History Sharkliveroil l What is squalene? l The Role of Squalene in Health  l  Dr. Carl A. Luer

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Health and dieet

The Scientific Basis for its Health Benefits

by Kevin C. Vigilante, MD, MPH, and Mary M. Flynn, PhD, RD
International Journal of Integrative Medicine, Vo3, No 2, Aug/Sep 2001


Note: The information on this website is  not a substitute  for the advice of  & treatment by a qualified professional.

The Mediterranean diet encompasses a broad range of cuisines native to the entire area bounding the Mediterranean Sea. Despite this diversity, all these cuisines that we collectively label "the Mediterranean diet"1 share many common characteristics. While not strictly vegetarian, these cuisines are traditionally plant-­based diets in which red meat is consumed only a few times a month. Fruits, vegetables, bread, cereals, legumes, and nuts are eaten in abundance, and red wine is a part of everyday life. Chicken and fish appear on the table in low to moderate amounts, and dairy is consumed mostly in the form of yogurt and cheese - and usually as a condiment.

Perhaps the most defining characteristic of this dietary approach is its use of olive oil, which is the principal fat source and the culinary foundation of these cuisines. Despite the high percentage of fat in this diet, the evidence suggests that this is one of the world's healthiest cuisines and should be considered a model for healthy eating.


In the early 1960s, Greece enjoyed the greatest longevity among all nations tracked by the World Health Organization,2 despite endemic poverty, a poor healthcare system, and pervasive smoking. About the same time, the Seven Country Study3 analyzed the diets and mortality among 12,700 men divided into 11 cohorts in 7 different countries: the United States, Finland, Japan, Italy, Greece, Yugoslavia, and the Netherlands.

The study results indicated that the healthiest participants were in Japan and Greece. However, when comparing the cohort from Greece with the Japanese, who are well known for their low rates of heart disease, the Greeks were found to have almost a 4-fold lower rate of heart disease. The Greeks achieved this low level of heart disease risk despite consuming the diet with the highest amount of fat (42%). However, the main source of dietary fat in Greece was olive oil.

In a 15-year follow up to this study,4 the greatest predictor of longevity was the ratio of dietary monounsaturated fat to saturated fat.


Some have suggested that lifestyle patterns other than diet account for Mediterranean health. However, the Lyon Heart Study5 suggests otherwise. This study randomized approximately 300 cardiac patients to a Mediterranean-style diet and a similar number to an American Heart Association-style diet. The 2 dietary regimens differed mainly in their fat source. The Mediterranean diet emphasized mostly monounsaturated fats (olive oil and canola oil), while the American Heart Association diet utilized polyunsaturated fats. 

After 27 months, the ethics committee stopped the study because the Mediterranean diet group had 70% fewer cardiac incidents. After following these groups over 4 years,6 the Mediterranean advantage persisted with a 61% lower rate of cancer and a 56% lower overall mortality. A retrospective analysis on the consumption patterns of the 2 groups revealed that the major difference was the fat source used. However, the Mediterranean group also ate more fruits, vegetables, and cereal. This impressive outcome suggests that the Mediterranean diet, and especially its fat source, influences health and disease processes on a very fundamental level.


For years, the evidence has been mounting that the Mediterranean diet can reduce the risk of chronic disease. However, it is only recently that we have begun to understand why. The underlying benefit of this diet is likely derived from its rich spectrum of phytochemicals.7 These biochemical compounds found in the plant kingdom often protect plants from environmental, infectious, predatory, and oxidative threats. When humans consume these phytochemicals, they may confer similarly protective advantages, particularly, but not exclusively, as antioxidants. In a happy synergy between form and function, health and aesthetics, nature often endows the most colorful fruits and vegetables with the highest concentration of phytonutrients. The Mediterranean cuisine is one of the most colorful cuisines in the world.


Health benefits of olive oil

Olive oil consists of approximately 75% oleic acid (a monounsaturated fat), 15% saturated fat, and 10% polyunsaturated fat. The benefits of olive oil are often attributed to a salutary, but unexplained, influence on low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL). However, the mechanisms of disease prevention extend far beyond an isolated influence on the cholesterol profile.

Olive oil is extracted from the highly pigmented olive and is therefore extremely rich in phytonutrients. Not only does olive oil reduce the absolute levels of LDL when it replaces saturated fat, but it also plays a role in preventing LDL oxidation. Researchers in one study found that the phenolic compounds in olive oil were highly effective in preventing LDL oxidation when LDL was exposed to ultraviolet light.8 Another study compared the ability of phenolic compounds extracted from olive oil, extra virgin olive oil, and processed olive oil to prevent LDL oxidation.9 The extracted phenolic compounds prevented LDL oxidation in a dose-response relationship. Both kinds of olive oil also prevented LDL oxidation; however, the extra virgin olive oil had a significantly greater antioxidant effect. This suggests that processed (non-virgin) olive oils lose some of their phenolic content in the refining process.

Olive oil consumption has also been inversely related to the risk of certain cancers, including breast,10,11 colorectal,12 esophageal,13 and prostate cancer.14 One study found that lignans, which have been found to protect against breast, colon, and prostate cancer, form a major component of the phenolic fraction of olive oil.15

Other studies have attributed the anti-carcinogenic effect of olive oil to its squalene content. In animal models, squalene appears to suppress tumor growth.16 Squalene has a strong inhibitory effect on HMG-COA reductase, thereby reducing farnesyl pyrophosphate availability for "prenylation" of the ras oncogene, which has been strongly associated with breast, colon, and pancreatic cancers. Research suggests that the phenolic fraction of olive oil can suppress the reactive oxygen species, free radicals generated in large amounts by the colonic mucosa of cancer patients, and patients with ulcerative colitis or Crohn's disease.17

Enhanced absorption

Not only does olive oil carry its own supply of potent phytochemicals, it also enhances the absorption of phytonutrients from other sources. This is particularly relevant in the case of carotenoids. Carotenoids are substances found in fruits and vegetables with a deep color, which are prevalent in the Mediterranean diet. There are at least 500 known carotenoids in nature, and many protect against disease. For example, intake of lycopene, a carotenoid found in tomatoes, has been inversely related to rates of prostate cancer.18 It also seems to protect against other cancers and heart disease.19 However, lycopene, like all carotenoids, including beta carotene, lutein, and zeaxanthin, is lipophilic, that is, it requires dietary fat to be absorbed and transported. Ingested carotenoids become part of the chylomicrons, microscopic particles of emulsified fat found in the blood and lymph, which transport them throughout the circulation.

Carotenoids consumed without dietary fat, or in the presence of factors that interfere with dietary fat, will not be maximally absorbed. This may adversely affect health. One estimate suggests that decreasing plasma lycopene by 10% in the general male population would result in about 10,000 additional cases of prostate cancer.20 Combining olive oil with colored vegetables, as is the Mediterranean custom, assures that carotenoid absorption will be maximized.

Olive oil offers a distinct advantage over corn, safflower, sunflower, and soybean oils. These predominately polyunsaturated fats have multiple double bonds and are therefore predisposed to oxidation and free radical production. Some of these fats are relatively rich in vitamin E. However, the pro-oxidant environment these fats create --- especially when heated --- partially consumes their vitamin E content. Corn, safflower, sunflower, and soybean oils contain linoleic acid, which converts into arachidonic acid. Arachidonic acid is, in turn, converted into inflammatory prostaglandins and leukotrienes, which could increase the risk for atherosclerosis, arthritis, autoimmune conditions, and other chronic conditions.

In contrast, olive oil is mostly monounsaturated, and therefore highly resistant to oxidation even when heated. This means that there is significantly less free-radical production and that vitamin E contained in olive oil is more bioavailable.

Red wine


Multiple epidemiological studies, including the Copenhagen Heart Study,21 the Nurses' Health Study, the Framingham study, and an American Cancer Society study22 have associated moderate alcohol consumption with health and longevity. Many of these studies did not distinguish between different types of alcohol, and the benefits of alcohol were often attributed to its effects on HDL. However, these effects are probably too modest to explain the magnitude of the health benefits that have been observed. In the case of red wine, however, an alternative explanation reaches far beyond its alcohol content: the phytonutrient content of the grapes in red wine is delivered in a highly concentrated form.

Red wine is endowed with an extraordinary array of phytonutrients. Many of them are flavonoids, which are, in turn, part of the larger category of polyphenols. These substances include anthocyanin, caffeic acid, catechin, ellagic acid, ferulic acid, fisetin, leucocyanidol, p-coumaric, quercitin, and resveratrol. These powerful antioxidants protect against LDL oxidation and other pathologic sequelae of the oxidative process.


Many of the phytonutrients in red wine have functions that extend beyond their antioxidant role. For instance, certain wines, particularly American reds, contain salicylic acid, which inhibits platelet aggregation, and its metabolite gentisic acid, which also has anti-inflammatory properties.23 Salicylic acid is in turn derived from cinnamic acid, which has been shown to have antimutagenic effects.24 The quercetin and resveratrol in red wine promote vasodilatation and suppress platelet adhesion by enhancing the synthesis of nitric oxide.25 Resveratrol, a COX II inhibitor, seems to further inhibit platelet aggregation by promoting prostacylin and minimizing thromboxane.26 Caffeic acid has been shown to block the production of carcinogenic heterocyclic amines,27 compounds formed when meat is seared and browned.28 P-coumaric helps prevent the formation of potentially carcinogenic nitrosamines, which arise during the digestion of processed meats.29 These carcinogen-neutralizing effects underscore the importance of the Mediterranean habit of consuming wine with food.

Red wine versus other alcoholic beverages

Polyphenols inhibit proliferation of vascular smooth muscle cells,30 an important step in atherogenesis. A study reported in the British Medical Journal31 suggests that moderate alcohol consumption may promote insulin sensitivity. White wine, and alcohol consumption in general, has been associated with increased breast density on mammograms, a significant risk marker for breast cancer. However, red wine consumption was associated with decreased breast density.32 In addition, the polyphenols contained in red wine may inhibit proliferation of breast cancer cell lines in a dose - and time-dependent manner.33 These findings may help explain why alcohol consumption is associated with breast cancer in northern European countries but not in Mediterranean countries, where red wine is the principle alcoholic beverage.

A study at the University of Wisconsin compared the capacity of red wine, white wine, and other alcoholic beverages to inhibit platelet aggregation in humans. It found that red wine achieves this effect at much lower doses (J. Folts, personal communication, University of Wisconsin, January 1999). Other alcoholic beverages require a highly intoxicating dose to achieve a similar effect. However, platelet inhibition only lasts 24 to 48 hours.34 This finding demonstrates why the Mediterranean habit of drinking wine on a daily basis is important to its therapeutic effect.

A study at the University of Tokyo compared the vasodilatory effects of red and white wine in human subjects.30  It found that only red wine produced the desired effect. In addition, purple grape juice has been found to inhibit LDL oxidation, inhibit platelet aggregation, and promote vasodilation in much the same way as red wine.34 These results strongly suggest that the phytonutrients described above, not the alcohol, mediate the benefits of red wine.

Fruits, vegetables, and nuts

Multiple epidemiological studies have demonstrated the protective effect of fruits and vegetables. The Mediterranean diet encompasses an enormous variety of highly colorful fruits and vegetables. Each plant food in this diet brings to the table its own complement of phytonutrients.

Along with the olive and the grape, broccoli --- which is also plentiful in the Mediterranean diet --- has been one of the more well-studied plant foods. It is a very rich source of phytonutrients, including allyl sulfide, anthocyanin, catechin, chlorogenic acid, ferulic acid, fisetin, geraniol, isoprenoids, limonene, lutein, lycopene, oleuropein, resveratrol, squalene, tangeritin, and urosolic acid, to name a few. In addition to being powerful, all-purpose antioxidants, many of these compounds have demonstrated antimutagenic effects in both in vitro and animal studies. Some of the better known anticarcinogenic compounds in broccoli are sulphorophane, which is found to be highly concentrated in broccoli sprouts, and indol-3-carbinol, which is being evaluated by the NCI's Division of Cancer Prevention as a potential chemopreventive agent.35 Indol-3-carbinol is found in other cruciferous vegetables, such as broccoli rabe, kale, and cauliflower. One would expect additive or perhaps even synergistic contributions from the scores of other fruits and vegetables common to the Mediterranean diet.

Nuts, especially walnuts, are common condiments and snacks in the Mediterranean diet. Even in small numbers, they may significantly affect health. The Nurses' Health Study found that women who ate 5 oz of nuts a week had 35% fewer heart attack.36 Walnuts are a good source of omega-3 fatty acids. Other sources of this beneficial fat are cold-water fish, canola oil, and purslane, a leafy green herb commonly consumed in Greece.

Omega-3 fatty acids are associated with lower rates of heart disease. One commonly advanced explanation is that omega-3 polyunsaturated fats are precursors to noninflammatory prostaglandins, while the omega-6 polyunsaturated fats, found in corn oil and other seed oils, are precursors to the inflammatory prostaglandins. Omega-3 and omega-6 fats compete in metabolic pathways. By increasing the omega-3-to-omega-6 ratio, a less inflammatory milieu is created.


Beans are avidly consumed in the Mediterranean and appear to contribute to health. A study of the dietary habits of elderly Greeks found that those who departed from traditional ways of eating suffered significantly higher rates of chronic disease.37 The biggest difference in their new diet, as compared with the traditional Mediterranean diet, was a reduced intake of beans and a greater intake of meat. The improved health of the traditional cohort could be attributed to a substitution effect in which beans merely replaced meat. However, evidence suggests that beans have inherent health benefits. Beans are not highly pigmented, but they do carry a complement of phytonutrients. They are also important sources of dietary fiber. Even though recent results from the Nurses' Health Study have raised doubts about the role of fiber in preventing colon cancer,38 fiber is still associated with cardiac health.39

The importance of what Mediterraneans don't eat

Perhaps just as important as what Mediterraneans do eat is what they don't eat. This is especially true when it comes to meat, which is consumed infrequently. In addition to saturated fat, meat carries with it a host of other substances that may pose a threat to health.40 Heterocyclic amines are known to be carcinogenic and are readily formed when meat is seared and browned.28 Carcinogenic nitrosamines are associated with the digestion of processed meats. Some researchers have proposed that because iron easily oxidizes, meat consumption increases the oxidative burden. Meat also contains iron and methionine, which is a precursor to homocysteine and which may pose a cardiovascular threat.

Mediterraneans do not traditionally consume large amounts of seed oil, such as corn, safflower, sunflower, and soybean oils. Once thought to be healthy replacements for saturated fats, growing evidence indicates that these polyunsaturated fats may pose problems of their own. Animal data suggest that they promote carcinogenesis. There is evidence that women who consume these fats instead of olive oil have higher rates of breast cancer.41 In addition to having multiple double bonds, which predispose seed oils to oxidation, as noted above, they are highly refined. It is likely that whatever limited phytochemical content they possess is reduced further in the refining process.

Mediterraneans traditionally consume very little butter and milk, further reducing their saturated fat intake. Also, trans-fats are not part of the traditional Mediterranean diet. In contrast, the prevalence of trans-fatty acids in the diet closely tracks the North American epidemic of heart disease over the last 60 years.

Ease of transportation and international commerce have made the world "smaller" and hence more homogeneous. Mediterraneans have begun to follow a diet more similar to that of the North American population, including fast food. They are already beginning to pay the price with higher rates of heart disease and cancer. Therefore, it is important to make the traditional Mediterranean diet our model of healthy eating.


Considerable evidence indicates that the Mediterranean diet lowers the risk of cancer, heart disease, and other chronic illnesses. Recent research has revealed the role of phytonutrients in health and disease. It is likely that the Mediterranean diet mediates its effects through its rich phytonutrient content. Limited intake of red meat, seed oils, dairy products, and trans-fats also contributes to the health benefits of this diet.


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16. Newmark HL. Squalene, olive oil, and cancer risk: review and hypothesis. Ann N 2'Acad Sci. 1999;889:193-203.

17. Owen RW, Giacosa A, Hull WE, Haubner R, Spiegelhalder B, Bartsch H. The antioxidant/anticancer potential of phenolic compounds isolated from olive oil. EurJCancer. 2000;36(10):1235-1247.

18. Giovannucci E, Clinton SK. Tomatoes, lycopene, and prostate cancer. Proc Soc Exp Biol Med. 1998;218(2):129-139.

19. Kohlmeier L, Kark JD, Gomez-Gracia E, et al. Lycopene and myocardial infarction risk in the EURAMIC Study. Am jEpidemiol.1997;146(8):618-626.

20. Stampfer M. Effects of carotenoid reduction on disease incidence: quantitative estimates. In: Anderson D, ed. Potential Effects of Reducing Carotenoid Levels on Human Health. Harvard School of Public Health; 1996:71-76

21. Gronbaek M, Deis A, Sorensen TI, Becker U, Schnohr P, Jensen G. Mortality associated with moderate intakes of wine, beer, or spirits. BMJ. 1995;310(6988):1165-1169.

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27. Oguri A, Suda M, Totsuka Y, Sugimura T, Wakabayashi K Inhibitory effects of antioxidants on formation ofheterocyche amines. MutatRes.1998;402(1­2):237-245.

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32. Vachon CM, Kushi LH, Cerhan JR, Kuni CC, Sellers TA. Association of diet and mammographic breast density in the Minnesota breast cancer family cohort. Cancer Epidemiol Biomarkers Prev. 2000;9(2):151-160.

33. Damianaki A, Bakogeorgou E, Kampa M, et al. Potent inhibitory action of red wine polyphenols on human breast cancer cells. J Cell Biochem. 2000;78(3):429-441.

34. Stein JH, Keevil JG, Wiebe DA, Aeschlimann S, Folts JD. Purple grape juice improves endothelial function and reduces the susceptibility of LDL cholesterol to oxidation in patients with coronary artery disease. Circulation. 1999;100(10):1050-1055.

35. Summary of data for chemical selection: Indole-3-carbinol. NIH Environmental Health Science; 1998.

36. Hu FB, Stampfer MJ, Manson JE, et al. Frequent nut consumption and risk of coronary heart disease in women: prospective cohort study. BMJ. 1998;317(7169):1341-1345.

37. Trichopoulou A, Kouris-Blazos A, Wahlqvist ML, et al. Diet and overall survival in elderly people. BMJ. 1995;311(7018):1457-1460.

38. Fuchs CS, Giovannucci EL, Colditz GA, et al. Dietary fiber and the risk of colorectalcancer andadenoma inwomen. NEnglJMed.1999;340(3):169-176. 39. Wolk A, Manson JE, Stampfer MJ, et al. Long-term intake of dietary fiber and decreased risk of coronary heart disease among women. JAMA. 1999;281(21):1998-2004.

40. Kushi LH, Lenart EB, Willett WC. health implications of Mediterranean diets in light of contemporary knowledge. 2. Meat, wine, fats, and oils. Am J Clin Nutr. 1995;61(6 suppl):1416S-14275.

41. Wolk A, Bergstrom R, Hunter D, et al. A prospective study of association of monounsaturated fat and other types of fat with risk of breast cancer. Arch Intern Med. 1998;158(l)

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