Alfredo Gea

Mediterranean dietary pattern and depression: the PREDIMED randomized trial.

BackgroundA few observational studies have found an inverse association between adherence to a Mediterranean diet and the risk of depression. Randomized trials with an intervention based on this dietary pattern could provide the most definitive answer to the findings reported by observational studies. The aim of this study was to compare in a randomized trial the effects of two Mediterranean diets versus a low-fat diet on depression risk after at least 3 years of intervention.MethodsThis was a multicenter, randomized, primary prevention field trial of cardiovascular disease (Prevención con Dieta Mediterránea (PREDIMED Study)) based on community-dwelling men aged 55 to 80 years and women aged 60 to 80 years at high risk of cardiovascular disease (51% of them had type 2 diabetes; DM2) attending primary care centers affiliated with 11 Spanish teaching hospitals. Primary analyses were performed on an intention-to-treat basis. Cox regression models were used to assess the relationship between the nutritional intervention groups and the incidence of depression.ResultsWe identified 224 new cases of depression during follow-up. There was an inverse association with depression for participants assigned to a Mediterranean diet supplemented with nuts (multivariate hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.55 to 1.10) compared with participants assigned to the control group, although this was not significant. However, when the analysis was restricted to participants with DM2, the magnitude of the effect of the intervention with the Mediterranean diet supplemented with nuts did reach statistical significance (multivariate HR = 0.59; 95% CI 0.36 to 0.98).ConclusionsThe result suggest that a Mediterranean diet supplemented with nuts could exert a beneficial effect on the risk of depression in patients with DM2.Trial registrationThis trial has been registered in the Current Controlled Trials with the number ISRCTN 35739639

Dietary fat intake and risk of cardiovascular disease and all-cause mortality in a population at high risk of cardiovascular disease

BACKGROUND Dietary fat quality and fat replacement are more important for cardiovascular disease (CVD) prevention than is total dietary fat intake. OBJECTIVE The aim was to evaluate the association between total fat intake and fat subtypes with the risk of CVD (myocardial infarction, stroke, or death from cardiovascular causes) and cardiovascular and all-cause death. We also examined the hypothetical effect of the isocaloric substitution of one macronutrient for another. DESIGN We prospectively studied 7038 participants at high CVD risk from the PREvención con DIeta MEDiterránea (PREDIMED) study. The trial was conducted from 2003 to 2010, but the present analysis was based on an expanded follow-up until 2012. At baseline and yearly thereafter, total and specific fat subtypes were repeatedly measured by using validated food-frequency questionnaires. Time-dependent Cox proportional hazards models were used. RESULTS After 6 y of follow-up, we documented 336 CVD cases and 414 total deaths. HRs (95% CIs) for CVD for those in the highest quintile of total fat, monounsaturated fatty acid (MUFA), and polyunsaturated fatty acid (PUFA) intake compared with those in the lowest quintile were 0.58 (0.39, 0.86), 0.50 (0.31, 0.81), and 0.68 (0.48, 0.96), respectively. In the comparison between extreme quintiles, higher saturated fatty acid (SFA) and trans-fat intakes were associated with 81% (HR: 1.81; 95% CI: 1.05, 3.13) and 67% (HR: 1.67; 95% CI: 1.09, 2.57) higher risk of CVD. Inverse associations with all-cause death were also observed for PUFA and MUFA intakes. Isocaloric replacements of SFAs with MUFAs and PUFAs or trans fat with MUFAs were associated with a lower risk of CVD. SFAs from pastries and processed foods were associated with a higher risk of CVD. CONCLUSIONS Intakes of MUFAs and PUFAs were associated with a lower risk of CVD and death, whereas SFA and trans-fat intakes were associated with a higher risk of CVD. The replacement of SFAs with MUFAs and PUFAs or of trans fat with MUFAs was inversely associated with CVD. This trial was registered at www.controlled-trials.com as ISRCTN 35739639.

Longitudinal association of telomere length and obesity indices in an intervention study with a Mediterranean diet: the PREDIMED-NAVARRA trial

Background:Telomeres are nucleoprotein structures that protect the ends of eukaryote chromosomes. Shorter telomere length (TL) is associated with some age-related human disorders, but its relationship with obesity or adiposity parameters remains unclear.Objective:The aim of this study was to assess the relationship between TL and changes in adiposity indices after a 5-year nutritional intervention.Design and subjects:TL was measured by quantitative real-time PCR in 521 subjects (55–80 years, 55% women). Participants were randomly selected from the PREDIMED-NAVARRA centre after they completed a 5-year intervention programme. Anthropometric parameters were directly measured by trained personnel at baseline and on a yearly basis thereafter. TL at baseline and changes in TL after a 5-year intervention were assessed.Results:Higher baseline TL significantly predicted a greater decrease in body weight (B=−1.09 kg, 95% confidence interval (CI): −2.01 to −0.16), body mass index (BMI) (B=−0.47 kg m−2, 95% CI: −0.83 to −0.11), waist circumference (B=−1.15 cm, 95% CI: −2.28 to −0.01) and waist to height ratio (B=−0.008, 95% CI: −0.010 to −0.001) in multiple-adjusted models. In addition, changes in TL during the 5-year intervention were inversely associated with changes in the four anthropometric variables. The reduction in adiposity indices during the intervention, associated with increasing TL, was even higher among subjects with the longest telomeres at baseline. Logistic regression analysis showed that the risk of remaining obese after 5 years was lower in those participants who initially had the longest telomeres and increased their TL after intervention (odds ratio=0.27, 95% CI: 0.03–2.03).Conclusions:Our research suggests that TL is inversely associated with changes in obesity parameters. The assessment of TL can provide further insights for biological pathways leading to adiposity. We show for the first time an improvement of obesity indices when an increase in TL is observed after a 5-year Mediterranean diet intervention.

Alcohol intake, wine consumption and the development of depression: the PREDIMED study

BackgroundAlcoholic beverages are widely consumed. Depression, the most prevalent mental disorder worldwide, has been related to alcohol intake. We aimed to prospectively assess the association between alcohol intake and incident depression using repeated measurements of alcohol intake.MethodsWe followed-up 5,505 high-risk men and women (55 to 80 y) of the PREDIMED Trial for up to seven years. Participants were initially free of depression or a history of depression, and did not have any history of alcohol-related problems. A 137-item validated food frequency questionnaire administered by a dietician was repeated annually to assess alcohol intake. Participants were classified as incident cases of depression when they reported a new clinical diagnosis of depression, and/or initiated the use of antidepressant drugs. Cox regression analyses were fitted over 23,655 person-years.ResultsModerate alcohol intake within the range of 5 to 15 g/day was significantly associated with lower risk of incident depression (hazard ratio (HR) and 95% confidence interval (95% CI) = 0.72 (0.53 to 0.98) versus abstainers). Specifically, wine consumption in the range of two to seven drinks/week was significantly associated with lower rates of depression (HR (95% CI) = 0.68 (0.47 to 0.98)).ConclusionsModerate consumption of wine may reduce the incidence of depression, while heavy drinkers seem to be at higher risk.

Television Viewing, Computer Use, Time Driving and All-Cause Mortality: The SUN Cohort

Background Sedentary behaviors have been directly associated with all‐cause mortality. However, little is known about different types of sedentary behaviors in relation to overall mortality. Our objective was to assess the association between different sedentary behaviors and all‐cause mortality. Methods and Results In this prospective, dynamic cohort study (the SUN Project) 13 284 Spanish university graduates with a mean age of 37 years were followed‐up for a median of 8.2 years. Television, computer, and driving time were assessed at baseline. Poisson regression models were fitted to examine the association between each sedentary behavior and total mortality. All‐cause mortality incidence rate ratios (IRRs) per 2 hours per day were 1.40 (95% confidence interval (CI): 1.06 to 1.84) for television viewing, 0.96 (95% CI: 0.79 to 1.18) for computer use, and 1.14 (95% CI: 0.90 to 1.44) for driving, after adjustment for age, sex, smoking status, total energy intake, Mediterranean diet adherence, body mass index, and physical activity. The risk of mortality was twofold higher for participants reporting ≥3 h/day of television viewing than for those reporting <1 h/d (IRR: 2.04 [95% CI 1.16 to 3.57]). Conclusions Television viewing was directly associated with all‐cause mortality. However, computer use and time spent driving were not significantly associated with higher mortality. Further cohort studies and trials designed to assess whether reductions in television viewing are able to reduce mortality are warranted. The lack of association between computer use or time spent driving and mortality needs further confirmation.

Yogurt consumption, weight change and risk of overweight/obesity: The SUN cohort study

BACKGROUND AND AIMS Epidemiological studies on the association between yogurt consumption and the risk of overweight/obesity are scarce. We prospectively examined the association of yogurt consumption with overweight/obesity and average annual weight gain. METHODS AND RESULTS Prospective cohort study of 8516 men and women (mean age 37.1, SD: 10.8 y). Participants were followed-up every two years. Participants were classified in 5 categories of yogurt consumption at baseline: 0-2, >2-<5, 5-<7, 7 and ≥ 7 servings/week. Outcomes were: 1) average yearly weight change during follow-up; and 2) incidence of overweight/obesity. Linear regression models and Cox models were used to adjust for potential confounders. After a median follow-up of 6.6 years, 1860 incident cases of overweight/obesity were identified. A high (>7 servings/week) consumption of total and whole-fat yogurt was associated with lower incidence of overweight/obesity [multivariable adjusted hazard ratios = 0.80 (95% CI: 0.68-0.94); and 0.62 (0.47-0.82) respectively] in comparison with low consumption (0-2 servings/week). This inverse association was stronger among participants with higher fruit consumption. CONCLUSION In this Mediterranean cohort, yogurt consumption was inversely associated with the incidence of overweight/obesity, especially among participants with higher fruit consumption.

Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts

Background Observational cohort studies and a secondary prevention trial have shown inverse associations between adherence to the Mediterranean diet and cardiovascular risk. Methods In a multicenter trial in Spain, we assigned 7447 participants (55 to 80 years of age, 57% women) who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra‐virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly educational sessions and, depending on group assignment, free provision of extra‐virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was a major cardiovascular event (myocardial infarction, stroke, or death from cardiovascular causes). After a median follow‐up of 4.8 years, the trial was stopped on the basis of a prespecified interim analysis. In 2013, we reported the results for the primary end point in the Journal. We subsequently identified protocol deviations, including enrollment of household members without randomization, assignment to a study group without randomization of some participants at 1 of 11 study sites, and apparent inconsistent use of randomization tables at another site. We have withdrawn our previously published report and now report revised effect estimates based on analyses that do not rely exclusively on the assumption that all the participants were randomly assigned. Results A primary end‐point event occurred in 288 participants; there were 96 events in the group assigned to a Mediterranean diet with extra‐virgin olive oil (3.8%), 83 in the group assigned to a Mediterranean diet with nuts (3.4%), and 109 in the control group (4.4%). In the intention‐to‐treat analysis including all the participants and adjusting for baseline characteristics and propensity scores, the hazard ratio was 0.69 (95% confidence interval [CI], 0.53 to 0.91) for a Mediterranean diet with extra‐virgin olive oil and 0.72 (95% CI, 0.54 to 0.95) for a Mediterranean diet with nuts, as compared with the control diet. Results were similar after the omission of 1588 participants whose study‐group assignments were known or suspected to have departed from the protocol. Conclusions In this study involving persons at high cardiovascular risk, the incidence of major cardiovascular events was lower among those assigned to a Mediterranean diet supplemented with extra‐virgin olive oil or nuts than among those assigned to a reduced‐fat diet. (Funded by Instituto de Salud Carlos III, Spanish Ministry of Health, and others; Current Controlled Trials number, ISRCTN35739639.)

Mediterranean alcohol-drinking pattern and mortality in the SUN (Seguimiento Universidad de Navarra) Project: a prospective cohort study

Moderate alcohol intake has been related to lower mortality. However, alcohol use includes other dimensions beyond the amount of alcohol consumed. These aspects have not been sufficiently studied as a comprehensive entity. We aimed to test the relationship between an overall alcohol-drinking pattern and all-cause mortality. In a Mediterranean cohort study, we followed 18 394 Spanish participants up to 12 years. A validated 136-item FFQ was used to assess baseline alcohol intake. We developed a score assessing simultaneously seven aspects of alcohol consumption to capture the conformity to a traditional Mediterranean alcohol-drinking pattern (MADP). It positively scored moderate alcohol intake, alcohol intake spread out over the week, low spirit consumption, wine preference, red wine consumption, wine consumed during meals and avoidance of binge drinking. During the follow-up, 206 deaths were identified. For each 2-point increment in a 0-9 score of adherence to the MADP, we observed a 25% relative risk reduction in mortality (95% CI 11, 38%). Within each category of alcohol intake, a higher adherence to the MADP was associated with lower mortality. Abstainers (excluded from the calculations of the MADP) exhibited higher mortality (hazard ratio 1·82, 95% CI 1·14, 2·90) than participants highly adherent to the MADP. In conclusion, better adherence to an overall healthy alcohol-drinking pattern was associated with reduced mortality when compared with abstention or departure from this pattern. This reduction goes beyond the inverse association usually observed for moderate alcohol drinking. Even moderate drinkers can benefit from the advice to follow a traditional MADP.

Dietary inflammatory index, cardiometabolic conditions and depression in the Seguimiento Universidad de Navarra cohort study

Only one prospective study has analysed the relationship between the inflammatory properties of diet and risk of depression thus far. The aim of this study was to assess the association between the dietary inflammatory index (DII) and the incidence of depression. In a cohort study of 15 093 university graduates, participants completed a validated FFQ at baseline and after 10 years of follow-up. The DII was calculated based on the FFQ. Each of the twenty-eight nutrients or foods received a score based on findings from the peer-reviewed literature reporting on the relationships between diet and inflammatory biomarkers (IL-1β, IL-4, IL-6, IL-10, TNF-α and C-reactive protein). Participants were classified as having depression if they reported a new clinical diagnosis of depression by a physician, antidepressant drugs, or both. Multivariable Cox regression models were used to estimate hazard ratios (HR) of depression according to quintiles of the DII. After a median 8·5 years of follow-up, we observed 1051 incident cases of depression. The HR for participants in the highest quintile of DII (strongly pro-inflammatory) was 1·47 (95% CI 1·17, 1·85) compared with those in the bottom quintile, with a significant dose-response relationship (P trend=0·01). In the subgroup analyses, the association between DII and depression was stronger among participants >55 years and among those with cardiometabolic comorbidities (HR 2·70; 95% CI 1·22, 5·97 and HR 1·80; 95% CI 1·27, 2·57, respectively). A pro-inflammatory diet was associated with a significantly higher risk of depression in a Mediterranean population. This association was stronger among older subjects and subjects with cardiometabolic diseases.

Sugar-sweetened carbonated beverage consumption and childhood/adolescent obesity: a case-control study

OBJECTIVE To assess the association between the consumption of sugar-sweetened carbonated beverages (SSCB) and obesity in children and adolescents from Navarra (Spain). DESIGN We used a matched case-control study design. The exposure, SSCB consumption (1 serving: 200 ml), was measured with a previously validated FFQ. Anthropometrical measures were taken using standardized protocols. The outcome, obesity, was defined as BMI above the age- and sex-specific 97th percentile according to the Spanish reference charts. In the analysis we used conditional logistic regression. Potential confounders were controlled using a multivariable model. SETTING Subjects were recruited in the paediatric departments of the Universidad de Navarra Clinic and the Navarra Hospital Complex, and in three primary health centres of Navarra. Controls were recruited when attending for a routine medical examination or vaccination. SUBJECTS One hundred and seventy-four obese children and 174 individually sex- and age-matched controls, 52·87% boys, with a mean age of 11·6 years. Exclusion criteria were dietary interventions, exposure to hormone treatment, development of secondary obesity due to endocrinopathy and serious intercurrent illness. RESULTS Independently of other factors, high consumption of SSCB (>4 servings/week) was significantly associated with obesity (OR = 3·46; 95% CI 1·24, 9·62; P = 0·01). Besides, each additional daily serving of SSCB was associated with a 69% relative increase in the risk of obesity (OR = 1·69; 95% CI 1·04, 2·73; P = 0·03). CONCLUSIONS We found a strong and significant association between SSCB consumption and obesity risk. Our results suggest a monotonic dose-response linear shape for this association in children and adolescents (P for trend = 0·02).