Scott M.G., Abhimanyu G. Lipid, Glycemic, and Insulin Responses to Meals Rich in Saturated, Cis-Monounsaturated, and Polyunsaturated (n-3 and n-6) Fatty Acids in Subjects with Type 2 Diabetes. Diabetes Care. 2007;30:2993–2998. doi: 10.2337/dc07-1026.
    1. Pérez-Jiménez F., López-Miranda M.D., Pinillos P., Gómez E., Paz-Rojas P., Montilla C., Marín M.J., Velasco A., Blanco-Molina J.A., Jiménez P., et al. A Mediterranean and a High-Carbohydrate Diet Improve Glucose Metabolism in Healthy Young Persons. Diabetologia. 2001;44:2038–2043.
    1. Williams B., Mancia G., Spiering W., Agabiti Rosei E., Azizi M., Burnier M., Clement D.L., Coca A., de Simone G., Dominiczak A., et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. J. Hypertens. 2018;36:1953–2041.
    1. Mancia G., Fagard R., Narkiewicz K., Redón J., Zanchetti A., Böhm M., Christiaens T., Cifkova R., De Backer G., Dominiczak A., et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) J. Hypertens. 2013;31:1281–1357. doi: 10.1097/.
    1. Dickinson H.O., Mason J.M., Nicolson D.J., Campbell F., Beyer F.R., Cook J.V., Williams B., Ford G.A. Lifestyle interventions to reduce raised blood pressure: A systematic review of randomized controlled trials. J. Hypertens. 2006;24:215–233. doi: 10.1097/01.hjh.0000199800.72563.26.
    1. Mente A., de Koning L., Shannon H.S., Anand S.S. A systematic review of the evidence supporting a causal link between dietary factors and coronary heart disease. Arch. Intern. Med. 2009;169:659–669. doi: 10.1001/archinternmed.2009.38.
    1. Martínez-González M.Á., Corella D., Salas-Salvadó J., Ros E., Covas M.I., Fiol M., Wärnberg J., Arós F., Ruíz-Gutiérrez V., Lamuela-Raventós R.M., et al. Cohort profile: Design and methods of the PREDIMED study. Int. J. Epidemiol. 2012;41:377–385. doi: 10.1093/ije/dyq250.
    1. Nissensohn M., Román-Viñas B., Sánchez-Villegas A., Piscopo S., Serra-Majem L. The Effect of the Mediterranean Diet on Hypertension: A Systematic Review and Meta-Analysis. J. Nutr. Educ. Behav. 2016;48:42–53. doi: 10.1016/j.jneb.2015.08.023.
    1. Toledo E., Hu F.B., Estruch R., Buil-Cosiales P., Corella D., Salas-Salvadó J., Covas M.I., Arós F., Gómez-Gracia E., Fiol M., et al. Effect of the Mediterranean diet on blood pressure in the PREDIMED trial: Results from a randomized controlled trial. BMC Med. 2013;11:207. doi: 10.1186/1741-7015-11-207.
    1. Ignarro L.J., Buga G.M., Wood K.S., Byrns R.E., Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc. Natl. Acad. Sci. USA. 1987;84:9265–9269. doi: 10.1073/pnas.84.24.9265.
    1. Yanagisawa M., Kurihara H., Kimura S., Tomobe Y., Kobayashi M., Mitsui Y., Yazaki Y., Goto K., Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988;332:411–415. doi: 10.1038/332411a0.
    1. Furchgott R.F., Zawadzki J.V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980;288:373–376. doi: 10.1038/288373a0.
    1. Brunner H., Cockcroft J.R., Deanfield J., Donald A., Ferrannini E., Halcox J., Kiowski W., Lüscher T.F., Mancia G., Natali A., et al. Endothelial function and dysfunction. Part II: Association with cardiovascular risk factors and diseases. A statement by the Working Group on Endothelins and Endothelial Factors of the European Society of Hypertension. J. Hypertens. 2005;23:233–246. doi: 10.1097/00004872-200502000-00001.
    1. Dhaun N., Goddard J., Kohan D.E., Pollock D.M., Schiffrin E.L., Webb D.J. Role of endothelin-1 in clinical hypertension: 20 years on. Hypertension. 2008;52:452–459. doi: 10.1161/HYPERTENSIONAHA.108.117366.
    1. Storniolo C.E., Casillas R., Bulló M., Castañer O., Ros E., Sáez G.T., Toledo E., Estruch R., Ruiz-Gutiérrez V., Fitó M., et al. A Mediterranean diet supplemented with extra virgin olive oil or nuts improves endothelial markers involved in blood pressure control in hypertensive women. Eur. J. Nutr. 2017;56:89–97. doi: 10.1007/s00394-015-1060-5.
    1. Konstantinidou V., Covas M.-I., Muñoz-Aguayo D., Khymenets O., de la Torre R., Saez G., Tormos M.d.C., Toledo E., Marti A., Ruiz-Gutiérrez V., et al. In vivo nutrigenomic effects of virgin olive oil polyphenols within the frame of the Mediterranean diet: A randomized controlled trial. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 2010;24:2546–2557. doi: 10.1096/fj.09-148452.
    1. Fleming I. Molecular mechanisms underlying the activation of eNOS. Pflug. Arch. 2010;459:793–806. doi: 10.1007/s00424-009-0767-7.
    1. Camargo A., Delgado-Lista J., Garcia-Rios A., Cruz-Teno C., Yubero-Serrano E.M., Perez-Martinez P., Gutierrez-Mariscal F.M., Lora-Aguilar P., Rodriguez-Cantalejo F., Fuentes-Jimenez F., et al. Expression of proinflammatory, proatherogenic genes is reduced by the Mediterranean diet in elderly people. Br. J. Nutr. 2012;108:500–508. doi: 10.1017/S0007114511005812.
    1. Castañer O., Corella D., Covas M.-I., Sorlí J.V., Subirana I., Flores-Mateo G., Nonell L., Bulló M., de la Torre R., Portolés O., et al. In vivo transcriptomic profile after a Mediterranean diet in high-cardiovascular risk patients: A randomized controlled trial. Am. J. Clin. Nutr. 2013;98:845–853.
    1. Camargo A., Ruano J., Fernandez J.M., Parnell L.D., Jimenez A., Santos-Gonzalez M., Marin C., Perez-Martinez P., Uceda M., Lopez-Miranda J., et al. Gene expression changes in mononuclear cells in patients with metabolic syndrome after acute intake of phenol-rich virgin olive oil. BMC Genom. 2010;11:253. doi: 10.1186/1471-2164-11-253.
    1. Lukiw W.J., Ottlecz A., Lambrou G., Grueninger M., Finley J., Thompson H.W., Bazan N.G. Coordinate activation of HIF-1 and NF-kappaB DNA binding and COX-2 and VEGF expression in retinal cells by hypoxia. Investig. Ophthalmol. Vis. Sci. 2003;44:4163–4170. doi: 10.1167/iovs.02-0655.
    1. Moreno-Luna R., Muñoz-Hernandez R., Miranda M.L., Costa A.F., Jimenez-Jimenez L., Vallejo-Vaz A.J., Muriana F.J.G., Villar J., Stiefel P. Olive oil polyphenols decrease blood pressure and improve endothelial function in young women with mild hypertension. Am. J. Hypertens. 2012;25:1299–1304. doi: 10.1038/ajh.2012.128.
    1. Blackwell S. The biochemistry, measurement and current clinical significance of asymmetric dimethylarginine. Ann. Clin. Biochem. 2010;47:17–28. doi: 10.1258/acb.2009.009196.
    1. Luo P., Yan M., Frohlich E.D., Mehta J.L., Hu C. Novel concepts in the genesis of hypertension: Role of LOX-1. Cardiovasc. Drugs Ther. 2011;25:441–449. doi: 10.1007/s10557-011-6337-1.
    1. Devaraj S., Siegel D., Jialal I. Statin therapy in metabolic syndrome and hypertension post-JUPITER: What is the value of CRP? Curr. Atheroscler. Rep. 2011;13:31–42. doi: 10.1007/s11883-010-0143-2.
    1. Shih H.H., Zhang S., Cao W., Hahn A., Wang J., Paulsen J.E., Harnish D.C. CRP is a novel ligand for the oxidized LDL receptor LOX-1. Am. J. Physiol. Heart Circ. Physiol. 2009;296:H1643–H1650. doi: 10.1152/ajpheart.00938.2008.
    1. Psaltopoulou T., Naska A., Orfanos P., Trichopoulos D., Mountokalakis T., Trichopoulou A. Olive oil, the Mediterranean diet, and arterial blood pressure: The Greek European Prospective Investigation into Cancer and Nutrition (EPIC) study. Am. J. Clin. Nutr. 2004;80:1012–1018. doi: 10.1093/ajcn/80.4.1012.
    1. Trichopoulou A., Costacou T., Bamia C., Trichopoulos D. Adherence to a Mediterranean diet and survival in a Greek population. N. Engl. J. Med. 2003;348:2599–2608. doi: 10.1056/NEJMoa025039.
    1. Riboli E., Hunt K.J., Slimani N., Ferrari P., Norat T., Fahey M., Charrondière U.R., Hémon B., Casagrande C., Vignat J., et al. European Prospective Investigation into Cancer and Nutrition (EPIC): Study populations and data collection. Public Health Nutr. 2002;5:1113–1124. doi: 10.1079/PHN2002394.
    1. Sacks F.M., Katan M. Randomized clinical trials on the effects of dietary fat and carbohydrate on plasma lipoproteins and cardiovascular disease. Am. J. Med. 2002;113(Suppl. 9B):13S–24S. doi: 10.1016/S0002-9343(01)00987-1.
    1. Roysommuti S., Khongnakha T., Jirakulsomchok D., Wyss J.M. Excess dietary glucose alters renal function before increasing arterial pressure and inducing insulin resistance. Am. J. Hypertens. 2002;15:773–779. doi: 10.1016/S0895-7061(02)02974-6.
    1. Alonso A., Martínez-González M.A. Olive oil consumption and reduced incidence of hypertension: The SUN study. Lipids. 2004;39:1233–1238. doi: 10.1007/s11745-004-1352-x.
    1. Perona J.S., Vögler O., Sánchez-Domínguez J.M., Montero E., Escribá P.V., Ruiz-Gutierrez V. Consumption of virgin olive oil influences membrane lipid composition and regulates intracellular signaling in elderly adults with type 2 diabetes mellitus. J. Gerontol. A Biol. Sci. Med. Sci. 2007;62:256–263. doi: 10.1093/gerona/62.3.256.
    1. Ruíz-Gutiérrez V., Muriana F.J., Guerrero A., Cert A.M., Villar J. Plasma lipids, erythrocyte membrane lipids and blood pressure of hypertensive women after ingestion of dietary oleic acid from two different sources. J. Hypertens. 1996;14:1483–1490. doi: 10.1097/00004872-199612000-00016.
    1. Yang Q., Alemany R., Casas J., Kitajka K., Lanier S.M., Escribá P.V. Influence of the membrane lipid structure on signal processing via G protein-coupled receptors. Mol. Pharmacol. 2005;68:210–217. doi: 10.1124/mol.105.011692.
    1. Alemany R., Terés S., Baamonde C., Benet M., Vögler O., Escribá P.V. 2-hydroxyoleic acid: A new hypotensive molecule. Hypertension. 2004;43:249–254. doi: 10.1161/01.HYP.0000107778.85528.b5.
    1. Alemany R., Vögler O., Terés S., Egea C., Baamonde C., Barceló F., Delgado C., Jakobs K.H., Escribá P.V. Antihypertensive action of 2-hydroxyoleic acid in SHRs via modulation of the protein kinase A pathway and Rho kinase. J. Lipid Res. 2006;47:1762–1770. doi: 10.1194/jlr.M500520-JLR200.
    1. Visioli F., Galli C. Antiatherogenic components of olive oil. Curr. Atheroscler. Rep. 2001;3:64–67. doi: 10.1007/s11883-001-0012-0.
    1. Beauchamp G.K., Keast R.S.J., Morel D., Lin J., Pika J., Han Q., Lee C.-H., Smith A.B., Breslin P.A.S. Phytochemistry: Ibuprofen-like activity in extra-virgin olive oil. Nature. 2005;437:45–46. doi: 10.1038/437045a.
    1. Ferrara L.A., Raimondi A.S., d’Episcopo L., Guida L., Dello Russo A., Marotta T. Olive oil and reduced need for antihypertensive medications. Arch. Intern. Med. 2000;160:837–842. doi: 10.1001/archinte.160.6.837.
    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. Lehtonen J.Y., Holopainen J.M., Kinnunen P.K. Evidence for the formation of microdomains in liquid crystalline large unilamellar vesicles caused by hydrophobic mismatch of the constituent phospholipids. Biophys. J. 1996;70:1753–1760. doi: 10.1016/S0006-3495(96)79738-2.
    1. Kinnunen P.K.J. On the molecular-level mechanisms of peripheral protein-membrane interactions induced by lipids forming inverted non-lamellar phases. Chem. Phys. Lipids. 1996;81:151–166. doi: 10.1016/0009-3084(96)02579-0.
    1. Pérez F.R., Piñeiro V., De La Cruz L.F., Casanueva F.F., Casabiell X. Vascular wall: Potential target for the physicochemical effects of cis-unsaturated free fatty acids. Microsc. Res. Tech. 2003;60:23–29. doi: 10.1002/jemt.10239.
    1. Casabiell X., Pandiella A., Casanueva F.F. Regulation of epidermal-growth-factor-receptor signal transduction by cis-unsaturated fatty acids. Evidence for a protein kinase C-independent mechanism. Biochem. J. 1991;278:679–687. doi: 10.1042/bj2780679.
    1. Doménech M., Roman P., Lapetra J., García de la Corte F.J., Sala-Vila A., de la Torre R., Corella D., Salas-Salvadó J., Ruiz-Gutiérrez V., Lamuela-Raventós R.-M., et al. Mediterranean diet reduces 24-h ambulatory blood pressure, blood glucose, and lipids: One-year randomized, clinical trial. Hypertension. 2014;64:69–76. doi: 10.1161/HYPERTENSIONAHA.113.03353.
    1. Benjamin E.J., Virani S.S., Callaway C.W., Chamberlain A.M., Chang A.R., Cheng S., Chiuve S.E., Cushman M., Delling F.N., Deo R., et al. Heart Disease and Stroke Statistics-2018 Update: A Report from the American Heart Association. Circulation. 2018;137:e67–e492. doi: 10.1161/CIR.0000000000000558.
    1. Moore K., Sheedy F., Fisher E. Macrophages in atherosclerosis: A dynamic balance. Nat. Rev. Immunol. 2013;13:709–721. doi: 10.1038/nri3520.
    1. Tall A.R., Yvan-Charvet L. Cholesterol, inflammation and innate immunity. Nat. Rev. Immunol. 2015;15:104–116. doi: 10.1038/nri3793.
    1. Hu F.B., Stampfer M.J., Manson J.E., Rimm E.B., Colditz G.A., Rosner B.A., Speizer F.E., Hennekens C.H., Willett W.C. Frequent nut consumption and risk of coronary heart disease in women: Prospective cohort study. BMJ. 1998;317:1341–1345. doi: 10.1136/bmj.317.7169.1341.
    1. Kris-Etherton P.M., Yu-Poth S., Sabaté J., Ratcliffe H.E., Zhao G., Etherton T.D. Nuts and their bioactive constituents: Effects on serum lipids and other factors that affect disease risk. Am. J. Clin. Nutr. 1999;70:504S–511S. doi: 10.1093/ajcn/70.3.504s.
    1. Salas-Salvadó J., Farrés X., Luque X., Narejos S., Borrell M., Basora J., Anguera A., Torres F., Bulló M., Balanza R., et al. Effect of two doses of a mixture of soluble fibres on body weight and metabolic variables in overweight or obese patients: A randomised trial. Br. J. Nutr. 2008;99:1380–1387. doi: 10.1017/S0007114507868528.
    1. Theuwissen E., Mensink R.P. Water-soluble dietary fibers and cardiovascular disease. Physiol. Behav. 2008;94:285–292. doi: 10.1016/j.physbeh.2008.01.001.
    1. Allaire J., Couture P., Leclerc M., Charest A., Marin J., Lépine M.-C., Talbot D., Tchernof A., Lamarche B. A randomized, crossover, head-to-head comparison of eicosapentaenoic acid and docosahexaenoic acid supplementation to reduce inflammation markers in men and women: The Comparing EPA to DHA (ComparED) Study. Am. J. Clin. Nutr. 2016;104:280–287. doi: 10.3945/ajcn.116.131896.
    1. Saini R.K., Nile S.H., Park S.W. Carotenoids from fruits and vegetables: Chemistry, analysis, occurrence, bioavailability and biological activities. Food Res. Int. 2015;76:735–750. doi: 10.1016/j.foodres.2015.07.047.
    1. Skibsted L.H. Carotenoids in antioxidant networks. Colorants or radical scavengers. J. Agric. Food Chem. 2012;60:2409–2417. doi: 10.1021/jf2051416.
    1. Stephensen C.B. Provitamin A Carotenoids and Immune Function. In: Tanumihardjo S.A., editor. Carotenoids and Human Health. Nutrition and Health; Humana Press; Totowa, NJ, USA: 2013. pp. 261–270.
    1. Gammone M.A., Riccioni G., D’Orazio N. Carotenoids: Potential allies of cardiovascular health? Food Nutr. Res. 2015;59:26762.
    1. Kaulmann A., Bohn T. Carotenoids, inflammation, and oxidative stress--implications of cellular signaling pathways and relation to chronic disease prevention. Nutr. Res. N. Y. N. 2014;34:907–929. doi: 10.1016/j.nutres.2014.07.010.
    1. Mozos I., Stoian D., Caraba A., Malainer C., Horbańczuk J.O., Atanasov A.G. Lycopene and Vascular Health. Front. Pharmacol. 2018;9 doi: 10.3389/fphar.2018.00521.
    1. Gylling H., Simonen P. Phytosterols, Phytostanols, and Lipoprotein Metabolism. Nutrients. 2015;7:7965–7977. doi: 10.3390/nu7095374.
    1. Richelle M., Enslen M., Hager C., Groux M., Tavazzi I., Godin J.-P., Berger A., Métairon S., Quaile S., Piguet-Welsch C., et al. Both free and esterified plant sterols reduce cholesterol absorption and the bioavailability of beta-carotene and alpha-tocopherol in normocholesterolemic humans. Am. J. Clin. Nutr. 2004;80:171–177. doi: 10.1093/ajcn/80.1.171.
    1. Gylling H., Plat J., Turley S., Ginsberg H.N., Ellegård L., Jessup W., Jones P.J., Lütjohann D., Maerz W., Masana L., et al. Plant sterols and plant stanols in the management of dyslipidaemia and prevention of cardiovascular disease. Atherosclerosis. 2014;232:346–360. doi: 10.1016/j.atherosclerosis.2013.11.043.
    1. Pravst I., Zmitek K., Zmitek J. Coenzyme Q10 contents in foods and fortification strategies. Crit. Rev. Food Sci. Nutr. 2010;50:269–280. doi: 10.1080/10408390902773037.
    1. Moss J.W.E., Ramji D.P. Nutraceutical therapies for atherosclerosis. Nat. Rev. Cardiol. 2016;13:513–532. doi: 10.1038/nrcardio.2016.103.
    1. Hernández-Camacho J.D., Bernier M., López-Lluch G., Navas P. Coenzyme Q10 Supplementation in Aging and Disease. Front. Physiol. 2018;9:44. doi: 10.3389/fphys.2018.00044.
    1. Zhang S.-Y., Yang K.-L., Zeng L.-T., Wu X.-H., Huang H.-Y. Effectiveness of Coenzyme Q10 Supplementation for Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. Int. J. Endocrinol. 2018;2018:6484839. doi: 10.1155/2018/6484839.
    1. Ambring A., Friberg P., Axelsen M., Laffrenzen M., Taskinen M.-R., Basu S., Johansson M. Effects of a Mediterranean-inspired diet on blood lipids, vascular function and oxidative stress in healthy subjects. Clin. Sci. 2004;106:519–525. doi: 10.1042/CS20030315.
    1. Hernáez Á., Castañer O., Elosua R., Pintó X., Estruch R., Salas-Salvadó J., Corella D., Arós F., Serra-Majem L., Fiol M., et al. Mediterranean Diet Improves High-Density Lipoprotein Function in High-Cardiovascular-Risk Individuals: A Randomized Controlled Trial. Circulation. 2017;135:633–643. doi: 10.1161/CIRCULATIONAHA.116.023712.
    1. Khera A.V., Cuchel M., de la Llera-Moya M., Rodrigues A., Burke M.F., Jafri K., French B.C., Phillips J.A., Mucksavage M.L., Wilensky R.L., et al. Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. N. Engl. J. Med. 2011;364:127–135. doi: 10.1056/NEJMoa1001689.
    1. Rohatgi A., Khera A., Berry J.D., Givens E.G., Ayers C.R., Wedin K.E., Neeland I.J., Yuhanna I.S., Rader D.R., de Lemos J.A., et al. HDL cholesterol efflux capacity and incident cardiovascular events. N. Engl. J. Med. 2014;371:2383–2393. doi: 10.1056/NEJMoa1409065.
    1. Hovingh G.K., Hutten B.A., Holleboom A.G., Petersen W., Rol P., Stalenhoef A., Zwinderman A.H., de Groot E., Kastelein J.J.P., Kuivenhoven J.A. Compromised LCAT function is associated with increased atherosclerosis. Circulation. 2005;112:879–884. doi: 10.1161/CIRCULATIONAHA.105.540427.
    1. Wang K., Subbaiah P.V. Importance of the free sulfhydryl groups of lecithin-cholesterol acyltransferase for its sensitivity to oxidative inactivation. Biochim. Biophys. Acta. 2000;1488:268–277. doi: 10.1016/S1388-1981(00)00130-X.
    1. Rosenson R.S., Brewer H.B., Ansell B., Barter P., Chapman M.J., Heinecke J.W., Kontush A., Tall A.R., Webb N.R. Translation of high-density lipoprotein function into clinical practice: Current prospects and future challenges. Circulation. 2013;128:1256–1267. doi: 10.1161/CIRCULATIONAHA.113.000962.
    1. Ansell B.J., Navab M., Hama S., Kamranpour N., Fonarow G., Hough G., Rahmani S., Mottahedeh R., Dave R., Reddy S.T., et al. Inflammatory/antiinflammatory properties of high-density lipoprotein distinguish patients from control subjects better than high-density lipoprotein cholesterol levels and are favorably affected by simvastatin treatment. Circulation. 2003;108:2751–2756. doi: 10.1161/01.CIR.0000103624.14436.4B.
    1. Tang W.H.W., Hartiala J., Fan Y., Wu Y., Stewart A.F.R., Erdmann J., Kathiresan S., CARDIoGRAM Consortium. Roberts R., McPherson R., et al. Clinical and genetic association of serum paraoxonase and arylesterase activities with cardiovascular risk. Arterioscler. Thromb. Vasc. Biol. 2012;32:2803–2812. doi: 10.1161/ATVBAHA.112.253930.
    1. Kunutsor S.K., Bakker S.J.L., James R.W., Dullaart R.P.F. Serum paraoxonase-1 activity and risk of incident cardiovascular disease: The PREVEND study and meta-analysis of prospective population studies. Atherosclerosis. 2016;245:143–154. doi: 10.1016/j.atherosclerosis.2015.12.021.
    1. Besler C., Lüscher T.F., Landmesser U. Molecular mechanisms of vascular effects of High-density lipoprotein: Alterations in cardiovascular disease. EMBO Mol. Med. 2012;4:251–268. doi: 10.1002/emmm.201200224.
    1. Tuccinardi D., Farr O.M., Upadhyay J., Oussaada S.M., Klapa M.I., Candela M., Rampelli S., Lehoux S., Lázaro I., Sala-Vila A., et al. Mechanisms underlying the cardiometabolic protective effect of walnut consumption in obese people: A cross-over, randomized, double-blind, controlled inpatient physiology study. Diabetes Obes. Metab. 2019;21:2086–2095. doi: 10.1111/dom.13773.
    1. Chavez J.A., Summers S.A. A ceramide-centric view of insulin resistance. Cell Metab. 2012;15:585–594. doi: 10.1016/j.cmet.2012.04.002.
    1. El Harchaoui K., Arsenault B.J., Franssen R., Després J.-P., Hovingh G.K., Stroes E.S.G., Otvos J.D., Wareham N.J., Kastelein J.J.P., Khaw K.-T., et al. High-density lipoprotein particle size and concentration and coronary risk. Ann. Intern. Med. 2009;150:84–93. doi: 10.7326/0003-4819-150-2-200901200-00006.
    1. U.S. Food & Drug Qualified Health Claims: Letters of Enforcement Discretion. [(accessed on 19 June 2009)];2019 Available online: .
    1. Sala-Vila A., Cofán M., Núñez I., Gilabert R., Junyent M., Ros E. Carotid and femoral plaque burden is inversely associated with the α-linolenic acid proportion of serum phospholipids in Spanish subjects with primary dyslipidemia. Atherosclerosis. 2011;214:209–214. doi: 10.1016/j.atherosclerosis.2010.10.026.
    1. Sofi F., Dinu M., Pagliai G., Cesari F., Gori A.M., Sereni A., Becatti M., Fiorillo C., Marcucci R., Casini A. Low-Calorie Vegetarian Versus Mediterranean Diets for Reducing Body Weight and Improving Cardiovascular Risk Profile: CARDIVEG Study (Cardiovascular Prevention with Vegetarian Diet) Circulation. 2018;137:1103–1113. doi: 10.1161/CIRCULATIONAHA.117.030088.
    1. Gepner Y., Shelef I., Komy O., Cohen N., Schwarzfuchs D., Bril N., Rein M., Serfaty D., Kenigsbuch S., Zelicha H., et al. The beneficial effects of Mediterranean diet over low-fat diet may be mediated by decreasing hepatic fat content. J. Hepatol. 2019;71:379–388. doi: 10.1016/j.jhep.2019.04.013.
    1. Schröder H., Marrugat J., Elosua R., Covas M.I. REGICOR Investigators Relationship between body mass index, serum cholesterol, leisure-time physical activity, and diet in a Mediterranean Southern-Europe population. Br. J. Nutr. 2003;90:431–439.
    1. Tzima N., Pitsavos C., Panagiotakos D.B., Skoumas J., Zampelas A., Chrysohoou C., Stefanadis C. Mediterranean diet and insulin sensitivity, lipid profile and blood pressure levels, in overweight and obese people; the Attica study. Lipids Health Dis. 2007;6:22. doi: 10.1186/1476-511X-6-22.
    1. Summers S.A. Ceramides in insulin resistance and lipotoxicity. Prog. Lipid Res. 2006;45:42–72. doi: 10.1016/j.plipres.2005.11.002.
    1. Summers S.A. The ART of Lowering Ceramides. Cell Metab. 2015;22:195–196. doi: 10.1016/j.cmet.2015.07.019.
    1. Havulinna A.S., Sysi-Aho M., Hilvo M., Kauhanen D., Hurme R., Ekroos K., Salomaa V., Laaksonen R. Circulating Ceramides Predict Cardiovascular Outcomes in the Population-Based FINRISK 2002 Cohort. Arterioscler. Thromb. Vasc. Biol. 2016;36:2424–2430. doi: 10.1161/ATVBAHA.116.307497.
    1. Mantovani A., Bonapace S., Lunardi G., Salgarello M., Dugo C., Canali G., Byrne C.D., Gori S., Barbieri E., Targher G. Association between plasma ceramides and inducible myocardial ischemia in patients with established or suspected coronary artery disease undergoing myocardial perfusion scintigraphy. Metabolism. 2018;85:305–312. doi: 10.1016/j.metabol.2018.05.006.
    1. Ros E., Martínez-González M.A., Estruch R., Salas-Salvadó J., Fitó M., Martínez J.A., Corella D. Mediterranean diet and cardiovascular health: Teachings of the PREDIMED study. Adv. Nutr. Bethesda Md. 2014;5:330S–336S. doi: 10.3945/an.113.005389.
    1. Martínez-González M.Á., Toledo E., Arós F., Fiol M., Corella D., Salas-Salvadó J., Ros E., Covas M.I., Fernández-Crehuet J., Lapetra J., et al. Extravirgin olive oil consumption reduces risk of atrial fibrillation: The PREDIMED (Prevención con Dieta Mediterránea) trial. Circulation. 2014;130:18–26. doi: 10.1161/CIRCULATIONAHA.113.006921.
    1. Estruch R., Ros E., Salas-Salvadó J., Covas M.-I., 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 Supplemented with Extra-Virgin Olive Oil or Nuts. N. Engl. J. Med. 2018;378:e34. doi: 10.1056/NEJMoa1800389.
    1. Meisinger C., Baumert J., Khuseyinova N., Loewel H., Koenig W. Plasma oxidized low-density lipoprotein, a strong predictor for acute coronary heart disease events in apparently healthy, middle-aged men from the general population. Circulation. 2005;112:651–657. doi: 10.1161/CIRCULATIONAHA.104.529297.
    1. Fitó M., Guxens M., Corella D., Sáez G., Estruch R., de la Torre R., Francés F., Cabezas C., López-Sabater M.D.C., Marrugat J., et al. Effect of a traditional Mediterranean diet on lipoprotein oxidation: A randomized controlled trial. Arch. Intern. Med. 2007;167:1195–1203. doi: 10.1001/archinte.167.11.1195.
    1. Calder P.C., Ahluwalia N., Brouns F., Buetler T., Clement K., Cunningham K., Esposito K., Jönsson L.S., Kolb H., Lansink M., et al. Dietary factors and low-grade inflammation in relation to overweight and obesity. Br. J. Nutr. 2011;106:S5–S78. doi: 10.1017/S0007114511005460.
    1. Oh D.Y., Talukdar S., Bae E.J., Imamura T., Morinaga H., Fan W., Li P., Lu W.J., Watkins S.M., Olefsky J.M. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell. 2010;142:687–698. doi: 10.1016/j.cell.2010.07.041.
    1. Yan Y., Jiang W., Spinetti T., Tardivel A., Castillo R., Bourquin C., Guarda G., Tian Z., Tschopp J., Zhou R. Omega-3 fatty acids prevent inflammation and metabolic disorder through inhibition of NLRP3 inflammasome activation. Immunity. 2013;38:1154–1163. doi: 10.1016/j.immuni.2013.05.015.
    1. Visioli F., Poli A., Gall C. Antioxidant and other biological activities of phenols from olives and olive oil. Med. Res. Rev. 2002;22:65–75. doi: 10.1002/med.1028.
    1. Ogiwara T., Satoh K., Kadoma Y., Murakami Y., Unten S., Atsumi T., Sakagami H., Fujisawa S. Radical scavenging activity and cytotoxicity of ferulic acid. Anticancer Res. 2002;22:2711–2717.
    1. Eisenberg T., Abdellatif M., Schroeder S., Primessnig U., Stekovic S., Pendl T., Harger A., Schipke J., Zimmermann A., Schmidt A., et al. Cardioprotection and lifespan extension by the natural polyamine spermidine. Nat. Med. 2016;22:1428–1438. doi: 10.1038/nm.4222.
    1. Kouli G.-M., Panagiotakos D.B., Kyrou I., Magriplis E., Georgousopoulou E.N., Chrysohoou C., Tsigos C., Tousoulis D., Pitsavos C. Olive oil consumption and 10-year (2002–2012) cardiovascular disease incidence: The ATTICA study. Eur. J. Nutr. 2019;58:131–138. doi: 10.1007/s00394-017-1577-x.
    1. Urquiaga I., Strobel P., Perez D., Martinez C., Cuevas A., Castillo O., Marshall G., Rozowski J., Leighton F. Mediterranean diet and red wine protect against oxidative damage in young volunteers. Atherosclerosis. 2010;211:694–699. doi: 10.1016/j.atherosclerosis.2010.04.020.
    1. Wu L.L., Chiou C.C., Chang P.Y., Wu J.T. Urinary 8-OHdG: A marker of oxidative stress to DNA and a risk factor for cancer, atherosclerosis and diabetics. Clin. Chim. Acta Int. J. Clin. Chem. 2004;339:1–9. doi: 10.1016/j.cccn.2003.09.010.
    1. Quintero-Flórez A., Sinausia Nieva L., Sánchez-Ortíz A., Beltrán G., Perona J.S. The Fatty Acid Composition of Virgin Olive Oil from Different Cultivars Is Determinant for Foam Cell Formation by Macrophages. J. Agric. Food Chem. 2015;63:6731–6738. doi: 10.1021/acs.jafc.5b01626.
    1. Varela L.M., Ortega-Gomez A., Lopez S., Abia R., Muriana F.J.G., Bermudez B. The effects of dietary fatty acids on the postprandial triglyceride-rich lipoprotein/apoB48 receptor axis in human monocyte/macrophage cells. J. Nutr. Biochem. 2013;24:2031–2039. doi: 10.1016/j.jnutbio.2013.07.004.
    1. Vallvé J.-C., Uliaque K., Girona J., Cabré A., Ribalta J., Heras M., Masana L. Unsaturated fatty acids and their oxidation products stimulate CD36 gene expression in human macrophages. Atherosclerosis. 2002;164:45–56. doi: 10.1016/S0021-9150(02)00046-1.
    1. Endemann G., Stanton L.W., Madden K.S., Bryant C.M., White R.T., Protter A.A. CD36 is a receptor for oxidized low density lipoprotein. J. Biol. Chem. 1993;268:11811–11816.
    1. Tontonoz P., Nagy L., Alvarez J.G., Thomazy V.A., Evans R.M. PPARgamma promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell. 1998;93:241–252. doi: 10.1016/S0092-8674(00)81575-5.
    1. Tontonoz P., Nagy L. Regulation of macrophage gene expression by peroxisome-proliferator-activated receptor gamma: Implications for cardiovascular disease. Curr. Opin. Lipidol. 1999;10:485–490. doi: 10.1097/00041433-199912000-00002.
    1. Mancia G., Laurent S., Agabiti-Rosei E., Ambrosioni E., Burnier M., Caulfield M.J., Cifkova R., Clément D., Coca A., Dominiczak A., et al. Reappraisal of European guidelines on hypertension management: A European Society of Hypertension Task Force document. J. Hypertens. 2009;27:2121–2158. doi: 10.1097/HJH.0b013e328333146d.
    1. Jung J.Y., Hwang Y.-H., Lee H., Ro H., Lee H., Chung W., Chae D.-W., Joo K.W., Ahn C., Oh K.-H. Association of AHSG gene polymorphisms and aortic stiffness in peritoneal dialysis patients. Am. J. Nephrol. 2010;31:510–517. doi: 10.1159/000309789.
    1. Iemitsu M., Murakami H., Sanada K., Yamamoto K., Kawano H., Gando Y., Miyachi M. Lack of carotid stiffening associated with MTHFR 677TT genotype in cardiorespiratory fit adults. Physiol. Genom. 2010;42:259–265. doi: 10.1152/physiolgenomics.00039.2010.
    1. Van de Laar R.J.J., Stehouwer C.D.A., van Bussel B.C.T., Prins M.H., Twisk J.W.R., Ferreira I. Adherence to a Mediterranean dietary pattern in early life is associated with lower arterial stiffness in adulthood: The Amsterdam Growth and Health Longitudinal Study. J. Intern. Med. 2013;273:79–93. doi: 10.1111/j.1365-2796.2012.02577.x.
    1. Rodríguez-Martin C., Alonso-Domínguez R., Patino-Alonso M.C., Gómez-Marcos M.A., Maderuelo-Fernández J.A., Martin-Cantera C., García-Ortiz L., Recio-Rodríguez J.I. EVIDENT group The EVIDENT diet quality index is associated with cardiovascular risk and arterial stiffness in adults. BMC Public Health. 2017;17:305.
    1. Giugliano D., Ceriello A., Esposito K. The effects of diet on inflammation: Emphasis on the metabolic syndrome. J. Am. Coll. Cardiol. 2006;48:677–685. doi: 10.1016/j.jacc.2006.03.052.
    1. Shai I., Spence J.D., Schwarzfuchs D., Henkin Y., Parraga G., Rudich A., Fenster A., Mallett C., Liel-Cohen N., Tirosh A., et al. Dietary intervention to reverse carotid atherosclerosis. Circulation. 2010;121:1200–1208. doi: 10.1161/CIRCULATIONAHA.109.879254.
    1. Murie-Fernandez M., Irimia P., Toledo E., Martínez-Vila E., Buil-Cosiales P., Serrano-Martínez M., Ruiz-Gutiérrez V., Ros E., Estruch R., Martínez-González M.Á., et al. Carotid intima-media thickness changes with Mediterranean diet: A randomized trial (PREDIMED-Navarra) Atherosclerosis. 2011;219:158–162. doi: 10.1016/j.atherosclerosis.2011.06.050.
    1. Akgüllü Ç., Sırıken F., Eryılmaz U., Akdeniz M., Ömürlü İ.K., Pekcan G., Güngör H., Kurtoğlu T. The relation between compliance to the Mediterranean diet and the extensiveness of coronary artery disease. Turk. Kardiyol. Dern. Ars. Turk. Kardiyol. Dern. Yayin Organidir. 2015;43:340–349.
    1. Waldeyer C., Brunner F.J., Braetz J., Ruebsamen N., Zyriax B.-C., Blaum C., Kroeger F., Kohsiack R., Schrage B., Sinning C., et al. Adherence to Mediterranean diet, high-sensitive C-reactive protein, and severity of coronary artery disease: Contemporary data from the INTERCATH cohort. Atherosclerosis. 2018;275:256–261. doi: 10.1016/j.atherosclerosis.2018.06.877.
    1. Acar B., Gucuk Ipek E., Unal S., Yayla C., Karanfil M., Burak C., Kara M., Bayraktar F., Kuyumcu M.S., Aydogdu S. Evaluation of Mediterranean diet adherence in patients with a history of coronary revascularization. Rev. Clin. Esp. 2018;218:215–222. doi: 10.1016/j.rce.2018.02.015.
    1. De Lorgeril M., Salen P., Martin J.L., Monjaud I., Delaye J., Mamelle N. Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: Final report of the Lyon Diet Heart Study. Circulation. 1999;99:779–785. doi: 10.1161/01.CIR.99.6.779.
    1. Panagiotakos D.B., Chrysohoou C., Pitsavos C., Tzioumis K., Papaioannou I., Stefanadis C., Toutouzas P. The association of Mediterranean diet with lower risk of acute coronary syndromes in hypertensive subjects. Int. J. Cardiol. 2002;82:141–147. doi: 10.1016/S0167-5273(01)00611-8.
    1. Avery C.L., Loehr L.R., Baggett C., Chang P.P., Kucharska-Newton A.M., Matsushita K., Rosamond W.D., Heiss G. The population burden of heart failure attributable to modifiable risk factors: The ARIC (Atherosclerosis Risk in Communities) study. J. Am. Coll. Cardiol. 2012;60:1640–1646. doi: 10.1016/j.jacc.2012.07.022.
    1. Sanches Machado d’Almeida K., Ronchi Spillere S., Zuchinali P., Corrêa Souza G. Mediterranean Diet and Other Dietary Patterns in Primary Prevention of Heart Failure and Changes in Cardiac Function Markers: A Systematic Review. Nutrients. 2018;10:58. doi: 10.3390/nu10010058.
    1. He J., Ogden L.G., Bazzano L.A., Vupputuri S., Loria C., Whelton P.K. Risk factors for congestive heart failure in US men and women: NHANES I epidemiologic follow-up study. Arch. Intern. Med. 2001;161:996–1002. doi: 10.1001/archinte.161.7.996.
    1. Heckbert S.R., Post W., Pearson G.D.N., Arnett D.K., Gomes A.S., Jerosch-Herold M., Hundley W.G., Lima J.A., Bluemke D.A. Traditional cardiovascular risk factors in relation to left ventricular mass, volume, and systolic function by cardiac magnetic resonance imaging: The Multiethnic Study of Atherosclerosis. J. Am. Coll. Cardiol. 2006;48:2285–2292. doi: 10.1016/j.jacc.2006.03.072.
    1. Papadaki A., Martínez-González M.Á., Alonso-Gómez A., Rekondo J., Salas-Salvadó J., Corella D., Ros E., Fitó M., Estruch R., Lapetra J., et al. Mediterranean diet and risk of heart failure: Results from the PREDIMED randomized controlled trial. Eur. J. Heart Fail. 2017;19:1179–1185. doi: 10.1002/ejhf.750.
    1. Heidenreich P.A., Albert N.M., Allen L.A., Bluemke D.A., Butler J., Fonarow G.C., Ikonomidis J.S., Khavjou O., Konstam M.A., Maddox T.M., et al. Forecasting the impact of heart failure in the United States: A policy statement from the American Heart Association. Circ. Heart Fail. 2013;6:606–619. doi: 10.1161/HHF.0b013e318291329a.
    1. Dai J., Jones D.P., Goldberg J., Ziegler T.R., Bostick R.M., Wilson P.W., Manatunga A.K., Shallenberger L., Jones L., Vaccarino V. Association between adherence to the Mediterranean diet and oxidative stress. Am. J. Clin. Nutr. 2008;88:1364–1370.
    1. Tsutsui H., Kinugawa S., Matsushima S. Oxidative stress and heart failure. Am. J. Physiol. Heart Circ. Physiol. 2011;301:H2181–H2190. doi: 10.1152/ajpheart.00554.2011.
    1. Chrysohoou C., Pitsavos C., Barbetseas J., Kotroyiannis I., Brili S., Vasiliadou K., Papadimitriou L., Stefanadis C. Chronic systemic inflammation accompanies impaired ventricular diastolic function, detected by Doppler imaging, in patients with newly diagnosed systolic heart failure (Hellenic Heart Failure Study) Heart Vessels. 2009;24:22–26. doi: 10.1007/s00380-008-1080-7.
    1. Fitó M., Estruch R., Salas-Salvadó J., Martínez-Gonzalez M.A., Arós F., Vila J., Corella D., Díaz O., Sáez G., de la Torre R., et al. Effect of the Mediterranean diet on heart failure biomarkers: A randomized sample from the PREDIMED trial. Eur. J. Heart Fail. 2014;16:543–550. doi: 10.1002/ejhf.61.
    1. Brouwers F.P., de Boer R.A., van der Harst P., Voors A.A., Gansevoort R.T., Bakker S.J., Hillege H.L., van Veldhuisen D.J., van Gilst W.H. Incidence and epidemiology of new onset heart failure with preserved vs. reduced ejection fraction in a community-based cohort: 11-year follow-up of PREVEND. Eur. Heart J. 2013;34:1424–1431. doi: 10.1093/eurheartj/eht066.
    1. Kistorp C., Raymond I., Pedersen F., Gustafsson F., Faber J., Hildebrandt P. N-terminal pro-brain natriuretic peptide, C-reactive protein, and urinary albumin levels as predictors of mortality and cardiovascular events in older adults. JAMA. 2005;293:1609–1616. doi: 10.1001/jama.293.13.1609.
    1. Meirovich Y.F., Veinot J.P., de Bold M.L.K., Haddad H., Davies R.A., Masters R.G., Hendry P.J., de Bold A.J. Relationship between natriuretic peptides and inflammation: Proteomic evidence obtained during acute cellular cardiac allograft rejection in humans. J. Heart Lung Transplant. Off. Publ. Int. Soc. Heart Transplant. 2008;27:31–37. doi: 10.1016/j.healun.2007.09.025.
    1. Urpi-Sarda M., Casas R., Chiva-Blanch G., Romero-Mamani E.S., Valderas-Martínez P., Salas-Salvadó J., Covas M.I., Toledo E., Andres-Lacueva C., Llorach R., et al. The Mediterranean diet pattern and its main components are associated with lower plasma concentrations of tumor necrosis factor receptor 60 in patients at high risk for cardiovascular disease. J. Nutr. 2012;142:1019–1025. doi: 10.3945/jn.111.148726.
    1. Yubero-Serrano E.M., Gonzalez-Guardia L., Rangel-Zuñiga O., Delgado-Lista J., Gutierrez-Mariscal F.M., Perez-Martinez P., Delgado-Casado N., Cruz-Teno C., Tinahones F.J., Villalba J.M., et al. Mediterranean diet supplemented with coenzyme Q10 modifies the expression of proinflammatory and endoplasmic reticulum stress-related genes in elderly men and women. J. Gerontol. A. Biol. Sci. Med. Sci. 2012;67:3–10. doi: 10.1093/gerona/glr167.
    1. Belch J.J., Bridges A.B., Scott N., Chopra M. Oxygen free radicals and congestive heart failure. Br. Heart J. 1991;65:245–248. doi: 10.1136/hrt.65.5.245.
    1. Hill M.F., Singal P.K. Antioxidant and oxidative stress changes during heart failure subsequent to myocardial infarction in rats. Am. J. Pathol. 1996;148:291–300.
    1. Sawyer D.B., Colucci W.S. Mitochondrial oxidative stress in heart failure: “oxygen wastage” revisited. Circ. Res. 2000;86:119–120. doi: 10.1161/01.RES.86.2.119.
    1. Ide T., Tsutsui H., Hayashidani S., Kang D., Suematsu N., Nakamura K., Utsumi H., Hamasaki N., Takeshita A. Mitochondrial DNA damage and dysfunction associated with oxidative stress in failing hearts after myocardial infarction. Circ. Res. 2001;88:529–535. doi: 10.1161/01.RES.88.5.529.
    1. Sabri A., Hughie H.H., Lucchesi P.A. Regulation of hypertrophic and apoptotic signaling pathways by reactive oxygen species in cardiac myocytes. Antioxid. Redox Signal. 2003;5:731–740. doi: 10.1089/152308603770380034.
    1. Cesselli D., Jakoniuk I., Barlucchi L., Beltrami A.P., Hintze T.H., Nadal-Ginard B., Kajstura J., Leri A., Anversa P. Oxidative stress-mediated cardiac cell death is a major determinant of ventricular dysfunction and failure in dog dilated cardiomyopathy. Circ. Res. 2001;89:279–286. doi: 10.1161/hh1501.094115.
    1. Spinale F.G., Coker M.L., Thomas C.V., Walker J.D., Mukherjee R., Hebbar L. Time-dependent changes in matrix metalloproteinase activity and expression during the progression of congestive heart failure: Relation to ventricular and myocyte function. Circ. Res. 1998;82:482–495. doi: 10.1161/01.RES.82.4.482.
    1. Rajagopalan S., Meng X.P., Ramasamy S., Harrison D.G., Galis Z.S. Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. J. Clin. Investig. 1996;98:2572–2579. doi: 10.1172/JCI119076.
    1. Visioli F., Galli C. The role of antioxidants in the Mediterranean diet. Lipids. 2001;36:S49–S52. doi: 10.1007/s11745-001-0682-z.
    1. Álvarez P., Alvarado C., Mathieu F., Jiménez L., De la Fuente M. Diet supplementation for 5 weeks with polyphenol-rich cereals improves several functions and the redox state of mouse leucocytes. Eur. J. Nutr. 2006;45:428–438. doi: 10.1007/s00394-006-0616-9.
    1. Davis L., Stonehouse W., Loots D.T., Mukuddem-Petersen J., van der Westhuizen F.H., Hanekom S.M., Jerling J.C. The effects of high walnut and cashew nut diets on the antioxidant status of subjects with metabolic syndrome. Eur. J. Nutr. 2007;46:155–164. doi: 10.1007/s00394-007-0647-x.
    1. Le C.T., Hollaar L., Van der Valk E.J., Franken N.A., Van Ravels F.J., Wondergem J., Van der Laarse A. Protection of myocytes against free radical-induced damage by accelerated turnover of the glutathione redox cycle. Eur. Heart J. 1995;16:553–562. doi: 10.1093/oxfordjournals.eurheartj.a060950.
    1. Fico A., Paglialunga F., Cigliano L., Abrescia P., Verde P., Martini G., Iaccarino I., Filosa S. Glucose-6-phosphate dehydrogenase plays a crucial role in protection from redox-stress-induced apoptosis. Cell Death Differ. 2004;11:823–831. doi: 10.1038/sj.cdd.4401420.
    1. Fang Y.-Z., Yang S., Wu G. Free radicals, antioxidants, and nutrition. Nutr. Burbank Los Angel. Cty. Calif. 2002;18:872–879. doi: 10.1016/S0899-9007(02)00916-4.
    1. Rebrin I., Zicker S., Wedekind K.J., Paetau-Robinson I., Packer L., Sohal R.S. Effect of antioxidant-enriched diets on glutathione redox status in tissue homogenates and mitochondria of the senescence-accelerated mouse. Free Radic. Biol. Med. 2005;39:549–557. doi: 10.1016/j.freeradbiomed.2005.04.008.
    1. Yeung A.W.K., Aggarwal B.B., Orhan I.E., Horbanczuk O.K., Barreca D., Battino M., Belwal T., Bishayee A., Daglia M., Devkota H.P., et al. Resveratrol, a popular dietary supplement for human and animal health: Quantitative research literature analysis—A review. Anim. Sci. Pap. Rep. 2019
    1. Tsutsui T., Tsutamoto T., Wada A., Maeda K., Mabuchi N., Hayashi M., Ohnishi M., Kinoshita M. Plasma oxidized low-density lipoprotein as a prognostic predictor in patients with chronic congestive heart failure. J. Am. Coll. Cardiol. 2002;39:957–962. doi: 10.1016/S0735-1097(02)01721-7.
    1. Charach G., George J., Afek A., Wexler D., Sheps D., Keren G., Rubinstein A. Antibodies to oxidized LDL as predictors of morbidity and mortality in patients with chronic heart failure. J. Card. Fail. 2009;15:770–774. doi: 10.1016/j.cardfail.2009.05.009.
    1. Bergmark C., Dewan A., Orsoni A., Merki E., Miller E.R., Shin M.-J., Binder C.J., Hörkkö S., Krauss R.M., Chapman M.J., et al. A novel function of lipoprotein as a preferential carrier of oxidized phospholipids in human plasma. J. Lipid Res. 2008;49:2230–2239. doi: 10.1194/jlr.M800174-JLR200.
    1. Shin M.-J., Blanche P.J., Rawlings R.S., Fernstrom H.S., Krauss R.M. Increased plasma concentrations of lipoprotein(a) during a low-fat, high-carbohydrate diet are associated with increased plasma concentrations of apolipoprotein C-III bound to apolipoprotein B-containing lipoproteins. Am. J. Clin. Nutr. 2007;85:1527–1532. doi: 10.1093/ajcn/85.6.1527.
    1. Perona J.S., Covas M.-I., Fitó M., Cabello-Moruno R., Aros F., Corella D., Ros E., Garcia M., Estruch R., Martinez-Gonzalez M.A., et al. Reduction in systemic and VLDL triacylglycerol concentration after a 3-month Mediterranean-style diet in high-cardiovascular-risk subjects. J. Nutr. Biochem. 2010;21:892–898. doi: 10.1016/j.jnutbio.2009.07.005.
    1. Willett W.C., Stampfer M.J. Rebuilding the food pyramid. Sci. Am. 2003;288:64–71. doi: 10.1038/scientificamerican0103-64.
    1. Singh R.B., Dubnov G., Niaz M.A., Ghosh S., Singh R., Rastogi S.S., Manor O., Pella D., Berry E.M. Effect of an Indo-Mediterranean diet on progression of coronary artery disease in high risk patients (Indo-Mediterranean Diet Heart Study): A randomised single-blind trial. Lancet Lond. Engl. 2002;360:1455–1461. doi: 10.1016/S0140-6736(02)11472-3.
    1. Chen G.-C., Neelakantan N., Martín-Calvo N., Koh W.-P., Yuan J.-M., Bonaccio M., Iacoviello L., Martínez-González M.A., Qin L.-Q., van Dam R.M. Adherence to the Mediterranean diet and risk of stroke and stroke subtypes. Eur. J. Epidemiol. 2019;34:337–349. doi: 10.1007/s10654-019-00504-7.
    1. O’Donnell M.J., Chin S.L., Rangarajan S., Xavier D., Liu L., Zhang H., Rao-Melacini P., Zhang X., Pais P., Agapay S., et al. Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): A case-control study. Lancet Lond. Engl. 2016;388:761–775. doi: 10.1016/S0140-6736(16)30506-2.
    1. Sofi F., Abbate R., Gensini G.F., Casini A. Accruing evidence on benefits of adherence to the Mediterranean diet on health: An updated systematic review and meta-analysis. Am. J. Clin. Nutr. 2010;92:1189–1196. doi: 10.3945/ajcn.2010.29673.
    1. Bendinelli B., Masala G., Saieva C., Salvini S., Calonico C., Sacerdote C., Agnoli C., Grioni S., Frasca G., Mattiello A., et al. Fruit, vegetables, and olive oil and risk of coronary heart disease in Italian women: The EPICOR Study. Am. J. Clin. Nutr. 2011;93:275–283. doi: 10.3945/ajcn.110.000521.
    1. Salas-Salvadó J., Fernández-Ballart J., Ros E., Martínez-González M.-A., Fitó M., Estruch R., Corella D., Fiol M., Gómez-Gracia E., Arós F., et al. Effect of a Mediterranean diet supplemented with nuts on metabolic syndrome status: One-year results of the PREDIMED randomized trial. Arch. Intern. Med. 2008;168:2449–2458. doi: 10.1001/archinte.168.22.2449.
    1. Kastorini C.-M., Milionis H.J., Esposito K., Giugliano D., Goudevenos J.A., Panagiotakos D.B. The effect of Mediterranean diet on metabolic syndrome and its components: A meta-analysis of 50 studies and 534,906 individuals. J. Am. Coll. Cardiol. 2011;57:1299–1313. doi: 10.1016/j.jacc.2010.09.073.
    1. Esposito K., Maiorino M.I., Ceriello A., Giugliano D. Prevention and control of type 2 diabetes by Mediterranean diet: A systematic review. Diabetes Res. Clin. Pract. 2010;89:97–102. doi: 10.1016/j.diabres.2010.04.019.
    1. Sacks F.M., Lichtenstein A.H., Wu J.H.Y., Appel L.J., Creager M.A., Kris-Etherton P.M., Miller M., Rimm E.B., Rudel L.L., Robinson J.G., et al. Dietary Fats and Cardiovascular Disease: A Presidential Advisory from the American Heart Association. Circulation. 2017;136:e1–e23. doi: 10.1161/CIR.0000000000000510.
    1. Mihaylova B., Emberson J., Blackwell L., Keech A., Simes J., Barnes E.H., Voysey M., Gray A., Collins R. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: Meta-analysis of individual data from 27 randomised trials. Lancet Lond. Engl. 2012;380:581–590.
    1. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: The Scandinavian Simvastatin Survival Study (4S) Lancet Lond. Engl. 1994;344:1383–1389.
    1. Tuttolomondo A., Casuccio A., Buttà C., Pecoraro R., Di Raimondo D., Della Corte V., Arnao V., Clemente G., Maida C., Simonetta I., et al. Mediterranean Diet in patients with acute ischemic stroke: Relationships between Mediterranean Diet score, diagnostic subtype, and stroke severity index. Atherosclerosis. 2015;243:260–267. doi: 10.1016/j.atherosclerosis.2015.09.017.
    1. Tosti V., Bertozzi B., Fontana L. Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms. J. Gerontol. A Biol. Sci. Med. Sci. 2018;73:318–326. doi: 10.1093/gerona/glx227.
    1. Tuttolomondo A., Maida C., Pinto A. Diabetic foot syndrome as a possible cardiovascular marker in diabetic patients. J. Diabetes Res. 2015;2015:268390. doi: 10.1155/2015/268390.
    1. Siragusa S., Malato A., Saccullo G., Iorio A., Di Ianni M., Caracciolo C., Coco L.L., Raso S., Santoro M., Guarneri F.P., et al. Residual vein thrombosis for assessing duration of anticoagulation after unprovoked deep vein thrombosis of the lower limbs: The extended DACUS study. Am. J. Hematol. 2011;86:914–917. doi: 10.1002/ajh.22156.
    1. Conte G., Rigon N., Perrone A., Lauro S. Acute cardiovascular diseases and respiratory sleep disorders. Minerva Cardioangiol. 1999;47:195–202.

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