Estefanía Toledo

Relative validity of a semi-quantitative food-frequency questionnaire in an elderly Mediterranean population of Spain

The aim of the present study was to assess reproducibility and relative validity of a self-administered FFQ used in the PREDIMED Study, a clinical trial for primary prevention of CVD by Mediterranean diet in a population at high cardiovascular risk. The FFQ was administered twice (FFQ1 and FFQ2) to explore reproducibility at 1 year. Four 3 d dietary records (DR) were used as reference to explore validity; participants therefore recorded their food intake over 12 d in the course of 1 year. The degree of misclassification in the FFQ was also evaluated by a contingency table of quintiles comparing the information from the FFQ2 and the DR. A total of 158 men and women (aged 55-80 years) were asked not to modify their dietary habits during the study period. Reproducibility for food groups, energy and nutrient intake, explored by the Pearson correlation coefficient (r) ranged 0.50-0.82, and the intraclass correlation coefficient (ICC) ranged from 0.63 to 0.90. The FFQ2 tended to report higher energy and nutrient intake than the DR. The validity indices of the FFQ in relation to the DR for food groups and energy and nutrient intake ranged (r) from 0.24 to 0.72, while the range of the ICC was between 0.40 and 0.84. With regard to food groups, 68-83 % of individuals were in the same or adjacent quintile in both methods, a figure which decreased to 55-75 % for energy and nutrient intake. We concluded that FFQ measurements had good reproducibility and a relative validity similar to those of FFQ used in other prospective studies.

In vivo nutrigenomic effects of virgin olive oil polyphenols within the frame of the Mediterranean diet: a randomized controlled trial

The aim of the study was to assess whether benefits associated with the traditional Mediterranean diet (TMD) and virgin olive oil (VOO) consumption could be mediated through changes in the expression of atherosclerosis‐related genes. A randomized, parallel, controlled clinical trial in healthy volunteers (n=90) aged 20 to 50 yr was performed. Threemonth intervention groups were as follows: 1) TMD with VOO (TMD+VOO), 2) TMD with washed virgin olive oil (TMD+WOO), and 3) control with participants’ habitual diet. WOO was similar to VOO, but with a lower polyphenol content (55 vs. 328 mg/kg, respectively). TMD consumption decreased plasma oxidative and inflammatory status and the gene expression related with both inflammation [INF‐γ (INFy), Rho GTPase‐activating protein15 (ARHGAP15), and interleukin‐7 receptor (IL7R)] and oxidative stress [adrenergic ß2‐receptor (ADRB2) and polymerase (DNA‐directed) κ (POLK)] in peripheral blood mononuclear cells. All effects, with the exception of the decrease in POLK expression, were particularly observed when VOO, rich in polyphenols, was present in the TMD dietary pattern. Our results indicate a significant role of olive oil polyphenols in the down‐regulation of proatherogenic genes in the context of a TMD. In addition, the benefits associated with a TMD and olive oil polyphenol consumption on cardiovascular risk can be mediated through nutrigenomic effects.—Konstantinidou, V., Covas, M.‐I., Mun˜oz‐Aguayo, D., Khymenets, O., de la Torre, R., Saez, G., del Carmen Tormos, M., Toledo, E., Marti, A., Ruiz‐Gutiérrez, V., Ruiz Mendez, M. V., Fito, M. In vivo nutrigenomic effects of virgin olive oil polyphenols within the frame of the Mediterranean diet: a randomized controlled trial. FASEBJ. 24, 2546–2557 (2010). www.fasebj.org

A 14-Item Mediterranean Diet Assessment Tool and Obesity Indexes among High-Risk Subjects: The PREDIMED Trial

Objective Independently of total caloric intake, a better quality of the diet (for example, conformity to the Mediterranean diet) is associated with lower obesity risk. It is unclear whether a brief dietary assessment tool, instead of full-length comprehensive methods, can also capture this association. In addition to reduced costs, a brief tool has the interesting advantage of allowing immediate feedback to participants in interventional studies. Another relevant question is which individual items of such a brief tool are responsible for this association. We examined these associations using a 14-item tool of adherence to the Mediterranean diet as exposure and body mass index, waist circumference and waist-to-height ratio (WHtR) as outcomes. Design Cross-sectional assessment of all participants in the “PREvención con DIeta MEDiterránea” (PREDIMED) trial. Subjects 7,447 participants (55–80 years, 57% women) free of cardiovascular disease, but with either type 2 diabetes or ≥3 cardiovascular risk factors. Trained dietitians used both a validated 14-item questionnaire and a full-length validated 137-item food frequency questionnaire to assess dietary habits. Trained nurses measured weight, height and waist circumference. Results Strong inverse linear associations between the 14-item tool and all adiposity indexes were found. For a two-point increment in the 14-item score, the multivariable-adjusted differences in WHtR were −0.0066 (95% confidence interval, –0.0088 to −0.0049) for women and –0.0059 (–0.0079 to –0.0038) for men. The multivariable-adjusted odds ratio for a WHtR>0.6 in participants scoring ≥10 points versus ≤7 points was 0.68 (0.57 to 0.80) for women and 0.66 (0.54 to 0.80) for men. High consumption of nuts and low consumption of sweetened/carbonated beverages presented the strongest inverse associations with abdominal obesity. Conclusions A brief 14-item tool was able to capture a strong monotonic inverse association between adherence to a good quality dietary pattern (Mediterranean diet) and obesity indexes in a population of adults at high cardiovascular risk.

Mediterranean diet improves cognition: the PREDIMED-NAVARRA randomised trial

Objective Previous observational studies reported beneficial effects of the Mediterranean diet (MedDiet) on cognitive function, but results were inconsistent. We assessed the effect on cognition of a nutritional intervention using MedDiets in comparison with a low-fat control diet. Methods We assessed 522 participants at high vascular risk (44.6% men, age 74.6 ± 5.7 years at cognitive evaluation) enrolled in a multicentre, randomised, primary prevention trial (PREDIMED), after a nutritional intervention comparing two MedDiets (supplemented with either extra-virgin olive oil (EVOO) or mixed nuts) versus a low-fat control diet. Global cognitive performance was examined by Mini-Mental State Examination (MMSE) and Clock Drawing Test (CDT) after 6.5 years of nutritional intervention. Researchers who assessed the outcome were blinded to group assignment. We used general linear models to control for potential confounding. Results After adjustment for sex, age, education, Apolipoprotein E genotype, family history of cognitive impairment/dementia, smoking, physical activity, body mass index, hypertension, dyslipidaemia, diabetes, alcohol and total energy intake, participants allocated to the MedDiet+EVOO showed higher mean MMSE and CDT scores with significant differences versus control (adjusted differences: +0.62 95% CI +0.18 to +1.05, p=0.005 for MMSE, and +0.51 95% CI +0.20 to +0.82, p=0.001 for CDT). The adjusted means of MMSE and CDT scores were also higher for participants allocated to the MedDiet+Nuts versus control (adjusted differences: +0.57 (95% CI +0.11 to +1.03), p=0.015 for MMSE and +0.33 (95% CI +0.003 to +0.67), p=0.048 for CDT). These results did not differ after controlling for incident depression. Conclusions An intervention with MedDiets enhanced with either EVOO or nuts appears to improve cognition compared with a low-fat diet. ISRCTN:35739639

Mediterranean diet and the incidence of cardiovascular disease: A Spanish cohort

BACKGROUND AND AIM The Mediterranean diet is considered a model for healthy eating. However, prospective evidence in Mediterranean countries evaluating the relationship between this dietary pattern and non-fatal cardiovascular events is scarce. The aim of the present study was to evaluate the association between the adherence to the Mediterranean diet and the incidence of fatal and non-fatal cardiovascular events among initially healthy middle-aged adults from the Mediterranean area. METHODS AND RESULTS We followed-up 13,609 participants (60 percent women, mean age: 38 years) initially free of cardiovascular disease (CVD) during 4.9 years. Participants were part of a prospective cohort study of university graduates from all regions of Spain. Baseline diet was assessed using a validated 136-item food-frequency questionnaire. A 9-point score was used to appraise adherence to the Mediterranean diet. Incident clinical events were confirmed by a review of medical records. We observed 100 incident cases of CVD. In multivariate analyses, participants with the highest adherence to the Mediterranean diet (score>6) exhibited a lower cardiovascular risk (hazard ratio=0.41, 95% confidence interval [CI]: 0.18-0.95) compared to those with the lowest score (<3). For each 2-point increment in the score, the adjusted hazard ratios were 0.80 (95% CI: 0.62-1.02) for total CVD and 0.74 (0.55-0.99) for coronary heart disease. CONCLUSIONS There is an inverse association between adherence to the Mediterranean diet and the incidence of fatal and non-fatal CVD in initially healthy middle-aged adults.

Adherence to the Mediterranean diet, long-term weight change, and incident overweight or obesity: the Seguimiento Universidad de Navarra (SUN) cohort.

BACKGROUND The Mediterranean dietary pattern might be a potential tool for the prevention of obesity. OBJECTIVES We studied the association between adherence to 6 previously published scores used to assess the adherence to the Mediterranean diet and weight change. We also assessed the risk of relevant weight gain (≥ 5 kg) or the risk of developing overweight or obesity. DESIGN The study population included 10,376 Spanish men and women who were university graduates (mean age = 38 y) and were followed up for a mean (± SD) of 5.7 ± 2.2 y. Diet was assessed at baseline with a 136-item, previously validated food-frequency questionnaire. Weight was assessed at baseline and biennially during follow-up. RESULTS Participants with the lowest adherence (≤ 3 points) to the Mediterranean dietary score (MDS) proposed by Trichopoulou et al (range: 0-9; N Engl J Med 2003;348:2599-608) exhibited the highest average yearly weight gain, whereas participants with the highest (≥ 6 points) adherence exhibited the lowest weight gain (adjusted difference: -0.059 kg/y; 95% CI: -0.111, -0.008 kg/y; P for trend = 0.02). This inverse association was extended to other a priori-defined MDSs. The group with the highest adherence to the MDS also showed the lowest risk of relevant weight gain (≥ 5 kg) during the first 4 y of follow-up (odds ratio: 0.76; 95% CI: 0.64, 0.90). CONCLUSIONS Adherence to the Mediterranean dietary pattern is significantly associated with reduced weight gain. This dietary pattern can be recommended to slow down age-related weight gain.

Virgin olive oil supplementation and long-term cognition: the Predimed-Navarra randomized, trial

ObjectiveXXXto assess the effect on cognition of a controlled intervention testing Mediterranean diets (MedDiet).DesignXXXrandomized trial after 6.5 years of nutritional intervention.SettingEight primary care centers affiliated to the University of Navarra.ParticipantsA random subsample of 285 participants (95 randomly allocated to each of 3 groups) of the PREDIMED-NAVARRA trial. All of them were at high vascular risk (44.8% men, 74.1± 5.7 years at cognitive evaluation).InterventionsNutritional intervention comparing two MedDiets (supplemented with extra-virgin olive oil [EVOO] or mixed nuts) versus a low-fat control diet. Participants received intensive education to increase adherence to the intended intervention. Participants allocated to the MedDiet groups received EVOO (1 l/week) or 30 g/day of mixed nuts. Dietary habits were evaluated using a validated 137-item food frequency questionnaire (FFQ). Additionally, adherence to MedDiet was appraised using a 14-item questionnaire both at baseline and yearly thereafter.MeasurementsXXXcognitive performance as a main outcome and cognitive status (normal, mild cognitive impairment [MCI] or dementia) as a secondary outcome were evaluated by two neurologists blinded to group assignment after 6.5 years of nutritional intervention.ResultsBetter post-trial cognitive performance versus control in all cognitive domains and significantly better performance across fluency and memory tasks were observed for participants allocated to the MedDiet+EVOO group. After adjustment for sex, age, education, apolipoprotein E genotype, family history of cognitive impairment/dementia, smoking, physical activity, body mass index, hypertension, dyslipidaemia, diabetes, alcohol and total energy intake, this group also showed lower MCI (OR=0.34 95% CI: 0.12–0.97) compared with control group. Participants assigned to MedDiet+Nuts group did not differ from controls.ConclusionA long-term intervention with an EVOO-rich MedDiet resulted in a better cognitive function in comparison with a control diet. However, non-significant differences were found for most cognitive domains. Participants allocated to an EVOO-rich MedDiet had less MCI than controls.

The Mediterranean Diet and Incidence of Hypertension The Seguimiento Universidad de Navarra (SUN) Study

The Mediterranean diet is receiving increasing attention in cardiovascular epidemiology. The association of adherence to the Mediterranean diet with the incidence of hypertension was evaluated among 9,408 men and women enrolled in a dynamic Spanish prospective cohort study during 1999-2005. Dietary intake was assessed at baseline with a validated semiquantitative food frequency questionnaire, and a 9-point Mediterranean diet score was constructed. During a median follow-up period of 4.2 years (range, 1.9-7.9), 501 incident cases of hypertension were identified. After adjustment for major hypertension risk factors and nutritional covariates, adherence to the Mediterranean diet was not associated with hypertension (the hazard ratio was 1.10 (95% confidence interval (CI): 0.81, 1.41) for moderate adherence and 1.12 (95% CI: 0.79, 1.60) for high adherence). However, it was associated with reduced changes in mean levels of systolic blood pressure (moderate adherence, -2.4 mm Hg (95% CI: -4.0, -0.8); high adherence, -3.1 mm Hg (95% CI: -5.4, -0.8)) and diastolic blood pressure (moderate adherence, -1.3 mm Hg (95% CI: -2.5, -0.1); high adherence, -1.9 mm Hg (95% CI: -3.6, -0.1)) after 6 years of follow-up. These results suggest that adhering to a Mediterranean-type diet could contribute to the prevention of age-related changes in blood pressure.

Mediterranean Diet and Invasive Breast Cancer Risk Among Women at High Cardiovascular Risk in the PREDIMED Trial: A Randomized Clinical Trial

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.

Dietary Fat Intake and the Risk of Depression: The SUN Project

Emerging evidence relates some nutritional factors to depression risk. However, there is a scarcity of longitudinal assessments on this relationship. Objective To evaluate the association between fatty acid intake or the use of culinary fats and depression incidence in a Mediterranean population. Material and Methods Prospective cohort study (1999–2010) of 12,059 Spanish university graduates (mean age: 37.5 years) initially free of depression with permanently open enrolment. At baseline, a 136-item validated food frequency questionnaire was used to estimate the intake of fatty acids (saturated fatty acids (SFA), polyunsaturated fatty acids (PUFA), trans unsaturated fatty acids (TFA) and monounsaturated fatty acids (MUFA) and culinary fats (olive oil, seed oils, butter and margarine) During follow-up participants were classified as incident cases of depression if they reported a new clinical diagnosis of depression by a physician and/or initiated the use of antidepressant drugs. Cox regression models were used to calculate Hazard Ratios (HR) of incident depression and their 95% confidence intervals (CI) for successive quintiles of fats. Results During follow-up (median: 6.1 years), 657 new cases of depression were identified. Multivariable-adjusted HR (95% CI) for depression incidence across successive quintiles of TFA intake were: 1 (ref), 1.08 (0.82–1.43), 1.17 (0.88–1.53), 1.28 (0.97–1.68), 1.42 (1.09–1.84) with a significant dose-response relationship (p for trend = 0.003). Results did not substantially change after adjusting for potential lifestyle or dietary confounders, including adherence to a Mediterranean Dietary Pattern. On the other hand, an inverse and significant dose-response relationship was obtained for MUFA (p for trend = 0.05) and PUFA (p for trend = 0.03) intake. Conclusions A detrimental relationship was found between TFA intake and depression risk, whereas weak inverse associations were found for MUFA, PUFA and olive oil. These findings suggest that cardiovascular disease and depression may share some common nutritional determinants related to subtypes of fat intake.