Maria-Isabel Covas

Primary Prevention of Cardiovascular Disease with a Mediterranean Diet

BACKGROUND Observational cohort studies and a secondary prevention trial have shown an inverse association between adherence to the Mediterranean diet and cardiovascular risk. We conducted a randomized trial of this diet pattern for the primary prevention of cardiovascular events. METHODS In a multicenter trial in Spain, we randomly assigned participants who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly individual and group educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was the rate of major cardiovascular events (myocardial infarction, stroke, or death from cardiovascular causes). On the basis of the results of an interim analysis, the trial was stopped after a median follow-up of 4.8 years. RESULTS A total of 7447 persons were enrolled (age range, 55 to 80 years); 57% were women. The two Mediterranean-diet groups had good adherence to the intervention, according to self-reported intake and biomarker analyses. A primary end-point event occurred in 288 participants. The multivariable-adjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.54 to 0.92) and 0.72 (95% CI, 0.54 to 0.96) for the group assigned to a Mediterranean diet with extra-virgin olive oil (96 events) and the group assigned to a Mediterranean diet with nuts (83 events), respectively, versus the control group (109 events). No diet-related adverse effects were reported. CONCLUSIONS Among persons at high cardiovascular risk, a Mediterranean diet supplemented with extra-virgin olive oil or nuts reduced the incidence of major cardiovascular events. (Funded by the Spanish governments Instituto de Salud Carlos III and others; Controlled-Trials.com number, ISRCTN35739639.).

The Effect of Polyphenols in Olive Oil on Heart Disease Risk Factors: A Randomized Trial

Context Olive oil, the main fat in the Mediterranean diet, contains polyphenols, which have antioxidant properties and may affect serum lipid levels. Contribution The authors studied virgin olive oil (high in polyphenols), refined olive oil (low in polyphenols), and a mixture of the 2 oils in equal parts. Two hundred healthy young men consumed 25 mL of an olive oil daily for 3 weeks followed by the other olive oils in a randomly assigned sequence. Olive oils with greater polyphenol content increased high-density lipoprotein (HDL) cholesterol levels and decreased serum markers of oxidation. Cautions The increase in HDL cholesterol level was small. Implications Virgin olive oil might have greater health benefits than refined olive oil. The Editors Polyphenol intake has been associated with low cancer and coronary heart disease (CHD) mortality rates (1). Antioxidant and anti-inflammatory properties and improvements in endothelial dysfunction and the lipid profile have been reported for dietary polyphenols (2). Studies have recently suggested that Mediterranean health benefits may be due to a synergistic combination of phytochemicals and fatty acids (3). Olive oil, rich in oleic acid (a monounsaturated fatty acid), is the main fat of the Mediterranean diet (4). To date, most of the protective effect of olive oil within the Mediterranean diet has been attributed to its high monounsaturated fatty acid content (5). However, if the effect of olive oil can be attributed solely to its monounsaturated fatty acid content, any type of olive oil, rapeseed or canola oil, or monounsaturated fatty acidenriched fat would provide similar health benefits. Whether the beneficial effects of olive oil on the cardiovascular system are exclusively due to oleic acid remains to be elucidated. The minor components, particularly the phenolic compounds, in olive oil may contribute to the health benefits derived from the Mediterranean diet. Among olive oils usually present on the market, virgin olive oils produced by direct-press or centrifugation methods have higher phenolic content (150 to 350 mg/kg of olive oil) (6). In experimental studies, phenolic compounds in olive oil showed strong antioxidant properties (7, 8). Oxidized low-density lipoprotein (LDL) is currently thought to be more damaging to the arterial wall than native LDL cholesterol (9). Results of randomized, crossover, controlled clinical trials on the antioxidant effect of polyphenols from real-life daily doses of olive oil in humans are, however, conflicting (10). Growing evidence suggests that dietary phenols (1115) and plant-based diets (16) can modulate lipid and lipoprotein metabolism. The Effect of Olive Oil on Oxidative Damage in European Populations (EUROLIVE) Study is a multicenter, randomized, crossover, clinical intervention trial that aims to assess the effect of sustained daily doses of olive oil, as a function of its phenolic content, on the oxidative damage to lipid and LDL cholesterol levels and the lipid profile as cardiovascular risk factors. Methods Participants We recruited healthy men, 20 to 60 years of age, from 6 European cities through newspaper and university advertisements. Of the 344 persons who agreed to be screened, 200 persons were eligible (32 men from Barcelona, Spain; 33 men from Copenhagen, Denmark; 30 men from Kuopio, Finland; 31 men from Bologna, Italy; 40 men from Postdam, Germany; and 34 men from Berlin, Germany) and were enrolled from September 2002 through June 2003 (Figure 1). Participants were eligible for study inclusion if they provided written informed consent, were willing to adhere to the protocol, and were in good health. We preselected volunteers when clinical record, physical examination, and blood pressure were strictly normal and the candidate was a nonsmoker. Next, we performed a complete blood count, biochemical laboratory analyses, and urinary dipstick tests to measure levels of serum glucose, total cholesterol, creatinine, alanine aminotransferase, and triglycerides. We included candidates with values within the reference range. Exclusion criteria were smoking; use of antioxidant supplements, aspirin, or drugs with established antioxidant properties; hyperlipidemia; obesity; diabetes; hypertension; intestinal disease; or any other disease or condition that would impair adherence. We excluded women to avoid the possible interference of estrogens, which are considered to be potential antioxidants (17). All participants provided written informed consent, and the local institutional ethics committees approved the protocol. Figure 1. Study flow diagram. Sequence of olive oil administration: 1) high-, medium-, and low-polyphenol olive oil; 2) medium-, low-, and high-polyphenol olive oil; and 3) low-, high-, and medium-polyphenol olive oil. Design and Study Procedure The trial was a randomized, crossover, controlled study. We randomly assigned participants consecutively to 1 of 3 sequences of olive oil administration. Participants received a daily dose of 25 mL (22 g) of 3 olive oils with high (366 mg/kg), medium (164 mg/kg), and low (2.7 mg/kg) polyphenol content (Figure 1) in replacement of other raw fats. Sequences were high-, medium-, and low-polyphenol olive oil (sequence 1); medium-, low-, and high-polyphenol olive oil (sequence 2); and low-, high-, and medium-polyphenol olive oil (sequence 3). In the coordinating center, we prepared random allocation to each sequence, taken from a Latin square, for each center by blocks of 42 participants (14 persons in each sequence), using specific software that was developed at the Municipal Institute for Medical Research, Barcelona, Spain (Aleator, Municipal Institute for Medical Research). The random allocation was faxed to the participating centers upon request for each individual included in the study. Treatment containers were assigned a code number that was concealed from participants and investigators, and the coordinating center disclosed the code number only after completion of statistical analyses. Olive oils were specially prepared for the trial. We selected a virgin olive oil with high natural phenolic content (366 mg/kg) and measured its fatty acid and vitamin E composition. We tested refined olive oil harvested from the same cultivar and soil to find an olive oil with similar quantities of fatty acid and a similar micronutrient profile. Vitamin E was adjusted to values similar to those of the selected virgin olive oil. Because phenolic compounds are lost in the refinement process, the refined olive oil had a low phenolic content (2.7 mg/kg). By mixing virgin and refined olive oil, we obtained an olive oil with an intermediate phenolic content (164 mg/kg). Olive oils did not differ in fat and micronutrient composition (that is, vitamin E, triterpenes, and sitosterols), with the exception of phenolic content. Three-week interventions were preceded by 2-week washout periods, in which we requested that participants avoid olive and olive oil consumption. We chose the 2-week washout period to reach the equilibrium in the plasma lipid profile because longer intervention periods with fat-rich diets did not modify the lipid concentrations (18). Daily doses of 25 mL of olive oil were blindly prepared in containers delivered to the participants at the beginning of each intervention period. We instructed participants to return the 21 containers at the end of each intervention period so that the daily amount of unconsumed olive oil could be registered. Dietary Adherence We measured tyrosol and hydroxytyrosol, the 2 major phenolic compounds in olive oil as simple forms or conjugates (7), by gas chromatography and mass spectrometry in 24-hour urine before and after each intervention period as biomarkers of adherence to the type of olive oil ingested. We asked participants to keep a 3-day dietary record at baseline and after each intervention period. We requested that participants in all centers avoid a high intake of foods that contain antioxidants (that is, vegetables, legumes, fruits, tea, coffee, chocolate, wine, and beer). A nutritionist also personally advised participants to replace all types of habitually consumed raw fats with the olive oils (for example, spread the assigned olive oil on bread instead of butter, put the assigned olive oil on boiled vegetables instead of margarine, and use the assigned olive oil on salads instead of other vegetable oils or standard salad dressings). Data Collection Main outcome measures were changes in biomarkers of oxidative damage to lipids. Secondary outcomes were changes in lipid levels and in biomarkers of the antioxidant status of the participants. We assessed outcome measures at the beginning of the study (baseline) and before (preintervention) and after (postintervention) each olive oil intervention period. We collected blood samples at fasting state together with 24-hour urine and recorded anthropometric variables. We measured blood pressure with a mercury sphygmomanometer after at least a 10-minute rest in the seated position. We recorded physical activity at baseline and at the end of the study and assessed it by using the Minnesota Leisure Time Physical Activity Questionnaire (19). We measured 1) glucose and lipid profile, including serum glucose, total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride levels determined by enzymatic methods (2023) and LDL cholesterol levels calculated by the Friedewald formula; 2) oxidative damage to lipids, including plasma-circulating oxidized LDL measured by enzyme immunoassay, plasma total F2-isoprostanes determined by using high-performance liquid chromatography and stable isotope-dilution and mass spectrometry, plasma C18 hydroxy fatty acids measured by gas chromatography and mass spectrometry, and serum LDL cholesterol uninduced conjugated dienes measured by spectrophotometry and adjusted for the cholesterol concentration in LDL cholesterol levels; 3) antioxidant sta

Effect of a traditional Mediterranean diet on lipoprotein oxidation: a randomized controlled trial.

BACKGROUND Despite the richness in antioxidants of the Mediterranean diet, to our knowledge, no randomized controlled trials have assessed its effect on in vivo lipoprotein oxidation. METHODS A total of 372 subjects at high cardiovascular risk (210 women and 162 men; age range, 55-80 years), who were recruited into a large, multicenter, randomized, controlled, parallel-group clinical trial (the Prevención con Dieta Mediterránea [PREDIMED] Study) directed at testing the efficacy of the traditional Mediterranean diet (TMD) on the primary prevention of coronary heart disease, were assigned to a low-fat diet (n = 121) or one of 2 TMDs (TMD + virgin olive oil or TMD + nuts). The TMD participants received nutritional education and either free virgin olive oil for all the family (1 L/wk) or free nuts (30 g/d). Diets were ad libitum. Changes in oxidative stress markers were evaluated at 3 months. RESULTS After the 3-month interventions, mean (95% confidence intervals) oxidized low-density lipoprotein (LDL) levels decreased in the TMD + virgin olive oil (-10.6 U/L [-14.2 to -6.1]) and TMD + nuts (-7.3 U/L [-11.2 to -3.3]) groups, without changes in the low-fat diet group (-2.9 U/L [-7.3 to 1.5]). Change in oxidized LDL levels in the TMD + virgin olive oil group reached significance vs that of the low-fat group (P = .02). Malondialdehyde changes in mononuclear cells paralleled those of oxidized LDL. No changes in serum glutathione peroxidase activity were observed. CONCLUSIONS Individuals at high cardiovascular risk who improved their diet toward a TMD pattern showed significant reductions in cellular lipid levels and LDL oxidation. Results provide further evidence to recommend the TMD as a useful tool against risk factors for CHD. Trial Registration isrctn.org Identifier: ISRCTN35739639.

Prevention of Diabetes With Mediterranean Diets: A Subgroup Analysis of a Randomized Trial

Context Can changes in diet prevent diabetes in older adults? Contribution This subgroup analysis of a multicenter trial involved older adults with high risk for heart disease who were randomly assigned to a Mediterranean diet supplemented with either extra-virgin olive oil or mixed nuts or to a low-fat control diet. Neither energy restriction nor increased physical activity was advised. After 4 years of follow-up, fewer persons in the Mediterranean diet groups developed diabetes than in the control group. Implication Changes in dietary patterns that do not necessarily lead to weight loss or include energy restrictions could help prevent diabetes in some older adults. The Editors Type 2 diabetes mellitus represents a major health problem because worldwide prevalence has more than doubled in the past 3 decades, with nearly 347 million persons with diabetes in 2010 (1), and is a potent risk factor for cardiovascular disease (CVD), blindness, renal failure, and lower limb amputation (2). Compelling evidence shows that diabetes can be prevented with lifestyle changes. Intensive lifestyle modification promoting weight loss through energy-restricted diets together with increased physical activity can decrease incident diabetes to as low as 50% (3). Indeed, lifestyle modification has performed better than pharmacologic approaches (such as metformin or rosiglitazone) in diabetes prevention (46). Of interest, the benefit of lifestyle changes in decreasing diabetes risk seems to extend beyond the termination of active intervention (68). However, there is little information on whether changes in the overall dietary pattern, without energy restriction, increased physical activity, and ensuing weight loss, may also be effective to prevent diabetes. Prospective epidemiologic studies strongly suggest that dietary patterns characterized by high consumption of fruit, vegetables, whole grains, and fish and reduced consumption of red and processed meat, sugar-sweetened beverages, and starchy foods delay diabetes onset (9). In the last 6 years, the traditional Mediterranean diet has emerged as a healthy dietary pattern that is also associated with a decreased risk for diabetes (1012). The Mediterranean diet is moderately rich in fat (35% to 40% of energy), especially from vegetable sources (rich in olive oil and nuts), and relatively low in dairy products. Moderate consumption of alcohol, mostly wine, and frequent use of sauces with tomato, onions, garlic, and spices for meal preparation are also typical. Preliminary data from the PREDIMED (Prevencin con Dieta Mediterrnea) study (1317) showed that traditional Mediterranean diets enriched with high-fat foods of vegetable origin decreased the incidence of diabetes (18). However, that report studied participants only from 1 of the 11 PREDIMED recruiting centers. In this analysis, we provide the final results on diabetes incidence in the whole multicenter trial after a median follow-up of 4.1 years. Methods Design Overview The PREDIMED study is a parallel-group, randomized, primary cardiovascular prevention trial done in Spain in persons at high risk but without CVD at baseline. The protocol, design, objectives, and methods have been reported in detail elsewhere (13, 14). Briefly, participants were randomly assigned in a 1:1:1 ratio to 1 of 3 nutrition interventions: Mediterranean diet supplemented with extra-virgin olive oil (EVOO), Mediterranean diet supplemented with mixed nuts, or a control diet consisting of advice to reduce intake of all types of fat. A complete list of PREDIMED study investigators is available in Supplement 1. The local institutional review boards approved the protocol at each study location, and all participants provided written informed consent. Supplement. Original Version (PDF) Supplement 1. List of Prevencin con Dieta Mediterrnea Study Investigators Setting and Participants Eligible participants were community-dwelling men (aged 55 to 80 years) and women (aged 60 to 80 years) without CVD at baseline who had either type 2 diabetes or at least 3 or more cardiovascular risk factors, namely current smoking, hypertension, hypercholesterolemia, low high-density lipoprotein cholesterol levels, overweight or obesity, and family history of premature CVD. Exclusion criteria have previously been reported (13). Randomization and Intervention From October 2003 to June 2009, 7447 suitable candidates were enrolled in the trial. The study nurse from each recruiting center randomly assigned each participant to the corresponding intervention group following computer-generated random numbers for allocation contained in sealed envelopes, which were centrally prepared for each center by the coordinating unit. Four strata of randomization were built by sex and age (cutoff, 70 years) but not by baseline diabetes status. The primary care physicians did not participate in the randomization process. The study nurses were independent of the nursing staff of the primary care health centers. Therefore, they were not involved in the usual clinical care of participants, and their exclusive role was to collect data for the trial. Given the nature of the interventions (nutritional advice and provision of foods), only investigators assessing outcomes were blinded with respect to intervention assignment. This was done by providing them with coded data sets and medical records blinded with respect to the personal identity of the participant and without any information on treatment allocation. Because our main objective was to determine the effect of the 3 interventions on diabetes incidence, this report includes data only on participants who did not have diabetes at baseline and for whom we could ascertain the incidence of diabetes during follow-up (n= 3541) (Figure 1). Figure 1. Study flow diagram. EVOO = extra-virgin olive oil; MedDiet = Mediterranean diet. A behavioral intervention promoting the Mediterranean diet was implemented in the corresponding groups of the trial, as described (13). Dietitians gave personalized advice to participants about the amount and use of EVOO for cooking and dressing; weekly intake of nuts; increased consumption of vegetables, fruits, legumes, and fish; recommended intake of white meat instead of red or processed meat; avoidance of butter, fast food, sweets, pastries, or sugar-sweetened beverages; and the dressing of dishes with sofrito sauce (using tomato, garlic, onion, and spices simmered in olive oil). Reduction of alcoholic beverages other than wine was advised to all participants. Wine with meals was recommended with moderation only to habitual drinkers. At baseline and quarterly thereafter, dietitians conducted individual and group dietary training sessions to provide information on typical Mediterranean foods, seasonal shopping lists, meal plans, and recipes for each group. In each session, a 14-item questionnaire was used to assess adherence to the Mediterranean diet (13, 14) so that personalized advice could be provided to upgrade participants adherence. The same questionnaire was assessed yearly in the control group. Participants assigned to the 2 Mediterranean diet groups received allotments of either EVOO (50 mL/d) or mixed nuts (30 g/d: 15 g of walnuts, 7.5 g of almonds, and 7.5 g of hazelnuts) at no cost. Participants assigned to the control diet received recommendations to reduce intake of all types of fat (from both animal and vegetable sources) and received nonfood gifts (kitchenware, tableware, aprons, or shopping bags). Through October 2006, participants in the control group received only a leaflet describing the low-fat diet. Thereafter, participants assigned to the control diet also received personalized advice and were invited to group sessions with the same frequency and intensity as those in the Mediterranean diet groups. A separate 9-item dietary questionnaire (14) was used to assess adherence to the low-fat diet. Neither energy restriction nor increased physical activity was advised for any intervention group. At baseline examination and yearly during follow-up, we administered a 137-item validated semiquantitative food-frequency questionnaire (19); the validated Spanish version of the Minnesota Leisure-time Physical Activity Questionnaire (20); and a 47-item questionnaire about education, lifestyle, medical history, and medication use. At baseline, trained personnel performed electrocardiography and anthropometric and blood pressure measurements. Blood pressure was measured in triplicate by using a validated semiautomatic oscillometer with a 5-minute interval between measurements and the participant in a sitting position (Omron HEM-705CP, Omron, Hoofddorp, the Netherlands). Fasting blood and spot urine were sampled at baseline and follow-up years 1, 3, 5, and 7. After an overnight fast, tubes for EDTA plasma, citrate plasma, and serum and urine samples were collected and aliquots were coded and stored at 80C in the central laboratory until analysis. Serum glucose, cholesterol, and triglyceride levels were measured using standard enzymatic methods. High-density lipoprotein cholesterol was measured after precipitation with phosphotungstic acid and magnesium chloride. Biomarkers of adherence to the supplemental foods, including urine hydroxytyrosol levels and plasma -linolenic acid proportions, which are reliable biomarkers of EVOO and walnut intake, respectively, were measured in random subsamples of participants during the first 5 years of follow-up (by gas chromatographymass spectrometry and by gas chromatography, respectively). Laboratory technicians were blinded to intervention group. Outcomes and Follow-up Diabetes was a prespecified secondary outcome of the PREDIMED trial. IT was considered to be present at baseline by clinical diagnosis or use of antidiabetic medication. New-onset diabetes during follow-up was diagnosed using the American Diabetes Association criteria, namely fasting plasma glucose levels of 7.0 mmol/L or g

Hydroxytyrosol Disposition in Humans

BACKGROUND Animal and in vitro studies suggest that phenolic compounds in virgin olive oil are effective antioxidants. In animal and in vitro studies, hydroxytyrosol and its metabolites have been shown to be strong antioxidants. One of the prerequisites to assess their in vivo physiologic significance is to determine their presence in human plasma. METHODS We developed an analytical method for both hydroxytyrosol and 3-O-methyl-hydroxytyrosol in plasma. The administered dose of phenolic compounds was estimated from methanolic extracts of virgin olive oil after subjecting them to different hydrolytic treatments. Plasma and urine samples were collected from 0 to 12 h before and after 25 mL of virgin olive oil intake, a dose close to that used as daily intake in Mediterranean countries. Samples were analyzed by capillary gas chromatography-mass spectrometry before and after being subjected to acidic and enzymatic hydrolytic treatments. RESULTS Calibration curves were linear (r >0.99). Analytical recoveries were 42-60%. Limits of quantification were <1.5 mg/L. Plasma hydroxytyrosol and 3-O-methyl-hydroxytyrosol increased as a response to virgin olive oil administration, reaching maximum concentrations at 32 and 53 min, respectively (P <0.001 for quadratic trend). The estimated hydroxytyrosol elimination half-life was 2.43 h. Free forms of these phenolic compounds were not detected in plasma samples. CONCLUSIONS The proposed analytical method permits quantification of hydroxytyrosol and 3-O-methyl-hydroxytyrosol in plasma after real-life doses of virgin olive oil. From our results, approximately 98% of hydroxytyrosol appears to be present in plasma and urine in conjugated forms, mainly glucuronoconjugates, suggesting extensive first-pass intestinal/hepatic metabolism of the ingested hydroxytyrosol.

In vivo nutrigenomic effects of virgin olive oil polyphenols within the frame of the Mediterranean diet: a randomized controlled trial

The aim of the study was to assess whether benefits associated with the traditional Mediterranean diet (TMD) and virgin olive oil (VOO) consumption could be mediated through changes in the expression of atherosclerosis‐related genes. A randomized, parallel, controlled clinical trial in healthy volunteers (n=90) aged 20 to 50 yr was performed. Threemonth intervention groups were as follows: 1) TMD with VOO (TMD+VOO), 2) TMD with washed virgin olive oil (TMD+WOO), and 3) control with participants’ habitual diet. WOO was similar to VOO, but with a lower polyphenol content (55 vs. 328 mg/kg, respectively). TMD consumption decreased plasma oxidative and inflammatory status and the gene expression related with both inflammation [INF‐γ (INFy), Rho GTPase‐activating protein15 (ARHGAP15), and interleukin‐7 receptor (IL7R)] and oxidative stress [adrenergic ß2‐receptor (ADRB2) and polymerase (DNA‐directed) κ (POLK)] in peripheral blood mononuclear cells. All effects, with the exception of the decrease in POLK expression, were particularly observed when VOO, rich in polyphenols, was present in the TMD dietary pattern. Our results indicate a significant role of olive oil polyphenols in the down‐regulation of proatherogenic genes in the context of a TMD. In addition, the benefits associated with a TMD and olive oil polyphenol consumption on cardiovascular risk can be mediated through nutrigenomic effects.—Konstantinidou, V., Covas, M.‐I., Mun˜oz‐Aguayo, D., Khymenets, O., de la Torre, R., Saez, G., del Carmen Tormos, M., Toledo, E., Marti, A., Ruiz‐Gutiérrez, V., Ruiz Mendez, M. V., Fito, M. In vivo nutrigenomic effects of virgin olive oil polyphenols within the frame of the Mediterranean diet: a randomized controlled trial. FASEBJ. 24, 2546–2557 (2010). www.fasebj.org

Effect of olive oils on biomarkers of oxidative DNA stress in Northern and Southern Europeans

High consumption of olive oil in the Mediterranean diet has been suggested to protect DNA against oxidative damage and to reduce cancer incidence. We investigated the impact of the phenolic compounds in olive oil, and the oil proper, on DNA and RNA oxidation in North, Central, and South European populations. In a multicenter, double‐blind, randomized, controlled crossover intervention trial, the effect of olive oil phenolic content on urinary oxidation products of guanine (8‐oxo‐guanine, 8‐oxo‐guanosine and 8‐oxo‐deoxyguanosine) was investigated. Twenty‐five mililiters of three olive oils with low, medium, and high phenolic content were administered to healthy males (n=182) daily for 3 wk. At study baseline the urinary excretion of 8‐oxo‐guanosine (RNA oxidation) and 8‐oxo‐deoxyguanosine (DNA oxidation) was higher in the Northern regions of Europe compared with Central and Southern European regions (P=0.035). Urinary excretion of the 8 hydroxylated forms of guanine, guanosine, deoxyguanosine and their nonoxidized forms were not different when comparing olive oils with low, medium, and high phenolic content given for 2 wk. Testing the effect of oil from urinary 8‐oxodeoxyguanosine changes from baseline to post‐treatment showed a reduction of DNA oxidation by 13% (P=0.008). These findings support the idea that ingestion of olive oil is beneficial and can reduce the rate of oxidation of DNA. This effect is not due to the phenolic content in the olive oil. The higher DNA and RNA oxidation in Northern European regions compared with that in Central and Southern regions supports the contention that olive oil consumption may explain some of the North‐South differences in cancer incidences in Europe. Machowetz, A., Poulsen, H. E., Gruendel, S., Weimann, A., Fitã, M., Marrugat, J., de la Torre, R., Salonen, J. T., Nyyssönen, K., Mursu, J., Nascetti, S., Gaddi, A., Kiesewetter, H., Bäumler, H., Selmi, H., Kaikkonen, J., Zunft, H. J‐F., Covas, M‐I., Koebnick, C. Effect of olive oils on biomarkers of oxidative DNA stress in Northern and Southern Europeans. FASEB J. 21, 45–52 (2007)

Olive oil and cardiovascular health.

The Mediterranean diet, in which olive oil is the primary source of fat, is associated with a low mortality for cardiovascular disease. Data concerning olive oil consumption and primary end points for cardiovascular disease are scarce. However, a large body of knowledge exists providing evidence of the benefits of olive oil consumption on secondary end points for the disease. Besides the classical benefits on the lipid profile provided by olive oil consumption compared with that of saturated fat, a broad spectrum of benefits on cardiovascular risk factors is now emerging associated with olive oil consumption. We review the state of the art concerning the knowledge of the most important biological and clinical effects related to olive oil and its minor components. The recent advances in human nutrigenomics associated with olive oil consumption will also be assessed. The wide range of benefits associated with olive oil consumption could contribute to explaining the low rate of cardiovascular mortality found in southern European-Mediterranean countries, in comparison with other westernized countries, despite a high prevalence of coronary heart disease risk factors.

Adherence to a Mediterranean-type diet and reduced prevalence of clustered cardiovascular risk factors in a cohort of 3204 high-risk patients

Background The Mediterranean food pattern (MeDiet) has been suggested to have beneficial effects on cardiovascular risk factors. Scarcity of assessment of this effect on large samples of patients at high risk is, however, observed. Our objective was to estimate the association between adherence to MeDiet and the prevalence of risk factors in 3204 asymptomatic high-risk patients. Design Cross-sectional assessment of baseline characteristics of participants in a primary prevention trial. Methods Participants were assessed by their usual primary-care physicians to ascertain the prevalence of diet-related cardiovascular risk factors (diabetes, hypertension, dyslipidemia, or obesity) using standard diagnostic criteria. A dietitian interviewed each participant to obtain a 14-point score measuring the degree of adherence to MeDiet. Results Adherence to MeDiet was inversely associated with individual risk factors and, above all, with the clustering of them. The multivariate adjusted odds ratio to present simultaneously the four risk factors for those above the median value of the MeDiet score was 0.67 (95% confidence interval: 0.53–0.85). The multivariate odds ratios for successive categories of adherence to MeDiet were 1 (ref.), 1.03, 0.85, 0.70 and 0.54 (P for trend ≤0.001). Conclusion Following a MeDiet was inversely associated with the clustering of hypertension, diabetes, obesity, and hypercholesterolemia among high-risk patients.

Adherence to the Mediterranean diet is associated with better mental and physical health

The aim of the present study was to analyse the association between adherence to the Mediterranean diet and self-perceived mental and physical health function, controlled for confounding effects of age, smoking, BMI, alcohol consumption, educational level, leisure-time physical activity and the presence of chronic conditions. A random sample of the 35-74-year-old population (3910 men and 4285 women) of Gerona, Spain, was examined in 2000 and 2005 in two independent population-based cross-sectional surveys. Dietary intake was assessed using a validated FFQ. The Mediterranean diet score (MDS) was calculated according to tertile distribution of energy-adjusted food consumption considered characteristic for the Mediterranean region. Health-related quality of life was measured using the SF-12 questionnaire. Alcohol consumption, leisure-time physical activity and smoking habits were recorded. Weight and height were measured. Age-adjusted linear regression analysis revealed a significant (P < 0.01) direct association of the MDS with self-reported mental and physical health in both sexes. An increase of 5 units of the MDS was directly associated with changes of 0.74 and 1.15 units in men and women, respectively, in the mental component score after controlling for potential confounders. The age-adjusted direct association of the MDS with self-reported scoring of physical health remained stable after adjusting for several confounders in men but was attenuated in women. Adherence to the Mediterranean diet was associated with higher scoring for self-perceived health.