Increasingly, studies showing the protective effects of the Mediterranean diet (MedDiet) on different diseases (cardiovascular, diabetes, some cancers, and even total mortality and aging indicators) are being published. The scientific evidence level for each outcome is variable, and 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. 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. 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 critical review of the limitations of the studies undertaken and propose new analyses and greater bioinformatic integration to better understand the most important molecular mechanisms whereby the MedDiet as a whole, or its main food components, may exercise their protective effects.


Article metrics loading...

Loading full text...

Full text loading...


Literature Cited

  1. Aparicio-Soto M, Sánchez-Hidalgo M, Rosillo, Castejón ML, Alarcón-de-la-Lastra C. 2016. Extra virgin olive oil: a key functional food for prevention of immune-inflammatory diseases. Food Funct 7:114492–505 [Google Scholar]
  2. Arneson D, Bhattacharya A, Shu L, Mäkinen VP, Yang X. 2016. Mergeomics: a web server for identifying pathological pathways, networks, and key regulators via multidimensional data integration. BMC Genom 17:1722 [Google Scholar]
  3. Arneson D, Shu L, Tsai B, Barrere-Cain R, Sun C, Yang X. 2017. Multidimensional integrative genomics approaches to dissecting cardiovascular disease. Front. Cardiovasc. Med. 4:8 [Google Scholar]
  4. Arpón A, Riezu-Boj JI, Milagro FI, Razquin C, Martínez-González MA. et al. 2016. Adherence to Mediterranean diet is associated with methylation changes in inflammation-related genes in peripheral blood cells. J. Physiol. Biochem. 73:3445–55 [Google Scholar]
  5. Assmann KE, Adjibade M, Andreeva VA, Hercberg S, Galan P, Kesse-Guyot E. 2017. Association between adherence to the Mediterranean diet at midlife and healthy aging in a cohort of French adults. J. Gerontol. A In press [Google Scholar]
  6. Bach-Faig A, Berry EM, Lairon D, Reguant J, Trichopoulou A. et al. 2011. Mediterranean diet pyramid today. Science and cultural updates. Public Health Nutr 14:12A2274–84 [Google Scholar]
  7. Badimon L, Vilahur G, Padro T. 2017. Systems biology approaches to understand the effects of nutrition and promote health. Br. J. Clin. Pharmacol. 83:138–45 [Google Scholar]
  8. Barrès R, Zierath JR. 2016. The role of diet and exercise in the transgenerational epigenetic landscape of T2DM. Nat. Rev. Endocrinol. 12:8441–51 [Google Scholar]
  9. Bayoumi AS, Sayed A, Broskova Z, Teoh JP, Wilson J. et al. 2016. Crosstalk between long noncoding RNAs and microRNAs in health and disease. Int. J. Mol. Sci. 17:3356 [Google Scholar]
  10. Bloomfield HE, Koeller E, Greer N, MacDonald R, Kane R, Wilt TJ. 2016. Effects on health outcomes of a Mediterranean diet with no restriction on fat intake: a systematic review and meta-analysis. Ann. Intern. Med. 165:7491–500 [Google Scholar]
  11. Boccardi V, Esposito A, Rizzo MR, Marfella R, Barbieri M, Paolisso G. 2013. Mediterranean diet, telomere maintenance and health status among elderly. PLOS ONE 8:4e62781 [Google Scholar]
  12. Bonaccio M, Di Castelnuovo A, Bonanni A, Costanzo S, De Lucia F. et al. 2013. Adherence to a Mediterranean diet is associated with a better health-related quality of life: a possible role of high dietary antioxidant content. BMJ Open 3:8e003003 [Google Scholar]
  13. Bravo-San Pedro JM, Kroemer G, Galluzzi L. 2017. Autophagy and mitophagy in cardiovascular disease. Circ. Res. 120:111812–24 [Google Scholar]
  14. Brown SA. 2016. Circadian metabolism: from mechanisms to metabolomics and medicine. Trends Endocrinol. Metab. 27:6415–26 [Google Scholar]
  15. Bu H, Wedel S, Cavinato M, Jansen-Dürr P. 2017. MicroRNA regulation of oxidative stress-induced cellular senescence. Oxid. Med. Cell. Longev. 2017:2398696 [Google Scholar]
  16. Buckland G, Agudo A, Luján L, Jakszyn P, Bueno-de-Mesquita HB. et al. 2010. Adherence to a Mediterranean diet and risk of gastric adenocarcinoma within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study. Am. J. Clin. Nutr. 91:381–90 [Google Scholar]
  17. Camargo A, Delgado-Lista J, Garcia-Rios A, Cruz-Teno C, Yubero-Serrano EM. et al. 2012. Expression of proinflammatory, proatherogenic genes is reduced by the Mediterranean diet in elderly people. Br. J. Nutr. 108:3500–8 [Google Scholar]
  18. Casas R, Urpi-Sardà M, Sacanella E, Arranz S, Corella D. et al. 2017. Anti-inflammatory effects of the Mediterranean diet in the early and late stages of atheroma plaque development. Mediat. Inflamm. 2017:3674390 [Google Scholar]
  19. Castañer O, Corella D, Covas MI, Sorlí JV, Subirana I. et al. 2013. In vivo transcriptomic profile after a Mediterranean diet in high-cardiovascular risk patients: a randomized controlled trial. Am. J. Clin. Nutr. 98:3845–53 [Google Scholar]
  20. Ceriello A, Testa R, Genovese S. 2016. Clinical implications of oxidative stress and potential role of natural antioxidants in diabetic vascular complications. Nutr. Metab. Cardiovasc. Dis. 26:4285–92 [Google Scholar]
  21. Charles RL, Rudyk O, Prysyazhna O, Kamynina A, Yang J. et al. 2014. Protection from hypertension in mice by the Mediterranean diet is mediated by nitro fatty acid inhibition of soluble epoxide hydrolase. PNAS 111:228167–72 [Google Scholar]
  22. Chatzianagnostou K, Del Turco S, Pingitore A, Sabatino L, Vassalle C. 2015. The Mediterranean lifestyle as a non-pharmacological and natural antioxidant for healthy aging. Antioxidants 4:4719–36 [Google Scholar]
  23. Collado-González J, Grosso C, Valentão P, Andrade PB, Ferreres F. et al. 2017. Inhibition of α-glucosidase and α-amylase by Spanish extra virgin olive oils: the involvement of bioactive compounds other than oleuropein and hydroxytyrosol. Food Chem 235:298–307 [Google Scholar]
  24. Cora D, Re A, Caselle M, Bussolino F. 2017. MicroRNA-mediated regulatory circuits: outlook and perspectives. Phys. Biol. 14:4045001 [Google Scholar]
  25. Corella D, Asensio EM, Coltell O, Sorlí JV, Estruch R. et al. 2016. CLOCK gene variation is associated with incidence of type-2 diabetes and cardiovascular diseases in type-2 diabetic subjects: dietary modulation in the PREDIMED randomized trial. Cardiovasc. Diabetol. 15:4 [Google Scholar]
  26. Corella D, Carrasco P, Sorlí JV, Estruch R, Rico-Sanz J. et al. 2013. Mediterranean diet reduces the adverse effect of the TCF7L2-rs7903146 polymorphism on cardiovascular risk factors and stroke incidence: a randomized controlled trial in a high-cardiovascular-risk population. Diabetes Care 36:113803–11 [Google Scholar]
  27. Corella D, Coltell O, Mattingley G, Sorlí JV, Ordovás JM. 2017. Utilizing nutritional genomics to tailor diets for the prevention of cardiovascular disease: a guide for upcoming studies and implementations. Expert Rev. Mol. Diagn. 17:5495–513 [Google Scholar]
  28. Corella D, Ordovás JM. 2014. 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 36:5526–37 [Google Scholar]
  29. Corella D, Ordovás JM. 2005. Single nucleotide polymorphisms that influence lipid metabolism: interaction with dietary factors. Annu. Rev. Nutr. 25:341–90 [Google Scholar]
  30. Corella D, Ordovás JM. 2009. Nutrigenomics in cardiovascular medicine. Circ. Cardiovasc. Genet. 2:6637–51 [Google Scholar]
  31. Corella D, Sorlí JV, Estruch R, Coltell O, Ortega-Azorín C. et al. 2014. MicroRNA-410 regulated lipoprotein lipase variant rs13702 is associated with stroke incidence and modulated by diet in the randomized controlled PREDIMED trial. Am. J. Clin. Nutr. 100:2719–31 [Google Scholar]
  32. Coughlin SS. 2014. Toward a road map for global -omics: a primer on -omic technologies. Am. J. Epidemiol. 180:121188–95 [Google Scholar]
  33. Covas MI, de la Torre R, Fitó M. 2015. Virgin olive oil: a key food for cardiovascular risk protection. Br. J. Nutr. 113:Suppl. 2S19–28 [Google Scholar]
  34. Cuervo AM. 2008. Calorie restriction and aging: the ultimate “cleansing diet.”. J. Gerontol. A 63:6547–49 [Google Scholar]
  35. D'Alessandro A, De Pergola G, Silvestris F. 2016. Mediterranean diet and cancer risk: an open issue. Int. J. Food Sci. Nutr. 67:6593–605 [Google Scholar]
  36. D'Alessandro A, De Pergola G. 2015. Mediterranean diet and cardiovascular disease: a critical evaluation of a priori dietary indexes. Nutrients 7:97863–88 [Google Scholar]
  37. Davis C, Hodgson J, Bryan J, Garg M, Woodman R, Murphy K. 2017. Older Australians can achieve high adherence to the Mediterranean Diet during a 6 month randomised intervention; results from the Medley Study. Nutrients 9:6pii:E534 [Google Scholar]
  38. De Angelis M, Garruti G, Minervini F, Bonfrate L, Portincasa P, Gobbetti M. 2017. The food-gut human axis: the effects of diet on gut microbiota and metabolome. Curr. Med. Chem In press [Google Scholar]
  39. De Filippis F, Pellegrini N, Vannini L, Jeffery IB, La Storia A. et al. 2016. High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome. Gut 65:111812–21 [Google Scholar]
  40. De la Torre R, Corella D, Castañer O, Martínez-González MA, Salas-Salvador J. et al. 2017. Protective effect of homovanillyl alcohol on cardiovascular disease and total mortality: virgin olive oil, wine, and catechol-methylathion. Am. J. Clin. Nutr. 105:61297–304 [Google Scholar]
  41. Delgado-Lista J, Perez-Martinez P, Garcia-Rios A, Alcala-Diaz JF, Perez-Caballero AI. et al. 2016. CORonary diet intervention with olive oil and cardiovascular PREVention study (the CORDIOPREV study): rationale, methods, and baseline characteristics: a clinical trial comparing the efficacy of a Mediterranean diet rich in olive oil versus a low-fat diet on cardiovascular disease in coronary patients. Am. Heart J. 177:42–50 [Google Scholar]
  42. De Meyer GR, Grootaert MO, Michiels CF, Kurdi A, Schrijvers DM, Martinet W. 2015. Autophagy in vascular disease. Circ. Res. 116:3468–79 [Google Scholar]
  43. Deretic V, Saitoh T, Akira S. 2013. Autophagy in infection, inflammation and immunity. Nat. Rev. Immunol. 13:10722–37 [Google Scholar]
  44. Dernini S, Berry EM. 2015. Mediterranean diet: from a healthy diet to a sustainable dietary pattern. Front. Nutr. 2:15 [Google Scholar]
  45. Dernini S, Berry EM, Serra-Majem L, La Vecchia C, Capone R. et al. 2017. Med Diet 4.0: the Mediterranean diet with four sustainable benefits. Public Health Nutr 20:71322–30 [Google Scholar]
  46. Desgagné V, Guay SP, Guérin R, Corbin F, Couture P. et al. 2016. Variations in HDL-carried miR-223 and miR-135a concentrations after consumption of dietary trans fat are associated with changes in blood lipid and inflammatory markers in healthy men: an exploratory study. Epigenetics 11:6438–48 [Google Scholar]
  47. Desgagné V, Guérin R, Guay SP, Corbin F, Couture P. et al. 2017. Changes in high-density lipoprotein-carried miRNA contribution to the plasmatic pool after consumption of dietary trans fat in healthy men. Epigenomics 9:5669–88 [Google Scholar]
  48. Di Francesco A, Falconi A, Di Germanio C, Micioni Di Bonaventura MV. et al. 2015. Extravirgin olive oil up-regulates CB1 tumor suppressor gene in human colon cancer cells and in rat colon via epigenetic mechanisms. J. Nutr. Biochem. 26:3250–58 [Google Scholar]
  49. Ding Y, Sun X, Shan PF. 2017. MicroRNAs and cardiovascular disease in diabetes mellitus. Biomed. Res. Int. 2017:4080364 [Google Scholar]
  50. Dinu M, Pagliai G, Casini A, Sofi F. 2018. Mediterranean diet and multiple health outcomes: an umbrella review of meta-analyses of observational studies and randomised trials. Eur. J. Clin. Nutr. 72:30–43 [Google Scholar]
  51. Eming SA, Wynn TA, Martin P. 2017. Inflammation and metabolism in tissue repair and regeneration. Science 356:63421026–30 [Google Scholar]
  52. Espín JC, González-Sarrías A, Tomás-Barberán FA. 2017. The gut microbiota: a key factor in the therapeutic effects of (poly)phenols. Biochem. Pharmacol. 139:82–93 [Google Scholar]
  53. Estruch R, Martínez-González MA, Corella D, Salas-Salvadó J, Ruiz-Gutiérrez V. et al. 2006. Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial. Ann. Intern. Med. 145:11–11 [Google Scholar]
  54. Estruch R, Salas-Salvadó J. 2013. Towards an even healthier Mediterranean diet. Nutr. Metab. Cardiovasc. Dis. 23:121163–66 [Google Scholar]
  55. Fasanelli F, Zugna D, Giraudo MT, Krogh V, Grioni S. et al. 2017. Abdominal adiposity is not a mediator of the protective effect of Mediterranean diet on colorectal cancer. Int. J. Cancer 140:102265–71 [Google Scholar]
  56. Fitó M, Melander O, Martínez JA, Toledo E, Carpéné C. et al. 2016. Advances in integrating traditional and omic biomarkers when analyzing the effects of the Mediterranean diet intervention in cardiovascular prevention. Int. J. Mol. Sci. 17:9pii:E1469 [Google Scholar]
  57. Fredman G, Tabas I. 2017. Boosting inflammation resolution in atherosclerosis: the next frontier for therapy. Am. J. Pathol. 187:61211–21 [Google Scholar]
  58. Fung TT, Hu FB, McCullough ML, Newby PK, Willett WC, Holmes MD. 2006. Diet quality is associated with the risk of estrogen receptor–negative breast cancer in postmenopausal women. J. Nutr. 136:466–72 [Google Scholar]
  59. García-Calzón S, Martínez-González MA, Razquin C, Corella D, Salas-Salvadó J. et al. 2015. Pro12Ala polymorphism of the PPARγ2 gene interacts with a Mediterranean diet to prevent telomere shortening in the PREDIMED-NAVARRA randomized trial. Circ. Cardiovasc. Genet. 8:191–99 [Google Scholar]
  60. Gardener H, Wright CB, Gu Y, Demmer RT, Boden-Albala B. et al. 2011. Mediterranean-style diet and risk of ischemic stroke, myocardial infarction, and vascular death: the Northern Manhattan Study. Am. J. Clin. Nutr. 94:61458–64 [Google Scholar]
  61. Golan-Gerstl R, Shiff YE, Lavi-Moshayoff V, Leshkowitz DSD, Reif S. 2017. Characterization and biological function of milk-derived miRNAs. Mol. Nutr. Food Res. 61:10 In press [Google Scholar]
  62. Grosso G, Marventano S, Yang J, Micek A, Pajak A. et al. 2017. A comprehensive meta-analysis on evidence of Mediterranean diet and cardiovascular disease: Are individual components equal?. Crit. Rev. Food Sci. Nutr. 57:153218–32 [Google Scholar]
  63. Haussmann MF, Mauck RA. 2008. Telomeres and longevity: testing an evolutionary hypothesis. Mol. Biol. Evol. 25:1220–28 [Google Scholar]
  64. Hebestreit K, Yahiaoui-Doktor M, Engel C, Vetter W, Siniatchkin M. et al. 2017. Validation of the German version of the Mediterranean Diet Adherence Screener (MEDAS) questionnaire. BMC Cancer 17:1341 [Google Scholar]
  65. Hernáez Á, Castañer O, Elosua R, Pintó X, Estruch R. et al. 2017. Mediterranean diet improves high-density lipoprotein function in high-cardiovascular-risk individuals: a randomized controlled trial. Circulation 135:7633–43 [Google Scholar]
  66. Herrera-Marcos LV, Lou-Bonafonte JM, Arnal C, Navarro MA, Osada J. 2017. Transcriptomics and the Mediterranean diet: a systematic review. Nutrients 9:5pii:E472 [Google Scholar]
  67. Hoevenaar-Blom MP, Nooyens AC, Kromhout D, Spijkerman AM, Beulens JW. et al. 2012. Mediterranean style diet and 12-year incidence of cardiovascular diseases: the EPIC-NL cohort study. PLOS ONE 7:9e45458 [Google Scholar]
  68. Hoffman R, Gerber M. 2013. Evaluating and adapting the Mediterranean diet for non-Mediterranean populations: a critical appraisal. Nutr. Rev. 71:9573–84 [Google Scholar]
  69. Hoffman R, Gerber M. 2015. Food processing and the Mediterranean diet. Nutrients 7:97925–64 [Google Scholar]
  70. Huang B, Zhang R. 2014. Regulatory non-coding RNAs: revolutionizing the RNA world. Mol. Biol. Rep. 41:63915–23 [Google Scholar]
  71. Huang W. 2017. MicroRNAs: biomarkers, diagnostics, and therapeutics. Methods Mol. Biol. 1617:57–67 [Google Scholar]
  72. Isac S, Panaitescu AM, Spataru A, Iesanu M, Totan A. et al. 2017. Trans-resveratrol enriched maternal diet protects the immature hippocampus from perinatal asphyxia in rats. Neurosci. Lett. 653:308–13 [Google Scholar]
  73. Islam MA, Alam F, Solayman M, Khalil MI, Kamal MA, Gan SH. 2016. Dietary phytochemicals: natural swords combating inflammation and oxidation-mediated degenerative diseases. Oxid. Med. Cell. Longev. 2016:5137431 [Google Scholar]
  74. Javed M, Solanki M, Sinha A, Shukla LI. 2017. Position based nucleotide analysis of miR168 family in higher plants and its targets in mammalian transcripts. MicroRNA 6:136–42 [Google Scholar]
  75. Jiang M, Sang X, Hong Z. 2012. Beyond nutrients: food-derived microRNAs provide cross-kingdom regulation. BioEssays 34:4280–84 [Google Scholar]
  76. Kalaiselvan I, Samuthirapandi M, Govindaraju A, Sheeja Malar D, Kasi PD. 2016. Olive oil and its phenolic compounds (hydroxytyrosol and tyrosol) ameliorated TCDD-induced heptotoxicity in rats via inhibition of oxidative stress and apoptosis. Pharm. Biol. 54:2338–46 [Google Scholar]
  77. Keating ST, Plutzky J, El-Osta A. 2016. Epigenetic changes in diabetes and cardiovascular risk. Circ. Res. 118:111706–22 [Google Scholar]
  78. Kiefte-de Jong JC, Mathers JC, Franco OH. 2014. Nutrition and healthy ageing: the key ingredients. Proc. Nutr. Soc. 73:2249–59 [Google Scholar]
  79. Knoops KT, de Groot LC, Kromhout D, Perrin AE, Moreiras-Varela O. et al. 2004. Mediterranean diet, lifestyle factors, and 10-year mortality in elderly European men and women: the HALE project. JAMA 292:1433–39 [Google Scholar]
  80. Knutson MD, Leeuwenburgh C. 2008. Resveratrol and novel potent activators of SIRT1: effects on aging and age-related diseases. Nutr. Rev. 66:10591–96 [Google Scholar]
  81. Kochmanski J, Marchlewicz EH, Savidge M, Montrose L, Faulk C, Dolinoy DC. 2017. Longitudinal effects of developmental bisphenol A and variable diet exposures on epigenetic drift in mice. Reprod. Toxicol. 68:154–63 [Google Scholar]
  82. Luo H, Chiang HH, Louw M, Susanto A, Chen D. 2017. Nutrient sensing and the oxidative stress response. Trends Endocrinol. Metab. 28:6449–60 [Google Scholar]
  83. Ma W, Hagan KA, Heianza Y, Sun Q, Rimm EB, Qi L. 2017. Adult height, dietary patterns, and healthy aging. Am. J. Clin. Nutr. 106:589–96 [Google Scholar]
  84. Madrigal-Matute J, Cuervo AM. 2016. Regulation of liver metabolism by autophagy. Gastroenterology 150:2328–39 [Google Scholar]
  85. Malcomson FC, Willis ND, McCallum I, Xie L, Lagerwaard B. et al. 2017. Non-digestible carbohydrates supplementation increases miR-32 expression in the healthy human colorectal epithelium: a randomized controlled trial. Mol Carcinog 56:92104–11 [Google Scholar]
  86. Marín C, Yubero-Serrano EM, López-Miranda J, Pérez-Jiménez F. 2013. Endothelial aging associated with oxidative stress can be modulated by a healthy Mediterranean diet. Int. J. Mol. Sci. 14:58869–89 [Google Scholar]
  87. Marlow G, Ellett S, Ferguson IR, Zhu S, Karunasinghe N. et al. 2013. Transcriptomics to study the effect of a Mediterranean-inspired diet on inflammation in Crohn's disease patients. Hum. Genom. 7:24 [Google Scholar]
  88. Marques-Rocha JL, Milagro FI, Mansego ML, Zulet MA, Bressan J, Martínez JA. 2016. Expression of inflammation-related miRNAs in white blood cells from subjects with metabolic syndrome after 8 wk of following a Mediterranean diet–based weight loss program. Nutrition 32:148–55 [Google Scholar]
  89. Matboli M, Eissa S, Ibrahim D, Hegazy MGA, Imam SS, Habib EK. 2017. Caffeic acid attenuates diabetic kidney disease via modulation of autophagy in a high-fat diet/streptozotocin-induced diabetic rat. Sci. Rep. 7:12263 [Google Scholar]
  90. Mazidi M, Kengne AP, Sahebkar A, Banach M. 2017. Telomere length is associated with cardiometabolic factors in US adults. Angiology 1:3319717712860 [Google Scholar]
  91. Medina-Remón A, Tresserra-Rimbau A, Pons A, Tur JA, Martorell M. et al. 2015. Effects of total dietary polyphenols on plasma nitric oxide and blood pressure in a high cardiovascular risk cohort. The PREDIMED randomized trial. Nutr. Metab. Cardiovasc. Dis. 25:160–67 [Google Scholar]
  92. Menzies FM, Fleming A, Caricasole A, Bento CF, Andrews SP. et al. 2017. Autophagy and neurodegeneration: pathogenic mechanisms and therapeutic opportunities. Neuron 93:51015–34 [Google Scholar]
  93. Micó V, Martín R, Lasunción MA, Ordovás JM, Daimiel L. 2016. Unsuccessful detection of plant microRNAs in beer, extra virgin olive oil and human plasma after an acute ingestion of extra virgin olive oil. Plant Foods Hum. Nutr. 71:1102–8 [Google Scholar]
  94. Mitrou PN, Kipnis V, Thiébaut AC, Reedy J, Subar AF. et al. 2007. Mediterranean dietary pattern and prediction of all-cause mortality in a US population: results from the NIH-AARP Diet and Health Study. Arch. Intern. Med. 167:222461–68 [Google Scholar]
  95. Mizowaki Y, Sugawara S, Yamamoto K, Sakamoto Y, Iwagaki Y. et al. 2017. Japanese diet and the modern Mediterranean diet on lipid metabolism in mice. J Oleo Sci 66:5507–19 [Google Scholar]
  96. Mizushima N, Komatsu M. 2011. Autophagy: renovation of cells and tissues. Cell 147:4728–41 [Google Scholar]
  97. Morselli E, Marino G, Bennetzen MV, Eisenberg T, Megalou E. et al. 2011. Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome. J. Cell Biol. 192:4615–29 [Google Scholar]
  98. Nie L, Shuai L, Zhu M, Liu P, Xie ZF. et al. 2017. The landscape of histone modifications in a high-fat-diet-induced obese (DIO) mouse model. Mol. Cell. Proteom. 16:71324–34 [Google Scholar]
  99. Ortega-Azorín C, Sorlí JV, Estruch R, Asensio EM, Coltell O. et al. 2014. 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. 7:149–58 [Google Scholar]
  100. Osman WA, Labib DA, Abdelhalim MO, Elrokh EM. 2017. Synergistic analgesic, anti-pyretic and anti-inflammatory effects of extra virgin olive oil and ibuprofen in different experimental models in albino mice. Int. J. Rheum. Dis. 20:101326–36 [Google Scholar]
  101. Ostan R, Lanzarini C, Pini E, Scurti M, Vianello D. et al. 2015. Inflammaging and cancer: a challenge for the Mediterranean diet. Nutrients 7:42589–621 [Google Scholar]
  102. Pal S, Tyler JK. 2016. Epigenetics and aging. Sci. Adv. 2:7e1600584 [Google Scholar]
  103. Pan JH, Abernathy B, Kim YJ, Lee JH, Kim JH. et al. 2017. Cruciferous vegetables and colorectal cancer prevention through microRNA regulation: a review. Crit. Rev. Food Sci. Nutr. 10:1–13 [Google Scholar]
  104. Parkinson L, Cicerale S. 2016. The health benefiting mechanisms of virgin olive oil phenolic compounds. Molecules 21:12pii:E1734 [Google Scholar]
  105. Pastori D, Carnevale R, Nocella C, Novo M, Santulli M. et al. 2017. Gut-derived serum lipopolysaccharide is associated with enhanced risk of major adverse cardiovascular events in atrial fibrillation: effect of adherence to Mediterranean diet. J. Am. Heart Assoc. 6:6e005784 [Google Scholar]
  106. Patel CJ. 2017. Analytic complexity and challenges in identifying mixtures of exposures associated with phenotypes in the exposome era. Curr. Epidemiol. Rep. 4:122–30 [Google Scholar]
  107. Paul P, Chakraborty A, Sarkar D, Langthasa M, Rahman M. et al. 2017. Interplay between miRNAs and human diseases. J. Cell. Physiol. 233:32007–18 [Google Scholar]
  108. Pérez-Heras AM, Mayneris-Perxachs J, Cofán M, Serra-Mir M, Castellote AI. et al. 2016. Long-chain n-3 PUFA supplied by the usual diet decrease plasma stearoyl-CoA desaturase index in non-hypertriglyceridemic older adults at high vascular risk. Clin. Nutr. http://doi.org/10.1016/j.clnu.2016.11.009 [Crossref] [Google Scholar]
  109. Petersson SD, Philippou E. 2016. Mediterranean diet, cognitive function, and dementia: a systematic review of the evidence. Adv. Nutr. 7:5889–904 [Google Scholar]
  110. Piroddi M, Albini A, Fabiani R, Giovannelli L, Luceri C. et al. 2017. Nutrigenomics of extra-virgin olive oil: a review. Biofactors 43:117–41 [Google Scholar]
  111. Pirola L, Ferraz JC. 2017. Role of pro- and anti-inflammatory phenomena in the physiopathology of type 2 diabetes and obesity. World J. Biol. Chem. 8:2120–28 [Google Scholar]
  112. Rallidis LS, Kolomvotsou A, Lekakis J, Farajian P, Vamvakou G. et al. 2017. Short-term effects of Mediterranean-type diet intervention on soluble cellular adhesion molecules in subjects with abdominal obesity. Clin. Nutr. ESPEN 17:38–43 [Google Scholar]
  113. Rangel-Zuñiga OA, Haro C, Tormos C, Perez-Martinez P, Delgado-Lista J. et al. 2017. Frying oils with high natural or added antioxidants content, which protect against postprandial oxidative stress, also protect against DNA oxidation damage. Eur. J. Nutr. 56:41597–607 [Google Scholar]
  114. Razani B, Feng C, Coleman T, Emanuel R, Wen H. et al. 2012. Autophagy links inflammasomes to atherosclerotic progression. Cell Metab 15:4534–44 [Google Scholar]
  115. Reboredo-Rodríguez P, Figueiredo-González M, González-Barreiro C, Simal-Gándara J, Salvador MD. et al. 2017. State of the art on functional virgin olive oils enriched with bioactive compounds and their properties. Int. J. Mol. Sci. 18:3668 [Google Scholar]
  116. Rehm J, Gmel GE, Gmel G, Hasan OSM, Imtiaz S. et al. 2017. The relationship between different dimensions of alcohol use and the burden of disease-an update. Addiction 112:6968–1001 [Google Scholar]
  117. Révész D, Milaneschi Y, Verhoeven JE, Penninx BW. 2014. Telomere length as a marker of cellular aging is associated with prevalence and progression of metabolic syndrome. J. Clin. Endocrinol. Metab. 99:124607–15 [Google Scholar]
  118. Rigacci S. 2015. Olive oil phenols as promising multi-targeting agents against Alzheimer's disease. Adv. Exp. Med. Biol 863:1–20 [Google Scholar]
  119. Rodriguez-Rodriguez R, Jiménez-Altayó F, Alsina L, Onetti Y, Rinaldi de Alvarenga JF. et al. 2017. Mediterranean tomato-based sofrito protects against vascular alterations in obese Zucker rats by preserving NO bioavailability. Mol. Nutr. Food Res. http://doi.org/10.1002/mnfr.201601010 [Crossref] [Google Scholar]
  120. Rotini A, Martínez-Sarrà E, Pozzo E, Sampaolesi M. 2017. Interactions between microRNAs and long non-coding RNAs in cardiac development and repair. Pharmacol. Res. http://doi.org/10.1016/j.phrs.2017.05.029 [Crossref] [Google Scholar]
  121. Sacks FM, Katan M. 2002. Randomized clinical trials on the effects of dietary fat and carbohydrate on plasma lipoproteins and cardiovascular disease. Am. J. Med. 113:Suppl. 9B13S–24 [Google Scholar]
  122. Salas-Salvadó J, Bulló M, Estruch R, Ros E, Covas MI. et al. 2014. Prevention of diabetes with Mediterranean diets: a subgroup analysis of a randomized trial. Ann. Intern. Med. 160:11–10 [Google Scholar]
  123. Sanders K, Johnson L, O'Dea K, Sinclair AJ. 1994. The effect of dietary fat level and quality on plasma lipoprotein lipids and plasma fatty acids in normocholesterolemic subjects. Lipids 29:2129–38 [Google Scholar]
  124. Schröder H, Fitó M, Estruch R, Martínez-González MA, Corella D, Salas-Salvadó J. et al. 2011. A short screener is valid for assessing Mediterranean diet adherence among older Spanish men and women. J. Nutr. 141:61140–45 [Google Scholar]
  125. Serra-Majem L, Ribas L, Ngo J, Ortega RM, García A. et al. 2004. Food, youth and the Mediterranean diet in Spain. Development of KIDMED, Mediterranean Diet Quality Index in children and adolescents. Public Health Nutr 7:7931–35 [Google Scholar]
  126. Serra-Majem L, Roman B, Estruch R. 2006. Scientific evidence of interventions using the Mediterranean diet: a systematic review. Nutr. Rev. 64:2 Pt. 2S27–47 [Google Scholar]
  127. Shen J, Wilmot KA, Ghasemzadeh N, Molloy DL, Burkman G. et al. 2015. Mediterranean dietary patterns and cardiovascular health. Annu. Rev. Nutr. 35:425–49 [Google Scholar]
  128. Simopoulos AP. 2001. The Mediterranean diets: What is so special about the diet of Greece? The scientific evidence. J. Nutr. 131:11 Suppl.3065S–73 [Google Scholar]
  129. Smith CE, Coltell O, Sorlí JV, Estruch R, Martínez-González . et al. 2016. Associations of the MCM6-rs3754686 proxy for milk intake in Mediterranean and American populations with cardiovascular biomarkers, disease and mortality: Mendelian randomization. Sci. Rep. 6:33188 [Google Scholar]
  130. Stojanovic J, Giraldi L, Arzani D, Pastorino R, Biondi A. et al. 2017. Adherence to Mediterranean diet and risk of gastric cancer: results of a case-control study in Italy. Eur. J. Cancer Prev. 26:6491–96 [Google Scholar]
  131. Sun YV, Hu YJ. 2016. Integrative analysis of multi-omics data for discovery and functional studies of complex human diseases. Adv. Genet. 93:147–90 [Google Scholar]
  132. Tapia-Vieyra JV, Delgado-Coello B, Mas-Oliva J. 2017. Atherosclerosis and cancer; a resemblance with far-reaching implications. Arch. Med. Res 48:112–26 [Google Scholar]
  133. Tektonidis TG, Åkesson A, Gigante B, Wolk A, Larsson SC. 2015. A Mediterranean diet and risk of myocardial infarction, heart failure and stroke: a population-based cohort study. Atherosclerosis 243:193–98 [Google Scholar]
  134. Tognon G, Lissner L, Sæbye D, Walker KZ, Heitmann BL. 2014. The Mediterranean diet in relation to mortality and CVD: a Danish cohort study. Br. J. Nutr. 111:1151–59 [Google Scholar]
  135. Tognon G, Nilsson LM, Lissner L, Johansson I, Hallmans G. et al. 2012. The Mediterranean diet score and mortality are inversely associated in adults living in the subarctic region. J. Nutr. 142:1547–53 [Google Scholar]
  136. Toma A, Paré G, Leong DP. 2017. Alcohol and cardiovascular disease: How much is too much?. Curr. Atheroscler. Rep. 19:313 [Google Scholar]
  137. Tong TY, Wareham NJ, Khaw KT, Imamura F, Forouhi NG. 2016. Prospective association of the Mediterranean diet with cardiovascular disease incidence and mortality and its population impact in a non-Mediterranean population: the EPIC-Norfolk study. BMC Med 14:1135 [Google Scholar]
  138. Trichopoulou A, Costacou T, Bamia C, Trichopoulos D. 2003. Adherence to a Mediterranean diet and survival in a Greek population. N. Engl. J. Med. 348:262599–608 [Google Scholar]
  139. Trichopoulou A, Kouris-Blazos A, Wahlqvist ML, Gnardellis C, Lagiou P. et al. 1995. Diet and overall survival in elderly people. BMJ 311:70181457–60 [Google Scholar]
  140. Trichopoulou A, Lagiou P. 1997. Healthy traditional Mediterranean diet: an expression of culture, history, and lifestyle. Nutr. Rev. 55:11 Pt. 1383–89 [Google Scholar]
  141. Trichopoulou A, Orfanos P, Norat T, Bueno-de-Mesquita B, Ocké MC. et al. 2005. Modified Mediterranean diet and survival: EPIC-elderly prospective cohort study. BMJ 330:991 [Google Scholar]
  142. Urpi-Sarda M, Casas R, Chiva-Blanch G, Romero-Mamani ES, Valderas-Martínez P. et al. 2012. Virgin olive oil and nuts as key foods of the Mediterranean diet effects on inflammatory biomakers related to atherosclerosis. Pharmacol. Res. 65:6577–83 [Google Scholar]
  143. Vallverdu-Queralt A, Regueiro J, Rinaldi de Alvarenga JF, Torrado X, Lamuela-Raventos RM. 2014. Home cooking and phenolics: effect of thermal treatment and addition of extra virgin olive oil on the phenolic profile of tomato sauces. J. Agric. Food Chem. 62:143314–20 [Google Scholar]
  144. van Breda SG, Wilms LC, Gaj S, Jennen DG, Briedé JJ. et al. 2015. The exposome concept in a human nutrigenomics study: evaluating the impact of exposure to a complex mixture of phytochemicals using transcriptomics signatures. Mutagenesis 30:6723–31 [Google Scholar]
  145. van den Brandt PA, Schulpen M. 2017. Mediterranean diet adherence and risk of postmenopausal breast cancer: results of a cohort study and meta-analysis. Int. J. Cancer 140:102220–31 [Google Scholar]
  146. van Dijk SJ, Feskens EJ, Bos MB, de Groot LC, de Vries JH, Müller M, Afman LA. 2012. Consumption of a high monounsaturated fat diet reduces oxidative phosphorylation gene expression in peripheral blood mononuclear cells of abdominally overweight men and women. J. Nutr. 142:71219–25 [Google Scholar]
  147. Vidacek , Nanic L, Ravlic S, Sopta M, Geric M. et al. 2017. Telomeres, nutrition, and longevity: Can we really navigate our aging?. J. Gerontol. A. 73:139–47 [Google Scholar]
  148. Viereck J, Thum T. 2017. Circulating noncoding RNAs as biomarkers of cardiovascular disease and injury. Circ. Res. 120:2381–99 [Google Scholar]
  149. Vitaglione P, Savarese M, Paduano A, Scalfi L, Fogliano V, Sacchi R. 2015. Healthy virgin olive oil: a matter of bitterness. Crit. Rev. Food Sci. Nutr. 55:131808–18 [Google Scholar]
  150. Welty FK, Alfaddagh A, Elajami TK. 2016. Targeting inflammation in metabolic syndrome. Transl. Res. 167:1257–80 [Google Scholar]
  151. Xi Y, Jiang X, Li R, Chen M, Song W, Li X. 2016. The levels of human milk microRNAs and their association with maternal weight characteristics. Eur. J. Clin. Nutr. 70:4445–49 [Google Scholar]
  152. Zamora-Ros R, Serafini M, Estruch R, Lamuela-Raventós RM, Martínez-González MA. et al. 2013. Mediterranean diet and non enzymatic antioxidant capacity in the PREDIMED study: evidence for a mechanism of antioxidant tuning. Nutr. Metab. Cardiovasc. Dis. 23:121167–74 [Google Scholar]
  153. Zhang L, Hou D, Chen X, Li D, Zhu L. et al. 2012. Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA. Cell Res 22:1107–26 [Google Scholar]
  154. Zhang X, Zhao Q, Zhu W, Liu T, Xie SH. et al. 2017. The association of telomere length in peripheral blood cells with cancer risk: a systematic review and meta-analysis of prospective studies. Cancer Epidemiol. Biomark. Prev 26:91381–90 [Google Scholar]
  155. Zhao Q, Li S, Li N, Yang X, Ma S. et al. 2017. miR-34a targets HDAC1-tegulated H3K9 acetylation on lipid accumulation induced by homocysteine in foam cells. J. Cell. Biochem 118:124617–27 [Google Scholar]

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error