Summary
Statistics have shown that Mediterranean populations such as Spain, Italy & Greece, have significantly lower rates of coronary heart disease (CHD) than that seen throughout the rest of the world. [1] This observation was initially met with confusion, because the typical Mediterranean diet is as high in fat as the typical American diet and even higher in fat than the diets of other European populations. [2]
Because studies among these other populations had shown a significant association between fat intake and the risk of heart disease, it was not known why the reverse was true among the Mediterranean people. It was soon discovered that it was the quality, not the quantity of fat which was associated with heart disease. The fat intake of typical American diets consisted largely of saturated fats from animal foods such as meat and dairy, whereas the fat intake among typical Mediterranean diets consisted largely of monounsaturated fats from plant sources such as olive oil. It was then discovered that diets high in monounsaturated fatty acids (MUFA’s) and low in saturated fatty acids (SUFA’s) could favourably affect blood cholesterol levels and consequently decrease the risk of developing cardiovascular diseases such as coronary heart disease (CHD); even when providing the same amount of total fat. Further studies have revealed that other than its high MUFA content, unprocessed (extra-virgin) olive oil contains non-fat components such as certain phenolic compounds which have been found to have a wide range of beneficial health effects which include favourable effects on cholesterol (both ‘good’ and ‘bad’) levels and oxidation, as well as posessing an anti-inflamatory effect and potentially having healthy influences on our blood pressure and blood clotting [3].
The rate of cancer among Mediterranean populations is also significantly lower than the rest of the world. There is some preliminary evidence to suggest that these lower rates of cancer, particularly breast cancer, may also be at least in part due to olive oil consumption, as a component of olive oil called oleic acid has shown the potential to prevent breast cancer in laboratory studies. This evidence is very preliminary however.
For these reasons, extra-virgin olive oil intake, especially when used to replace fat intake from saturated fat sources, should be an important part of a nutra-smart diet.
Olive Oil and Coronary Heart Disease (CHD)
Epidemiology
Several epidemiological (population-based) studies have found significantly lower rates of death from all causes, particularly heart disease, among those whose dietary habits are closets to traditional Mediterranean diets (rich in plant foods, olive oil and low in saturated animal fats). [4,5]
Recently, researchers from the University Of Athens School Of Medicine reviewed all of the epidemiological studies which evaluated the association between adherence to a Mediterranean diet and the occurrence of coronary heart disease outcomes. These studies showed that Mediterranean diet adherence resulted in a reduction in the risk of CHD varying from 8% to 45%. [6]
The seven countries study followed approximately 13,000 healthy middle aged men from Europe, Japan and the U.S. for 15 years. [7] Throughout this time, a total of 2,288 of the men had died. Analyses of the participant’s dietary habits revealed that although total fat intake and polyunsaturated fat intake were not significantly correlated with the risk of death, the greatest dietary correlation was the intake of monounsaturated fats. Those who consumed a greater ratio of mono-unsaturated fats to saturated fats had the most protection against all causes of death, especially CHD. The greatest source of monounsaturated fats among most of these countries was of course olive oil. Additionally, the populations with the highest monounsaturated fat intakes had the lowest rates of heart disease throughout this study.
A recent case-control study in Spain compared the diets of 171 patients who had recently suffered a non-fatal heart attack, with 171 non-heart attack patients of the same age (age-matched controls). [8] The results of this study found that those who consumed the most olive oil had an 82% reduced risk of heart attack compared with those who rarely consumed olive oil.
These studies provide at least some good evidence that adherence to a Mediterranean-like diet low in saturated fats and high in monounsaturated fats, specifically rich in olive oil, may significantly decrease the risk of heart disease. Discussed below are some of the mechanisms by which Olive oil may exert its cardio-protective effect, such as it’s ability to lower total and LDL “bad” cholesterol levels, reduce LDL cholesterol oxidation, increase HDL “good” cholesterol levels, inhibit unnecessary blood clotting, exert an anti-inflammatory action and lower blood pressure in hypertensive patients, as well as the potent anti-oxidant properties of olive oils non-fat components such as its phenolic content; particularly higher in the lesser-processed “extra-virgin” olive oil.
Effect of Olive Oil on Total and LDL “bad” Cholesterol
Many human clinical trials have shown that replacement of high saturated fat diets for diets high in monounsaturated fats, mostly from olive oil, have resulted in a significant decrease in both total cholesterol (TC) and particularly LDL “bad” cholesterol; the type of cholesterol known to build up in the arteries and cause atherosclerosis; the hardening and narrowing of the arteries that may lead to blockages and coronary heart disease (CHD) or stroke. These results have been confirmed in studies involving both men and women of varying ages. [9-16]
Whilst higher levels of LDL cholesterol (also known as “bad” cholesterol) are associated with the development of atherosclerosis and thus increase the risk of cardiovascular disease, [17-20] higher levels of high density lipoprotein (HDL) cholesterol, also referred to as “good” cholesterol, is associated with a reduced risk of developing cardiovascular disease. [21] This is because the HDL particles carry cholesterol away from the arteries and back to the liver, whereas LDL particles carry it from the liver and deposit it in the arteries where it causes atherosclerosis and plaque build- up. Some studies have also shown an increase in HDL “good” cholesterol after olive oil consumption [22] as well as other beneficial effects on blood lipid (fat) levels such as reduction in the levels of apolipoprotein B and beneficial changes in platelet function. [23] This is important because higher levels of apolipoprotein B are also associated with an increased risk of cardiovascular disease, and blood platelets are also involved in the development of atherosclerosis by stimulating arterial plaque growth when they come in contact with the inner wall of blood vessels.
LDL particles themselves only become a problem when they are taken up by a type of white blood cell found in arterial plaques called macrophages, and become oxidized, forming “foam cells”. When these LDL particles become oxidized and form foam cells, this further stimulates the progression of plaque build up in arterial walls, hardening and narrowing the arteries. Therefore, decreasing the amount of LDL particles in the blood is an important means of preventing atherosclerosis development, but trying to limit the amount of oxidization of those LDL particles that are present, is also important. This leads to the next important point.
LDL Oxidation
Diets high in saturated fatty acids (SUFA’s) are known to raise LDL levels whilst diets high in polyunsaturated fatty acids (PUFA’s) and monounsaturated fatty acids (MUFA’s) tend to decrease LDL levels. In fact, a meta-analysis of 27 human trials designed to examine the effect of polyunsaturated and monounsaturated fatty acid rich diets on blood lipid levels found that both types of dietary fats may potentially lower total and LDL cholesterol levels. [24]
The problem with diets high in PUFA’s however, is that although they may decrease the total levels of LDL particles in the blood, they tend to create a higher concentration of polyunsaturated fats within the LDL particles, which in turn increases the amount of LDL oxidation. [25,26] This is because PUFA’s are more readily oxidized than MUFA’s due to the higher number of double bonds in their hydrocarbon chains.
Human trials have found that subjects given a diet high in Olive Oil and other oils rich in monounsaturated fats such as Oleic acid, have not only been able to lower LDL levels but significantly decreased LDL oxidation, particularly compared to those given a high PUFA diet. [27-33]
Anti-hypertensive action
Epidemiological studies have not always found a correlation between fat intake and high-blood pressure (hypertension). [34-36] In regards to Olive oil however, a cross-sectional study which compared the fatty acid levels of middle aged men throughout Europe, found that Italian men had significantly higher tissue levels of Oleic acid ( a type of MFA found in Olive oil), and also had lower blood pressures.[37]
Most clinical trials have found no difference in blood pressure among normotensive subjects (people with normal blood pressure) when given Mediterranean-type diets. [38,39] One trial however found that healthy patients given a diet high in Olive oil (40% fat, 22% MUFA) had reductions in blood pressure when compared to those given the National Cholesterol Education Program (NCEP) Step 1 diet (30% fat, 12% MUFA) [40]
Another trial found that giving a diet high in saturated fats to people who were used to consuming a Mediterranean style diet (low in SFA, high in MUFA) significantly increased their blood pressure. When they resumed their normal Mediterranean style diet however, their blood pressure went back to normal. [41]
These studies however examined the effect of Olive oil containing diets in normotensive people (people with normal blood pressure). The results of a randomized, crossover trial involving 23 hypertensive patients (people with high-blood pressure) who were given different diets over a year, found that extra virgin olive oil significantly decreased the need for anti-hypertensive medications. It was suggested that this occurs due to the ability of phenolic compounds found in un-processed (extra-virgin) olive oils to enhance nitric oxide (NO) levels. [42] This study provides preliminary evidence that whilst Olive oil may not significantly affect blood pressure in normotensive individuals, it may have at least some beneficial effects in patients with high blood pressure.
Non-fatty acid components
Although it has been speculated that the beneficial effects of a Mediterranean-like diet are due to certain MUFA’s such as Oleic acid in Olive oil, recent investigations have found that the non-fatty acid component of olive oil such as certain phenols, possess beneficial biologic activities that may contribute to the lower incidence of coronary heart disease (CHD) in the Mediterranean area. [43] This is why Olive oil, particularly “extra virgin olive oil”, may be healthier than other foods and oils high in MUFA’s. In fact, the main peculiarity of extra-virgin olive oil is the presence of remarkable quantities of phenolic compounds which not only provide high stability and strong taste but may be at least in part responsible for extra-virgin olive oils anti-atherogenic potential (the ability to inhibit the development of atherosclerotic plaques). [44,45]
Many of these beneficial phenolic compounds are not present in other oils, and are lost in the processing that occurs in olive oils other than those classed as “extra virgin”. “Extra-virgin” olive oil is considered the best, is the least processed and is made from the first pressing of the olives. “Virgin” olive oil comes from the second pressing and has lost much of the beneficial phenolic compounds. “Pure” olive oil is actually even less pure than “virgin” and “extra-virgin” because it undergoes more processing such as filtering and refining. “Extra light” olive oil undergoes even more processing. Because further processing results in further losses of these antioxidant phenols, “extra-virgin” olive oil is the most pure form and contains the highest concentration of phenolic compounds.
Among the protective phenolic compounds found in extra-virgin olive oil are the antioxidants Hydroxytyrosol [46] and oleuropein, both of which are readily absorbed by the body [47] and have shown to possess potent free-radical scavenging properties. [48] Studies have shown that administration of even relatively low doses of olive oil phenols can significantly increase antioxidant levels in the body and decrease oxidative stress in both humans [49] and animals. [50]
Anti-inflammatory effect
Laboratory studies have also shown anti-inflammatory effects of olive oil. Rats fed virgin olive oil had less inflammation when injected with carrageenan (a substance used to induce arthritis) than what rats fed other oils did. Moreover, the rats fed virgin olive oil with an added phenolic component (similar to that found in extra virgin olive oil) had even less inflammation. [51]
A similar study found that both the “un-saponifiable fraction” (non-fat portion) of virgin olive oil including beta-sitosterol and erythrodiol, as well as its phenolic compounds oleuropein, tyrosol, hydroxytyrosol and caffeic acid, all exerted a significant anti-inflammatory effect almost as effective as the anti-inflammatory drug indomethacin (an NSAID) did. [52]
The anti-inflammatory properties of olive oil’s non-fat components may also contribute towards its cardio-protective effects, as inflammation and inflammatory responses of the vascular endothelium are known to play an important role in the development of atherosclerosis. [53,54]
Anti-platelet activity
Laboratory studies have also found that 2-(3,4-di-hydroxyphenyl)-ethanol (DHPE), a phenol component of extra-virgin olive oil with potent antioxidant properties, is able to inhibit platelet aggregation (blood clotting) more effectively that other flavonoids (a class of antioxidant polyphenols found in plant foods known to have potentially healthful effects on a multitude of common chronic health problems). The phenol enriched portion of olive oil also demonstrated similar activity. [55]
This is important because heart attacks and strokes are caused by blood clots which build up in the arteries of the heart or brain which have been narrowed due to atherosclerotic plaque formation. The ability to form normal blood clots to physical trauma is of course necessary to prevent haemorrhage (uncontrolled bleeding), however the degree of blood clot inhibition which would occur due to olive oil consumption would not be so severe that it would be dangerous at all.
Anti-Oxidant Components
Olive oil is very high in vitamin E, but other than that, most of its antioxidant properties come from its phenolic components. Phenolic compounds such as flavonoids are widespread in many plant foods and influence the quality, palatability, and stability of foods by acting as flavourants, colourants, and antioxidants. When consumed, certain phenolic compounds are known to exhibit pharmacological effects on the body, such as anti-carcinogenic (anti-cancer), anti-inflammatory, anti-oxidant, anti-atherogenic effects etc. [56]
Laboratory investigations have found that the phenolic constituents of olive oil can significantly inhibit the oxidation of LDL “bad” cholesterol. [57,58] Animal experiments have revealed that greater reductions in LDL oxidation occurred in rats, rabbits and hamsters when fed olive oil than when fed oils similar to olive oil other than its phenolic components. [59-61] Human investigations have revealed greater reductions in LDL oxidation when given extra-virgin olive oil or virgin olive oil with a higher phenolic content than when given other olive oils. [62,63]
These studies suggest that the reduction in LDL oxidation that occurs after consumption of extra-virgin olive oil may be due to its phenolic constituents rather than just its monounsaturated Oleic acid and vitamin E content.
Effects on HDL “good” Cholesterol
Animal studies have shown that rats fed olive oil enriched with the non-fatty acid components had greater beneficial effects on HLD “good” cholesterol than did those fed ordinary virgin olive oil, or oil enriched with Oleic acid. [64] This study suggests that substances other than the fatty acid in olive oil may exert beneficial effects on the cardiovascular system.
The Bottom Line
This evidence strongly suggests not only that Olive oil has superior protective effects than other foods high in monounsaturated fatty acids (MUFA’s) due to its non-fat components, but extra-virgin olive oil may be the most beneficial type of olive oil due to its higher concentration of these protective non-fat components, including a variety of phenolic compounds and other antioxidants.
Olive Oil and Breast Cancer
Epidemiology
It has been found that the rates of cancer among the Mediterranean populations are significantly lower than the rest of Europe and the United States. This has been attributed to the high dietary intake of plant foods and olive oil. [65] Although it has been observed that per capita fat consumption around the world is highly correlated with breast cancer incidence and mortality, [66,67] the incidence rates of breast cancer in Mediterranean countries are relatively low compared with those in most other Western countries [68] despite Mediterranean diets being relatively high in fat. In fact, the incidence of breast cancer in Spain is about 40% lower than that in the U.S, Canada or northern Europe. [69] Studies have shown that Greek women derive approximately 42% of their energy intake from fat, (mostly from olive oil), [70] however they have a substantially lower rate of death from breast cancer than women in the U.S, despite American women deriving only 35% of their average energy intake from fat. [71]
Several case-control studies throughout Mediterranean populations have found that women who consume olive oil frequently have a reduced risk of breast cancer. Among these was a study in Spain which compared the diets of 100 breast cancer patients with 100 women without breast cancer. The results showed 70% less breast cancer among frequent consumers of olive oil. [72]
Another study in Greece compared the diets of 820 women diagnosed with breast cancer and 1,548 women without breast cancer. This study found a 25% reduction in breast cancer risk among the more frequent consumers of olive oil. [73] The other case-control studies conducted in Spain [74] and Italy [75,76] also found a modest protective association between olive oil consumption and breast cancer.
Oleic Acid
Although it is not clear precisely what component of olive oil its protective effect on breast cancer can be attributed to, it has been suggested that a type of fatty acid called Oleic acid may be at least in part responsible. Animal studies have found that olive oils higher in Oleic acid have prevented carcinogen-induced breast cancer better than olive oils with lower concentrations of Oleic acid. [77]
Recent Laboratory studies have found that Oleic acid can induce apoptosis (normal cell death which fails to occur in cancer cells) in breast cancer cells. It was found that Oleic acid can significantly reduced the levels of a gene called Her-2/neu – which is thought to trigger breast cancer. [78] This gene is found in high levels in around one in five breast cancer patients and is associated with a poor prognosis.
Further research is needed to better understand what kind of anti-cancer activity olive oil may possess.
REFERENCES
[1] Ferro-Luzzi A, Branca F: Mediterranean diet, Italian type: prototype of a healthy diet. Am J Clin Nutr 61: 1338S-1345S (1995).
[2] Keys A, Menotti A, Karvonen MJ, et al.: The diet and 15-year death rate in the Seven Countries Study. Am J Epidemiol 124: 903-915 (1986).
[3] Visioli F, Galli C. Biological properties of olive oil phytochemicals. Crit Rev Food Sci Nutr. 2002;42(3):209-21.
[4] Martinez-Gonzalez MA, Fernandez-Jarne E, Serrano-Martinez M, Marti A, Martinez JA, Martin-Moreno JM. Mediterranean diet and reduction in the risk of a first acute myocardial infarction: an operational healthy dietary score. Eur J Nutr. 2002 Aug;41(4):153-60.]
[5] Panagiotakos DB, Pitsavos Ch, Chrysohoou Ch, Stefanadis Ch, Toutouzas P. The role of traditional mediterranean type of diet and lifestyle, in the development of acute coronary syndromes: preliminary results from CARDIO 2000 study. Cent Eur J Public Health. 2002 Jun;10(1-2):11-5.
[6] Panagiotakos DB, Pitsavos C, Polychronopoulos E, Chrysohoou C, Zampelas A, Trichopoulou A. Can a Mediterranean diet moderate the development and clinical progression of coronary heart disease? A systematic review Med Sci Monit. 2004 Aug;10(8):RA193-8. Epub 2004 Jul 23.
[7] Keys A, Menotti A, Karvonen MJ, et al.: The diet and 15-year death rate in the Seven Countries Study. Am J Epidemiol 124: 903-915 (1986).
[8] Fernandez-Jarne E, Martinez-Losa E, Prado-Santamaria M, Brugarolas-Brufau C, Serrano-Martinez M, Martinez-Gonzalez MA. Risk of first non-fatal myocardial infarction negatively associated with olive oil consumption: a case-control study in Spain. Int J Epidemiol. 2002 Apr;31(2):474-80.
[9] Berry EM, Eisenberg S, Haratz D, Frielander Y, Norman Y, Kaufmann NA, Stein Y. Effects of diets rich in monounsaturated fatty acids on plasma lipoproteins – The Jerusalem Nutrition Study: high MUFAs vs high PUFAs. Am J Clin Nutr 53: 899-907 (1991)
[10] Berry EM, Eisenberg S, Frielander Y, et al. Effects of diets rich in monounsaturated fatty acids on plasma lipoproteins – The Jerusalem Nutrition Study II: monounsaturated fatty acids vs carbohydrates. Am J Clin Nutr 56: 394-403 (1992)
[11] Berry EM, Eisenberg S, Friedlander Y, Harats D, Kaufmann NA, Norman Y, Stein Y. Effects of diets rich in monounsaturated fatty acids on plasma lipoproteins. The Jerusalem Nutrition Study: monounsaturated vs saturated fatty acids. Nutr Metab Cardiovasc Dis 5: 55-62 (1995)
[12] Gustafsson IB, Vessby B, Nydahl M. Effects of lipid-lowering diets enriched with monounsatured and polyunsaturated fatty acids on serum lipoprotein composition in patients with hyperlipoproteinaemia. Atherosclerosis 96: 109-118 (1992)
[13] Gustafsson IB, Vessby B, Öhrvall M, Nydahl M. A diet rich in monounsaturated rapeseed oil reduces the lipoprotein cholesterol concentration and increases the relative content of n-3 fatty acids in serum in hyperlipidemic subjects. Am J Clin Nutr 59: 667-674 (1994)
[4] Mata P, Garrido JA, Ordovas JM, et al. Effect of dietary monounsaturated fatty acids on plasma lipoproteins and apolipoproteins in women. Am J Clin Nutr 56: 77-83 (1992)
[15] Mensink RP, Katan MB. Effect of a diet enriched with monounsaturated or polyunsaturated fatty acids on levels of low-density and high-density lipoprotein cholesterol in healthy women and men. N Engl J Med 321: 436-441 (1989)
[16] Wahrburg U, Martin H, Sandkamp M, Schulte H, Assmann G. Comparative effects of a recommended lipid-lowering diet vs a diet rich in monounsaturated fatty acids on serum lipid profiles in healthy young adults. Am J Clin Nutr 56: 678-683 (1992)
[17] European Atherosclerosis Society (EAS). Prevention of coronary heart disease: scientific background and new clinical guidelines. Recommendations of the European Atherosclerosis Society prepared by the International Task Force for Prevention of Coronary Heart Disease. Nutr Metab Cardiovasc Dis 2: 113-156 (1992)
[18] Frick MH, Elo O, Haapa K, et al. Helsinki Heart Study: Primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia: Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med 317: 1237-1245 (1987)
[19] Internation Lipid Information Bureau. The ILIP Lipid Handbook for Clinical Practice. Blood Lipids and Coronary Heart Disease. 1995
[20] Lipid Research Clinics Program. The Lipid Research Clinics Coronary Primary Prevention Trial results. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA 251: 365-374 (1984)
[21] National Institutes of Health. National Cholesterol Education Programm. Second Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). NIH Publication No. 93-3095, September 1993
[22] Mata P, Alvarezsala LA, Rubio MJ, Nuno J, De Oya M. Effects of long-term monounsaturated-enriched vs polyunsaturated-enriched diets on lipoproteins in healthy men and women. Am J Clin Nutr 55: 846-850 (1992)
[23] Sirtori CR, Tremoli E, Gatti E, et al. Controlled evaluation of fat intake in the Mediterranean diet: comparative activities of olive oil and corn oil on plasma lipids and platelets in high-risk patients. Am J Clin Nutr 44: 635-642 (1986)
[24] Mensink RP, Katan MB. Effect of a dietary fatty acids on serum lipids and lipoproteins – A meta-analysis of 27 trials. Arteriosclerosis Thromb 12: 911-919 (1992)
[25] Reaven P, Parthasarathy S, Grasse BJ, et al.: Feasibility of using an oleate-rich diet to reduce the susceptibility of low-density lipoprotein to oxidative modification in humans. Am J Clin Nutr 54: 701-706 (1991).
[26] Bonanome A, Pagnan A, Biffanti S, et al.: Effect of dietary monounsaturated fatty acids on the susceptibility of plasma low density lipoproteins to oxidative modification. Arterioscler Thromb 12: 529-533 (1992).
[27] Reaven P, Parthasarathy S, Grasse BJ, et al.: Feasibility of using an oleate-rich diet to reduce the susceptibility of low-density lipoprotein to oxidative modification in humans. Am J Clin Nutr 54: 701-706 (1991).
[28] Bonanome A, Pagnan A, Biffanti S, et al.: Effect of dietary monounsaturated fatty acids on the susceptibility of plasma low density lipoproteins to oxidative modification. Arterioscler Thromb 12: 529-533 (1992).
[29] Reaven P, Parthasarathy S, Grasse BJ, et al.: Effects of oleate-rich and linoleate-rich diets on the susceptibility of low density lipoprotein to oxidative modification in mildly hypercholesterolemic subjects. J Clin Invest 91: 668-676 (1993)
[30] Abbey M, Belling GB, Noakes M, et al.: Oxidation of low-density lipoproteins: intraindividual variability and the effect of dietary linoleate supplementation. Am J Clin Nutr 57: 391-398 (1993).
[31] Mata P, Alonso R, Lopez-Farre A, et al.: Effect of dietary fat saturation on LDL oxidation and monoycte adhesion to human endothelial cells in vitro. Arterioscler Throm Vasc Biol 16: 1347-1355 (1996).
[32] Berry EM, Eisenberg S, Friedlander Y, et al.: Effects of diets rich in monounsaturated fatty acids on plasma lipoproteins-the Jerusalem Nutrition study. II Monounsaturated fatty acids vs carbohydrates. Am J Clin Nutr 56: 394-403 (1992).
[33] Aviram M, Eias K: Dietary olive oil reduces low-density lipoprotein uptake by macrophages and decreases the susceptibility of the lipoprotein to undergo lipid peroxidation. Ann Nutr Metab 37: 75-84 (1993).
[34] Stamler J, Caggiula A, Grandits A: Relationships of dietary variables to blood pressure (BP): findings of the Multiple Risk Factor Intervention Trial (MRFIT). Circulation 85: 867 ( 1992).
[35] Witteman J, Willett W, Stampfer M, et al.: A prospective study of nutritional factors and hypertension among US women. Circulation 80: 1320-1327 (1989).
[36] Ascherio A, Rimm E, Giovannucci E, et al.: A prospective study of nutritional factors and hypertension among US men. Circulation 86: 1475-1484 (1992).
[37] Riemersma RA, Wood DA, Butler RA, et al.: Linoleic acid content in adipose tissue and coronary heart disease. BMJ 292: 1423-1427 (1986).
[38] Mensink R, Janssen M, Katan M: Effect on blood pressure of two diets differing in total fat but not in saturated and polyunsaturated fatty acids in healthy volunteers. Am J Clin Nutr 47: 976-980 (1988).
[39] Mensink R, Stowijk A, Katan M: Effect of monounsaturated diet versus polyunsaturated fatty acid enriched diet on blood pressure in normotensive women and men. Eur J Clin Invest 20: 463-469 (1990).
[40] Espino-Montoro A, Lopez-Miranda J, Castro P, et al.: Monounsaturated fatty acid enriched diets lower plasma insulin levels and blood pressure in healthy young men. Nutr Metab Cardiovasc Dis 6: 147-154 (1996).
[41] Strazullo P, Ferro-Luzzi A, Saini, A, et al.: Changing the Mediterranean diet: effects on blood pressure. J Hypertension 4: 407-412 (1986).
[42] Ferrara, L. A.; Raimondi, A. S.; d’Episcopo, L.; Guida, L.; Dello, R. A.; Marotta, T. Olive Oil and Reduced Need for Antihypertensive Medications. Arch. Intern. Med.2000,160, 837-842.
[43] Visioli, F.; Galli, C. The Effect of Minor Constituents of Olive Oil on Cardiovascular Disease: New Findings. Nutr. Rev. 1998,56, 142-147.
[44] Visioli, F.; Galli, C. Antiatherogenic Components of Olive Oil. Curr. Atheroscler. Rep.2001,3, 64-67.
[45] 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.
[46] Deiana, M.; Aruoma, O. I.; Bianchi, M. L.; Spencer, J. P.; Kaur, H.; Halliwell, B.; Aeschbach, R.; Banni, S.; Dessi, M. A.; Corongiu, F. P. Inhibition of Peroxynitrite Dependent DNA Base Modification and Tyrosine Nitration by the Extra Virgin Olive Oil-Derived Antioxidant Hydroxytyrosol. Free Radic. Biol. Med.1999,26, 762-769.
[47] Vissers, M. N.; Zock, P. L.; Roodenburg, A. J.; Leenen, R.; Katan, M. B. Olive Oil Phenols Are Absorbed in Humans. J Nutr 2002,132, 409-417.
[48] Visioli, F.; Bellomo, G.; Galli, C. Free Radical-Scavenging Properties of Olive Oil Polyphenols. Biochem. Biophys. Res. Commun.1998,247, 60-64.
[49] Visioli, F.; Caruso, D.; Galli, C.; Viappiani, S.; Galli, G.; Sala, A. Olive Oils Rich in Natural Catecholic Phenols Decrease Isoprostane Excretion in Humans. Biochem Biophys Res Commun 2000, 278, 797-799.
[50] Visioli, F.; Galli, C.; Plasmati, E.; Viappiani, S.; Hernandez, A.; Colombo, C.; Sala, A. Olive Phenol Hydroxytyrosol Prevents Passive Smoking-Induced Oxidative Stress. Circulation 2000,102, 2169-2171.
[51] Martinez-Dominguez, E.; de la, P. R.; Ruiz-Gutierrez, V. Protective Effects Upon Experimental Inflammation Models of a Polyphenol-Supplemented Virgin Olive Oil Diet. Inflamm. Res 2001,50, 102-106.
[52] de la, P. R.; Martinez-Dominguez, E.; Ruiz-Gutierrez, V. Effect of Minor Components of Virgin Olive Oil on Topical Antiinflammatory Assays. Z Naturforsch. [C. ]2000,55, 814-819.
[53] Zebrack JS, Anderson JL. Role of inflammation in cardiovascular disease: how to use C-reactive protein in clinical practice Prog Cardiovasc Nurs. 2002 Fall;17(4):174-85.
[54] Shen CX, Chen HZ, Ge JB. The role of inflammatory stress in acute coronary syndrome. Chin Med J (Engl). 2004 Jan;117(1):133-9.
[55] Petroni, A.; Blasevich, M.; Salami, M.; Papini, N.; Montedoro, G. F.; Galli, C. Inhibition of Platelet Aggregation and Eicosanoid Production by Phenolic Components of Olive Oil. Thromb. Res.1995, 78, 151-160.
[56] Decker EA: The role of phenolics, conjugated linoleic acid, carnosine, and pyrroloquinoline quinone as non essential dietary antioxidants. Nutr Rev 53: 49-58 (1995).
[57] Visioli, F.; Bellomo, G.; Montedoro, G.; Galli, C. Low Density Lipoprotein Oxidation Is Inhibited in Vitro by Olive Oil Constituents. Atherosclerosis 1995, 117, 25-32.
[58] Caruso, D.; Berra, B.; Giavarini, F.; Cortesi, N.; Fedeli, E.; Galli, G. Effect of Virgin Olive Oil Phenolic Compounds on in Vitro Oxidation of Human Low Density Lipoproteins. Nutr. Metab Cardiovasc. Dis.1999, 9 , 102-107.
[59] Scaccini C, Nardini M, D’Aquino M, et al.: Effect of dietary oils on lipid peroxidation and on antioxidant parameters of rat plasma and lipoprotein fractions. J Lipid Res 33: 627-633 (1992).
[60] Wiseman SA, Mathot JNNJ, de Fouw NJ, Tijburg LBM: Dietary non-tocopherol antioxidants present in extra virgin olive oil increase the resistance of low density lipoproteins to oxidation in rabbits. Atherosclerosis 120: 15-23 (1996).
[61] 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
[62] Ramirez-Tortosa, M. C.; Urbano, G.; Lopez-Jurado, M.; Nestares, T.; Gomez, M. C.; Mir, A.; Ros, E.; Mataix, J.; Gil, A. Extra-Virgin Olive Oil Increases the Resistance of LDL to Oxidation More Than Refined Olive Oil in Free-Living Men With Peripheral Vascular Disease. J Nutr 1999,129, 2177-2183.
[63] Marrugat J, Covas MI, Fito M, Schroder H, Miro-Casas E, Gimeno E, Lopez-Sabater MC, de la Torre R, Farre M; SOLOS Investigators. 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. Epub 2004 Jan 06.
[64] Mangas-Cruz, M. A.; Fernandez-Moyano, A.; Albi, T.; Guinda, A.; Relimpio, F.; Lanzon, A.; Pereira, J. L.; Serrera, J. L.; Montilla, C.; Astorga, R.; Garcia-Luna, P. P. Effects of Minor Constituents (Non-Glyceride Compounds) of Virgin Olive Oil on Plasma Lipid Concentrations in Male Wistar Rats. Clin Nutr 2001,20, 211-215.
[65] Trichopoulou A, Lagiou P, Kuper H, Trichopoulos D. Cancer and Mediterranean dietary traditions. Cancer Epidemiol Biomarkers Prev. 2000 Sep;9(9):869-73
[66] Carroll KK. Experimental evidence of dietary factors and hormone- dependent cancers. Cancer Res 1975;35:3374–83.
[67] Armstrong B, Doll R. Environmental factors and cancer incidence and mortality in different countries, with special reference to dietary practices. Int J Cancer 1975;15:617–31.
[68] Cohen LA, Wynder EI. Do dietary monounsaturated fatty acids play a protective role in carcinogenesis and cardiovascular disease? Med Hypotheses 1990;31:83–9.
[69] Esteve J, Kriker A, Ferlay J, Parkin DM. Facts and figures of cancer in the European Community. Lyon: International Agency for Research on Cancer, 1993.
[70] Trichopoulou A, Toupadaki N, Tzonou A, Katsouyanni K, Manousos O, Kada E, et al. The macronutrient composition of the Greek diet: estimates derived from six case–control studies. Eur J Clin Nutr 1993;47:549–58.
[71] Lenfant C, Ernst N. Daily dietary fat and total food-energy intakes Third National Health and Nutrition Examination Survey, Phase 1, 1988–91. MMWR 1994;43:116–7, 123–5.
[72] Landa M-C, Frago N, Tres A. Diet and the risk of breast cancer in Spain. Eur J Cancer Prev 1994;3:313–29.
[73] Trichopoulou A, Katsouyanni K, Stuver S, Tzala L, Gnardellis C, Rimm E, et al. Consumption of olive oil and specific food groups in relation to breast cancer risk in Greece. J Natl Cancer Inst 1995;87:110–6.
[74] Martin-Moreno JM, Willett WC, Gorgojo L, Banegas JR, Rodriguez- Artalejo F, Fernandez-Rodriguez JC, et al. Dietary fat, olive oil intake and breast cancer risk. Int J Cancer 1994;58: 774–80.
[75] Toniolo P, Riboli E, Protta F, Charrel M, Cappa APM. Calorieproviding nutrients and risk of breast cancer. J Natl Cancer Inst 1989;81:278–86.
[76] La Vecchia C, Negri E, Franceschi S, Decarli A, Giacosa A, Lipworth L. Olive oil, other dietary fats, and the risk of breast
[77] Cohen LA, Epstein M, Pittman B, Rivenson A. The influence of different varieties of olive oil on N-methylnitrosourea(NMU)-induced mammary tumorigenesis. Anticancer Res. 2000 Jul-Aug;20(4):2307-12.
[78] Menendez JA, Vellon L, Colomer R, Lupu R. Oleic acid, the main monounsaturated fatty acid of olive oil, suppresses Her-2/neu (erbB-2) expression and synergistically enhances the growth inhibitory effects of trastuzumab (HerceptinTM) in breast cancer cells with Her-2/neu oncogene amplification. Ann Oncol. 2005 Jan 10