PDF file - 172KB, Supplementary Figure 1. Cut-off points for categories of alcohol consumption by study included in the metaanalysis. Supplementary Table 1. Description of the BCAC studies. Supplementary Table 2. Characteristics of the SEARCH study by post-diagnosis alcohol consumption. Supplementary Table 3. Characteristics of the EPIC study by pre-diagnosis alcohol consumption. Supplementary Table 4. Distribution of alcohol consumption by country in the EPIC cohort. Supplementary Table 5. Characteristics of the BCAC studies. Supplementary Table 6. Association of alcohol consumption and mortality. Supplementary Table 7. Association of alcohol consumption and mortality in patients with stage I and II tumours compared to all patients in SEARCH.

In a recent Article published in The Lancet Planetary Health, Jessica Laine and colleagues1Laine JE Huybrechts I Gunter MJ et al.Co-benefits from sustainable dietary shifts for population and environmental health: an assessment from a large European cohort study.Lancet Planet Health. 2021; 5: e786-e796Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar emphasised the relevance of the inter-relationship between dietary habits, human health, and planetary health. They showed an association of dietary greenhouse gas emissions with all-cause mortality and several forms of cause-specific mortality, and the incidence of cancer, based on a large cohort of almost half a million people from nine countries included in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. In our study,2González CA Bonet C de Pablo M et al.Greenhouse gases emissions from the diet and risk of death and chronic diseases in the EPIC-Spain cohort.Eur J Public Health. 2021; 31: 130-135Crossref PubMed Scopus (4) Google Scholar based on the Spanish EPIC cohort and comprising 40 621 participants, we found a similar association between dietary greenhouse gas emissions and total mortality, and a slightly lower association with overall cancer incidence. However, we expanded the assessment of the potential associations between dietary greenhouse gas emissions and human health, including the risk of coronary heart disease and type 2 diabetes—two of the most common causes of death. Comparing the highest versus lowest tertile of dietary greenhouse gas emissions, we found a significant association with the risk of coronary heart disease (hazard ratio [HR] 1·26; 95% CI 1·08–1·48), based on 1007 confirmed and validated incident cases identified during a mean follow-up of 10·4 years. We also found a significant association between dietary greenhouse gas emissions and the risk of type 2 diabetes, based on 2025 incident confirmed cases during 12·1 years of follow-up (HR 1·24; 95% CI 1·11–1·38). It is worth noting that our assessment of dietary greenhouse gas emissions was based on a different database,3Clune S Crossin E Verghese K Systematic review of greenhouse gas emissions for different fresh food categories.J Clean Prod. 2017; 140: 766-783Crossref Scopus (389) Google Scholar and our results need to be replicated in other cohort studies. However, taken in the context of the referred Article,1Laine JE Huybrechts I Gunter MJ et al.Co-benefits from sustainable dietary shifts for population and environmental health: an assessment from a large European cohort study.Lancet Planet Health. 2021; 5: e786-e796Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar these findings strongly point to a substantial impact of a sustainable diet on the most important chronic diseases, apart from cancer. Therefore, we support the claim by Laine and colleagues that reducing dietary greenhouse gas emissions not only mitigates climate change but also improves the health of the population. We declare no competing interests. Co-benefits from sustainable dietary shifts for population and environmental health: an assessment from a large European cohort studyOur results indicate that shifts towards universally sustainable diets could lead to co-benefits, such as minimising diet-related greenhouse gas emissions and land use, reducing the environmental footprint, aiding in climate change mitigation, and improving population health. Full-Text PDF Open Access

To adopt prevention strategies in gastric cancer, it is imperative to develop robust biomarkers with acceptable costs and feasibility in clinical practice to stratified populations according to risk scores. With this aim, we applied an unbiased genome-wide CpG methylation approach to a discovery cohort composed of gastric cancer (n = 24), and non-malignant precursor lesions (n = 64). Then, candidate-methylation approaches were performed in a validation cohort of precursor lesions obtained from an observational longitudinal study (n = 264), with a 12-year follow-up to identify repression or progression cases. H. pylori stratification and histology were considered to determine their influence on the methylation dynamics. As a result, we ascertained that intestinal metaplasia partially recapitulates patterns of aberrant methylation of intestinal type of gastric cancer, independently of the H. pylori status. Two epigenetically regulated genes in cancer, RPRM and ZNF793, consistently showed increased methylation in intestinal metaplasia with respect to earlier precursor lesions. In summary, our result supports the need to investigate the practical utilities of the quantification of DNA methylation in candidate genes as a marker for disease progression. In addition, the H. pylori-dependent methylation in intestinal metaplasia suggests that pharmacological treatments aimed at H. pylori eradication in the late stages of precursor lesions do not prevent epigenome reprogramming toward a cancer signature.

Nutritional epidemiology currently studies the diet-disease relationships. In order to evaluate these associations, an accurate estimation of nutritional exposure is essential. Traditional dietary questionnaires are being complemented with the measurement of nutritional biomarkers. New methodologies, including the use of new dietary assessments, metabolomics for increasing the quantity and quality of biomarkers, and statistical approaches to combine both techniques, are required to move forward in this field. In this review, we have selected five of the more relevant accomplishments in this field as examples of the importance of dietary factors in the prevention of non-communicable diseases. This theoretical knowledge needs to be finally translated by public health experts into dietary recommendations to the general population.

BACKGROUND:Evidence from the scientific literature shows a significant variation in greenhouse gas (GHG) emissions from the diet, according to the type of food consumed. We aim to analyze the relationship between the daily dietary GHG emissions according to red meat, fruit and vegetables consumption and their relationship with risk of total mortality, and incident risk of chronic diseases.METHODS:We examined data on the EPIC-Spain prospective study, with a sample of 40 621 participants. Dietary GHG emission values were calculated for 57 food items of the EPIC study using mean emission data from a systematic review of 369 published studies.RESULTS:Dietary GHG emissions (kgCO2eq/day), per 2000 kcal, were 4.7 times higher in those with high red-meat consumption (>140 g/day) than those with low consumption (<70 g/day). The average dietary GHG emissions were similar in males and females, but it was significantly higher in youngest people and in those individuals with lower educational level, as well as for northern EPIC centers of Spain. We found a significant association with the risk of mortality comparing the third vs. the first tertile of dietary GHG emissions [hazard ratio (HR) 1.095; 95% confidence interval (CI) 1.007-1.19; trend test 0.037]. Risk of coronary heart disease (HR 1.26; 95% CI 1.08-1.48; trend test 0.003) and risk of type 2 diabetes (HR 1.24; 95% CI 1.11-1.38; trend test 0.002) showed significant association as well.CONCLUSIONS:Decreasing red-meat consumption would lead to reduce GHG emissions from diet and would reduce risk of mortality, coronary heart disease and type 2 diabetes.

Introduction: In Spain, one third of all children and two-thirds of adults suffer from excess weight, a condition that generates a direct excess medical cost of 2000 million Euros. Obesogenic food environments cause obesity by promoting the consumption of sugar-sweetened beverages and ultra-processed foods. Accordingly, we propose five priority policies capable of reversing the epidemic of obesity and related non-communicable diseases through the creation of healthy food environments. The power (PODER in Spanish) of food policies: Advertising (Publicidad): regulation of unhealthy food and drink advertisements carried by all media and targeted at children, and prohibition of sponsorships of congresses, conferences or sports events and endorsements by scientific associations or health professionals. Supply (Oferta): promotion of a 100% healthy supply of goods on sale in vending machines sited at educational, health and sports centres. Demand (Demanda): levying a tax of at least 20% on sugar-sweetened beverages, accompanied by subsidies or reduced taxes on healthy foods and availability of drinking water free of charge at all public venues and areas. Labelling (Etiquetado): effective application of the Nutri-Score through the use of incentives, regulation and public-tender mechanisms. Reformulation (Reformulacion): revising and redrawing reformulation agreements with the industry, setting more ambitious goals and mandatory compliance. A final thought: These five proposed interventions, all of which have been successfully applied in other countries, will serve to raise population awareness and have a positive impact on health and the economy, through reducing the health care costs of obesity and enhancing work productivity. These measures should form part of a wide-ranging transformation of the food system, with agri-food policies that foster the sustainable production of healthy foods. (C) 2019 SESPAS. Published by Elsevier Espana, S.L.U.

Resumen: Introducción: En España, un tercio de los menores y dos tercios de los adultos padecen exceso de peso, una condición que genera un sobrecoste médico directo de 2000 millones de euros. El entorno alimentario obesogénico causa obesidad al promover el consumo de bebidas azucaradas y de alimentos ultraprocesados. Por ello, proponemos cinco políticas prioritarias con el PODER de revertir la epidemia de obesidad y de enfermedades no transmisibles asociadas a ella, mediante la creación de entornos alimentarios saludables. El PODER de las políticas alimentarias: P (Publicidad): regulación de la publicidad de alimentos y bebidas no saludables dirigida a menores por todos los medios y prohibición de patrocinios de congresos o eventos deportivos y avales de asociaciones científicas o profesionales de la salud. O (Oferta): promoción de una oferta 100% saludable en máquinas expendedoras de centros educativos, sanitarios y deportivos.D (Demanda): implantación de un impuesto, al menos del 20%, a las bebidas azucaradas, acompañado de subvenciones o bajadas de impuestos a alimentos saludables y disponibilidad de agua potable a coste cero en todos los centros y espacios públicos. E (Etiquetado): aplicación efectiva del Nutri-Score mediante el uso de incentivos, regulación y mecanismos de contratación pública. R (Reformulación): reformular los acuerdos de reformulación con la industria con objetivos más ambiciosos y de obligado cumplimiento. Reflexión final: Las cinco intervenciones propuestas, aplicadas con éxito en otros países, contribuirán a concienciar a la población y tendrán un impacto positivo en la salud y en la economía, por una reducción de los costes sanitarios de la obesidad y un aumento de la productividad laboral. Estas medidas deberían formar parte de una gran transformación del sistema alimentario, con políticas agroalimentarias que fomenten una producción sostenible de alimentos saludables. Abstract: Introduction: In Spain, one third of all children and two-thirds of adults suffer from excess weight, a condition that generates a direct excess medical cost of 2000 million Euros. Obesogenic food environments cause obesity by promoting the consumption of sugar-sweetened beverages and ultra-processed foods. Accordingly, we propose five priority policies capable of reversing the epidemic of obesity and related non-communicable diseases through the creation of healthy food environments. The power (PODER in Spanish) of food policies: Advertising (Publicidad): regulation of unhealthy food and drink advertisements carried by all media and targeted at children, and prohibition of sponsorships of congresses, conferences or sports events and endorsements by scientific associations or health professionals. Supply (Oferta): promotion of a 100% healthy supply of goods on sale in vending machines sited at educational, health and sports centres. Demand (Demanda): levying a tax of at least 20% on sugar-sweetened beverages, accompanied by subsidies or reduced taxes on healthy foods and availability of drinking water free of charge at all public venues and areas. Labelling (Etiquetado): effective application of the Nutri-Score through the use of incentives, regulation and public-tender mechanisms. Reformulation (Reformulación): revising and redrawing reformulation agreements with the industry, setting more ambitious goals and mandatory compliance. A final thought: These five proposed interventions, all of which have been successfully applied in other countries, will serve to raise population awareness and have a positive impact on health and the economy, through reducing the health care costs of obesity and enhancing work productivity. These measures should form part of a wide-ranging transformation of the food system, with agri-food policies that foster the sustainable production of healthy foods. Palabras clave: Política alimentaria, Impuestos, Publicidad alimentaria, Etiquetado alimentario, Obesidad, Enfermedades no transmisibles, Keywords: Food policy, Taxes, Food advertising, Food labelling, Obesity, Non-transmissible diseases

Background MicroRNAs are small regulatory RNAs with important roles in carcinogenesis. Genetic variants in these regulatory molecules may contribute to disease. We aim to identify allelic variants in microRNAs as susceptibility factors to gastric cancer using association studies and functional approaches. Methods Twenty-one single nucleotide variants potentially functional, because of their location in either the seed, mature or precursor region of 22 microRNAs, were selected for association studies. Genetic association with gastric cancer in 365 cases and 1,284 matched controls (European Prospective Investigation into Cancer and Nutrition Cohort) was analysed using logistic regression. MicroRNA overexpression, transcriptome analysis, and target gene validation experiments were performed for functional studies. Results rs3746444:T>C, in the seed of MIR499A and mature MIR499B, associated with the cardia adenocarcinoma location; rs12416605:C>T, in the seed of MIR938, associated with the diffuse subtype; and rs2114358:T>C, in the precursor MIR1206, associated with the noncardia phenotype. In all cases, the association was inverse, indicating a protective affect against gastric cancer of the three minor allelic variants. MIR499 rs3746444:T>C and MIR1206 rs2114358:T>C are reported to affect the expression of these miRNAs, but the effect of MIR938 rs12416605:C>T is unknown yet. Functional approaches showed that the expression of MIR938 is affected by rs12416605:C>T and revealed that MIR938 could regulate a subset of cancer-related genes in an allele-specific fashion. Furthermore, we demonstrated that CXCL12, a chemokine participating in gastric cancer metastasis, is specifically regulated by only one of the rs12416605:C>T alleles. Conclusion rs12416605 appears to be involved in gastric cancer by affecting the regulatory function of MIR938 on genes related to this cancer type, particularly on CXCL12 posttranscriptional regulation.

Background: Adherence to a Mediterranean diet (MedDiet) is thought to reduce liver steatosis. Objectives: To explore the associations with liver steatosis of 3 different diets: aMedDiet+ extra-virgin olive oil (EVOO), MedDiet + nuts, or a control diet. Methods: This was a subgroup analysis nested within a multicenter, randomized, parallel-group clinical trial, PREvencion con DIeta MEDiterranea (PREDIMED trial: ISRCTN35739639), aimed at assessing the effect of a MedDiet on the primary prevention of cardiovascular disease. One hundred men and women (mean age: 64 +/- 6 y), at high cardiovascular risk (62% with type 2 diabetes) from the Bellvitge-PREDIMED center were randomly assigned to a MedDiet supplemented with EVOO, a MedDiet supplemented with mixed nuts, or a control diet (advice to reduce all dietary fat). No recommendations to lose weight or increase physical activity were given. Main measurements were the percentage of liver fat and the diagnosis of steatosis, which were determined by NMR imaging. The association of diet with liver fat content was analyzed by bivariate analysis after a median follow-up of 3 y. Results: Baseline adiposity and cardiometabolic risk factors were similar among the 3 treatment arms. At 3 y after the intervention hepatic steatosis was present in 3 (8.8%), 12 (33.3%), and 10 (33.3%) of the participants in the MedDiet + EVOO, MedDiet + nuts, and control diet groups, respectively (P = 0.027). Respective mean values of liver fat content were 1.2%, 2.7%, and 4.1% (P = 0.07). A tendency toward significance was observed for the MedDiet + EVOO group compared with the control group. Median values of urinary 12(S)-hydroxyeicosatetraenoic acid/creatinine concentrations were significantly (P = 0.001) lower in the MedDiet + EVOO (2.3 ng/mg) than in the MedDiet + nuts (5.0 ng/mg) and control (3.9 ng/mg) groups. No differences in adiposity or glycemic control changes were seen between groups. Conclusions: An energy-unrestricted MedDiet supplemented with EVOO, a food with potent antioxidant and anti-inflammatory properties, is associated with a reduced prevalence of hepatic steatosis in older individuals at high cardiovascular risk.

Four epidemiologic studies have assessed the association between nut intake and pancreatic cancer risk with contradictory results. The present study aims to investigate the relation between nut intake (including seeds) and pancreatic ductal adenocarcinoma (PDAC) risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards models were used to estimate hazards ratio (HR) and 95% confidence intervals (95% CI) for nut intake and PDAC risk. Information on intake of nuts was obtained from the EPIC country‐specific dietary questionnaires. After a mean follow‐up of 14 years, 476,160 participants were eligible for the present study and included 1,283 PDAC cases. No association was observed between consumption of nuts and PDAC risk (highest intake vs nonconsumers: HR, 0.89; 95% CI, 0.72–1.10; p ‐trend = 0.70). Furthermore, no evidence for effect‐measure modification was observed when different subgroups were analyzed. Overall, in EPIC, the highest intake of nuts was not statistically significantly associated with PDAC risk.

Gastric carcinogenesis proceeds through a series of gastric cancer precursor lesions (GCPLs) leading to gastric cancer (GC) development. Although Helicobacter pylori infection initiates this process, genetic factors also play a role. We previously reported that genetic variability in MUC2 is associated with the evolution of GCPLs. In order to replicate previous results in an independent sample series and to explore whether genetic variability in other candidate genes plays a role in the evolution of GCPL, genomic DNA from 559 patients with GCPLs, recruited from 9 Spanish hospitals and followed for a mean of 12 years, was genotyped for 141 SNPs in 29 genes. After follow‐up, 45.5% of the lesions remained stable, 37% regressed and 17.5% progressed to a more severe lesion. Genetic association with the evolution of the lesions (progression or regression) was analyzed by multinomial and binomial logistic regression. After correction for multiple comparisons, the results obtained confirmed the inverse association between MUC2 variants and the regression of the lesions. A significant association was also observed between NFKB1 and CD14 variants and the evolution of the lesions; interestingly, this association was with both progression and regression in the same direction, which could reflect the dual role of inflammation in cancer. Stratified analyses according to H. pylori virulence factors indicated some significant and differential effects but none of them passed the FDR test. These results confirm that genetic variability in MUC2, NFKB1 and CD14 may have a role in the evolution of the GCPLs along time and in gastric carcinogenesis.

Epidemiologic evidence linking environmental exposure to polycyclic aromatic hydrocarbons (PAH) with breast cancer is limited. Measurement of DNA adducts formed by aromatic compounds, including PAH, has been carried in breast tissue samples and white blood cells from women with breast cancer and different kinds of controls. However, these studies provide inconsistent results and bias cannot be ruled out. During the 7-year follow-up period, 305 women were diagnosed with first primary breast cancer in the EPIC-Spain cohort, and were compared with a sample of 149 women without breast cancer at recruitment, using a case-cohort approach. Aromatic adducts to DNA from leukocytes collected at recruitment were measured by means of the 32P-post-labelling technique. The relative risk and 95% confidence interval (CI), adjusted by relevant confounders, were estimated by a modified version of Cox proportional hazards model. There was a significant increased risk for developing breast cancer when DNA adduct concentrations were doubled, with adjusted RR of 1.61 (95% CI 1.29-2.01). The increase in breast cancer risk was observed both for pre- and post-menopausal women. There was a significant interaction with tobacco smoking and body mass index, with higher effect of DNA adducts on breast cancer risk among smokers and women with normal weight. The results from our study support the hypothesis that factors leading to higher levels of aromatic DNA adducts in white blood cells may be involved in development of breast cancer.

Intestinal metaplasia (IM) is a gastric cancer precursor lesion (GCPL) and an extremely high risk factor for progression to gastric cancer (GC). Clinical guidelines recommend that patients with extensive IM undergo a gastroscopy every 3 years. However, protein biomarkers that indicate a transition from IM to GC are lacking. Our group recently identified an interferon-alpha (IFNα)-responsive gene, Schlafen 4 (Slfn4), in immune cells that correlates with metaplastic changes in Helicobacter-infected mice. We therefore tested the hypothesis that a human homolog of Slfn4, namely, Schlafen 5 (SLFN5), correlates with progression of GCPL to GC.

BACKGROUND:Intestinal metaplasia (IM) is a precursor lesion that precedes gastric cancer (GC). There are two IM histological subtypes, complete (CIM) and incomplete (IIM), the latter having higher progression rates to GC. This study was aimed at analysing gene expression and molecular processes involved in the progression from normal mucosa to IM, and also from IM subtypes to GC. METHODOLOGY:We used expression data to compare the transcriptome of healthy gastric mucosa to that of IM not progressing to GC, and the transcriptome of IM subtypes that had progressed to GC to those that did not progress. Some deregulated genes were validated and pathway analyses were performed. RESULTS:Comparison of IM subtypes that had progressed to GC with those that did not progress showed smaller differences in the expression profiles than the comparison of IM that did not progress with healthy mucosa. New transcripts identified in IM not progressing to GC included TRIM, TMEM, homeobox and transporter genes and SNORD116. Comparison to normal mucosa identified non tumoral Warburg effect and melatonin degradation as previously unreported processes involved in IM. Overexpressed antigen processing is common to both IM-subtypes progressing to GC, but IIM showed more over-expressed oncogenic genes and molecular processes than CIM. CONCLUSIONS:There are greater differences in gene expression and molecular processes involved in the progression from normal healthy mucosa to IM than from IM to gastric cancer. While antigen processing is common in both IM-subtypes progressing to GC, more oncogenic processes are observed in the progression of IIM.

In high or moderate risk populations, periodic surveillance of patients at risk of progression from gastric precursor lesions (PL) to gastric cancer (GC) is the most effective strategy for reducing the burden of GC. Incomplete type of intestinal metaplasia (IIM) may be considered as the best candidate, but it is still controversial and more research is needed. To further assess the progression of subtypes of IM as predictors of GC occurrence.

Volume 50, no. 12, p. [3983–3989][1], 2012. Page 3988: The following sentence should be inserted after the first sentence of the Acknowledgments section. “This work was also supported by FEDER funds through Programa Operacional Factores de Competitividade—COMPETE (FCOMP-01-0124-FEDER 021251

BACKGROUND/OBJECTIVES:High intakes of unprocessed red or processed meat may increase the risk of stroke. We aimed to examine the association between unprocessed red meat, processed meat and total red meat consumption and risk of total stroke and ischaemic stroke.SUBJECTS/METHODS:Cox proportional hazards regression analyses were conducted based on the data for 41,020 men and women aged 29-69 years at baseline.RESULTS:During a mean follow-up of 13.8 years, 674 incident cases of stroke (531 ischaemic strokes, 79 haemorrhagic strokes, 42 subarachnoid haemorrhages and 22 mixed or unspecified events) were identified. After multiple adjustment, unprocessed red meat, processed meat and total red meat consumption were not correlated with incidence of total stroke or ischaemic stroke in either men or women. The hazard ratios (HRs) for unprocessed red meat and processed meat and risk of total stroke comparing the highest with the lowest quintiles were, respectively, 0.81 (95% confidence interval (CI) 0.54-1.21; P-trend=0.15) and 0.92 (95% CI 0.64-1.32; P-trend=0.82) in men and 1.21 (95% CI 0.79-1.85; P-trend=0.10) and 0.81 (95% CI 0.51-1.27; P-trend=0.17) in women. The HRs for unprocessed red meat and processed meat and risk of ischaemic stroke were, respectively, 0.80 (95% CI 0.51-1.25; P-trend=0.51) and 0.86 (95% CI 0.57-1.29; P-trend=0.77) in men and 1.24 (95% CI 0.74-2.05; P-trend=0.13) and 0.82 (95% CI 0.47-1.42; P-trend=0.31) in women.CONCLUSIONS:In the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, unprocessed red meat and processed meat consumption were not associated with risk of stroke in men or women.

Several modifiable lifestyle factors, including smoking, alcohol, certain dietary factors and weight are independently associated with gastric cancer (GC); however, their combined impact on GC risk is unknown. We constructed a healthy lifestyle index to investigate the joint influence of these behaviors on GC risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The analysis included 461,550 participants (662 first incident GC cases) with a mean follow-up of 11.4 years. A healthy lifestyle index was constructed, assigning 1 point for each healthy behavior related to smoking status, alcohol consumption and diet quality (represented by the Mediterranean diet) for assessing overall GC and also body mass index for cardia GC and 0 points otherwise. Risk of GC was calculated using Cox proportional hazards regression models while adjusting for relevant confounders. The highest versus lowest score in the healthy lifestyle index was associated with a significant lower risk of GC, by 51% overall (HR 0.49 95% CI 0.35, 0.70), by 77% for cardia GC (HR 0.23 95% CI 0.08, 0.68) and by 47% for noncardia GC (HR 0.53 (95% CI 0.32, 0.87), p-trends<0.001. Population attributable risk calculations showed that 18.8% of all GC and 62.4% of cardia GC cases could have been prevented if participants in this population had followed the healthy lifestyle behaviors of this index. Adopting several healthy lifestyle behaviors including not smoking, limiting alcohol consumption, eating a healthy diet and maintaining a normal weight is associated with a large decreased risk of GC.

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.

by the cells (p<0.001).However, GABA significantly suppressed both PGE 2 -induced cell proliferation and cytokine production (<0.01).Conclusions: These data demonstrate that exogenous GABA exerts a direct anti-tumorigenic effect on key parameters of tumorigenesis including proliferation, migration and invasive capacity.Furthermore GABA seems to exert a direct effect through suppression of PGE 2 signalling, indicating cross-talk between these signaling pathways.