BACKGROUND/OBJECTIVES: The aim of this study was to analyze the influence of a Mediterranean dietary pattern on plasma total antioxidant capacity (TAC) after 3 years of intervention and the associations with adiposity indexes in a randomized dietary trial (PREDIMED trial) with high cardiovascular risk patients.

SUBJECTS/METHODS: 187 subjects were randomly selected from the PREDIMED-UNAV center after they completed 3-year intervention program. Participants were following a Mediterranean-style diet with high intake of virgin olive oil or high intake of nuts, or a conventional low-fat diet. Adiposity indexes were measured at baseline and at year 3. Plasma TAC was evaluated using a commercially available colorimetric assay kit.

RESULTS: Plasma TAC in the control, olive oil and nuts groups was 2.01+/-0.15, 3.51+/-0.14 and 3.02+/-0.14 mM Trolox, respectively after adjusting for age and sex. The differences between the Mediterranean diet and control groups were statistically significant (P<0.001). Moreover higher levels of TAC were significantly associated with a reduction in body weight after 3 years of intervention among subjects allocated to the virgin olive oil group (B=-1.306; 95% CI=-2.439 to -0.173; P=0.025, after adjusting for age, sex and baseline body mass index).

CONCLUSIONS: Mediterranean diet, especially rich in virgin olive oil, is associated with higher levels of plasma antioxidant capacity. Plasma TAC is related to a reduction in body weight after 3 years of intervention in a high cardiovascular risk population with a Mediterranean-style diet rich in virgin olive oil.

AIMS:The aim of the study was to evaluate the effect of a Mediterranean diet (MedDiet), enhanced with extra virgin olive oil (EVOO) and nuts, on a composite of adverse maternofoetal outcomes of women with normoglycemia during pregnancy.

METHODS:This was a sub-analysis of the St Carlos gestational diabetes mellitus Prevention Study. Only normoglycemic women were analysed (697). They were randomized (at 8-12th gestational weeks) to: standard-care control group (337), where fat consumption was limited to 30% of total caloric intake; or intervention group (360), where a MedDiet, enhanced with EVOO and pistachios (40-42% fats of total caloric intake) was recommended. The primary outcome was a composite of maternofoetal outcomes (CMFOs): at least having 1 event of emergency C-section, perineal trauma, pregnancy-induced hypertension and preeclampsia, prematurity, large-for-gestational-age and small-for gestational-age.

RESULTS:Crude relative risk showed that the intervention was associated with a significant reduction in the risk of CMFOs (0.48 [0.37-0.63]; p = 0.0001), with a number-needed-to-treat = 5. Risk of urinary tract infections, emergency C-sections, perineal trauma, large-for-gestational-age and small-for gestational age new-borns were also significantly reduced.

CONCLUSION:A MedDiet, enhanced with EVOO and nuts, was associated with a risk reduction of CMFOs in over 50% in normoglycemic pregnant women. Therefore, it might be a potentially adequate diet for pregnant women.

TRIAL REGISTRATION:Identifier ISRCTN84389045. The study was registered on September 27, 2013. Last edited on September 26, 2018.

BACKGROUND AND OBJECTIVE: Several epidemiological and experimental studies have associated the intake of antioxidants, which are abundant in the Mediterranean diet, with a low incidence of cardiovascular disease. One possible mechanism of this action is the oxidative protection in low density lipoproteins (LDL). The aim of our study was to compare the antioxidative activity of diverse phenolic compounds present in virgin olive oil on these lipoproteins.

SUBJECTS AND METHOD: LDL was isolated from blood plasma of healthy volunteers by sequential ultracentrifugation. This was followed by oxidation with CuC12 in the presence of different concentrations of phenolic compounds and virgin olive oil extract. Production of conjugated dienes was determined by the continuous monitoring of increased absorbency at 234 nm as an indicator of LDL oxidation.

RESULTS: Virgin olive oil extract prolonged the latency phase and significantly lowered the progression rate (p<0.05) at low concentrations (2 g/ml). This antioxidative effect was also observed with low concentrations (2 M) of caffeic acid and oleuropein (p<0.05). However, it was necessary to increase the concentration of flavone up to 50 times to observe a similar effect (p<0.05).

CONCLUSION: Both virgin olive oil extract enriched in phenolic compounds and phenolic compounds present in olive oil (caffeic acid and oleuropein) are potent antioxidants at very low concentrations. Thus, the beneficial effects of a Mediterranean diet may be partly due to the protective action of these compounds.

DNA methylation could be reversible and mouldable by environmental factors, such as dietary exposures. The objective was to analyse whether an intervention with two Mediterranean diets, one rich in extra-virgin olive oil (MedDiet + EVOO) and the other one in nuts (MedDiet + nuts), was influencing the methylation status of peripheral white blood cells (PWBCs) genes. A subset of 36 representative individuals were selected within the PREvención con DIeta MEDiterránea (PREDIMED-Navarra) trial, with three intervention groups in high cardiovascular risk volunteers: MedDiet + EVOO, MedDiet + nuts, and a low-fat control group. Methylation was assessed at baseline and at five-year follow-up. Ingenuity pathway analysis showed routes with differentially methylated CpG sites (CpGs) related to intermediate metabolism, diabetes, inflammation, and signal transduction. Two CpGs were specifically selected: cg01081346-CPT1B/CHKB-CPT1B and cg17071192-GNAS/GNASAS, being associated with intermediate metabolism. Furthermore, cg01081346 was associated with PUFAs intake, showing a role for specific fatty acids on epigenetic modulation. Specific components of MedDiet, particularly nuts and EVOO, were able to induce methylation changes in several PWBCs genes. These changes may have potential benefits in health; especially those changes in genesrelated to intermediate metabolism, diabetes, inflammation and signal transduction, which may contribute to explain the role of MedDiet and fat quality on health outcomes.

Importance:Breast cancer is the leading cause of female cancer burden, and its incidence has increased by more than 20% worldwide since 2008. Some observational studies have suggested that the Mediterranean diet may reduce the risk of breast cancer.

Objective:To evaluate the effect of 2 interventions with Mediterranean diet vs the advice to follow a low-fat diet (control) on breast cancer incidence.

Design, Setting, and Participants:The PREDIMED study is a 1:1:1 randomized, single-blind, controlled field trial conducted at primary health care centers in Spain. From 2003 to 2009, 4282 women aged 60 to 80 years and at high cardiovascular disease risk were recruited after invitation by their primary care physicians.

Interventions:Participants were randomly allocated to 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).

Main Outcomes and Measures:Breast cancer incidence was a prespecified secondary outcome of the trial for women without a prior history of breast cancer (n = 4152).

Results:After a median follow-up of 4.8 years, we identified 35 confirmed incident cases of breast cancer. Observed rates (per 1000 person-years) were 1.1 for the Mediterranean diet with extra-virgin olive oil group, 1.8 for the Mediterranean diet with nuts group, and 2.9 for the control group. The multivariable-adjusted hazard ratios vs the control group were 0.32 (95% CI, 0.13-0.79) for the Mediterranean diet with extra-virgin olive oil group and 0.59 (95% CI, 0.26-1.35) for the Mediterranean diet with nuts group. In analyses with yearly cumulative updated dietary exposures, the hazard ratio for each additional 5% of calories from extra-virgin olive oil was 0.72 (95% CI, 0.57-0.90).

Conclusions and Relevance:This is the first randomized trial finding an effect of a long-term dietary intervention on breast cancer incidence. Our results suggest a beneficial effect of a Mediterranean diet supplemented with extra-virgin olive oil in the primary prevention of breast cancer. These results come from a secondary analysis of a previous trial and are based on few incident cases and, therefore, need to be confirmed in longer-term and larger studies.

Trial Registration:ISRCTN.org Identifier: ISRCTN35739639.

BACKGROUND: Although an important secondary prevention trial reported an impressive protection by a Mediterranean dietary pattern on reinfarction and cardiovascular death, scarce direct epidemiologic evidence is currently available regarding the role of the Mediterranean diet in the aetiology of coronary heart disease.

AIMS: The aim of the study was to quantify the risk reduction of incident myocardial infarction provided by a Mediterranean dietary pattern.

METHODS: We included 342 subjects (171 patients who suffered their first acute myocardial infarction and 171 matched controls) in a case-control study. A validated semi-quantitative food frequency questionnaire (136 items) was used. We defined an a priori Mediterranean dietary pattern. We assessed six food items that we considered protective: 1) olive oil, 2) fiber, 3) fruits, 4)vegetables, 5) fish and 6) alcohol. For each of these six dietary factors, we calculated the distribution according to quintiles within the study and assigned each participant a score of 1 to 5 corresponding to the quintile of intake, with 1 representing the lowest and 5 representing the highest quintile. We also estimated the quintiles of two other elements assumed to be associated with a higher risk: 7) meat/meat products and 8) some items with high glycaemic load (white bread, pasta and rice). For these two elements we inversely ranked the score, with 1 representing the highest and 5 representing the lowest quintile. Finally, we summed up the eight quintile values for each participant.A second score ( post hoc pattern) was built using only a single cut-off point for these eight elements. The cut-off points for each element in this post hoc pattern were decided according to the dose-response relationships between the consumption of each food item and the risk of myocardial infarction observed in the analyses that used quintiles of each food item.

RESULTS: For both patterns, we found that the higher the score, the lower the odds ratio of myocardial infarction. A significant linear trend was apparent after adjustment for the main cardiovascular risk factors. For each additional point in the a priori Mediterranean pattern (observed range: 9-38) the odds ratio (95 % confidence intervals) was 0.92 (0.86-0.98). This estimate was 0.55 (0.42-0.73) when we used the post hoc pattern (range: 0-8).

CONCLUSIONS: Our data support the hypothesis that a Mediterranean diet (that emphasizes olive oil, fiber, fruits, vegetables, fish and alcohol and reduces meat/meat products) can be an effective measure for reducing the risk of myocardial infarction. However, our results support the exclusion of refined cereals with a high glycaemic load as healthy elements of this pattern.

BACKGROUND AND AIMS:Endothelial dysfunction (ED) plays a key role in the development of atherosclerotic cardiovascular disease (ASCVD). Likewise, type 2 diabetes (T2D) is a major CVD risk factor. Therefore, our objective was to explore whether long-term consumption of a Mediterranean diet (MedDiet) rich in olive oil or a low-fat diet (LF diet) was associated with an improvement in ED and whether the potential benefits were similar in patients with or without T2D in the CORDIOPREV clinical trial (NCT00924937).

METHODS:Endothelial function was measured in 805 participants who had completed follow-up ultrasound image studies, using ultrasonography of brachial artery to calculate flow mediated vasodilatation (FMD) before and after 1.5 years of intervention with a MedDiet [35% of calories from fat (22% monounsaturated) and 50% from carbohydrates] and LF diet [28% fat (12% monounsaturated) and 55% of calories from carbohydrates]. We categorized participants as patients with T2D, prediabetes, and without T2D according to the American Diabetes Association (ADA) criteria.

RESULTS:MedDiet increased FMD in patients with T2D [5.2 ± 0.4 at 1.5 years vs. 3.8 ± 0.4 at baseline; p=0.04] and prediabetes [4.9 ± 0.4 vs. 3.8 ± 0.4; p=0.04] and induced an improvement in FMD compared to LF diet in patients with diabetes [5.2 ± 0.4 (MedDiet) vs.3.7 ± 0.4 (LF diet); p=0.01]; whereas both diets maintained FMD stablein patients without diabetes.

CONCLUSIONS:Habitual consumption of a MedDiet rich in extra virgin olive oil improves endothelial function in patients with prediabetes and diabetes. This takes great importance given that diet must be the cornerstone of treatment of patients with diabetes at high cardiovascular risk.

OBJECTIVES:To investigate eating habits and adherence to Mediterranean Diet (MD) in relation to the risk of depression in a cohort of nonagenarians enrolled within the Mugello Study, an epidemiological study aimed at investigating both clinically relevant geriatric items and various health issues, including those related to nutritional status.

DESIGN:Cross-sectional study.

SETTING:Homes and nursing homes in the Mugello area, Florence, Italy.

PARTICIPANTS:Subjects aged 90-99 years [N=388 (271F; 117M) mean age: 92.7±3.1].

MEASUREMENTS:All subjects were evaluated through questionnaires and instrumental examinations. Adherence to MD was assessed through the Mediterranean Diet Score. A shorter version of the Geriatric Depression Scale (GDS) was used to detect the possible presence of depressive symptoms. In addition, cognitive and functional status was assessed using the Mini-Mental State Examination, the Clock Drawing Test, as well as the Basic and Instrumental Activities of Daily Living test.

RESULTS:Depressed subjects (DS) (GDS score≥5, 43.8%) were older, females and widows, than non-depressed subjects (NDS). DS reported a slightly but not statistically significant lower MD score than NDS (33.9±3.9 vs. 34.6±3.3, p=0.149). Subjects who reported to consume a greater amount of olive oil and fruit were associated with a lower risk of depression (OR=0.35, 95%CI=0.20-0.59, p<0.001 and OR=0.46, 95%CI=0.26-0.84, p=0.011, respectively) after adjustment for many possible confounders. Similar results were obtained for women, while no statistically significant differences emerged for men.

CONCLUSION:Our results support the hypothesis that a diet rich in olive oil and fruit, characteristics of MD, may protect against the development of depressive symptoms in older age.

SCOPE:This study assessed plasmatic antioxidant capabilities and xanthine oxidase activity in metabolic syndrome (MetS) patients after 5 years intervention with Mediterranean Diet (MeDiet) supplemented with extra-virgin olive oil (MeDiet+EVOO) or with nuts or with low-fat diet (the PREDIMED study).

METHODS AND RESULTS:75 participants were randomly selected. Daily energy and nutrient intake were assessed with a validated 137-item food frequency questionnaire, and adherence to the MeDiet was assessed using a 14-item questionnaire. Catalase, superoxide dismutase, myeloperoxidase, xanthine oxidase activities and protein levels, and protein carbonyl derivatives, nitrotyrosine, nitrite and nitrate levels were determined in overnight fasting venous blood samples. The plasma activity and protein levels of superoxide dismutase and catalase were significantly higher and xanthine oxidase activity lower in MeDiet+EVOO and MeDiet+nuts than in the control group. Participants in both MeDiet groups showed higher plasma nitrate levels than in the control group. Adherence to the MeDiet showed a positive correlation with superoxide dismutase and catalase plasma antioxidant activities.

CONCLUSION:A MeDiet enriched with either virgin olive oil or nuts enhances the plasma antioxidant capabilities and decreases xanthine oxidase activity in patients with the metabolic syndrome but we did not observe changes in myeloperoxidase or markers of oxidative damage. This article is protected by copyright. All rights reserved.

Multiple sclerosis (MS) is an autoimmune disease triggered by a combination of genetic and environmental risk factors which are however individually insufficient to provoke the disease. Previous investigations studied the coexistence of cancer in MS patients, and only a few relations between the geographic distribution of MS and that of cancer. The aim of this research was to find an environmental link between the aetiology of MS and cancers in Croatia. Incidence and prevalence of MS in Croatia were compared with the incidence of the most frequent cancer sites: stomach cancer, cancer of the colon and the rectum, pancreatic cancer, lung cancer, cancer of the kidneys and brain cancer. Data for MS were collected from seven population-based epidemiologic studies which used Poser's diagnostic criteria and reported the number of cases and the magnitude of the studied population. Data for cancers were drawn from the Croatian National Cancer Registry. The analysis was done for single municipalities, grouped in their belonging regions or counties, and separately for the continental and the coastal area. For each rate a 95% confidence interval was calculated. The differences between rates were tested with the chi-square test as well. In addition, MS incidence or prevalence were correlated with the corresponding cancer incidence data. Pearson's correlation coefficients were used to measure the correlation between both diseases. Calculations were done with the statistical package Statistica V 7.1. and the Smith's Statistical Package freeware In the continental area of Croatia the mean annual incidence (per 100,000 inhabitants) of MS was nearly two folds higher than in the coastal area: 2.1 vs. 1.3 (p = 0.0029). The difference was lower when expressed by prevalence: 46.5 vs. 36.7 (p = 0.0601). Among the malignant neoplasms, in the continental area significantly higher incidence rates were found for stomach (32.9 vs. 20.8; p = 3.14E-14) and lung cancer (55.8 vs. 46.4; p = 1.21E-05), whilst colon cancer alone (20.4 vs. 15.7; p = 9.44E-05) or colorectal cancer (38.3 vs. 31.6; p = 8.18E-05) had a significantly higher incidence in the coastal area. The geographic distribution of MS expressed by incidence was significantly correlated with pancreatic (r = 0.62024, df=23, p = 0.00094) and lung cancer (r = 0.46380, df=23, p = 0.01953). This research adds further malignant neoplasms, possibly exposure-related, to the list of diseases with geographic distribution like MS. The similarity of MS distribution with the named malignancies is unlikely to be incidental. MS in Gorski Kotar and Slavonia seems to be associated with a diet rich in meat and fat. A diet rich in fat and meat and poor in vegetables is a risk factor for stomach, colorectum, pancreatic as well as lung cancers. Some authors have documented a possible protective role of the "Mediterranean diet" for the named cancers. Olive oil is the main source of fat in the "Mediterranean diet". Oleocanthal, aphenolic compound of the extra-virgin olive oil was found to inhibit the cyclooxigenase enzymes which are involved in demyelination and tumorigenesis. We hypothesize that the "Mediterranean diet", olive oil and particularly oleocanthal, to have a protective role in MS too.

Olive oil (OO) is the primary source of fat in the Mediterranean diet and has been associated with longevity and a lower incidence of chronic diseases, particularly CHD. Cardioprotective effects of OO consumption have been widely related with improved lipoprotein profile, endothelial function and inflammation, linked to health claims of oleic acid and phenolic content of OO. With CVD being a leading cause of death worldwide, a review of the potential mechanisms underpinning the impact of OO in the prevention of disease is warranted. The current body of evidence relies on mechanistic studies involving animal and cell-based models, epidemiological studies of OO intake and risk factor, small- and large-scale human interventions, and the emerging use of novel biomarker techniques associated with disease risk. Although model systems are important for mechanistic research nutrition, methodologies and experimental designs with strong translational value are still lacking. The present review critically appraises the available evidence to date, with particular focus on emerging novel biomarkers for disease risk assessment. New perspectives on OO research are outlined, especially those with scope to clarify key mechanisms by which OO consumption exerts health benefits. The use of urinary proteomic biomarkers, as highly specific disease biomarkers, is highlighted towards a higher translational approach involving OO in nutritional recommendations.

The clinical implications of non-alcoholic fatty liver diseases (NAFLD) derive from their potential to progress to fibrosis and cirrhosis. Inappropriate dietary fat intake, excessive intake of soft drinks, insulin resistance and increased oxidative stress results in increased free fatty acid delivery to the liver and increased hepatic triglyceride (TG) accumulation. An olive oil-rich diet decreases accumulation of TGs in the liver, improves postprandial TGs, glucose and glucagon-like peptide-1 responses in insulin-resistant subjects, and upregulates glucose transporter-2 expression in the liver. The principal mechanisms include: decreased nuclear factor-kappaB activation, decreased low-density lipoprotein oxidation, and improved insulin resistance by reduced production of inflammatory cytokines (tumor necrosis factor, interleukin-6) and improvement of jun N-terminal kinase-mediated phosphorylation of insulin receptor substrate-1. The beneficial effect of the Mediterranean diet is derived from monounsaturated fatty acids, mainly from olive oil. In this review, we describe the dietary sources of the monounsaturated fatty acids, the composition of olive oil, dietary fats and their relationship to insulin resistance and postprandial lipid and glucose responses in non-alcoholic steatohepatitis, clinical and experimental studies that assess the relationship between olive oil and NAFLD, and the mechanism by which olive oil ameliorates fatty liver, and we discuss future perspectives.

We report the results of in vivo studies in Caenorhabditis elegans nematodes in which addition of extra virgin olive oil (EVOO) to their diet significantly increased their life span with respect to the control group. Furthermore, when nematodes were exposed to the pesticide paraquat, they started to die after two days, but after the addition of EVOO to their diet, both survival percentage and lifespans of paraquat-exposed nematodes increased. Since paraquat is associated with superoxide radical production, a test for scavenging this radical was performed using cyclovoltammetry and the EVOO efficiently scavenged the superoxide. Thus, a linear correlation (y = -0.0838x +19.73, regression factor = 0.99348) was observed for superoxide presence (y) in the voltaic cell as a function of aliquot (x) additions of EVOO, 10μL each. The originally generated supoeroxide was approximately halved after 10 aliquots (100 μL total). The superoxide scavenging ability was analyzed, theoretically, using Density Functional Theory for tyrosol and hydroxytyrosol, two components of EVOO and was also confirmed experimentally for the galvinoxyl radical, using Electron Paramagnetic Resonance (EPR) spectroscopy. The galvinoxyl signal disappeared after adding 1 μL of EVOO to the EPR cell in 10 minutes. In addition, EVOO significantly decreased the proliferation of human leukemic THP-1 cells, while it kept the proliferation at about normal levels in rat L6 myoblasts, a non-tumoral skeletal muscle cell line. The protection due to EVOO was also assessed in L6 cells and THP-1 exposed to the radical generator cumene hydroperoxide, in which cell viability was reduced. Also in this case the oxidative stress was ameliorated by EVOO, in line with results obtained with tetrazolium dye reduction assays, cell cycle analysis and reactive oxygen species measurements. We ascribe these beneficial effects to EVOO antioxidant properties and our results are in agreement with a clear health benefit of EVOO use in the Mediterranean diet.

A growing interest has emerged in the beneficial effects of plant-based diets for the prevention of cardiovascular disease, diabetes and obesity. The Mediterranean diet, one of the most widely evaluated dietary patterns in scientific literature, includes in its nutrients two fluid foods: olive oil, as the main source of fats, and a low-to-moderate consumption of wine, mainly red, particularly during meals. Current mechanisms underlying the beneficial effects of the Mediterranean diet include a reduction in inflammatory and oxidative stress markers, improvement in lipid profile, insulin sensitivity and endothelial function, as well as antithrombotic properties. Most of these effects are attributable to bioactive ingredients including polyphenols, mono- and poly-unsaturated fatty acids. Polyphenols are a heterogeneous group of phytochemicals containing phenol rings. The principal classes of red wine polyphenols include flavonols (quercetin and myricetin), flavanols (catechin and epicatechin), anthocyanin and stilbenes (resveratrol). Olive oil has at least 30 phenolic compounds. Among them, the main are simple phenols (tyrosol and hydroxytyrosol), secoroids and lignans. The present narrative review focuses on phenols, part of red wine and virgin olive oil, discussing the evidence of their effects on lipids, blood pressure, atheromatous plaque and glucose metabolism.