The Disease-Preventive Power of the Mediterranean Diet
By Dale Kiefer
The Mediterranean diet has well-substantiated health- and longevity-promoting effects.
Critical components of this diet that may account for the impressive benefits described in scientific studies include potent antioxidants from phytonutrients, the critical omega-3 fatty acids DHA and EPA, and health-enhancing polyphenols derived from olive fruit.
While the remarkable health benefits associated with antioxidant-rich phytonutrients and the omega-3 fatty acids DHA and EPA are well established, emerging research supporting the benefits of olive polyphenols is equally impressive. Particularly striking is the study just described, in which a combination of EPA/DHA and hydroxytyrosol-rich olive polyphenols produced synergistic benefitsin controlling inflammation in rheumatoid arthritis patients.
Hydroxytyrosol, a potent antioxidant, is the major polyphenol present in olive extract. This and other olive polyphenols are most concentrated in water-soluble olive fruit extract, not in the oil itself. Concentrated, standardized extracts of olive fruit enable health-conscious people to consume high concentrations of these powerful nutrients without ingesting servings of extra-virgin olive oil containing inadvisably large amounts of dietary fat and calories.
Extensive research strongly supports phytonutrients, omega-3 polyunsaturated fatty acids, and olive polyphenols as critical nutrients that likely account for many of the remarkable anti-aging and health benefits of the Mediterranean diet.
1. Eposito K, Marfella R, Ciotola M, et al. Effect of a Mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial. JAMA. 2004 Sep 22;292(12):1440-6.
2. Osler M, Heitmann BL, Gerdes LU, Jorgensen LM, Schroll M. Dietary patterns and mortality in Danish men and women: a prospective observational study. Br J Nutr. 2001 Feb;85(2):219-25.
3. Osler M, Schroll M. Diet and mortality in a cohort of elderly people in a north European community. Int J Epidemiol. 1997 Feb;26(1):155-9.
4. Trichopoulou A, Costacou T, Bamia C, Trichopoulos D. Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med. 2003 Jun 26;348(26):2599-608.
5. Trichopoulou A, Vasilopoulou E. Mediterranean diet and longevity. Br J Nutr. 2000 Dec;84 Suppl 2:S205-9.
6. Trichopoulou A, Kouris-Blazos A, Wahlqvist ML, et al. Diet and overall survival in elderly people. BMJ. 1995 Dec 2;311(7018):1457-60.
7. Knoops KT, de Groot LC, Kromhout D, et al. Mediterranean diet, lifestyle factors, and 10-year mortality in elderly European men and women: the HALE project. JAMA. 2004 Sep 22;292(12):1433-9.
8. Lasheras C, Fernandez S, Patterson AM. Mediterranean diet and age with respect to overall survival in institutionalized, nonsmoking elderly people. Am J Clin Nutr. 2000 Apr;71(4):987-92.
9. Trichopoulou A, Orfanos P, Norat T, et al. Modified Mediterranean diet and survival: EPIC-elderly prospective cohort study. BMJ. 2005 Apr 30;330(7498):991.
10. Trichopoulou A, Bania C, Trichopoulos D. Mediterranean diet and survival among patients with coronary heart disease in Greece. Arch Intern Med. 2005 Apr 25;165(8):929-35.
11. Trichopoulou A, Lagiou P, Kuper H, Trichopoulos D. Cancer and Mediterranean dietary traditions. Cancer Epidemiol Biomarkers Prev. 2000 Sep;9(9):869-73.
12. Zamaria N. Alteration of polyunsaturated fatty acid status and metabolism in health and disease. Reprod Nutr Dev. 2004 May-Jun;44(3):273-82.
13. Kris-Etherton PM, Taylor DS, Yu-Poth S, et al. Polyunsaturated fatty acids in the food chain in the United States. Am J Clin Nutr. 2000 Jan;71(1 Suppl):179S-88S.
14. Mori TA, Beilin LJ. Omega-3 fatty acids and inflammation. Curr Atheroscler Rep. 2004 Nov;6(6):461-7.
15. Hardman WE. n-3 fatty acids and cancer therapy. J Nutr. 2004 Dec;134(12 Suppl):3427S-430S.
16. Berbert AA, Kondo CR, Almendra CL, Matsuo T, Dichi I. Supplementation of fish oil and olive oil in patients with rheumatoid arthritis. Nutrition. 2005 Feb;21(2):131-6.
17. Guesnet P, Alessandri JM, Vancassel S, Zamaria N. Analysis of the 2nd symposium “Anomalies of fatty acids, ageing and degenerating pathologies.” Reprod Nutr Dev. 2004 May-Jun;44(3):263-71.
18. Conquer JA, Tierney MC, Zecevic J, Bettger WJ, Fisher RH. Fatty acid analysis of blood plasma of patients with Alzheimer’s disease, other types of dementia, and cognitive impairment. Lipids. 2000 Dec;35(12):1305-12.
19. Horrocks LA, Yeo YK. Health benefits of docosahexaenoic acid (DHA) Pharmacol Res. 1999 Sep;40(3):211-25.
20. Hjerkinn EM, Seljeflot I, Ellingsen I, et al. Influence of long-term intervention with dietary counseling, long-chain n-3 fatty acid supplements, or both on circulating markers of endothelial activation in men with long-standing hyperlipidemia. Am J Clin Nutr. 2005 Mar;81(3):583-9.
21. Nettleton JA, Katz R. n-3 long-chain polyunsaturated fatty acids in type 2 diabetes: a review. J Am Diet Assoc. 2005 Mar;105(3):428-40.
22. Jayasooriya AP, Weisinger RS, Weisinger HS, et al. Influence of dietary omega-3 polyunsaturated fatty acid (PUFA) supply on brain gene expression. Asia Pac J Clin Nutr. 2004;13(Suppl):S77.
23. Goyens PL, Spilker ME, Zock PL, Katan MB, Mensink RP. Development of a compartmental model to quantify alpha-linolenic acid conversion after longer-term intake of multiple tracer boluses. J Lipid Res. 2005 Apr 16.
24. Gerster H. Can adults adequately convert alpha-linolenic acid (18:3n-3) to eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3)? Int J Vitam Nutr Res. 1998;68(3):159-73.
25. Ismail HM. The role of omega-3 fatty acids in cardiac protection: an overview. Front Biosci. 2005 May 1;10:1079-88.
26. Carrero JJ, Martin-Bautista E, Baro L,
et al. Cardiovascular effects of omega-3-fatty acids and alternatives to increase their intake. Nutr Hosp. 2005 Jan-Feb;20(1):63-9.
27. Bourre JM. Omega-3 fatty acids in psychiatry. Med Sci (Paris). 2005 Feb;21(2):216-21.
28. Bourre JM. Dietary omega-3 fatty acids and psychiatry: mood, behaviour, stress, depression, dementia and aging. J Nutr Health Aging. 2005;9(1):31-8.
29. Bourre JM. The role of nutritional factors on the structure and function of the brain: an update on dietary requirements. Rev Neurol (Paris). 2004 Sep;160(8-9):767-92.
30. Singh M. Essential fatty acids, DHA and human brain. Indian J Pediatr. 2005 Mar;72(3):239-42.
31. Oh R. Practical applications of fish oil (omega-3 fatty acids) in primary care. J Am Board Fam Pract. 2005 Jan-Feb;18(1):28-36.
32. Seo T, Blaner WS, Deckelbaum RJ. Omega-3 fatty acids: molecular approaches to optimal biological outcomes. Curr Opin Lipidol. 2005 Feb;16(1):11-8.
33. Youdim KA, Martin A, Joseph JA. Essential fatty acids and the brain: possible health implications. Int J Dev Neurosci. 2000 Jul-Aug;18(4-5):383-99.
34. Favreliere S, Perault MC, Huguet F, et al. DHA-enriched phospholipid diets modulate age-related alterations in rat hippocampus. Neurobiol Aging. 2003 Mar-Apr;24(2):233-43.
35. Yehuda S, Rabinovitz S, Carasso RL, Mostofsky DI. The role of polyunsaturated fatty acids in restoring the aging neuronal membrane. Neurobiol Aging. 2002 Sep-Oct;23(5):843-53.
36. Martin DS, Lonergan PE, Boland B, et al. Apoptotic changes in the aged brain are triggered by interleukin-1beta-induced activation of p38 and reversed by treatment with eicosapentaenoic acid. J Biol Chem. 2002 Sep 13;277(37):34239-46.
37. Marrugat J, Covas MI, Fito M, et al. Effects of differing phenolic content in dietary olive oils on lipids and LDL oxidation—a randomized controlled trial. Eur J Nutr. 2004 Jun;43(3):140-7.
38. Gimeno E, Fito M, Lamuela-Raventos RM, et al. Effect of ingestion of virgin olive oil on human low-density lipoprotein composition. Eur J Clin Nutr. 2002 Feb;56(2):114-20.
39. Weinbrenner T, Fito M, de la Torre R, et al. Olive oils high in phenolic compounds modulate oxidative/antioxidative status in men. J Nutr. 2004 Sep;134(9):2314-21.
40. Fito M, Gimeno E, Covas MI, et al. Postprandial and short-term effects of dietary virgin olive oil on oxidant/antioxidant status. Lipids. 2002 Mar;37(3):245-51.
41. Covas MI, Fito M, Lamuela-Raventos RM, Sebastia N, de la Torre-Boronat C, Marrugat J. Virgin olive oil phenolic compounds: binding to human low density lipoprotein (LDL) and effect on LDL oxidation. Int J Clin Pharmacol Res. 2000;20(3-4):49-54.
42. O’Dowd Y, Driss F, Dang PM, et al. Antioxidant effect of hydroxytyrosol, a polyphenol from olive oil: scavenging of hydrogen peroxide but not superoxide anion produced by human neutrophils. Biochem Pharmacol. 2004 Nov 15;68(10):2003-8.
43. Visioli F, Bogani P, Grande S, Galli C. Mediterranean food and health: building human evidence. J Physiol Pharmacol. 2005 Mar;56 Suppl 1:37-49.
44. Vissers MN, Zock PL, Leenen R, Roodenburg AJ, van Putte KP, Katan MB. Effect of consumption of phenols from olives and extra virgin olive oil on LDL oxidizability in healthy humans. Free Radic Res. 2001 Nov;35(5):619-29.
45. Visioli F, Bellomo G, Galli C. Free radical-scavenging properties of olive oil polyphenols. Biochem Biophys Res Commun. 1998 Jun 9;247(1):60-4.
46. Visioli F, Galli C. Oleuropein protects low density lipoprotein from oxidation. Life Sci. 1994;55(24):1965-71.
47. Masella R, Vari R, D’Archivio M, et al. Extra virgin olive oil biophenols inhibit cell-mediated oxidation of LDL by increasing the mRNA transcription of glutathione-related enzymes. J Nutr. 2004 Apr;134(4):785-91.
48. Kris-Etherton PM, Hecker KD, Bonanome A, et al. Bioactive compounds in foods: their role in the prevention of cardiovascular disease and cancer. Am J Med. 2002 Dec 30;113 Suppl 9B:71S-88S.
49. Simopoulos AP. The Mediterranean diets: what is so special about the diet of Greece? The scientific evidence. J Nutr. 2001 Nov;131(11 Suppl):3065S-73S.
50. Romero C, Brenes M, Garcia P, Garrido A. Hydroxytyrosol 4-beta-D-glucoside, an important phenolic compound in olive fruits and derived products. J Agric Food Chem. 2002 Jun 19;50(13):3835-9.
51. Romero C, Brenes M, Garcia P, Garcia A, Garrido A. Polyphenol changes during fermentation of naturally black olives. J Agric Food Chem. 2004 Apr 7;52(7):1973-9.
52. Aviram M. Interaction of oxidized low density lipoprotein with macrophages in atherosclerosis, and the antiatherogenicity of antioxidants. Eur J Clin Chem Clin Biochem. 1996 Aug;34(8):599-608.
53. Mateos R, Dominguez MM, Espartero JL, Cert A. Antioxidant effect of phenolic compounds, alpha-tocopherol, and other minor components in virgin olive oil. J Agric Food Chem. 2003 Nov 19;51(24):7170-5.
54. Masella R, Giovannini C, Vari R, et al. Effects of dietary virgin olive oil phenols on low density lipoprotein oxidation in hyperlipidemic patients. Lipids. 2001 Nov;36(11):1195-202.
55. Vissers MN, Zock PL, Katan MB. Bioavailability and antioxidant effects of olive oil phenols in humans: a review. Eur J Clin Nutr. 2004 Jun;58(6):955-65.
56. Lavelli V. Comparison of the antioxidant activities of extra virgin olive oils. J Agric Food Chem. 2002 Dec 18;50(26):7704-8.
57. de la Puerta R, Martinez-Dominguez E, Ruiz-Gutierrez V. Effect of minor components of virgin olive oil on topical antiinflammatory assays. Z Naturforsch [C]. 2000 Sep-Oct;55(9-10):814-9.
58. de la Puerta R, Martinez Dominguez ME, Ruiz-Gutierrez V, Flavill JA, Hoult JR. Effects of virgin olive oil phenolics on scavenging of reactive nitrogen species and upon nitrergic neurotransmission. Life Sci. 2001 Jul 27;69(10):1213-22.
59. Wiseman SA, Tijburg LB, van de Put FH. Olive oil phenolics protect LDL and spare vitamin E in the hamster. Lipids. 2002 Nov;37(11):1053-7.
60. Owen RW, Giacosa A, Hull WE, Haubner R, Spiegelhalder B, Bartsch H. The antioxidant/anticancer potential of phenolic compounds isolated from olive oil. Eur J Cancer. 2000 Jun;36(10):1235-47.
61. Tuck KL, Freeman MP, Hayball PJ, Stretch GL, Stupans I. The in vivo fate of hydroxytyrosol and tyrosol, antioxidant phenolic constituents of olive oil, after intravenous and oral dosing of labeled compounds to rats. J Nutr. 2001 Jul;131(7):1993-6.
62. Miles EA, Zoubouli P, Calder PC. Differential anti-inflammatory effects of phenolic compounds from extra virgin olive oil identified in human whole blood cultures. Nutrition. 2005 Mar;21(3):389-94.
63 Balaban RS, Nemoto S, Finkel T. Mitochondria, oxidants, and aging. Cell. 2005 Feb 25;120(4):483-95.
64. Inoue M, Sato EF, Nishikawa M, Hiramoto K, Kashiwagi A, Utsumi K. Free radical theory of apoptosis and metamorphosis. Redox Rep. 2004;9(5):237-47.
65. Harman D. The free radical theory of aging. Antioxid Redox Signal. 2003 Oct;5(5):557-61.
66. Donaldson MS. Nutrition and cancer: A review of the evidence for an anti-cancer diet. Nutr J. 2004 Oct 20;3(1):19.
67. Lucas EA, Lightfoot SA, Hammond LJ, et al. Flaxseed reduces plasma cholesterol and atherosclerotic lesion formation in ovariectomized Golden Syrian hamsters. Atherosclerosis. 2004 Apr;173(2):223-9.
68. Jenkins DJ, Kendall CW, Vidgen E, et al. Health aspects of partially defatted flaxseed, including effects on serum lipids, oxidative measures, and ex vivo androgen and progestin activity: a controlled crossover trial. Am J Clin Nutr. 1999 Mar;69(3):395-402.
69. Prasad K. Flaxseed: a source of hypocholesterolemic and antiatherogenic agents. Drug News Perspect. 2000 Mar;13(2):99-104.
70. Prasad K, Mantha SV, Muir AD, Westcott ND. Reduction of hypercholesterolemic atherosclerosis by CDC-flaxseed with very low alpha-linolenic acid. Atherosclerosis. 1998 Feb;136(2):367-75.
71. Dabrosin C, Chen J, Wang L, Thompson LU. Flaxseed inhibits metastasis and decreases extracellular vascular endothelial growth factor in human breast cancer xenografts. Cancer Lett. 2002 Nov 8;185(1):31-7.
72. Platt R. Current concepts in optimum nutrition for cardiovascular disease. Prev Cardiol. 2000 Spring;3(2):83-7.
73. Bierenbaum ML, Reichstein R, Watkins TR. Reducing atherogenic risk in hyperlipemic humans with flax seed supplementation: a preliminary report. J Am Coll Nutr. 1993 Oct;12(5):501-4.
74. Kamal-Eldin A, Pettersson D, Appelqvist LA. Sesamin (a compound from sesame oil) increases tocopherol levels in rats fed ad libitum. Lipids. 1995 Jun;30(6):499-505.
75. Matsumura Y, Kita S, Tanida Y, et al. Antihypertensive effect of sesamin. III. Protection against development and maintenance of hypertension in stroke-prone spontaneously hypertensive rats. Biol Pharm Bull. 1998 May;21(5):469-73.
76. Noguchi T, Ikeda K, Sasaki Y, et al. Effects of vitamin E and sesamin on hypertension and cerebral thrombogenesis in stroke-prone spontaneously hypertensive rats. Hypertens Res. 2001 Nov;24(6):735-42.
77. Utsunomiya T, Shimada M, Rikimaru T, et al. Antioxidant and anti-inflammatory effects of a diet supplemented with sesamin on hepatic ischemia-reperfusion injury in rats. Hepatogastroenterology. 2003 Sep-Oct;50(53):1609-13.
78. McGeer PL, McGeer EG. Inflammation and the degenerative diseases of aging. Ann N Y Acad Sci. 2004 Dec;1035:104-16.
79. Larbi A, Dupuis G, Douziech N, Khalil A, Fulop T Jr. Low-grade inflammation with aging has consequences for T-lymphocyte signaling. Ann N Y Acad Sci. 2004 Dec;1030:125-33.
80. Napoli C, Palinski W. Neurodegenerative diseases: insights into pathogenic mechanisms from atherosclerosis. Neurobiol Aging. 2005 Mar;26(3):293-302.
81. Finch CE. Developmental origins of aging in brain and blood vessels: an overview. Neurobiol Aging. 2005 Mar;26(3):281-91.
82. Schwartsburd PM. Age-promoted creation of a pro-cancer microenvironment by inflammation: pathogenesis of dyscoordinated feedback control. Mech Ageing Dev. 2004 Sep;125(9):581-90.
83. Weinreb O, Mandel S, Amit T, Youdim MB. Neurological mechanisms of green tea polyphenols in Alzheimer’s and Parkinson’s diseases. J Nutr Biochem. 2004 Sep;15(9):506-16.
84. Nagatsu T, Sawada M. Inflammatory process in Parkinson’s disease: role for cytokines. Curr Pharm Des. 2005;11(8):999-1016.
85. Roland I, De Leval X, Evrard B