The role of olive oil in disease prevention: a focus on the recent epidemiological evidence from cohort studies and dietary intervention trials.

Consumption of olive oil within the Mediterranean diet has been long known to have many health benefits. However, only over the last decade has epidemiological research confirmed its protective role against developing several chronic diseases. The objective of this review was to give an overview of the state of art epidemiological evidence concerning the relationship between olive oil and key public health outcomes including mortality, CVD, diabetes, metabolic syndrome (MetS), obesity and cancer, with a particular focus on recent results from cohort studies and dietary intervention trials. Recent epidemiological research has shown that regular consumption of olive oil is associated with increased longevity. This benefit is partly due to the olive oil's unequivocal cardio-protective role. There is converging evidence on the benefits of olive oil for preventing several CVD risk factors, including diabetes, MetS and obesity. Olive oil is also implicated in preventing certain cancers, with the most promising findings for breast and digestive tract cancers, although the data are still not entirely consistent and mainly from case-control studies. These health benefits are supported by strong mechanistic evidence from experimental studies, demonstrating that specific components of olive oil have antihypertensive, antithrombotic, antioxidant, antiinflammatory and anticarcinogenic action. Despite the accumulating epidemiological research, there is still a lack of consistent results from high-quality studies for many health outcomes (i.e. certain cancers and metabolism-related disorders). Further research is mandatory, above all from prospective studies and randomised dietary intervention trials when feasible, to confirm some of the still potential health benefits.

Total, caffeinated and decaffeinated coffee and tea intake and gastric cancer risk: results from the EPIC cohort study.

Prospective studies examining the association between coffee and tea consumption and gastric cancer risk have shown inconsistent results. We investigated the association between coffee (total, caffeinated and decaffeinated) and tea consumption and the risk of gastric cancer by anatomical site and histological type in the European Prospective Investigation into Cancer and Nutrition study. Coffee and tea consumption were assessed by dietary questionnaires at baseline. Adjusted hazard ratios (HRs) were calculated using Cox regression models. During 11.6 years of follow up, 683 gastric adenocarcinoma cases were identified among 477,312 participants. We found no significant association between overall gastric cancer risk and consumption of total coffee (HR 1.09, 95%-confidence intervals [CI]: 0.84-1.43; quartile 4 vs. non/quartile 1), caffeinated coffee (HR 1.14, 95%-CI: 0.82-1.59; quartile 4 vs. non/quartile 1), decaffeinated coffee (HR 1.07, 95%-CI: 0.75-1.53; tertile 3 vs. non/tertile 1) and tea (HR 0.81, 95%-CI: 0.59-1.09; quartile 4 vs. non/quartile 1). When stratified by anatomical site, we observed a significant positive association between gastric cardia cancer risk and total coffee consumption per increment of 100 mL/day (HR 1.06, 95%-CI: 1.03-1.11). Similarly, a significant positive association was observed between gastric cardia cancer risk and caffeinated coffee consumption (HR 1.98, 95%-CI: 1.16-3.36, p-trend=0.06; quartile 3 vs. non/quartile 1) and per increment of 100 mL/day (HR 1.09, 95%-CI: 1.04-1.14). In conclusion, consumption of total, caffeinated and decaffeinated coffee and tea is not associated with overall gastric cancer risk. However, total and caffeinated coffee consumption may be associated with an increased risk of gastric cardia cancer. Further prospective studies are needed to rule out chance or confounding.

Tea and coffee consumption and risk of esophageal cancer: the European prospective investigation into cancer and nutrition study.

Epidemiological data regarding tea and coffee consumption and risk of esophageal cancer (EC) is still inconclusive. We examined the association of tea and coffee consumption with EC risk among 442,143 men and women without cancer at baseline from 9 countries of the European Prospective Investigation into Cancer and Nutrition. Tea and coffee intakes were recorded using country-specific validated dietary questionnaires. Cox regression models were used to analyze the relationships between tea and coffee intake and EC risk. During a mean follow-up of 11.1 years, 339 participants developed EC, of which 142 were esophageal adenocarcinoma (EAC) and 174 were esophageal squamous cell carcinoma (ESCC). In the multivariable models, no significant associations between tea (mostly black tea), and coffee intake and risk of EC, EAC and ESCC were observed. In stratified analyses, among men coffee consumption was inversely related to ESCC (HR for comparison of extreme tertiles 0.42, 95% CI 0.20-0.88; p-trend=0.022), but not among women. In current smokers, a significant and inverse association was observed between ESCC risk and tea (HR 0.46, 95% CI 0.23-0.93; p-trend=0.053) and coffee consumption (HR 0.37, 95% CI 0.19-0.73; p-trend=0.011). However, no statistically significant findings were observed using the continuous variable (per 100 mL/d). These data did not show a significant association between tea and coffee consumption and EC, EAC and ESCC, although a decreased risk of ESCC among men and current smokers is suggested, but need to be confirmed in further prospective studies including more cases.

Dietary intakes and food sources of phenolic acids in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Phenolic acids are secondary plant metabolites that may have protective effects against oxidative stress, inflammation and cancer in experimental studies. To date, limited data exist on the quantitative intake of phenolic acids. We estimated the intake of phenolic acids and their food sources and associated lifestyle factors in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Phenolic acid intakes were estimated for 36,037 subjects aged 35-74 years and recruited between 1992 and 2000 in ten European countries using a standardised 24 h recall software (EPIC-Soft), and their food sources were identified. Dietary data were linked to the Phenol-Explorer database, which contains data on forty-five aglycones of phenolic acids in 452 foods. The total phenolic acid intake was highest in Aarhus, Denmark (1265·5 and 980·7 mg/d in men and women, respectively), while the intake was lowest in Greece (213·2 and 158·6 mg/d in men and women, respectively). The hydroxycinnamic acid subclass was the main contributor to the total phenolic acid intake, accounting for 84·6-95·3% of intake depending on the region. Hydroxybenzoic acids accounted for 4·6-14·4%, hydroxyphenylacetic acids 0·1-0·8% and hydroxyphenylpropanoic acids ≤ 0·1% for all regions. An increasing south-north gradient of consumption was also found. Coffee was the main food source of phenolic acids and accounted for 55·3-80·7% of the total phenolic acid intake, followed by fruits, vegetables and nuts. A high heterogeneity in phenolic acid intake was observed across the European countries in the EPIC cohort, which will allow further exploration of the associations with the risk of diseases.

Differences in dietary intakes, food sources and determinants of total flavonoids between Mediterranean and non-Mediterranean countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

A greater adherence to the traditional Mediterranean (MED) diet is associated with a reduced risk of developing chronic diseases. This dietary pattern is based on higher consumption of plant products that are rich in flavonoids. We compared the total flavonoid dietary intakes, their food sources and various lifestyle factors between MED and non-MED countries participating in the EPIC study. Flavonoid intakes and their food sources for 35,628 subjects, aged 35-74 years and recruited between 1992 and 2000, in twenty-six study centres were estimated using standardised 24 h dietary recall software (EPIC-Soft®). An ad hoc food composition database on flavonoids was compiled using analytical data from the United States Department of Agriculture and Phenol-Explorer databases. Moreover, it was expanded to include using recipes, estimations of missing values and flavonoid retention factors. No significant differences in total flavonoid mean intake between non-MED countries (373·7 mg/d) and MED countries (370·2 mg/d) were observed. In the non-MED region, the main contributors were proanthocyanidins (48·2%) and flavan-3-ol monomers (24·9%) and the principal food sources were tea (25·7%) and fruits (32·8%). In the MED region, proanthocyanidins (59·0%) were by far the most abundant contributor and fruits (55·1%), wines (16·7%) and tea (6·8%) were the main food sources. The present study shows similar results for total dietary flavonoid intakes, but significant differences in flavonoid class intakes, food sources and some characteristics between MED and non-MED countries. These differences should be considered in studies about the relationships between flavonoid intake and chronic diseases.

Olive oil intake and CHD in the European Prospective Investigation into Cancer and Nutrition Spanish cohort.

Olive oil is well known for its cardioprotective properties; however, epidemiological data showing that olive oil consumption reduces incident CHD events are still limited. Therefore, we studied the association between olive oil and CHD in the European Prospective Investigation into Cancer and Nutrition (EPIC) Spanish cohort study. The analysis included 40 142 participants (38 % male), free of CHD events at baseline, recruited from five EPIC-Spain centres from 1992 to 1996 and followed up until 2004. Baseline dietary and lifestyle information was collected using interview-administered questionnaires. Cox proportional regression models were used to assess the relationship between validated incident CHD events and olive oil intake (energy-adjusted quartiles and each 10 g/d per 8368 kJ (2000 kcal) increment), while adjusting for potential confounders. During a 10·4-year follow-up, 587 (79 % male) CHD events were recorded. Olive oil intake was negatively associated with CHD risk after excluding dietary mis-reporters (hazard ratio (HR) 0·93; 95 % CI 0·87, 1·00 for each 10 g/d per 8368 kJ (2000 kcal) and HR 0·78; 95 % CI 0·59, 1·03 for upper v. lower quartile). The inverse association between olive oil intake (per 10 g/d per 8368 kJ (2000 kcal)) and CHD was more pronounced in never smokers (11 % reduced CHD risk (P = 0·048)), in never/low alcohol drinkers (25 % reduced CHD risk (P < 0·001)) and in virgin olive oil consumers (14 % reduced CHD risk (P = 0·072)). In conclusion, olive oil consumption was related to a reduced risk of incident CHD events. This emphasises the need to conserve the traditional culinary use of olive oil within the Mediterranean diet to reduce the CHD burden.

Olive oil intake and mortality within the Spanish population (EPIC-Spain).

BACKGROUND: Olive oil consumption is associated with a decreased risk of several chronic diseases, in particular cardiovascular disease (CVD). However, data on the effects of olive oil on overall mortality are scarce. OBJECTIVE: We evaluated the association between olive oil and overall and cause-specific mortality in the Spanish population in the European Prospective Investigation into Cancer and Nutrition (EPIC-Spain). DESIGN: A total of 40,622 participants (62% female) aged 29-69 y were recruited from 5 Spanish regions in 1992-1996. The association between olive oil (analyzed as a categorical and continuous variable) and overall and cause-specific mortality (CVD, cancer, and other causes) was analyzed by using Cox proportional hazards regression models adjusted for potential confounders. RESULTS: A total of 1915 deaths were reported during 13.4 y of follow-up: 416 CVD deaths, 956 cancer deaths, and 417 deaths from other causes (for 126 deaths the cause was not available). In comparison with nonconsumers, the highest quartile of olive oil consumption was associated with a 26% (95% CI: 13%, 36%) reduction in risk of overall mortality and a 44% (95% CI: 21%, 60%) reduction in CVD mortality. For each increase in olive oil of 10 g · 2000 kcal⁻¹ · d⁻¹, there was a 7% (95% CI: 3%, 10%) decreased risk of overall mortality and a 13% (95% CI: 6%, 20%) decreased risk of CVD mortality. No significant association was observed between olive oil and cancer mortality. CONCLUSIONS: Olive oil was associated with a decreased risk of overall mortality and an important reduction in CVD mortality in this large Mediterranean cohort. This provides further evidence on the beneficial effects of one of the key Mediterranean dietary components.

Olive oil intake and breast cancer risk in the Mediterranean countries of the European Prospective Investigation into Cancer and Nutrition study.

Although there is some evidence suggesting that olive oil could reduce breast cancer (BC) risk, the epidemiological data are still relatively limited, not entirely consistent and mainly based on case-control studies. Therefore, we prospectively assessed the association between olive oil and BC risk in postmenopausal women from the Mediterranean cohorts within the European Prospective Investigation into Cancer and Nutrition. The analysis included 62,284 postmenopausal women recruited from Spain, Italy and Greece who had complete dietary data (collected from validated country-specific dietary questionnaires). The risk of BC (overall and by hormone receptor subtypes) was assessed using hazards ratios (HRs) obtained from Cox proportional hazards regression, while adjusting for known BC risk factors. After a mean follow-up of 9 years, 1,256 women were diagnosed with a primary incident invasive BC. The multivariate HRs for BC risk by olive oil intake (highest vs. lowest tertile of g/day/2,000 kcal) were 1.07 (95% CI = 0.91-1.25) in the adjusted model, 1.06 (95% CI = 0.91-1.24) in the model additionally adjusted for reproductive-related factors and 1.10 (95% CI = 0.92-1.31) for the model additionally adjusted for dietary factors. There was no association between olive oil and risk of estrogen or progesterone receptor-positive tumors, but a suggestion of a negative association with estrogens and progesterone receptor-negative tumors. The results from our prospective study showed that olive oil consumption during adult life was not associated with the risk of BC. However, larger prospective studies are still needed to explore possible differences related to hormone receptor status.

Consumption of fried foods and risk of coronary heart disease: Spanish cohort of the European Prospective Investigation into Cancer and Nutrition study.

OBJECTIVE: To assess the association between consumption of fried foods and risk of coronary heart disease. DESIGN: Prospective cohort study. SETTING: Spanish cohort of the European Prospective Investigation into Cancer and Nutrition. PARTICIPANTS: 40 757 adults aged 29-69 and free of coronary heart disease at baseline (1992-6), followed up until 2004. MAIN OUTCOME MEASURES: Coronary heart disease events and vital status identified by record linkage with hospital discharge registers, population based registers of myocardial infarction, and mortality registers. RESULTS: During a median follow-up of 11 years, 606 coronary heart disease events and 1135 deaths from all causes occurred. Compared with being in the first (lowest) quarter of fried food consumption, the multivariate hazard ratio of coronary heart disease in the second quarter was 1.15 (95% confidence interval 0.91 to 1.45), in the third quarter was 1.07 (0.83 to 1.38), and in the fourth quarter was 1.08 (0.82 to 1.43; P for trend 0.74). The results did not vary between those who used olive oil for frying and those who used sunflower oil. Likewise, no association was observed between fried food consumption and all cause mortality: multivariate hazard ratio for the highest versus the lowest quarter of fried food consumption was 0.93 (95% confidence interval 0.77 to 1.14; P for trend 0.98). CONCLUSION: In Spain, a Mediterranean country where olive or sunflower oil is used for frying, the consumption of fried foods was not associated with coronary heart disease or with all cause mortality.

Intake estimation of total and individual flavan-3-ols, proanthocyanidins and theaflavins, their food sources and determinants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Epidemiological studies suggest health-protective effects of flavan-3-ols and their derived compounds on chronic diseases. The present study aimed to estimate dietary flavan-3-ol, proanthocyanidin (PA) and theaflavin intakes, their food sources and potential determinants in the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration cohort. Dietary data were collected using a standardised 24 h dietary recall software administered to 36 037 subjects aged 35-74 years. Dietary data were linked with a flavanoid food composition database compiled from the latest US Department of Agriculture and Phenol-Explorer databases and expanded to include recipes, estimations and retention factors. Total flavan-3-ol intake was the highest in UK Health-conscious men (453·6 mg/d) and women of UK General population (377·6 mg/d), while the intake was the lowest in Greece (men: 160·5 mg/d; women: 124·8 mg/d). Monomer intake was the highest in UK General population (men: 213·5 mg/d; women: 178·6 mg/d) and the lowest in Greece (men: 26·6 mg/d in men; women: 20·7 mg/d). Theaflavin intake was the highest in UK General population (men: 29·3 mg/d; women: 25·3 mg/d) and close to zero in Greece and Spain. PA intake was the highest in Asturias (men: 455·2 mg/d) and San Sebastian (women: 253 mg/d), while being the lowest in Greece (men: 134·6 mg/d; women: 101·0 mg/d). Except for the UK, non-citrus fruits (apples/pears) were the highest contributors to the total flavan-3-ol intake. Tea was the main contributor of total flavan-3-ols in the UK. Flavan-3-ol, PA and theaflavin intakes were significantly different among all assessed groups. This study showed heterogeneity in flavan-3-ol, PA and theaflavin intake throughout the EPIC countries.

Carcinogenesis, prevention and early detection of gastric cancer: where we are and where we should go.

Helicobacter pylori is the most common cause of gastric cancer (GC), though smoking, alcohol, diet, genetics and epigenetic factors may also have a role in the occurrence of the disease. Why H. pylori cause GC in only a minority of those infected remains unknown. Although mechanisms of H. pylori-induced carcinogenesis are not yet well understood, several genotypes of H. pylori have been associated with strain virulence and disease risk. Primary prevention of GC should be addressed by avoiding exposure to factors that increase the risk and to promote factors associated with decrease risk. Vaccines against H. pylori are an ongoing promise and not yet available. Chemoprevention through vitamin supplementation has shown no benefit. Screening and eradication of H. pylori in the general population is not advised. Given that GC is a multiple-steps process, the identification of patients with preneoplastic lesions with high risk of progression, and periodic endoscopic surveillance of them represents the most effective way for early diagnosis of GC. However, clinical guidelines for surveillance are lacking and there are no clear criteria to classify patients into high or low risk of progressing to GC. No study has shown the potential usefulness of combining the information on the type of preneoplastic lesions, genetic and epigenetic, lifestyle and virulence bacterial factors in order to identify high risk patients who need more intensive surveillance. The integration of all this information, in a prediction model requires further research and could be the most important contribution for reducing the burden of GC.

Menopausal hormone therapy and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition.

Menopausal hormone therapy (HT) may influence colorectal cancer risk. A total of 136,275 postmenopausal women from the European Prospective Investigation into Cancer and Nutrition were followed for an average of 9 years, during which time 1,186 colorectal cancers were diagnosed. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models stratified by center and age, and adjusted for body mass index, smoking, diabetes, physical activity and alcohol consumption. Compared to never use of HT at study enrollment, current use of estrogen-only (HR, 1.02; 95% CI, 0.79-1.31) or estrogen plus progestin (HR, 0.94; 95% CI, 0.77-1.14) was not significantly associated with the risk of colorectal cancer, and these associations did not vary by recency, duration, route of administration, regimen or specific constituent of HT. Our results show no significant association of estrogen-only or estrogen plus progestin therapy with colorectal cancer risk.

Menopausal hormone therapy and breast cancer risk: impact of different treatments. The European Prospective Investigation into Cancer and Nutrition.

Menopausal hormone therapy (MHT) is characterized by use of different constituents, regimens and routes of administration. We investigated the association between the use of different types of MHT and breast cancer risk in the EPIC cohort study. The analysis is based on data from 133,744 postmenopausal women. Approximately 133,744 postmenopausal women contributed to this analysis. Information on MHT was derived from country-specific self-administered questionnaires with a single baseline assessment. Incident breast cancers were identified through population cancer registries or by active follow-up (mean: 8.6 yr). Overall relative risks (RR) and 95% confidence interval (CI) were derived from country-specific Cox proportional hazard models estimates. A total of 4312 primary breast cancers were diagnosed during 1,153,747 person-years of follow-up. Compared with MHT never users, breast cancer risk was higher among current users of estrogen only (RR: 1.42, 95% CI 1.23-1.64) and higher still among current users of combined MHT (RR: 1.77, 95% CI 1.40-2.24; p = 0.02 for combined vs. estrogen-only). Continuous combined regimens conferred a 43% (95% CI: 19-72%) greater risk compared with sequential regimens. There was no significant difference between progesterone and testosterone derivatives in sequential regimens. There was no significant variation in risk linked to the estrogenic component of MHT, neither for oral vs. cutaneous administration nor for estradiol compounds vs. conjugated equine estrogens. Estrogen-only and combined MHT uses were associated with increased breast cancer risk. Continuous combined preparations were associated with the highest risk. Further studies are needed to disentangle the effects of the regimen and the progestin component.

Plasma phospholipid fatty acid profiles and their association with food intakes: results from a cross-sectional study within the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Plasma phospholipid fatty acids have been correlated with food intakes in populations with homogeneous dietary patterns. However, few data are available on populations with heterogeneous dietary patterns. OBJECTIVE: The objective was to investigate whether plasma phospholipid fatty acids are suitable biomarkers of dietary intakes across populations involved in a large European multicenter study. DESIGN: A cross-sectional study design nested to the European Prospective Investigation into Cancer and Nutrition (EPIC) was conducted to determine plasma fatty acid profiles in >3,000 subjects from 16 centers, who had also completed 24-h dietary recalls and dietary questionnaires. Plasma fatty acids were assessed by capillary gas chromatography. Ecological and individual correlations were calculated between fatty acids and select food groups. RESULTS: The most important determinant of plasma fatty acids was region, which suggests that the variations across regions are largely due to different food intakes. Strong ecological correlations were observed between fish intake and long-chain n-3 polyunsaturated fatty acids (r = 0.78, P < 0.01), olive oil and oleic acid (r = 0.73, P < 0.01), and margarine and elaidic acid (r = 0.76, P < 0.01). Individual correlations varied across the regions, particularly between olive oil and oleic acid and between alcohol and the saturation index, as an indicator of stearoyl CoA desaturase activity. CONCLUSIONS: These findings indicate that specific plasma phospholipid fatty acids are suitable biomarkers of some food intakes in the EPIC Study. Moreover, these findings suggest complex interactions between alcohol intake and fatty acid metabolism, which warrants further attention in epidemiologic studies relating dietary fatty acids to alcohol-related cancers and other chronic diseases.

Plasma and dietary vitamin C levels and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST).

Vitamin C is an antioxidant and inhibitor of carcinogenic N-nitroso compound production in the stomach. Higher dietary vitamin C consumption is associated with decreased risk of gastric cancer (GC) in numerous case-control studies, but data from prospective studies are limited, particularly so for blood measures of vitamin C. The objective of this study was to determine the association of plasma and dietary vitamin C levels with the risk of GC in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 European countries. Using a fluorometric method, vitamin C was measured in pre-diagnostic plasma from 215 GC cases (matched controls = 416). Conditional logistic regression models adjusted by body mass index, total energy intake, smoking status/duration/intensity and Helicobacter pylori infection status were used to estimate relative cancer risks. No association with GC risk was observed for dietary vitamin C, whereas an inverse GC risk was observed in the highest versus lowest quartile of plasma vitamin C [odds ratio (OR) = 0.55, 95% confidence interval (CI) = 0.31-0.97, P(trend) = 0.043], which was maintained after exclusion of cases with

Changes in food supply in Mediterranean countries from 1961 to 2001.

OBJECTIVE: To describe geographical differences and time trends in the supply of the most important food components of the traditional Mediterranean diet. DESIGN: Food supply data collected from national food balance sheets for the period 1961-2001. SETTING: Selected Mediterranean countries: Spain, Italy, France, Greece, Algeria, Morocco, Tunisia and Turkey. RESULTS: Differences of almost 30-fold and five-fold were found in the supply of olive oil and fruits and vegetables, respectively, among the Mediterranean countries studied during the 1960s. A favourable increasing trend for the supply of fruit and vegetables was observed in most Mediterranean countries. However, an increase in the supply of meats and dairy products and a decrease in the supply of cereals and wine were observed in European Mediterranean countries from 1961 until 2001. Only in African and Asiatic Mediterranean countries were cereals the base of food supply. During the 1990s, Greece's food supply pattern was closest to the traditional Mediterranean diet, while Italy and Spain maintained a high availability of fruits, vegetables and olive oil, but were losing the other typical components. Among African and Asiatic Mediterranean countries, only Turkey presented a traditional Mediterranean dietary pattern except with respect to olive oil, the supply of which was very low. France showed a Western dietary pattern, with a high supply of animal products and a low supply of olive oil. CONCLUSIONS: Dietary supplies in the Mediterranean area were quite heterogeneous in the 1960s and have experienced a process of Westernization, especially in European Mediterranean countries.