Gemma Chiva-Blanch

Wine, beer, alcohol and polyphenols on cardiovascular disease and cancer.

Since ancient times, people have attributed a variety of health benefits to moderate consumption of fermented beverages such as wine and beer, often without any scientific basis. There is evidence that excessive or binge alcohol consumption is associated with increased morbidity and mortality, as well as with work related and traffic accidents. On the contrary, at the moment, several epidemiological studies have suggested that moderate consumption of alcohol reduces overall mortality, mainly from coronary diseases. However, there are discrepancies regarding the specific effects of different types of beverages (wine, beer and spirits) on the cardiovascular system and cancer, and also whether the possible protective effects of alcoholic beverages are due to their alcoholic content (ethanol) or to their non-alcoholic components (mainly polyphenols). Epidemiological and clinical studies have pointed out that regular and moderate wine consumption (one to two glasses a day) is associated with decreased incidence of cardiovascular disease (CVD), hypertension, diabetes, and certain types of cancer, including colon, basal cell, ovarian, and prostate carcinoma. Moderate beer consumption has also been associated with these effects, but to a lesser degree, probably because of beer’s lower phenolic content. These health benefits have mainly been attributed to an increase in antioxidant capacity, changes in lipid profiles, and the anti-inflammatory effects produced by these alcoholic beverages. This review summarizes the main protective effects on the cardiovascular system and cancer resulting from moderate wine and beer intake due mainly to their common components, alcohol and polyphenols.

Virgin olive oil and nuts as key foods of the Mediterranean diet effects on inflammatory biomarkers related to atherosclerosis

Previous epidemiological and feeding studies have observed that adherence to Mediterranean diet (Med-Diet) is associated with reduced cardiovascular risk. However, the molecular mechanisms involved are not fully understood. Since atherosclerosis is nowadays considered a low-grade inflammatory disease, recent studies have explored the anti-inflammatory effects of a Med-Diet intervention on serum and cellular biomarkers related to atherosclerosis. In two sub-studies of the PREDIMED (PREvencion con DIeta MEDiterranea) trial, we analyzed the effects at 3 months of two Med-Diet interventions supplemented with either virgin olive oil (VOO) or nuts compared with a control low-fat diet (LFD). Both Med-Diets showed an anti-inflammatory effect reducing serum C-reactive protein, interleukin-6 (IL6) and endothelial and monocytary adhesion molecules and chemokines (P<0.05; all), whereas these parameters increased after the LFD intervention (P<0.05; all). In another substudy, we evaluated the long-term (1 year) effects of these interventions on vascular risk factors in 516 high-risk subjects, as well as the effect of different Med-Diet components in the reduction of these biomarkers. At 1 year, the Med-Diet groups had significant decreases in the plasma concentrations of IL6, tumor necrosis factor receptor (TNFR) 60 and TNFR80 (P<0.05), while intercellular adhesion molecule 1 (ICAM-1), TNFR60 and TNFR80 concentrations increased in the LFD group (P<0.002). In addition, those allocated in the highest tertile of VOO and vegetables consumption had a significant diminution of plasma TNFR60 concentration compared with those in tertile 1 (P<0.02). In conclusion, Med-Diet exerts an anti-inflammatory effect on cardiovascular system since it down-regulates cellular and circulating inflammatory biomarkers related to atherogenesis in subjects at high cardiovascular risk.

Effects of Wine, Alcohol and Polyphenols on Cardiovascular Disease Risk Factors: Evidences from Human Studies

AIMS The aim of this review was to focus on the knowledge of the cardiovascular benefits of moderate alcohol consumption, as well as to analyze the effects of the different types of alcoholic beverages. METHODS Systematic revision of human clinical studies and meta-analyses related to moderate alcohol consumption and cardiovascular disease (CVD) from 2000 to 2012. RESULTS Heavy or binge alcohol consumption unquestionably leads to increased morbidity and mortality. Nevertheless, moderate alcohol consumption, especially alcoholic beverages rich in polyphenols, such as wine and beer, seems to confer cardiovascular protective effects in patients with documented CVD and even in healthy subjects. CONCLUSIONS In conclusion, wine and beer (but especially red wine) seem to confer greater cardiovascular protection than spirits because of their polyphenolic content. However, caution should be taken when making recommendations related to alcohol consumption.

Differential effects of polyphenols and alcohol of red wine on the expression of adhesion molecules and inflammatory cytokines related to atherosclerosis: a randomized clinical trial

BACKGROUND Few clinical studies have focused on the alcohol-independent cardiovascular effects of the phenolic compounds of red wine (RW). OBJECTIVE We aimed to evaluate the effects of ethanol and phenolic compounds of RW on the expression of inflammatory biomarkers related to atherosclerosis in subjects at high risk of cardiovascular disease. DESIGN Sixty-seven high-risk, male volunteers were included in a randomized, crossover consumption trial. After a washout period, all subjects received RW (30 g alcohol/d), the equivalent amount of dealcoholized red wine (DRW), or gin (30 g alcohol/d) for 4 wk. Before and after each intervention period, 7 cellular and 18 serum inflammatory biomarkers were evaluated. RESULTS Alcohol increased IL-10 and decreased macrophage-derived chemokine concentrations, whereas the phenolic compounds of RW decreased serum concentrations of intercellular adhesion molecule-1, E-selectin, and IL-6 and inhibited the expression of lymphocyte function-associated antigen 1 in T lymphocytes and macrophage-1 receptor, Sialil-Lewis X, and C-C chemokine receptor type 2 expression in monocytes. Both ethanol and phenolic compounds of RW downregulated serum concentrations of CD40 antigen, CD40 ligand, IL-16, monocyte chemotactic protein-1, and vascular cell adhesion molecule-1. CONCLUSION The results suggest that the phenolic content of RW may modulate leukocyte adhesion molecules, whereas both ethanol and polyphenols of RW may modulate soluble inflammatory mediators in high-risk patients. The trial was registered in the International Standard Randomized Controlled Trial Number Register at http://www.isrctn.org/ as ISRCTN88720134.

The Effects of the Mediterranean Diet on Biomarkers of Vascular Wall Inflammation and Plaque Vulnerability in Subjects with High Risk for Cardiovascular Disease. A Randomized Trial

Background Adherence to the Mediterranean diet (MD) is associated with reduced morbidity and mortality due to cardiovascular disease. However, how the MD exerts its effects is not fully known. Aim To assess the 12-month effects of two enhanced MDs compared to a low-fat diet on inflammatory biomarkers related to atherosclerosis and plaque vulnerability in a subcohort of the PREDIMED (Prevención con Dieta Mediterránea) study. Methods A total of 164 participants at high risk for cardiovascular disease were randomized into three diet groups: MD supplemented with 50mL/d of extra virgin olive oil (MD+EVOO) or 30 g/d of nuts (MD+Nuts) and a low-fat diet. Changes in classical cardiovascular risk factors, inflammatory biomarkers of atherosclerosis and plaque vulnerability were measured after 12 months of intervention. Results Compared to participants in the low-fat diet group, those receiving MD+EVOO and MD+Nuts showed a higher decrease in systolic (6mmHg) and diastolic (3mmHg) blood pressure (P = 0.02; both), as well as a reduction of 10% and 8% in LDL-cholesterol (P = 0.04), respectively. Patients in the MD+Nuts group showed a significant reduction of 34% in CD40 expression on monocyte surface compared to low-fat diet patients (P = 0.03). In addition, inflammatory biomarkers related to plaque instability such as C-reactive protein and interleukin-6 were reduced by 45% and 35% and 95% and 90% in the MD+EVOO and MD+Nuts groups, respectively (P<0.05; all) compared to the low-fat diet group. Likewise, sICAM and P-selectin were also reduced by 50% and 27%, respectively in the MD+EVOO group (P = 0.04) and P-selectin by 19% in MD+Nuts group (P = 0.04) compared to the low-fat diet group. Conclusions Adherence to the MD is associated with an increase in serum markers of atheroma plaque stability which may explain, at least in part, the protective role of MD against ischemic heart disease. Trial Registration www.controlled-trials.com ISRCTN35739639

Moderate consumption of red wine, but not gin, decreases erythrocyte superoxide dismutase activity: A randomised cross-over trial☆

BACKGROUND AND AIMS Several studies have shown that moderate alcohol consumption reduces the risk of coronary heart disease, a disease related to oxidative stress. However, the effects of different alcoholic beverages on antioxidant status are not fully known. Our aim was therefore to compare the effects of a moderate intake of an alcoholic beverage with high polyphenol content (red wine) and another without polyphenol content (gin) on plasma antioxidant vitamins, lipid profile and oxidability of low-density lipoprotein (LDL) particles. METHODS AND RESULTS Forty healthy men (mean age, 38 years) were included in a randomised cross-over trial. After a 15-day washout period, subjects received 30 g/ethanol/d as either wine or gin for 28 days. Diet and exercise were monitored. Before and after each intervention, we measured serum vitamins, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase activities, lipid profile, oxidized LDL and LDL resistance to ex-vivo oxidative stress. Compared to gin intervention, wine intake reduced plasma SOD activity [-8.1 U/gHb (95% confidence interval, CI, -138 to -25; P=0.009)] and MDA levels [-11.9 nmol/L (CI, -21.4 to-2.5; P=0.020)]. Lag phase time of LDL oxidation analysis also increased 11.0 min (CI, 1.2-20.8; P=0.032) after wine, compared to gin, whereas no differences were observed between the two interventions in oxidation rate of LDL particles. Peroxide concentration in LDL particles also decreased after wine [-0.18 nmol/mL (CI, -0.3 to-0.08;P=0.020)], as did plasma oxidized LDL concentrations [-11.0 U/L (CI,-17.3 to -6.1; P=0.009)]. CONCLUSION Compared to gin, red wine intake has greater antioxidant effects, probably due to its high polyphenolic content.

Effect of a high-fat Mediterranean diet on bodyweight and waist circumference: a prespecified secondary outcomes analysis of the PREDIMED randomised controlled trial

BACKGROUND Because of the high density of fat, high-fat diets are perceived as likely to lead to increased bodyweight, hence health-care providers are reluctant to recommend them to overweight or obese individuals. We assessed the long-term effects of ad libitum, high-fat, high-vegetable-fat Mediterranean diets on bodyweight and waist circumference in older people at risk of cardiovascular disease, most of whom were overweight or obese. METHODS PREDIMED was a 5 year parallel-group, multicentre, randomised, controlled clinical trial done in primary care centres affiliated to 11 hospitals in Spain. 7447 asymptomatic men (aged 55-80 years) and women (aged 60-80 years) who had type 2 diabetes or three or more cardiovascular risk factors were randomly assigned (1:1:1) with a computer-generated number sequence to one of three interventions: Mediterranean diet supplemented with extra-virgin olive oil (n=2543); Mediterranean diet supplemented with nuts (n=2454); or a control diet (advice to reduce dietary fat; n=2450). Energy restriction was not advised, nor was physical activity promoted. In this analysis of the trial, we measured bodyweight and waist circumference at baseline and yearly for 5 years in the intention-to-treat population. The PREDIMED trial is registered with ISRCTN.com, number ISRCTN35739639. FINDINGS After a median 4·8 years (IQR 2·8-5·8) of follow-up, participants in all three groups had marginally reduced bodyweight and increased waist circumference. The adjusted difference in 5 year changes in bodyweight in the Mediterranean diet with olive oil group was -0·43 kg (95% CI -0·86 to -0·01; p=0·044) and in the nut group was -0·08 kg (-0·50 to 0·35; p=0·730), compared with the control group. The adjusted difference in 5 year changes in waist circumference was -0·55 cm (-1·16 to -0·06; p=0·048) in the Mediterranean diet with olive oil group and -0·94 cm (-1·60 to -0·27; p=0·006) in the nut group, compared with the control group. INTERPRETATION A long-term intervention with an unrestricted-calorie, high-vegetable-fat Mediterranean diet was associated with decreases in bodyweight and less gain in central adiposity compared with a control diet. These results lend support to advice not restricting intake of healthy fats for bodyweight maintenance. FUNDING Spanish Government, CIBERobn, Instituto de Salud Carlos III, Hojiblanca, Patrimonio Comunal Olivarero, California Walnut Commission, Borges SA, and Morella Nuts.

The Mediterranean Diet Pattern and Its Main Components Are Associated with Lower Plasma Concentrations of Tumor Necrosis Factor Receptor 60 in Patients at High Risk for Cardiovascular Disease

Adherence to a Mediterranean diet (MD) is associated with a reduced risk of coronary heart disease. However, the molecular mechanisms involved are not fully understood. The aim of this study was to compare the effects of 2 MD with those of a low-fat-diet (LFD) on circulating inflammatory biomarkers related to atherogenesis. A total of 516 participants included in the Prevention with Mediterranean Diet Study were randomized into 3 intervention groups [MD supplemented with virgin olive oil (MD-VOO); MD supplemented with mixed nuts (MD-Nuts); and LFD]. At baseline and after 1 y, participants completed FFQ and adherence to MD questionnaires, and plasma concentrations of inflammatory markers including intercellular adhesion molecule-1(ICAM-1), IL-6, and 2 TNF receptors (TNFR60 and TNFR80) were measured by ELISA. At 1 y, the MD groups had lower plasma concentrations of IL-6, TNFR60, and TNFR80 (P < 0.05), whereas ICAM-1, TNFR60, and TNFR80 concentrations increased in the LFD group (P < 0.002). Due to between-group differences, participants in the 2 MD groups had lower plasma concentrations of ICAM-1, IL-6, TNFR60, and TNFR80 compared to those in the LFD group (P ≤ 0.028). When participants were categorized in tertiles of 1-y changes in the consumption of selected foods, those in the highest tertile of virgin olive oil (VOO) and vegetable consumption had a lower plasma TNFR60 concentration compared with those in tertile 1 (P < 0.02). Moreover, the only changes in consumption that were associated with 1-y changes in the geometric mean TNFR60 concentrations were those of VOO and vegetables (P = 0.01). This study suggests that a MD reduces TNFR concentrations in patients at high cardiovascular risk.

Dealcoholized Red Wine Decreases Systolic and Diastolic Blood Pressure and Increases Plasma Nitric Oxide

Rationale: Experimental studies have shown a potential blood pressure (BP) lowering effect of red wine polyphenols, whereas the effects of ethanol and polyphenols on BP in humans are not yet clear. Objective: The aim of the present work was to evaluate the effects of red wine fractions (alcoholic and nonalcoholic) on BP and plasma nitric oxide (NO) in subjects at high cardiovascular risk. Methods and Results: Sixty-seven men at high cardiovascular risk were studied. After a 2-week run-in period, subjects were randomized into 3 treatment periods in a crossover clinical trial, with a common background diet plus red wine (30g alcohol/day), the equivalent amount of dealcoholized red wine, or gin (30g alcohol/day), lasting 4 weeks each intervention. At baseline and after each intervention, anthropometrical parameters, BP and plasma NO were measured. Systolic and diastolic BP decreased significantly after the dealcoholized red wine intervention and these changes correlated with increases in plasma NO. Conclusions: Dealcoholized red wine decreases systolic and diastolic BP. Our results point out through an NO-mediated mechanism. The daily consumption of dealcoholized red wine could be useful for the prevention of low to moderate hypertension. Trial registered at controlled-trials.com: ISRCTN88720134.

Dealcoholized Red Wine Decreases Systolic and Diastolic Blood Pressure and Increases Plasma Nitric Oxide Short Communication

Rationale: Experimental studies have shown a potential blood pressure (BP) lowering effect of red wine polyphenols, whereas the effects of ethanol and polyphenols on BP in humans are not yet clear. Objective: The aim of the present work was to evaluate the effects of red wine fractions (alcoholic and nonalcoholic) on BP and plasma nitric oxide (NO) in subjects at high cardiovascular risk. Methods and Results: Sixty-seven men at high cardiovascular risk were studied. After a 2-week run-in period, subjects were randomized into 3 treatment periods in a crossover clinical trial, with a common background diet plus red wine (30g alcohol/day), the equivalent amount of dealcoholized red wine, or gin (30g alcohol/day), lasting 4 weeks each intervention. At baseline and after each intervention, anthropometrical parameters, BP and plasma NO were measured. Systolic and diastolic BP decreased significantly after the dealcoholized red wine intervention and these changes correlated with increases in plasma NO. Conclusions: Dealcoholized red wine decreases systolic and diastolic BP. Our results point out through an NO-mediated mechanism. The daily consumption of dealcoholized red wine could be useful for the prevention of low to moderate hypertension. Trial registered at controlled-trials.com: ISRCTN88720134.