Login to MyKarger

New to MyKarger? Click here to sign up.

Login with Facebook

Forgot Password? Reset your password

Authors, Editors, Reviewers

For Manuscript Submission, Check or Review Login please go to Submission Websites List.

Submission Websites List

Institutional Login (Shibboleth)

For the academic login, please select your country in the dropdown list. You will be redirected to verify your credentials.

Table of Contents
Vol. 20, No. 2, 2011
Issue release date: January 2011
Section title: Review
Open Access Gateway
Med Princ Pract 2011;20:103–111

The Protective Effect of the Mediterranean Diet: Focus on Cancer and Cardiovascular Risk

Pauwels E.K.J.
University of Pisa Medical School, Pisa, Italy
email Corresponding Author

Prof. Dr. Ernest K.J. Pauwels

Via di San Gennaro 79 B

IT–55010 Cappanori (Italy)

Tel. +39 058 397 8080

E-Mail ernestpauwels@gmail.com


  1. Benetou V, Trichopoulou A, Orfanos P, Naska A, Lagiou P, Boffetta P, Trichopoulos D, Greek EPIC cohort: Conformity to traditional Mediterranean diet and cancer incidence: the Greek EPIC cohort. Br J Cancer 2008;99:191–195.
  2. Keys A, Menotti A, Karvonen MJ, Aravanis C, Blackburn H, Buzina R, Djordjevic BS, Dontas AS, Fidanza F, Keys MH, et al: The diet and 15-year death rate in the Seven Countries Study. Am J Epidemiol 1986;124:903–915.
  3. Cunnane SC: Problems with essential fatty acids: time for a new paradigm? Prog Lipid Res 2003;42:544–568.
  4. Serhan CN: Systems approach to inflammation resolution: identification of novel anti-inflammatory and pro-resolving mediators. J Thromb Haemost 2009;7(suppl 1):44–48.
  5. Allred CD, Talbert DR, Southard RC, Wang X, Kilgore MW: PPARgamma1 as a molecular target of eicosapentaenoic acid in human colon cancer (HT-29) cells. J Nutr 2008;138:250–256.
  6. Muralidhar B, Carpenter KL, Müller K, Skepper JN, Arends MJ: Potency of arachidonic acid in polyunsaturated fatty acid-induced death of human monocyte-macrophages: implications for atherosclerosis. Prostaglandins Leukot Essent Fatty Acids 2004;71:251–262.
  7. Zhao G, Etherton TD, Martin KR, Vanden Heuvel JP, Gillies PJ, West SG, Kris-Etherton PM: Anti-inflammatory effects of polyunsaturated fatty acids in THP-1 cells. Biochem Biophys Res Commun 2005;336:909–917.
  8. Hering J, Garrean S, Dekoj TR, Razzak A, Saied A, Trevino J, Babcock TA, Espat NJ: Inhibition of proliferation by omega-3 fatty acids in chemoresistant pancreatic cancer cells. Ann Surg Oncol 2007;14:3620–3628.
  9. Schley PD, Brindley DN, Field CJ: (n-3) PUFA alter raft lipid composition and decrease epidermal growth factor receptor levels in lipid rafts of human breast cancer cells. J Nutr 2007;137:548–553.
  10. Yao HT, Chang YW, Lan SJ, Chen CT, Hsu JT, Yeh TK: The inhibitory effect of polyunsaturated fatty acids on human CYP enzymes. Life Sci 2006;79:2432–2440.
  11. Yaqoob P, Calder PC: Fatty acids and immune function: new insights into mechanisms. Br J Nutr 2007;98(suppl 1):S41–S45.
    External Resources
  12. Kenar L, Karayilanoglu T, Aydin A, Serdar M, Kose S, Erbil MK: Protective effects of diets supplemented with omega-3 polyunsaturated fatty acids and calcium against colorectal tumor formation. Dig Dis Sci 2008;53:2177–2182.
  13. Tripoli E, Giammanco M, Tabacchi G, Di Majo D, Giammanco S, La Guardia M: The phenolic compounds of olive oil: structure, biological activity and beneficial effects on human health. Nutr Res Rev 2005;18:98–112.
  14. Lau AT, Wang Y, Chiu JF: Reactive oxygen species: current knowledge and applications in cancer research and therapeutic. J Cell Biochem 2008;104:657–667.
  15. Biesalski HK: Polyphenols and inflammation: basic interactions. Curr Opin Clin Nutr Metab Care 2007;10:724–728.
  16. Owen RW, Haubner R, Würtele G, Hull E, Spiegelhalder B, Bartsch H: Olives and olive oil in cancer prevention. Eur J Cancer Prev 2004;13:319–326.
  17. Booyse FM, Pan W, Grenett HE, Parks DA, Darley-Usmar VM, Bradley KM, Tabengwa EM: Mechanism by which alcohol and wine polyphenols affect coronary heart disease risk. Ann Epidemiol 2007;17:S24–S31.
  18. Sasaki S: Alcohol and its relation to all-cause and cardiovascular mortality. Acta Cardiol 2000;55:151–156.
  19. Opie LH, Lecour S: The red wine hypothesis: from concepts to protective signalling molecules. Eur Heart J 2007;28:1683–1693.
  20. Shankar S, Singh G, Srivastava RK: Chemoprevention by resveratrol: molecular mechanisms and therapeutic potential. Front Biosci 2007;12:4839–4854.
  21. Corder R, Mullen W, Khan NQ, Marks SC, Wood EG, Carrier MJ, Crozier A: Oenology: red wine procyanidins and vascular health. Nature 2006;444:566.
  22. van de Wiel A, van Golde PH, Hart HC: Blessings of the grape. Eur J Intern Med 2001;12:484–489.
  23. MacLean CH, Newberry SJ, Mojica WA, Khanna P, Issa AM, Suttorp MJ, Lim YW, Traina SB, Hilton L, Garland R, Morton SC: Effects of omega-3 fatty acids on cancer risk: a systematic review. JAMA 2006;295:403–415.
  24. Kuriki K, Hirose K, Wakai K, Matsuo K, Ito H, Suzuki T, Hiraki A, Saito T, Iwata H, Tatematsu M, Tajima K: Breast cancer risk and erythrocyte compositions of n-3 highly unsaturated fatty acids in Japanese. Int J Cancer 2007;121:377–385.
  25. Shannon J, King IB, Moshofsky R, Lampe JW, Gao DL, Ray RM, Thomas DB: Erythrocyte fatty acids and breast cancer risk: a case-control study in Shanghai, China. Am J Clin Nutr 2007;85:1090–1097.
  26. Kim J, Lim SY, Shin A, Sung MK, Ro J, Kang HS, Lee KS, Kim SW, Lee ES: Fatty fish and fish omega-3 fatty acid intakes decrease the breast cancer risk: a case-control study. BMC Cancer 2009;9:216.
  27. Leitzmann MF, Stampfer MJ, Michaud DS, Augustsson K, Colditz GC, Willett WC, Giovannucci EL: Dietary intake of n-3 and n-6 fatty acids and the risk of prostate cancer. Am J Clin Nutr 2004;80:204–216.
  28. Virtanen JK, Mozaffarian D, Chiuve SE, Rimm EB: Fish consumption and risk of major chronic disease in men. Am J Clin Nutr 2008;88:1618–1625.
  29. Domingo JL: Omega-3 fatty acids and the benefits of fish consumption: is all that glitters gold? Environ Int 2007;33:993–998.
  30. Amin M, Jeyaganth S, Fahmy N, Bégin LR, Aronson S, Jacobson S, Tanguay S, Kassouf W, Aprikian A: Dietary habits and prostate cancer detection: a case-control study. Can Urol Assoc J 2008;2:510–515.
    External Resources
  31. Ritch CR, Wan RL, Stephens LB, Taxy JB, Huo D, Gong EM, Zagaja GP, Brendler CB: Dietary fatty acids correlate with prostate cancer biopsy grade and volume in Jamaican men. J Urol 2007;177:97–101.
  32. Norat T, Bingham S, Ferrari P, Slimani N, Jenab M, Mazuir M, Overvad K, Olsen A, Tjønneland A, Clavel F, Boutron-Ruault MC, Kesse E, Boeing H, Bergmann MM, Nieters A, Linseisen J, Trichopoulou A, Trichopoulos D, Tountas Y, Berrino F, Palli D, Panico S, Tumino R, Vineis P, Bueno-de-Mesquita HB, Peeters PH, Engeset D, Lund E, Skeie G, Ardanaz E, González C, Navarro C, Quirós JR, Sanchez MJ, Berglund G, Mattisson I, Hallmans G, Palmqvist R, Day NE, Khaw KT, Key TJ, San Joaquin M, Hémon B, Saracci R, Kaaks R, Riboli E: Meat, fish, and colorectal cancer risk: the European Prospective Investigation into Cancer and Nutrition. J Natl Cancer Inst 2005;97:906–916.
  33. Hall MN, Chavarro JE, Lee IM, Willett WC, Ma J: A 22-year prospective study of fish, n-3 fatty acid intake, and colorectal cancer risk in men. Cancer Epidemiol Biomarkers Prev 2008;17:1136–1143.
  34. Kuriki K, Wakai K, Hirose K, Matsuo K, Ito H, Suzuki T, Saito T, Kanemitsu Y, Hirai T, Kato T, Tatematsu M, Tajima K: Risk of colorectal cancer is linked to erythrocyte compositions of fatty acids as biomarkers for dietary intakes of fish, fat, and fatty acids. Cancer Epidemiol Biomarkers Prev 2006;15:1791–1798.
  35. Wang J, John EM, Horn-Ross PL, Ingles SA: Dietary fat, cooking fat, and breast cancer risk in a multiethnic population. Nutr Cancer 2008;60:492–504.
  36. Schulz M, Hoffmann K, Weikert C, Nöthlings U, Schulze MB, Boeing H: Identification of a dietary pattern characterized by high-fat food choices associated with increased risk of breast cancer: the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Br J Nutr 2008;101:942–946.
    External Resources
  37. Chajès V, Thiébaut AC, Rotival M, Gauthier E, Maillard V, Boutron-Ruault MC, Joulin V, Lenoir GM, Clavel-Chapelon F: Association between serum trans-monounsaturated fatty acids and breast cancer risk in the E3N-EPIC Study. Am J Epidemiol 2008;167:1312–1320.
  38. Sieri S, Krogh V, Ferrari P, Berrino F, Pala V, Thiébaut AC, Tjønneland A, Olsen A, Overvad K, Jakobsen MU, Clavel-Chapelon F, Chajes V, Boutron-Ruault MC, Kaaks R, Linseisen J, Boeing H, Nöthlings U, Trichopoulou A, Naska A, Lagiou P, Panico S, Palli D, Vineis P, Tumino R, Lund E, Kumle M, Skeie G, González CA, Ardanaz E, Amiano P, Tormo MJ, Martínez-García C, Quirós JR, Berglund G, Gullberg B, Hallmans G, Lenner P, Bueno-de-Mesquita HB, van Duijnhoven FJ, Peeters PH, van Gils CH, Key TJ, Crowe FL, Bingham S, Khaw KT, Rinaldi S, Slimani N, Jenab M, Norat T, Riboli E: Dietary fat and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition. Am J Clin Nutr 2008;88:1304–1312.
  39. Fitó M, de la Torre R, Covas MI: Olive oil and oxidative stress. Mol Nutr Food Res 2007;51:1215–1224.
    External Resources
  40. Machowetz A, Poulsen HE, Gruendel S, Weimann A, Fitó M, Marrugat J, de la Torre R, Salonen JT, Nyyssönen K, Mursu J, Nascetti S, Gaddi A, Kiesewetter H, Bäumler H, Selmi H, Kaikkonen J, Zunft HJ, Covas MI, Koebnick C: Effect of olive oils on biomarkers of oxidative DNA stress in Northern and Southern Europeans. FASEB J 2007;21:45–52.
  41. Crowe FL, Key TJ, Appleby PN, Travis RC, Overvad K, Jakobsen MU, Johnsen NF, Tjønneland A, Linseisen J, Rohrmann S, Boeing H, Pischon T, Trichopoulou A, Lagiou P, Trichopoulos D, Sacerdote C, Palli D, Tumino R, Krogh V, Bueno-de-Mesquita HB, Kiemeney LA, Chirlaque MD, Ardanaz E, Sánchez MJ, Larrañaga N, González CA, Quirós JR, Manjer J, Wirfält E, Stattin P, Hallmans G, Khaw KT, Bingham S, Ferrari P, Slimani N, Jenab M, Riboli E: Dietary fat intake and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition. Am J Clin Nutr 2008;87:1405–1413.
  42. Park SY, Murphy SP, Wilkens LR, Henderson BE, Kolonel LN: Fat and meat intake and prostate cancer risk: the multiethnic cohort study. Int J Cancer 2007;121:1339–1345.
  43. Theodoratou E, McNeill G, Cetnarskyj R, Farrington SM, Tenesa A, Barnetson R, Porteous M, Dunlop M, Campbell H: Dietary fatty acids and colorectal cancer: a case-control study. Am J Epidemiol 2007;166:181–195.
  44. Stoneham M, Goldacre M, Seagroatt V, Gill L: Olive oil, diet and colorectal cancer: an ecological study and a hypothesis. J Epidemiol Community Health 2000;54:756–760.
  45. Cicerale S, Conlan XA, Sinclair AJ, Keast RS: Chemistry and health of olive oil phenolics. Crit Rev Food Sci Nutr 2009;49:218–236.
  46. St Leger AS, Cochrane AL, Moore F: Factors associated with cardiac mortality in developed countries with particular reference to the consumption of wine. Lancet 1979;1:1017–1020.
  47. Renaud S, de Lorgeril M: Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 1992;339:1523–1526.
  48. Di Castelnuovo A, Costanzo S, Bagnardi V, Donati MB, Iacoviello L, de Gaetano G: Alcohol dosing and total mortality in men and women: an updated meta-analysis of 34 prospective studies. Arch Intern Med 2006;166:2437–2445.
  49. Gaziano JM, Gaziano TA, Glynn RJ, Sesso HD, Ajani UA, Stampfer MJ, Manson JE, Hennekens CH, Buring JE: Light-to-moderate alcohol consumption and mortality in the Physicians’ Health Study enrollment cohort. J Am Coll Cardiol 2000;35:96–105.
  50. Klatsky AL, Armstrong MA, Friedman GD: Alcohol and mortality. Ann Intern Med 1992;117:646–654.
  51. Snow WM, Murray R, Ekuma O, Tyas SL, Barnes GE: Alcohol use and cardiovascular health outcomes: a comparison across age and gender in the Winnipeg Health and Drinking Survey Cohort. Age Ageing 2009;38:206–212.
  52. Bazzano LA, Gu D, Reynolds K, Chen J, Wu X, Chen CS, Duan X, Chen J, He J: Alcohol consumption and risk of coronary heart disease among Chinese men. Int J Cardiol 2009;135:78–85.
  53. Saremi A, Arora R: The cardiovascular implications of alcohol and red wine. Am J Ther 2008;15:265–277.
  54. Foerster M, Marques-Vidal P, Gmel G, Daeppen JB, Cornuz J, Hayoz D, Pécoud A, Mooser V, Waeber G, Vollenweider P, Paccaud F, Rodondi N: Alcohol drinking and cardiovascular risk in a population with high mean alcohol consumption. Am J Cardiol 2009;103:361–368.
  55. Grønbaek M, Becker U, Johansen D, Gottschau A, Schnohr P, Hein HO, Jensen G, Sørensen TI: Type of alcohol consumed and mortality from all causes, coronary heart disease, and cancer. Ann Intern Med 2000;133:411–419.
  56. Renaud SC, Guéguen R, Conard P, Lanzmann-Petithory D, Orgogozo JM, Henry O: Moderate wine drinkers have lower hypertension-related mortality: a prospective cohort study in French men. Am J Clin Nutr 2004;80:621–625.
  57. Klatsky AL, Friedman GD, Armstrong MA, Kipp H: Wine, liquor, beer, and mortality. Am J Epidemiol 2003;158:585–595.
  58. Karatzi K, Papamichael C, Aznaouridis K, Karatzis E, Lekakis J, Matsouka C, Boskou G, Chiou A, Sitara M, Feliou G, Kontoyiannis D, Zampelas A, Mavrikakis M: Constituents of red wine other than alcohol improve endothelial function in patients with coronary artery disease. Coron Artery Dis 2004;15:485–490.
  59. Agewall S, Wright S, Doughty RN, Whalley GA, Duxbury M, Sharpe N: Does a glass of red wine improve endothelial function? Eur Heart J 2000;21:74–78.
  60. Karatzi K, Papamichael C, Karatzis E, Papaioannou TG, Voidonikola PT, Lekakis J, Zampelas A: Acute smoking induces endothelial dysfunction in healthy smokers: is this reversible by red wine’s antioxidant constituents? J Am Coll Nutr 2007;26:10–15.
  61. Kiviniemi TO, Saraste A, Lehtimäki T, Toikka JO, Saraste M, Raitakari OT, Hartiala JJ, Viikari J, Koskenvuo JW: Decreased endothelin-1 levels after acute consumption of red wine and de-alcoholized red wine. Atherosclerosis 2010;211:283–286.
  62. Opie LH, Lecour S: The red wine hypothesis: from concepts to protective signalling molecules. Eur Heart J 2007;28:1683–1693.
  63. Mukamal KJ, Conigrave KM, Mittleman MA, Camargo CA Jr, Stampfer MJ, Willett WC, Rimm EB: Roles of drinking pattern and type of alcohol consumed in coronary heart disease in men. N Engl J Med 2003;348:109–118.
  64. van de Wiel A, de Lange DW: Cardiovascular risk is more related to drinking pattern than to the type of alcoholic drinks. Neth J Med 2008;66:467–473.
  65. Dudley JI, Lekli I, Mukherjee S, Das M, Bertelli AA, Das DK: Does white wine qualify for French paradox? Comparison of the cardioprotective effects of red and white wines and their constituents: resveratrol, tyrosol, and hydroxytyrosol. J Agric Food Chem 2008;56:9362–9373.
  66. Zamora-Ros R, Urpí-Sardà M, Lamuela-Raventós RM, Estruch R, Martínez-González MA, Bulló M, Arós F, Cherubini A, Andres-Lacueva C: Resveratrol metabolites in urine as a biomarker of wine intake in free-living subjects: the PREDIMED Study. Free Radic Biol Med 2009;46:1562–1566.
  67. Lairon D: Intervention studies on Mediterranean diet and cardiovascular risk. Mol Nutr Food Res 2007;51:1209–1124.
  68. Martínez-González MA, García-López M, Bes-Rastrollo M, Toledo E, Martínez-Lapiscina EH, Delgado-Rodriguez M, Vazquez Z, Benito S, Beunza JJ: Mediterranean diet and the incidence of cardiovascular disease: a Spanish cohort. Nutr Metab Cardiovasc Dis 2010, E-pub ahead of print.
  69. Bosetti C, Pelucchi C, La Vecchia C: Diet and cancer in Mediterranean countries: carbohydrates and fats. Public Health Nutr 2009;12:1595–1600.
  70. Martinez-Gonzalez MA, Bes-Rastrollo M, Serra-Majem L, Lairon D, Estruch R, Trichopoulou A: Mediterranean food pattern and the primary prevention of chronic disease: recent developments. Nutr Rev 2009;67 (suppl 1):S111–S116.
  71. Sofi F, Cesari F, Abbate R, Gensini GF, Casini A: Adherence to Mediterranean diet and health status: meta-analysis. BMJ 2008;337:a1344.
  72. Trichopoulou A, Bamia C, Trichopoulos D: Anatomy of health effects of Mediterranean diet: Greek EPIC prospective cohort study. BMJ 2009;338:b2337.
  73. Simopoulos AP: The Mediterranean diets: what is so special about the diet of Greece? The scientific evidence. J Nutr 2001;131:3065S–3073S.
  74. Kapiszewska M: A vegetable to meat consumption ratio as a relevant factor determining cancer preventive diet: the Mediterranean versus other European countries. Forum Nutr 2006;59:130–153.
  75. Ruidavets JB, Bataille V, Dallongeville J, Simon C, Bingham A, Amouyel P, Arveiler D, Ducimetière P, Ferrières J: Alcohol intake and diet in France, the prominent role of lifestyle. Eur Heart J. 2004;25:1153–1162.
  76. Barefoot JC, Grønbaek M, Feaganes JR, McPherson RS, Williams RB, Siegler IC: Alcoholic beverage preference, diet, and health habits in the UNC Alumni Heart Study. Am J Clin Nutr 2002;76:466–472.
  77. Bays HE, Tighe AP, Sadovsky R, Davidson MH: Prescription omega-3 fatty acids and their lipid effects: physiologic mechanisms of action and clinical implications. Expert Rev Cardiovasc Ther 2008;6:391–409.
  78. La Vecchia C: Mediterranean diet and cancer. Public Health Nutr 2004;7:965–968.
  79. Escrich E, Moral R, Grau L, Costa I, Solanas M: Molecular mechanisms of the effects of olive oil and other dietary lipids on cancer. Mol Nutr Food Res 2007;51:1279–1292.