Grasas y Aceites, Vol 67, No 4 (2016)

Cardiovascular risk protection from the Mediterranean diet and olive oil. A transcriptomic update in humans

S. Carrión
Cardiovascular Risk and Nutrition Research Group (CARIN), Hospital del Mar Medical Research Institute (IMIM) - Universitat Pompeu Fabra, Spain

L. Torres
Cardiovascular Risk and Nutrition Research Group (CARIN), Hospital del Mar Medical Research Institute (IMIM) - PhD Program in Food Sciences and Nutrition in Nutrition and Bromatology Department, Faculty of Pharmacy, University of Barcelona, Spain

O. Castañer
Cardiovascular Risk and Nutrition Research Group (CARIN), Hospital del Mar Medical Research Institute (IMIM) - CIBER of the physiopathology of obesity and nutrition (CIBEROBN), Spain


This review highlights the human studies that explore the benefits of the Mediterranean diet and olive oil, based on gene expression analysis. We summarized consistent human transcriptomic studies on cardiovascular risk, based on TMD and olive oil interventions, with real life doses and conditions. A literature review was carried out leading up to February 2016. The results show that the TMD, specially supplemented with virgin olive oil, produces beneficial changes in the transcriptomic response of relevant genes in cardiovascular risk such as CAT, GPX1 and SIRT2. p65 and MCP-1, IL1B, IL6, CXCL1, INF-γ, ARHGAP15 and IL7R, which are involved in inflammation; and ABCA1, SR-B1, PPARBP, PPARα, PPARγ, PPARδ, CD-36 and COX-1, which play an important role in cholesterol efflux. The available data illustrate a transcriptomic effect on atherosclerosis, inflammation and oxidative stress pathways as well as the mentioned genes.


Cardiovascular; Mediterranean Diet; MUFA; Nutrigenomics; Olive oil; Polyphenols; Transcriptomics

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Bach-Faig A, Berry EM, Lairon D, Reguant J, Trichopoulou A, Dernini S. 2011. Mediterranean diet pyramid today. Science and cultural updates. Public Health Nutr. 14, 2274– 2284. PMid:22166184

Bellido C, López-Miranda J, Blanco-Colio LM, Pérez-Martínez P, Muriana FJ, Martín-Ventura JL. 2004. Butter and walnuts, but not olive oil, elicit postprandial activation of nuclear transcription factor kappaB in peripheral blood mononuclear cells from healthy men. Am. J. Clin. Nutr. 80,1487–1491. PMid:15585759

Berliner JA, Navab M, Fogelman AM, Frank JS, Demer LL, Edwards PA. 1995. Atherosclerosis: basic mechanisms. Oxidation, inflammation, and genetics. Circulation 91, 2488–2496. PMid:7729036

Bos MB, de Vries JHM, Feskens EJM, van Dijk SJ, Hoelen DWM, Siebelink E. 2010. Effect of a high monounsaturated fatty acids diet and a Mediterranean diet on serum lipids and insulin sensitivity in adults with mild abdominal obesity. Nutr. Metab. Cardiovasc. Dis. 20, 591–598. PMid:19692213

Bustin SA. 2000. Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assays. J. Mol. Endocrinol. 25, 169–193. PMid:11013345

Camargo A, Delgado-Lista J, Garcia-Rios A, Cruz-Teno C, Yubero-Serrano EM, Perez-Martinez P. 2012. Expression of proinflammatory, proatherogenic genes is reduced by the Mediterranean diet in elderly people. Br. J. Nutr. 108, 500–508. PMid:22085595

Camargo A, Rangel-Zu-iga OA, Haro C, Meza-Miranda ER, Pe-a-Orihuela P, Meneses ME. 2014. Olive oil phenolic compounds decrease the postprandial inflammatory response by reducing postprandial plasma lipopolysaccharide levels. Food Chem. 162, 161–171. PMid:24874372

Camargo A, Ruano J, Fernandez JM, Parnell LD, Jimenez A, Santos-Gonzalez M. 2010. Gene expression changes in mononuclear cells in patients with metabolic syndrome after acute intake of phenol-rich virgin olive oil. BMC Genomics 11, 253. PMid:20406432 PMCid:PMC2874810

Casas-Agustench P, López-Uriarte P, Ros E, Bulló M, Salas- Salvadó J. 2011. Nuts, hypertension and endothelial function. Nutr. Metab. Cardiovasc. Dis. 21, S21-S33. PMid:21546229

Casta-er O, Corella D, Covas M-I, Sorlí JV, Subirana I, Flores- Mateo G. 2013. In vivo transcriptomic profile after a Mediterranean diet in high-cardiovascular risk patients: a randomized controlled trial. Am. J. Clin. Nutr. 98, 845–53. PMid:23902780

Casta-er O, Covas M-I, Khymenets O, Nyyssonen K, Konstantinidou V, Zunft H-F. 2012. Protection of LDL from oxidation by olive oil polyphenols is associated with a downregulation of CD40-ligand expression and its downstream products in vivo in humans. Am. J. Clin. Nutr. 95, 1238–1244. PMid:22440854

Covas M-I, Nyyssönen K, Poulsen HE, Kaikkonen J, Zunft H-JF, Kiesewetter H. 2006. The effect of polyphenols in olive oil on heart disease risk factors: a randomized trial. Ann. Intern. Med. 145, 333–341. PMid:16954359

Di Renzo L, Carraro A, Valente R, Iacopino L, Colica C, De Lorenzo A. 2014. Intake of red wine in different meals modulates oxidized LDL level, oxidative and inflammatory gene expression in healthy people: a randomized crossover trial. Oxid. Med. Cell Longev. 2014:681318. PMid:24876915 PMCid:PMC4021682

EFSA Journal. 2011. 9, 2033–2058. doi:10.2903/j.efsa.2011.2033. Available online:

Egert S, Kannenberg F, Somoza V, Erbersdobler HF, Wahrburg U. 2009. Dietary alpha-linolenic acid, EPA, and DHA have differential effects on LDL fatty acid composition but similar effects on serum lipid profiles in normolipidemic humans. J. Nutr. 139, 861–868. PMid:19261730

Estruch R, Ros E, Salas-Salvadó J, Covas M, Corella D, Arós F, Gómez-Gracia E, Ruiz-Gutiérrez V, Fiol Sala M, Lapetra J, Lamuela Raventós RM, Serra Majem L, Pintó Sala X, Basora-Gallisá J, Mu-oz MÁ, Sorlí JV, Martínez JA, Martínez-González MÁ. 2013. Primary prevention of cardiovascular disease with Mediterranean diet. N. Engl. J. Med. 365, 1279–1290. PMid:23432189

Farràs M, Valls RM, Fernández-Castillejo S, Giralt M, Solà R, Subirana I, Motilva MJ, Konstantinidou V, Covas MI, Fitó M. 2013. Olive oil polyphenols enhance the expression of cholesterol efflux related genes in vivo in humans. A randomized controlled trial. J. Nutr. Biochem. 24, 1334– 1339. PMid:23333095

Fitó M, Konstantinidou V. 2016. Nutritional Genomics and the Mediterranean Diet's Effects on Human Cardiovascular Health. Nutrients 8, 218. PMid:27089360 PMCid:PMC4848687

Gardner CD, Kraemer HC. 1995. Monounsaturated versus polyunsaturated dietary fat and serum lipids. A meta-analysis. Arterioscler. Thromb. Vasc. Biol. 15, 1917–1927. PMid:7583572

Gómez M, Valle V, Arós F, Sanz G, Sala J, Fiol M. 2009. Oxidized LDL, lipoprotein (a) and other emergent risk factors in acute myocardial infarction (FORTIAM study). Rev. Esp. Cardiol. 62, 373–382.

Granados-Principal S, Quiles JL, Ramirez-Tortosa CL, Sanchez-Rovira P, Ramirez-Tortosa MC. 2010. Hydroxytyrosol: from laboratory investigations to future clinical trials. Nutr. Rev. 68, 191–206. PMid:20416016

Hernáez A, Farràs M, Fitó M. 2016. Olive oil phenolic compounds and high-density lipoprotein function. Curr. Opin. Lipidol. 27, 47–53. PMid:26655289

Hernáez Á, Remaley AT, Farràs M, Fernández-Castillejo S, Subirana I, Schröder H, Fernández-Mampel M, Mu-oz- Aguayo D, Sampson M, Solà R, Farré M, de la Torre R, López-Sabater MC, Nyyssönen K, Zunft H-JF, Covas MI, Fitó M. 2015. Olive Oil Polyphenols Decrease LDL Concentrations and LDL Atherogenicity in Men in a Randomized Controlled Trial. J. Nutr. 145, 1692–7. PMid:26136585 PMCid:PMC4516770

Horgan RP, Kenny LC. 2011. "Omic" technologies: genomics, transcriptomics, proteomics and metabolomics. Obstet. Gynaecol. 13, 189–195.

Intangible Heritage Home - intangible heritage - Culture Sector - UNESCO [Internet]. [cited 2016 Apr 7]. Available from:

Jiménez-Gómez Y, López-Miranda J, Blanco-Colio LM, Marín C, Pérez-Martínez P, Ruano J, Paniagua JA, Rodríguez F, Egido J, Pérez-Jiménez F. 2009. Olive oil and walnut breakfasts reduce the postprandial inflammatory response in mononuclear cells compared with a butter breakfast in healthy men. Atherosclerosis 204, e70–e76. PMid:18952211

Jousilahti P, Tuomilehto J, Vartiainen E, Korhonen HJ, Pitkaniemi J, Nissinen A, 1995. Importance of Risk Factor Clustering in Coronary Heart Disease Mortality and Incidence in Eastern Finland. Eur. J. Cardiovasc. Prev. Rehabil. 2, 63–70.

Konstantinidou V, Covas MI, Mu-oz-Aguayo D, Khymenets O, de la Torre R, Saez G, Tormos MC, Toledo E, Marti A, Ruiz-Gutiérrez V, Ruiz Mendez MV, Fito M. 2010. In vivo nutrigenomic effects of virgin olive oil polyphenols within the frame of the Mediterranean diet: a randomized controlled trial. FASEB J. 24, 2546–2557. PMid:20179144

Konstantinidou V, Covas MI, Sola R, Fito M. 2013. Up-to date knowledge on the in vivo transcriptomic effect of the Mediterranean diet in humans. Mol. Nutr. Food Res. 57, 772–783. PMid:23417868

Kratz M, Gülbahçe E, von Eckardstein A, Cullen P, Cignarella A, Assmann G, Wahrburg U. 2002. Dietary mono- and polyunsaturated fatty acids similarly affect LDL size in healthy men and women. J. Nutr. 132, 715–718. PMid:11925466

Kruse M, von Loeffelholz C, Hoffmann D, Pohlmann A, Seltmann A-C, Osterhoff M, Hornemann S, Pivovarova O, Rohn S, Jahreis G, Pfeiffer AFH. 2015. Dietary rapeseed/ canola-oil supplementation reduces serum lipids and liver enzymes and alters postprandial inflammatory responses in adipose tissue compared to olive-oil supplementation in obese men. Mol. Nutr. Food Res. 59, 507–519. PMid:25403327

Llorente-Cortés V, Estruch R, Mena MP, Ros E, González MAM, Fitó M, Lamuela-Raventós RM, Badimon L. 2010, Effect of Mediterranean diet on the expression of pro-atherogenic genes in a population at high cardiovascular risk. Atherosclerosis 208, 442–450. PMid:19712933

Lorgeril M, Salen P, Martin JL, Monjaud I, Delaye J, Mamelle N. 1999. Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. Circulation 99, 779–85. PMid:9989963

Martín-Peláez S, Casta-er O, Konstantinidou V, Subirana I, Mu-oz-Aguayo D, Blanchart G, Gaixas S, de la Torre R, Farré M, Sáez GT, Nyyssönen Kr, Joachim Zunft H, Covas MI, Fitó M. 2015. Effect of olive oil phenolic compounds on the expression of blood pressure-related genes in healthy individuals. Eur. J. Nutr. 1–8.

Masson CJ, Mensink RP. 2011. Exchanging saturated fatty acids for (n-6) polyunsaturated fatty acids in a mixed meal may decrease postprandial lipemia and markers of inflammation and endothelial activity in overweight men. J. Nutr. 141, 816–821. PMid:21430255

Meisinger C, Baumert J, Khuseyinova N, Loewel H, Koenig W. 2005. 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 112, 651–657. PMid:16043640

Meza-Miranda ER, Camargo A, Rangel-Zu-iga OA, Delgado-Lista J, Garcia-Rios A, Perez-Martinez P. 2014. Postprandial oxidative stress is modulated by dietary fat in adipose tissue from elderly people. Age (Dordr) 36, 507– 517. PMid:23963800 PMCid:PMC4039280

Owen RW, Mier W, Giacosa A, Hull WE, Spiegelhalder B, Bartsch H. 2000. Phenolic compounds and squalene in olive oils: the concentration and antioxidant potential of total phenols, simple phenols, secoiridoids, lignansand squalene. Food Chem. Toxicol. 38, 647–59.

Perez-Herrera A, Rangel-Zu-iga OA, Delgado-Lista J, Marin C, Perez-Martinez P, Tasset I, 2013. The antioxidants in oils heated at frying temperature, whether natural or added, could protect against postprandial oxidative stress in obese people. Food Chem. 138, 2250–2259. PMid:23497883

Pietraszek A, Gregersen S, Pedersen SB, Holst JJ, Hermansen K. 2014. Acute effects of monounsaturated fat on postprandial lipemia and gene expression in first-degree relatives of subjects with type 2 diabetes. Eur. J. Clin. Nutr. 68, 1022–1028. PMid:24824014

Schröder H, Elosua R, Vila J, Marti H, Covas MI, Marrugat J. 2007. Secular trends of obesity and cardiovascular risk factors in a Mediterranean population. Obesity (Silver Spring) 15, 557–562. PMid:17372304

Smith BW, Adams LA. Non-alcoholic fatty liver disease. 2011. Crit. Rev. Clin. Lab. Sci. 48, 97–113. PMid:21875310

Storniolo CE, Casillas R, Bulló M, Casta-er O, Ros E, Sáez GT, Toledo E, Estruch R, Ruiz-Gutiérrez V, Fitó M, Martínez-González MA, Salas-Salvadó J, Mitjavila MT, Moreno JJ. 2015. 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. 1–9.

Strazzullo P, Ferro-Luzzi A, Siani A, Scaccini C, Sette S, Catasta G.1986. Changing the Mediterranean diet: effects on blood pressure. J. Hypertens 4, 407–412. PMid:3534087

Tripoli E, Giammanco M, Tabacchi G, Di Majo D, Giammanco S, La Guardia M. 2005. The phenolic compounds of olive oil: structure, biological activity and beneficial effects on human health. Nutr. Res. Rev. 18, 98–112. PMid:19079898

Tsimikas S, Brilakis ES, Miller ER, McConnell JP, Lennon RJ, Kornman KS. 2005. Oxidized phospholipids, Lp(a) lipoprotein, and coronary artery disease. N. Engl. J. Med. 353, 46–57. PMid:16000355

US Food and Drug Administration. Press Release P04-100. 11/2004. NEW01129.htlm.

Visioli F, Galli C, Plasmati E, Viappiani S, Hernandez A, Colombo C. 2000. Olive phenol hydroxytyrosol prevents passive smoking-induced oxidative stress. Circulation 102, 2169–2171. PMid:11056087

Willett WC, Sacks F, Trichopoulou A, Drescher G, Ferro- Luzzi A, Helsing E. 1995. Mediterranean diet pyramid: a cultural model for healthy eating. Am. J. Clin. Nutr. 616, 1402S–1406S. noncommunicable-diseases/cardiovascular-diseases2/ definition-of-cardiovascular-diseases

Zern T, Fernandez M. 2005. Cardioprotective effects of dietary polyphenols. J. Nutr. 135, 2291–4. PMid:16177184

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