Fact Sheet 1 - Executive Summary

Scientific Evidence for Olive oil and its effects on lipid metabolism
Author: Eurosciences Communication in co-operation with Arteriosclerosis Research at the University of Mnster, Germany. the Institute of

Coronary heart disease (CHD) is associated with a number of risk factors eg. smoking, high blood pressure and hyperlipidaemia. Of these risk factors, cholesterol is particularly important. Evidence from many sources (genetic, experimental, epidemiological and clinical trial data) consistently shows a strong, independent, relationship between plasma cholesterol and CHD. Lowering cholesterol levels produces a statistically significant reduction in the incidence of heart attacks. Typically, a 1% reduction in cholesterol produces a 2-3% reduction in CHD risk. It is now understood that there are two types of cholesterol - low density lipoprotein (LDL) and high density lipoprotein (HDL) - the so-called bad and good cholesterol respectively. High levels of HDL cholesterol reduces CHD risk whereas increased levels of LDL cholesterol increase CHD risk. In addition, high levels of another sort of fat triglycerides, particularly in the presence of low levels of HDL, and elevated LDL, also confer high risk. Because of the major contribution of dietary factors to serum lipids and lipoproteins, diet is a cornerstone in the prevention and treatment of CHD. In the Western diet the three saturated fatty acids (SFA), lauric (e.g. palm kernel oil, coconut) myristic (e.g. butter, coconut oil) and palmitic (e.g. animal fat) acids comprise 60-70% of all SFA and are responsible for the cholesterol-raising effect of saturated fat. Stearic acid, found in cocoa butter, is essentially neutral. A common strategy is to reduce SFA in the diet and replace it with polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs) or complex carbohydrates in order to retain a suitable energy balance. The major dietary PUFA is linoleic acid which is predominant in vegetable oils (e.g. sunflower oil); when substituted for SFA, this markedly reduces total cholesterol. Other PUFAs include, alpha-linolenic acid (e.g. soybean and rapeseed oils) and eicosapentaenoic and docosahexaenoic acid - contained in marine fats and oils (e.g. herring and mackerel) which effectively lower triglycerides, having only minor effects on HDL and LDL cholesterol. The major MUFA in the diet is oleic acid, which is the predominant fat in olive oil. Olive oil is a major component in the Mediterranean diet, to which it contributes more than 15% of energy. Studies have shown that blood cholesterol levels and the incidence of CHD is much lower in Mediterranean than other countries. Both MUFAs and PUFAs significantly reduce LDL when substituted for SFA. A high MUFA intake will not alter HDL cholesterol levels significantly. LDL cholesterol examined in subjects fed high-MUFA diets is more resistant to oxidation. (Oxidation

causes free radical production which is detrimental to cells). Because of the high consumption of MUFAs among the Mediterranean population over the centuries, MUFAs are generally regarded as being safe. In accordance with recent European and American dietary guidelines, both fat reduction and the modification of what type of fat you eat are important. Consumption of olive oil increases MUFA intake without significant elevation of SFA and ensures an appropriate intake of the essential PUFA. Therefore it can make a valuable contribution to a healthy diet, reducing the risk of CHD.

Fact Sheet 2 - Executive Summary

Scientific Evidence for Olive Oil in the Prevention of Cardiovascular Risk Factors and Coronary Heart Disease
Author: Eurosciences Communication in co-operation with Arteriosclerosis Research at the University of Mnster, Germany. Olive oil and Cardiovascular Risk Factors Olive oil and hypertension the Institute of

The relationship between dietary fats and blood pressure is not definitively answered. However, evidence suggests that the multiple components of the Mediterranean diet, i.e. low saturated fatty acids (SFAs), high monounsaturated fatty acids (MUFAs), and carbohydrate, fibre, and micronutrient content have favourable blood pressure effects, and therefore that this diet is desirable for health. Dietary MUFA may have a greater protective effect than initially realised. Olive oil and diabetes

The traditional Mediterranean diet meets all the demands of an adequate diabetes diet. It contains a lot of vegetables and cereals. Carbohydrates are mainly taken up as fibre-rich carbohydrates. It has a low SFA content and is rich in MUFA, mainly from olive oil. The absolute fat content can be varied depending on individual needs. Clearly it is important for diabetic obese patients to lose weight as well as to adopt a healthier diet. Olive oil and obesity

In Western countries we eat twice as much animal fat as is recommended. This can lead to obesity which is associated with a number of other disease risks. A diet rich in complex carbohydrates and fibre will protect against obesity. A Mediterranean diet will provide optimal energy intake and provides a means with which to treat or prevent obesity. Olive oil and thrombogenic risk factor

Most studies suggest that for antithrombotic effects a low fat or a vegetable-fat diet is preferable to a high-fat diet, particularly a high fat diet high in SFAs. The Mediterranean diet meets these requirements and therefore can be recommended for the prevention of thrombosis.

Olive Oil and Coronary Heart Disease

Epidemiological Studies The Seven Countries Study published in 1970 reported on the dietary intake, blood pressure and cholesterol levels of 13,000 men aged 40-59 years at entry living in Italy, Greece, the former Yugoslavia, the Netherlands, Finland, USA and Japan. CHD deaths were closely related to age, blood pressure and smoking. Saturated fat intake and serum cholesterol levels of the populations were significantly correlated at baseline, 5 and 10 year follow up. Major differences in the proportions of SFAs and MUFA consumption existed between the Mediterranean countries, northern Europe and the US. Death rates within 15 years were low among the high olive oil consumers where SFA was low (i.e. a high MUFA:SFA ratio): namely, Greece, Italy and Yugoslavia. However, high MUFA intake in the US was apparently counteracted by their high SFA intake (i.e. low MUFA:SFA ratio) and here the CHD mortality was high. Evidence from the Greek island Crete suggested that besides the cholesterol lowering properties of oleic acid (largely from olive oil), other cardioprotective benefits were derived from nutrients and non-nutrients in the Mediterranean diet (e.g. antioxidative vitamins). Some Mediterranean countries have retained their eating habits over the past 40 years and still show an advantage in terms of lower CHD mortality compared to western Europe and the US. Intervention Studies

Many randomised prevention studies have firmly established the links between dietary SFA, serum cholesterol and CHD. Most of the studies involved decreasing SFA and increasing polyunsaturated fatty acids (PUFAs) and they had positive outcomes. None of the trial diets were particularly high in MUFAs and therefore the typical Mediterranean diet has not been tested for the primary prevention of CHD. Diets similar to those of Mediterranean countries have been investigated in intervention trials and trials where compliance is highly controlled. These diets efficiently lower serum cholesterol and LDL cholesterol, without adversely affecting HDL cholesterol. Such reductions in cholesterol result in reduced morbidity and mortality. Recently it has been shown that intensive lipid-lowering with drugs in men with moderate hypercholesterolaemia and no history of cardiovascular events, reduces the incidence of heart attack and CHD morality, without increasing non-cardiovascular mortality. Dietary Recommendations

Many national and international guidelines recommend preventive diets similar to the traditional Mediterranean diet. They suggest the following: Total fat should be reduced to 30% of energy SFA intake be reduced to below 10% PUFA intake to be no more than 10% of energy (7-10%)

MUFA intake should constitute 10-15% of energy dietary cholesterol should be below 300mg/day intake of complex carbohydrates and fibre should be increased The Mediterranean diet has: Abundance of plant foods, bread, grain products, vegetables, legumes, fruit, low to moderate amounts of animal products, olive oil as principal source of fat/high MUFA content low in SFA, rich in carbohydrate and fibre With ingredients like this, these recommendations can be converted into a tasty and appetising diet. Olive oil in secondary prevention of CHD

Agressive treatment of all coronary risk factors, including diet, is an important management approach in secondary prevention of CHD. There is much evidence that diets low in animal products and SFA are associated with low cholesterol levels and reduced CHD rates. Diets high in MUFAs (mainly from oleic acid) also provide this benefit, which is achieved through direct effects on risk factors such as hyperlipidaemia, high blood pressure and so forth, but also via directly protective effects like antioxidant activity.

Fact Sheet 3 - Executive Summary

Scientific Basis for Olive Oil, Mediterranean Diet and Cancer Prevention
Author: Eurosciences Communication in co-operation with Arteriosclerosis Research at the University of Mnster, Germany. 1. Introduction Cancer accounts for about 20% of all deaths in Europe. However, cancer mortality rates are generally highest in the northern and eastern European countries and lowest in the Mediterranean countries. It is estimated that about 35% (range of 10-70%) of all cancer deaths may be attributed to dietary factors. Epidemiological studies provide most of the evidence on food and cancer. Good dietary intervention studies of cancer risk however need to be large and very long term, and so are rare. 2. Cancer and the Mediterranean diet 2.1 Role of body weight Obesity is a clear risk factor for postmenopausal breast cancer and cancer of the prostate, endometrium and gall-bladder. It is also probably a risk factor for renal-cell carcinoma and cervical cancer. The public health message is "avoid obesity and being overweight". This is reinforced by the link between obesity and diseases such as heart disease, diabetes, gallstones, etc. As noted in previous Fact Sheets, the Mediterranean diet is suitable for the prevention of obesity, and therefore for the prevention of obesity-related cancer. 2.2 Role of dietary fat Population studies show total fat intake is associated with cancer at a number of sites, particularly the colon, breast, endometrium, ovary and prostate. All these cancers are related to a Western-type diet and to excess energy intake. However, the public health message is not clear, because prospective studies with breast cancer have failed to show any relation to total fat intake, and one study on gastric cancer has suggested a protective effect of fat intake derived from meat and dairy products, against gastric cancers. International correlation studies suggest that the type of dietary fat is important in the aetiology of fat related cancers. Animal fat consumption per capita is positively correlated with colon, prostate, breast and ovary cancer mortality rates. The case for the relationship between animal fat intake and colorectal cancer risk is particularly strong. In contrast, mortality rates of colon cancer are relatively low in Greece, Spain and Southern Italy, where the intake of animal fat is low and olive oil is the most common type of fat consumed. Until recently vegetable fats/oils were considered to be neutral with respect to cancer risk. However, recent analyses suggest that olive oil may have a protective effect against the Institute of

cancer at certain sites, particularly breast cancer. PUFAs of the n-series in human studies show some protective properties against cancer whereas the n-series appears to be neutral with respect to cancer risk. However, the role of n-6 PUFA becomes less clear when also evaluating animal studies. Investigations have been carried out on laboratory animals indicating that n-6 PUFA are more likely to increase cancer risk than other types of fatty acids. 2.3 Role of protein There is no evidence showing that there is an independent relationship between protein consumption and cancer risk. 2.4 Role of complex carbohydrates and dietary fibre It is not clear which component of the total complex carbohydrates provides the protective effect which is seen. Cereals appear highly protective against cancers of the colon, breast, endometrium and prostate. A prospective study has confirmed the protective effect of high-fibre foods against colorectal cancer. 2.5 Role of fruit and vegetables Epidemiological evidence shows that a high intake of fruit and vegetables, particularly raw vegetables, protects against cancers at different sites, especially those of the digestive and respiratory tracts and the hormone related cancers. They have an anti-carcinogenic action at a wide range of sites and there is no positive correlation between fruit and vegetable intake and cancer. They contain a variety anti-carcinogenic agents: carotenoids, vitamin C and E, dietary fibre, selenium, glucosinolate, indoles, flavenoids, protease inhibitors, and plant sterols. Only the actions of anti-oxidant vitamins and provitamins have been supported by human epidemiology, at present. However, it is likely that no single agent functions as a key protective factor in isolation, but that all of them have some protective role under some mcircumstances. 3. Role of olive oil in cancer Various epidemiological studies indicate that the regular consumption of olive oil is inversely associated with cancer at different sites. Most of the studies address the relationship between olive oil and breast cancer or gastric cancer. While more research work is needed, the existing evidence consistently, although not conclusively, supports a protective role of olive oil in breast cancer prevention. A protective effect of olive oil in gastric cancer is less clear. The only conclusion that can be drawn at present for gastric cancer prevention is that increased fruit and vegetable intake seems to be helpful. Although there are also findings which suggest protective effects of olive oil for cancer at other sites, e.g. colon, endometrium and ovary, the evidence is limited, because the number of studies is small, and their results cannot be more than an indication for a possible effect. However, no study would support a tumor-promoting effect of olive oil.

4. International recommendations for cancer prevention There is general consensus that diet is an important component in the aetiology of cancer. Scientific evidence is primarily derived from epidemiological studies as well as from animal and in vitro experiments. In the former, foods or food groups are more strongly associated with cancer risk than nutrients, and for many foods the results are not persuasive or consistent. Well-designed, strictly controlled intervention studies in humans, which could support the role of single foods or nutrients in cancer prevention with sufficient strength, are missing. Thus, the scientific evidence for detailed recommendations with respect to cancer prevention is limited. Several health authorities have made dietary recommendations for cancer prevention. The recent guidelines of the American Cancer Society consist of 6 points: 1. Avoid obesity 2. Cut down on total fat intake 3. Include a variety of vegetables and fruits in the daily diet 4. Eat more high-fibre foods, such as whole grain cereals, vegetables and fruits. 5. Limit consumption of alcoholic beverages, if you drink at all 6. Limit consumption of smoked, salt-cured and nitrate-cured foods Similar recommendations are given by the National Cancer Institute, but their guidelines differ from those of the American Cancer Society by specifying levels of nutrient intake for the general population (no more than 30% of total calories from fat and 20-30 grams of dietary fibre daily). The United States has started to implement these guidelines with a nation-wide programme, called the "5-a-day for better health programme", disseminated via supermarkets, restaurants, media, the public and research. The recommendations are to consume mainly vegetable foods, to eat five or more portions of fruit and vegetables per day, and, in addition, to eat six or more portions of bread, cereals or grain per day. "Europe against Cancer", the programme by the European Commission, has some recommendations on nutrition and diet: Increase the daily intake of fresh fruits and vegetables, as well of high fibre grain products Avoid obesity, increase regular physical activity, and limit the intake of high-fat foods Reduce alcohol consumption The results of the November 1996 WHO conference "Nutrition in prevention and therapy of cancer" will be published as consensus statements in the course of 1997. As a general policy statement for reducing the risk of cancer it was said that fruits, vegetables and whole-meal cereals should be the main components of the daily diet. Avoidance of obesity and high alcohol intake as well as regular physical activity can contribute to a reduction of cancer risk. In addition, it was stated that there is no kind of diet with which colon, gastric, breast or lung cancer could be treated.

Fact Sheet 4 - Executive Summary

Scientific Basis for Olive Oil, Monounsaturated Fatty Acids, Antioxidants, and LDL Oxidation
Author: Eurosciences Communication in cooperation Arteriosclerosis Research, University of Mnster, Germany. Introduction Low density lipoprotein (LDL) is the major cholesterol carrying particle in plasma. There is wide agreement that increased levels of LDL are causally related to atherosclerosis and the development of coronary heart disease (CHD). There is increasing evidence that LDL in its native state is not harmful, but when it becomes altered by a process called oxidation, it becomes a real threat within the arterial wall. The susceptibility of LDL to become oxidised is determined by both internal (endogenous) and external (exogenous) factors. Among the latter, nutritional factors are extremely important, particularly the types of fatty acids and antioxidant vitamins in the diet. This Fact Sheet reviews the mechanisms of LDL oxidation and the role of nutritional factors in its prevention. LDL oxidation (in atherogenesis) with the Institute for

Half of the cholesterol in the blood is carried in LDL which is a spherical fat-protein particle, consisting of an outer monolayer containing the protein apolipoprotein B (apo B) which surrounds a core containing triglycerides and/or cholesterol esters (non-polar fats). One LDL particle contains about 3600 fatty acids, half of which are polyunsaturated fatty acids (PUFAs). LDL also contains antioxidants, the most important being (alpha) atocopherol (vitamin E). LDL oxidation (peroxidation) is a chain reaction initiated by free radicals, a mainly reactive oxygen species. PUFAs are very susceptible to lipid peroxidation and breakdown to a variety of byproducts which bond to LDL apo B. LDL can be oxidised in vitro by exposing them to smooth muscle and endothelial cells, macrophages (derived from large cells called monocytes), or metal ions (Copper or Iron). LDL oxidation in vivo is poorly understood, and it may be reduced by the presence of antioxidants in plasma such as ascorbic acid (vitamin C). It is therefore likely that LDL oxidation occurs in the artery wall rather than in the blood stream. Vitamin E-enriched LDL is significantly more difficult to oxidise. LDL oxidation is likely to occur when the antioxidant defences are down, especially when a-tocopherol is depleted. LDL oxidation and atherosclerosis

The essential step in the development of atherosclerosis begins as LDL filter into the arterial wall and become entrapped in the intima where they may undergo oxidative modification. Macrophages (cells formed when monocytes permeate the artery wall from the bloodstream) avidly take up this modified LDL, which contributes to their

transformation to foam cells. The accumulation of foam cells in the intima results in the formation of fatty streaks. These do not produce significant obstruction of the artery, but they are gradually converted into fibrous plaques by a mechanism similar to scar formation. These, in turn are gradually transformed into atherosclerotic lesions which underlie most clinical events. Olive oil and LDL oxidation

There are several potential ways by which dietary fatty acids may influence the oxidation of LDL. The amount and composition of dietary fats affects the amount of LDL in the artery wall. Replacement of dietary saturated fats with monounsaturated fats (MUFAs) or PUFAs lowers LDL levels, thereby decreasing the amount of LDL entering the artery wall and so reducing the amount (and composition) available for oxidation. Because of its high MUFA content, olive oil appears to protect against LDL oxidation (see Section entitled "Effects of dietary fatty acids on LDL oxidation"). Olive oil may afford additional protection by supplying LDL with potent antioxidants, such as vitamin E and phenolic compounds, which will be described later. Effects of dietary fatty acids on LDL oxidation.

Various studies have investigated the role of MUFA and PUFA in reducing susceptibility to LDL oxidation. Studies in the rabbit model show that oleate-rich (oleic acid is the predominant fatty acid of olive oil) LDL is remarkably resistant to oxidation. Dietary studies in humans support this finding and show that the linoleic acid (the major dietary PUFA which is predominant in vegetable oils) content of LDL is stronglyrelated to the rate and extent of oxidation, with LDL oxidation rate being increased during the PUFA diet compared to the MUFA diet. Further studies have tried to address whether such effects are due to PUFA caused enhancement or a MUFA caused inhibition of LDL oxidation. Dietary supplementation of olive oil suggests that the linoleic acid content of LDL is reduced and that there is less cellular uptake by macrophages and reduced susceptibility of LDL to oxidation. Pro-oxidant activities of dietary fatty acids

Certain dietary fatty acids can change the monocyte membrane composition, thereby enhancing free radical production, and producing pro-oxidant effects. A study compared the effects of dietary supplementation with MUFA, and n-3 (found in fish oils) or n-6 (linoleic acid) PUFA on superoxide anion, (a free radical), generation in monocytes and macrophages. Only n-3 fatty acids reduced free radical production, while the monocytes from the MUFA or n-6 PUFA showed no change or increased levels. The mechanisms for this are unknown, and these results have not been reproduced. More studies on the role of different fatty acids on cellular pro-oxidant activity are needed; however MUFA enriched cells are less susceptible to oxidative damage (in direct comparison to n-6 PUFA) probably as a result of cell membrane fatty acid composition.

Antioxidant constituents of olive oil

Oxidative stress may play an important role in the development of several chronic diseases such as CHD and cancer. The possibility that dietary antioxidants, such as those found in olive oil, may protect against LDL oxidation has led to epidemiological and intervention studies. Vitamin E (a-tocopherol)

Epidemiological studies have shown that high doses of vitamin E over at least two years, significantly reduce CHD risk (31-65%). Short term studies using lower doses have not shown this however. This is also the finding from the majority of randomised intervention trials with vitamin E. But these trials were not designed to assess cardiovascular end-points, their treatment duration was too short, and they employed suboptimal doses of the vitamin. Several on-going large scale trials may help to resolve this issue. To date only the Cambridge Heart Antioxidant Study (CHAOS) has been completed. This double-blind, placebo-controlled study of 2000 patients with established CHD, reported that high-dose vitamin E supplementation significantly reduced the incidence of non-fatal heart attacks but had no impact on cardiovascular or all-cause mortality. Intervention trials have been criticised on the grounds that a few years treatment may be inadequate to demonstrate benefit of antioxidants, and that antioxidant supplementation may be needed over 20 or more years, before any clinical benefit ensues. Several studies have demonstrated that vitamin E supplementation results in increased levels of a-tocopherol both in plasma and in LDL particles. Furthermore LDL showed a higher resistance against in-vitro oxidation compared to the pre-study baseline. The degree of resistance was closely related to the vitamin dose received. Oxidative resistance is also higher in non-supplementing individuals who have higher plasma levels of atocopherol, than those with naturally occurring lower levels. Phenolic compounds

In addition to vitamin E, olive oil contains a variety of constituents which are responsible for its unique taste. Among these (comprising 2-3% of unrefined oil) are phenolic compounds, which are also found in vegetable foods and are biologically extremely important. These include simple phenols and phenolic acids e.g. flavonoids. These play a vital role to scavenge and detoxify free radicals, and can provide increased resistance to LDL oxidation and inhibit lipid peroxidation. Phenolic compounds have additional antiinflammatory and anti-haemorrhagic effects. Health benefits derived from potent phenolic flavonoids, also present in fruits and beverages such as tea and wine, have been observed in the Seven Countries and the Zutphen Elderly studies, where the average intake of flavonoids was inversely and independently correlated with CHD mortality. Although, more studies are needed to confirm the cardioprotective properties of flavonoids.

Summary and conclusions

There is extensive evidence that oxidative modifications of LDL play a crucial role in atherogenesis. Oxidation of LDL begins with peroxidation of PUFA in the LDL particle. Thus the LDL fatty acid composition undoubtedly contributes to LDL oxidation. LDLs fatty acid composition (and therefore, susceptibility to oxidation) is influenced by dietary fatty acids. Diets rich in MUFA render LDL more resistant to LDL oxidative modification compared with diets rich in PUFA such as linoleic acid. In addition, the fatty acid composition of cell membranes is diet-dependent, and MUFA-rich diets also lead to a higher MUFA content of cell membranes and therefore higher cellular resistance to oxidative damage. Dietary antioxidants such as vitamins E and C, flavonoids etc, provide additional protection against oxidative stress. Recent studies indicate that not only a-tocopherol, but also phenolic compounds in olive oil may inhibit LDL oxidation and reduce risk of atherosclerosis. Further research is needed to fully elucidate the mechanisms of action of phenolic compounds in vivo. Much of the focus of attention of the Mediterranean diet has been on the cardiovascular benefits associated with a reduced saturated fat intake, and its high MUFA levels, as well as complex carbohydrate and fibre. Current evidence suggests that additional components, in abundance in the Mediterranean diet, namely antioxidants derived from fruit and vegetables, but additionally, from olive oil may contribute to protection from CHD, cancer and other chronic disorders. High intakes of MUFA from olive oil consumption in the Mediterranean diet, may combine the advantages of lowering cholesterol and decreasing LDL and cell susceptibility to oxidation.

International Consensus Statement Authors

Olive Oil and the Mediterranean Diet: Implications for Health in Europe
Introduction At a meeting convened by the European Commission at the Italian National Research Council in Rome, 11 April 1997, European nutrition, cardiology, lipidology and public health specialists gathered to reach a health consensus on olive oil and the Mediterranean diet. They agreed that there is strong evidence that a Mediterranean-style diet, in which olive oil is the principal source of fat, contributes to the prevention of cardio-vascular risk factors, such as dyslipidaemia, hypertension, diabetes and obesity, and therefore, in the primary and secondary prevention of coronary heart disease. In addition, there is evidence suggesting that the Mediterranean diet plays a preventive role against some cancers. In this consensus statement, the major evidence for the health benefits of the Mediterranean diet is detailed, the mechanisms by which its components are believed to contribute to the benefits are stated, and the role of the Mediterranean diet in the prevention of diseases is pointed out. A working definition of the traditional Mediterranean diet is described as follows: The traditional (European) Mediterranean diet, is characterised by an abundance of plant foods such as: bread, pasta, vegetables, salad, legumes, fruit, nuts; olive oil as the principal source of fat; low to moderate amounts of fish, poultry, dairy products and eggs; only little amounts of red meat; low to moderate amounts of wine, normally consumed with meals. This diet is low in saturated fatty acids, rich in carbohydrate and fibre, and has a high content of monounsaturated fatty acids. These are primarily derived from olive oil." Recommendations are made to develop practical measures to: Preserve the traditional Mediterranean diet containing olive oil in countries that already have this diet or who have recently adopted less healthy diets. Promote the traditional Mediterranean diet - and the principles of the diet - to Northern European countries Encourage suppliers and preparers of food to incorporate healthy nutrients, such as olive oil Amend national and international regulations and dietary recommendations to commend the Mediterranean diet. Targets for this information campaign include the food industry (including supermarkets, manufacturers, caterers), governments, consumers, public health departments, schools, the media, hospital doctors and GPs.

1. What is the real evidence that the Mediterranean-style (varied) diet containing olive oil is beneficial to health? Coronary Heart Disease (CHD) 1.1 Biochemical and clinical studies and a number of large European and US population studies, have shown beyond doubt,that a high-fat diet, rich in saturated fatty acids (SFA), as is common in most Western and Northern European countries, raises atherogenic LDL cholesterol and thus is causally related to high incidence of CHD (1-3). 1.2 In contrast, a diet rich in complex carbohydrates and fibre and whose fat source is primarily monounsaturated fatty acids (MUFA), as found in the olive oil-rich Mediterranean-style diet as can be found in Southern Europe, lowers LDL cholesterol and is associated with a low incidence of CHD (1-3). 1.3 Intervention studies with "soft end-points", such as serum lipid levels, indirectly support the health benefits of the Mediterranean-style diet (4). In addition, many controlled dietary studies show that diets rich in monounsaturated fatty acids lead to a reduction of total and low-density lipoprotein (LDL) cholesterol as compared to diets very rich in saturated fatty acids (5,6). Other diseases 1.4 The traditional Mediterranean-style diet has been shown to predispose to a lower blood pressure compared with typical Western diets (7,8). 1.5 Cross-cultural comparisons and studies on vegetarians show that a high intake of complex carbohydrate and dietary fibre such as found in the Mediterranean diet, and the low intake of SFA have beneficial effects that could lower the risk of diabetes (8-11). 1.6 Epidemiological data show a strong inverse relationship between carbohydrate intake and relative body weight (12). Due to its high content of complex carbohydrates, the Mediterranean-style diet has, on average, a lower energy content than a high-fat diet which makes it suitable for the prevention of obesity. Cancer 1.7 Epidemiological studies provide evidence that in Southern European countries, where a Mediterranean-style diet is consumed, colon cancer incidence is low compared with Northern European countries (13-16). 1.8 Epidemiological evidence shows that a high intake of fruit and vegetables, particularly raw vegetables, protects against cancers at different sites, especially those of the digestive and respiratory tracts and the hormone related cancers (17-21).

1.9 The major features of the Mediterranean-style diet are consistent with important findings which indicate reductions in the incidence of cancer at a number of important sites (22-25). 2.0 What are the mechanisms by which olive oil exerts its beneficial effect on health? 2.1 The major fatty acid of olive oil is oleic acid, a monounsaturated fatty acid (55-83% of total fatty acids). Olive oil contains further saturated fatty acids (range: 8-14%), polyunsaturated fatty acids (range: 4-20%), and other important minor constituents, particularly antioxidants, such as vitamin E and polyphenols. The beneficial health effects of olive oil are due to both its high content of monounsaturated fatty acids and its high content of antioxidative substances. When substituted for serum cholesterol-elevating saturated fatty acids, monounsaturated fatty acids - as contained in olive oil - reduce total and LDL cholesterol concentrations without reducing the levels of HDL cholesterol, thus leading to favourable changes in the serum lipid profile and possibly to changes in the physico-chemical properties of lipoproteins. In this way, olive oil with its high monounsaturated fatty acid content may contribute to the prevention and management of hypercholesterolaemia (LDL), a dominant risk factor for the development of atherosclerosis, and to the prevention of CHD. The consumption of olive oil increases the intake of monounsaturated fatty acids without any significant elevation of SFA, and simultaneously ensures an appropriate intake of the essential polyunsaturated fatty acids. 3.0 What role could olive oil and the Mediterranean-style diet play in the prevention of CHD? 3.1 The adoption of a Mediterranean-style diet, with olive oil as a principal source of dietary fat, within the recommended limits of total fat intake, will play an important role in providing a dietary shield for peoples health. The beneficial effect of olive oil on the risk of CHD is mostly due to its favourable effects on blood lipids, including their oxidizability. 3.2 The Lyon Diet Heart Study in patients recovering from heart attack showed a Mediterranean-style diet resembling that in Crete, high in monounsaturated fatty acids, even when adapted to a Western population, protects against CHD better than other recommended linoleic-acid rich diets for such patients (26,27). 3.3 The Mediterranean-style diet provides an excellent example of a tasty and healthy diet which, if preserved in countries where it is traditional and if adopted throughout Europe, will contribute to reducing the risk of CHD, both in primary and secondary prevention, and possibly also cancer, diabetes, obesity and hypertension. 3.4 Hospital clinicians, public health doctors, nurses, dietitians and primary health care workers have a duty to advise their patients on strategies for healthy living. Stopping

smoking, taking regular exercise and a healthy diet (such as a low fat Mediterranean-style diet comprising olive oil) are a sensible approach for all individuals. 4.0 What actions should be recommended to promote the adoption of a healthier diet? 4.1 The scientific evidence is sufficient to justify a campaign of focused action to influence policy makers in governments, health authorities, primary and secondary care physicians, health educationalists, the media, nutritionists, caterers, schools and the public to accept the benefits of olive oil and the principles of the Mediterranean diet and make it more of a part of the national diet of all countries. 4.2 Promote health education through advertising, TV, workshops, school programmes, etc. to get the message across. 4.3 On the basis of existing guidelines (28-30), the principles of the Mediterranean diet as a recommended dietary habit should be referred to more explicitly. 4.4 Each country should develop an action plan for change that includes the promotion of the Mediterranean-style diet, and introduction of more fruit and vegetables in the preparation of its own traditional products. 4.5 Ensure the availability of the ingredients for the Mediterranean-style diet containing, in particular, olive oil, fruit, vegetables, and fish and that food preparers and manufacturers, whether professional or the general public, have access to them and know how to use them. 4.6 Involve the food industry in implementing the changes through collaboration with government, consumer groups and researchers.

The Mediterrannean-Style Diet and Olive Oil

Mediterranean diet best choice in diabetes The Mediterranean diet containing olive oil is the best diet for diabetics and disorders involving insensitivity to insulin, and probably for hypertensive patients. This is the view of Dr M Mancini, Department of Clinical and Experimental Medicine, Federico II University Medical School, Naples, Italy. His research group has shown that a diet rich in olive oil, low in saturated fat, moderately rich in carbohydrates, and soluble fibre from fruit, vegetbles and cereals is the most effective dietary approach for diabetic patients. Not only does it reduce the increased concentration of atherogenic lipoproteins that diabetics have, but it also improves blood glucose control and enhances insulin sensitivity. In Italy people living in the regions of Naples, Florence, Genoa, and Bari consume a lot of olive oil. Around Milan, Rome and Bologna they tend to use more saturated fats. Dr Mancinis group studied 6000 people, men and women, divided into three groups according to the proportion of monounsaturated fats in their diet, and found that the cholesterol levels of people on the diets containing olive oil were much lower. This result was expected. In addition, and to the investigators surprise, the average systolic blood pressure was much lower on the olive oil diets. But even more surprising was the effect on fasting blood glucose. Said Dr Mancini, "The higher the consumption of olive oil, the lower the fasting blood sugar." He added, "The message is that this diet naturally rich in olive oil is evidently very protective on the fundamental risk factors for atherosclerosis." In a study of hypertensive patients a low-fat high-carbohydrate rice diet was found to increase the values of glucose measured every hour during the 14 hours of the study. Also, serum insulin was higher with this high carbohydrate diet. Said Mancini, "We know that hypertensive subjects usually have some insulin resistance, so we do not want to exacerbate the insulin resistance and worsen glucose tolerance in these patients." A few years later a similar observation was made about the low-fat, high-carbohydrate diet in diabetic patients. "When we use the low-fat, high-carbohydrate diet, there is a deterioration of glucose metabolism with significant increase in postprandial glucose, a significant increase in postprandial insulin levels and a decrease in glucose use". Dr Mancini concluded, "So we certainly cannot advise patients with non-insulin dependant diabetes to go on a low fat diet. We might instead, as Dr Grundy clearly indicated in his presentation, ask these patients to replace carbohydrate with olive oil." He stressed, "You can defend your diabetic patients from the risk of hyperglycaemia and the risk of complications by increasing the amount of olive oil in the diet". Atherosclerosis risk factors reduced with olive oil The cluster of metabolic risk factors for atherosclerosis known collectively as the "metabolic syndrome" can be ameliorated by a diet high in monounsaturated fatty acids like olive oil. Many lipid disorders typically occur in association with a cluster of metabolic risk factors the metabolic syndrome, according to Dr Scott Grundy of the University of Texas,

Southwestern Medical Center, Dallas, Texas, USA. "The metabolic syndrome can be considered a major risk factor for coronary heart disease". The metabolic risk factors in this syndrome include atherogenic lipoprotein, phenotype, high triglycerides, low high density lipoprotein cholesterol (HDL) , small low density lipoprotein cholesterol (LDL), raised blood pressure, insulin resistance, glucose intolerance, and a tendency of the blood to clot (procoagulant state). He said that there were at least five causes of the metabolic syndrome. Obesity and diet contribute to "nutrient overload" and this accentuates "insulin resistance". The other three causes are "genetics", "ageing" and "physical inactivity". These three causes modify the cellular response and interfere with insulin action. Dr Grundy explained how diet might affect this syndrome. "Saturated fatty acids consistently raise LDL cholesterol levels. However, diets high in monounsaturated fatty acids or high in polyunsaturated fatty acids have approximately the same lowering effects on LDL levels". He added, "On the other hand, we know that other factors lead us to limit the amount of polyunsaturated fatty acids. Almost no investigator is now recommending diets greater than 10% of polyunsaturated acids." He concluded, "So most of the leeway for dietary replacement for saturated fatty acids must come from monounsaturated fatty acids". For these reasons the major question is "which is more efficacious, monounsaturates or carbo-hydrates?" Both nutrients lower LDL cholesterol. Looking at the effect of these agents on insulin resistance (which is almost always in the cluster of risk factors) carbohydrates have the disadvantage of raising triglycerides and would therefore exacerbate the tendency to hypertriglyceridaemia. Said Dr Grundy, "From this alone it would seem that a diet high in monounsaturated fatty acids would be preferable in the metabolic syndrome". He also referred to the evidence of benefit from monounsaturates on insulin resistance and impaired glucose tolerance mentioned by Dr Mancini in overt diabetes. Phenols in olive oil prevent LDL oxidation Olive-oil derived phenols strongly prevent LDL oxidation and increase the production of a blood vessel relaxing factor, such as nitric oxide (NO). NO has also been shown to inhibit LDL oxidation, the process which makes LDL particularly likely to be taken into macrophages and contribute to atherosclerosis. Dr Francesco Visioli and colleagues of the Institute of Pharmacological Sciences, Milan, Italy, tested several phenolic antioxidants that are responsible for the stability and taste of extra-virgin olive oil. "We tested for the potential antioxidant activity of such compounds in a model of chemically-mediated oxidation of LDL". He said, "All the markers of oxidative stress that we evaluated showed the strong antioxidant activity of olive oil phenolics, in particular hydroxytyrosol and oleuropein, both toward lipid and protein oxidative modification". Previous studies have suggested that oleuropein (the bitter principle of olives), lowers blood pressure. Dr Visioli found that oleuropein markedly increases the vasorelaxant NO produced by mouse macrophages through increasing NO synthase. "These data support the hypothesis of a beneficial effect of olive oil derived antioxidants on the cardiovascular system", said Dr Visioli.