Montserrat Fitó

The Effect of Polyphenols in Olive Oil on Heart Disease Risk Factors: A Randomized Trial

Context Olive oil, the main fat in the Mediterranean diet, contains polyphenols, which have antioxidant properties and may affect serum lipid levels. Contribution The authors studied virgin olive oil (high in polyphenols), refined olive oil (low in polyphenols), and a mixture of the 2 oils in equal parts. Two hundred healthy young men consumed 25 mL of an olive oil daily for 3 weeks followed by the other olive oils in a randomly assigned sequence. Olive oils with greater polyphenol content increased high-density lipoprotein (HDL) cholesterol levels and decreased serum markers of oxidation. Cautions The increase in HDL cholesterol level was small. Implications Virgin olive oil might have greater health benefits than refined olive oil. The Editors Polyphenol intake has been associated with low cancer and coronary heart disease (CHD) mortality rates (1). Antioxidant and anti-inflammatory properties and improvements in endothelial dysfunction and the lipid profile have been reported for dietary polyphenols (2). Studies have recently suggested that Mediterranean health benefits may be due to a synergistic combination of phytochemicals and fatty acids (3). Olive oil, rich in oleic acid (a monounsaturated fatty acid), is the main fat of the Mediterranean diet (4). To date, most of the protective effect of olive oil within the Mediterranean diet has been attributed to its high monounsaturated fatty acid content (5). However, if the effect of olive oil can be attributed solely to its monounsaturated fatty acid content, any type of olive oil, rapeseed or canola oil, or monounsaturated fatty acidenriched fat would provide similar health benefits. Whether the beneficial effects of olive oil on the cardiovascular system are exclusively due to oleic acid remains to be elucidated. The minor components, particularly the phenolic compounds, in olive oil may contribute to the health benefits derived from the Mediterranean diet. Among olive oils usually present on the market, virgin olive oils produced by direct-press or centrifugation methods have higher phenolic content (150 to 350 mg/kg of olive oil) (6). In experimental studies, phenolic compounds in olive oil showed strong antioxidant properties (7, 8). Oxidized low-density lipoprotein (LDL) is currently thought to be more damaging to the arterial wall than native LDL cholesterol (9). Results of randomized, crossover, controlled clinical trials on the antioxidant effect of polyphenols from real-life daily doses of olive oil in humans are, however, conflicting (10). Growing evidence suggests that dietary phenols (1115) and plant-based diets (16) can modulate lipid and lipoprotein metabolism. The Effect of Olive Oil on Oxidative Damage in European Populations (EUROLIVE) Study is a multicenter, randomized, crossover, clinical intervention trial that aims to assess the effect of sustained daily doses of olive oil, as a function of its phenolic content, on the oxidative damage to lipid and LDL cholesterol levels and the lipid profile as cardiovascular risk factors. Methods Participants We recruited healthy men, 20 to 60 years of age, from 6 European cities through newspaper and university advertisements. Of the 344 persons who agreed to be screened, 200 persons were eligible (32 men from Barcelona, Spain; 33 men from Copenhagen, Denmark; 30 men from Kuopio, Finland; 31 men from Bologna, Italy; 40 men from Postdam, Germany; and 34 men from Berlin, Germany) and were enrolled from September 2002 through June 2003 (Figure 1). Participants were eligible for study inclusion if they provided written informed consent, were willing to adhere to the protocol, and were in good health. We preselected volunteers when clinical record, physical examination, and blood pressure were strictly normal and the candidate was a nonsmoker. Next, we performed a complete blood count, biochemical laboratory analyses, and urinary dipstick tests to measure levels of serum glucose, total cholesterol, creatinine, alanine aminotransferase, and triglycerides. We included candidates with values within the reference range. Exclusion criteria were smoking; use of antioxidant supplements, aspirin, or drugs with established antioxidant properties; hyperlipidemia; obesity; diabetes; hypertension; intestinal disease; or any other disease or condition that would impair adherence. We excluded women to avoid the possible interference of estrogens, which are considered to be potential antioxidants (17). All participants provided written informed consent, and the local institutional ethics committees approved the protocol. Figure 1. Study flow diagram. Sequence of olive oil administration: 1) high-, medium-, and low-polyphenol olive oil; 2) medium-, low-, and high-polyphenol olive oil; and 3) low-, high-, and medium-polyphenol olive oil. Design and Study Procedure The trial was a randomized, crossover, controlled study. We randomly assigned participants consecutively to 1 of 3 sequences of olive oil administration. Participants received a daily dose of 25 mL (22 g) of 3 olive oils with high (366 mg/kg), medium (164 mg/kg), and low (2.7 mg/kg) polyphenol content (Figure 1) in replacement of other raw fats. Sequences were high-, medium-, and low-polyphenol olive oil (sequence 1); medium-, low-, and high-polyphenol olive oil (sequence 2); and low-, high-, and medium-polyphenol olive oil (sequence 3). In the coordinating center, we prepared random allocation to each sequence, taken from a Latin square, for each center by blocks of 42 participants (14 persons in each sequence), using specific software that was developed at the Municipal Institute for Medical Research, Barcelona, Spain (Aleator, Municipal Institute for Medical Research). The random allocation was faxed to the participating centers upon request for each individual included in the study. Treatment containers were assigned a code number that was concealed from participants and investigators, and the coordinating center disclosed the code number only after completion of statistical analyses. Olive oils were specially prepared for the trial. We selected a virgin olive oil with high natural phenolic content (366 mg/kg) and measured its fatty acid and vitamin E composition. We tested refined olive oil harvested from the same cultivar and soil to find an olive oil with similar quantities of fatty acid and a similar micronutrient profile. Vitamin E was adjusted to values similar to those of the selected virgin olive oil. Because phenolic compounds are lost in the refinement process, the refined olive oil had a low phenolic content (2.7 mg/kg). By mixing virgin and refined olive oil, we obtained an olive oil with an intermediate phenolic content (164 mg/kg). Olive oils did not differ in fat and micronutrient composition (that is, vitamin E, triterpenes, and sitosterols), with the exception of phenolic content. Three-week interventions were preceded by 2-week washout periods, in which we requested that participants avoid olive and olive oil consumption. We chose the 2-week washout period to reach the equilibrium in the plasma lipid profile because longer intervention periods with fat-rich diets did not modify the lipid concentrations (18). Daily doses of 25 mL of olive oil were blindly prepared in containers delivered to the participants at the beginning of each intervention period. We instructed participants to return the 21 containers at the end of each intervention period so that the daily amount of unconsumed olive oil could be registered. Dietary Adherence We measured tyrosol and hydroxytyrosol, the 2 major phenolic compounds in olive oil as simple forms or conjugates (7), by gas chromatography and mass spectrometry in 24-hour urine before and after each intervention period as biomarkers of adherence to the type of olive oil ingested. We asked participants to keep a 3-day dietary record at baseline and after each intervention period. We requested that participants in all centers avoid a high intake of foods that contain antioxidants (that is, vegetables, legumes, fruits, tea, coffee, chocolate, wine, and beer). A nutritionist also personally advised participants to replace all types of habitually consumed raw fats with the olive oils (for example, spread the assigned olive oil on bread instead of butter, put the assigned olive oil on boiled vegetables instead of margarine, and use the assigned olive oil on salads instead of other vegetable oils or standard salad dressings). Data Collection Main outcome measures were changes in biomarkers of oxidative damage to lipids. Secondary outcomes were changes in lipid levels and in biomarkers of the antioxidant status of the participants. We assessed outcome measures at the beginning of the study (baseline) and before (preintervention) and after (postintervention) each olive oil intervention period. We collected blood samples at fasting state together with 24-hour urine and recorded anthropometric variables. We measured blood pressure with a mercury sphygmomanometer after at least a 10-minute rest in the seated position. We recorded physical activity at baseline and at the end of the study and assessed it by using the Minnesota Leisure Time Physical Activity Questionnaire (19). We measured 1) glucose and lipid profile, including serum glucose, total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride levels determined by enzymatic methods (2023) and LDL cholesterol levels calculated by the Friedewald formula; 2) oxidative damage to lipids, including plasma-circulating oxidized LDL measured by enzyme immunoassay, plasma total F2-isoprostanes determined by using high-performance liquid chromatography and stable isotope-dilution and mass spectrometry, plasma C18 hydroxy fatty acids measured by gas chromatography and mass spectrometry, and serum LDL cholesterol uninduced conjugated dienes measured by spectrophotometry and adjusted for the cholesterol concentration in LDL cholesterol levels; 3) antioxidant sta

Effect of a Mediterranean Diet Supplemented With Nuts on Metabolic Syndrome Status One-Year Results of the PREDIMED Randomized Trial

BACKGROUND Epidemiological studies suggest that the Mediterranean diet (MedDiet) may reduce the risk of developing the metabolic syndrome (MetS). We compared the 1-year effect of 2 behavioral interventions to implement the MedDiet vs advice on a low-fat diet on MetS status. METHODS A total of 1224 participants were recruited from the PREDIMED (Prevención con Dieta Mediterránea) Study, a multicenter, 3-arm, randomized clinical trial to determine the efficacy of the MedDiet on the primary prevention of cardiovascular disease. Participants were older subjects at high risk for cardiovascular disease. Interventions were quarterly education about the MedDiet plus provision of either 1 L/wk of virgin olive oil (MedDiet + VOO) or 30 g/d of mixed nuts (MedDiet + nuts), and advice on a low-fat diet (control diet). All diets were ad libitum, and there was no increase in physical activity for any of the interventions. Lifestyle variables and MetS features as defined by the National Cholesterol Education Program Adult Treatment Panel III criteria were assessed. RESULTS At baseline, 61.4% of participants met criteria for the MetS. One-year prevalence was reduced by 6.7%, 13.7%, and 2.0% in the MedDiet + VOO, MedDiet + nuts, and control diet groups, respectively (MedDiet + nuts vs control groups, P = .01; MedDiet + VOO vs control group, P = .18). Incident rates of the MetS were not significantly different among groups (22.9%, 17.9%, and 23.4%, respectively). After adjustment for sex, age, baseline obesity status, and weight changes, the odds ratios for reversion of MetS were 1.3 (95% confidence interval, 0.8-2.1) for the MedDiet + VOO group and 1.7 (1.1-2.6) for the MedDiet + nuts group compared with the control diet group. CONCLUSION A traditional MedDiet enriched with nuts could be a useful tool in the management of the MetS.

A Short Screener Is Valid for Assessing Mediterranean Diet Adherence among Older Spanish Men and Women

Ensuring the accuracy of dietary assessment instruments is paramount for interpreting diet-disease relationships. The present study assessed the relative and construct validity of the 14-point Mediterranean Diet Adherence Screener (MEDAS) used in the Prevención con Dieta Mediterránea (PREDIMED) study, a primary prevention nutrition-intervention trial. A validated FFQ and the MEDAS were administered to 7146 participants of the PREDIMED study. The MEDAS-derived PREDIMED score correlated significantly with the corresponding FFQ PREDIMED score (r = 0.52; intraclass correlation coefficient = 0.51) and in the anticipated directions with the dietary intakes reported on the FFQ. Using Bland Altmans analysis, the average MEDAS Mediterranean diet score estimate was 105% of the FFQ PREDIMED score estimate. Limits of agreement ranged between 57 and 153%. Multiple linear regression analyses revealed that a higher PREDIMED score related directly (P < 0.001) to HDL-cholesterol (HDL-C) and inversely (P < 0.038) to BMI, waist circumference, TG, the TG:HDL-C ratio, fasting glucose, and the cholesterol:HDL-C ratio. The 10-y estimated coronary artery disease risk decreased as the PREDIMED score increased (P < 0.001). The MEDAS is a valid instrument for rapid estimation of adherence to the Mediterranean diet and may be useful in clinical practice.

Effect of a traditional Mediterranean diet on lipoprotein oxidation: a randomized controlled trial.

BACKGROUND Despite the richness in antioxidants of the Mediterranean diet, to our knowledge, no randomized controlled trials have assessed its effect on in vivo lipoprotein oxidation. METHODS A total of 372 subjects at high cardiovascular risk (210 women and 162 men; age range, 55-80 years), who were recruited into a large, multicenter, randomized, controlled, parallel-group clinical trial (the Prevención con Dieta Mediterránea [PREDIMED] Study) directed at testing the efficacy of the traditional Mediterranean diet (TMD) on the primary prevention of coronary heart disease, were assigned to a low-fat diet (n = 121) or one of 2 TMDs (TMD + virgin olive oil or TMD + nuts). The TMD participants received nutritional education and either free virgin olive oil for all the family (1 L/wk) or free nuts (30 g/d). Diets were ad libitum. Changes in oxidative stress markers were evaluated at 3 months. RESULTS After the 3-month interventions, mean (95% confidence intervals) oxidized low-density lipoprotein (LDL) levels decreased in the TMD + virgin olive oil (-10.6 U/L [-14.2 to -6.1]) and TMD + nuts (-7.3 U/L [-11.2 to -3.3]) groups, without changes in the low-fat diet group (-2.9 U/L [-7.3 to 1.5]). Change in oxidized LDL levels in the TMD + virgin olive oil group reached significance vs that of the low-fat group (P = .02). Malondialdehyde changes in mononuclear cells paralleled those of oxidized LDL. No changes in serum glutathione peroxidase activity were observed. CONCLUSIONS Individuals at high cardiovascular risk who improved their diet toward a TMD pattern showed significant reductions in cellular lipid levels and LDL oxidation. Results provide further evidence to recommend the TMD as a useful tool against risk factors for CHD. Trial Registration isrctn.org Identifier: ISRCTN35739639.

Hydroxytyrosol Disposition in Humans

BACKGROUND Animal and in vitro studies suggest that phenolic compounds in virgin olive oil are effective antioxidants. In animal and in vitro studies, hydroxytyrosol and its metabolites have been shown to be strong antioxidants. One of the prerequisites to assess their in vivo physiologic significance is to determine their presence in human plasma. METHODS We developed an analytical method for both hydroxytyrosol and 3-O-methyl-hydroxytyrosol in plasma. The administered dose of phenolic compounds was estimated from methanolic extracts of virgin olive oil after subjecting them to different hydrolytic treatments. Plasma and urine samples were collected from 0 to 12 h before and after 25 mL of virgin olive oil intake, a dose close to that used as daily intake in Mediterranean countries. Samples were analyzed by capillary gas chromatography-mass spectrometry before and after being subjected to acidic and enzymatic hydrolytic treatments. RESULTS Calibration curves were linear (r >0.99). Analytical recoveries were 42-60%. Limits of quantification were <1.5 mg/L. Plasma hydroxytyrosol and 3-O-methyl-hydroxytyrosol increased as a response to virgin olive oil administration, reaching maximum concentrations at 32 and 53 min, respectively (P <0.001 for quadratic trend). The estimated hydroxytyrosol elimination half-life was 2.43 h. Free forms of these phenolic compounds were not detected in plasma samples. CONCLUSIONS The proposed analytical method permits quantification of hydroxytyrosol and 3-O-methyl-hydroxytyrosol in plasma after real-life doses of virgin olive oil. From our results, approximately 98% of hydroxytyrosol appears to be present in plasma and urine in conjugated forms, mainly glucuronoconjugates, suggesting extensive first-pass intestinal/hepatic metabolism of the ingested hydroxytyrosol.

Response of oxidative stress biomarkers to a 16-week aerobic physical activity program, and to acute physical activity, in healthy young men and women.

Physical activity (PA) is associated with a reduced risk of coronary heart disease, and may favorably modify the antioxidant-prooxidant balance. This study assessed the effects of aerobic PA training on antioxidant enzyme activity, oxidized LDL concentration, and LDL resistance to oxidation, as well as the effect of acute PA on antioxidant enzyme activity before and after the training period. Seventeen sedentary healthy young men and women were recruited for 16 weeks of training. The activity of superoxide dismutase in erythrocytes (E-SOD), glutathione peroxidase in whole blood (GSH-Px), and glutathione reductase in plasma (P-GR), and the oxidized LDL concentration and LDL composition, diameter, and resistance to oxidation were determined before and after training. Shortly before and after this training period they also performed a bout of aerobic PA for 30 min. The antioxidant enzyme activity was also determined at 0 min, 30 min, 60 min, 120 min, and 24 h after both bouts of PA. Training induces an increase in GSH-Px (27.7%), P-GR (17.6%), and LDL resistance to oxidation, and a decrease in oxidized LDL (-15.9%). After the bout of PA, an increase in E-SOD and GSH-Px was observed at 0 min, with a posterior decrease in enzyme activity until 30-60 min, and a tendency to recover the basal values at 120 min and 24 h. Training did not modify this global response pattern. Regular PA increases endogenous antioxidant activity and LDL resistance to oxidation, and decreases oxidized LDL concentration; 30 min of aerobic PA decreases P-GR and B-GSH-Px activity in the first 30-60 min with a posterior recovery.

Factores de riesgo cardiovascular en España en la primera década del siglo xxi: análisis agrupado con datos individuales de 11 estudios de base poblacional, estudio DARIOS ☆

INTRODUCTION AND OBJECTIVES To estimate the prevalence of cardiovascular risk factors in individuals aged 35-74 years in 10 of Spains autonomous communities and determine the geographic variation of cardiovascular risk factors distribution. METHODS Pooled analysis with individual data from 11 studies conducted in the first decade of the 21st century. The average response rate was 73%. Lipid profile (with laboratory cross-validation), glucose level, blood pressure, waist circumference, height, and weight were measured and standard questionnaires administered. Age-standardized prevalence of smoking, diabetes, hypertension, dyslipidemia, and obesity in the European population were calculated. Furthermore, the coefficient of variation between component studies was determined for the prevalence of each risk factor. RESULTS In total, 28,887 participants were included. The most prevalent cardiovascular risk factors were high blood pressure (47% in men, 39% in women), total cholesterol ≥ 250 mg/dL (43% and 40%, respectively), obesity (29% and 29%, respectively), tobacco use (33% and 21%, respectively), and diabetes (16% and 11%, respectively). Total cholesterol ≥ 190 and ≥ 250 mg/dL were the respective minimum and maximum coefficients of variation (7%-24% in men, 7%-26% in women). Average concordance in lipid measurements between laboratories was excellent. CONCLUSIONS Prevalence of high blood pressure, dyslipidemia, obesity, tobacco use and diabetes is high. Little variation was observed between autonomous communities in the population aged 35-74 years. However, presence of the most prevalent cardiovascular risk factors in the Canary Islands, Extremadura and Andalusia was greater than the mean of the 11 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

Inhibition of circulating immune cell activation: a molecular antiinflammatory effect of the Mediterranean diet

BACKGROUND Adherence to the Mediterranean diet (Med-Diet) is associated with a reduced risk of cardiovascular disease (CVD). However, the molecular mechanisms involved are not fully understood. OBJECTIVE The objective was to compare the effects of 2 Med-Diets with those of a low-fat diet on immune cell activation and soluble inflammatory biomarkers related to atherogenesis in subjects at high risk of CVD. DESIGN In a controlled study, we randomly assigned 112 older subjects with diabetes or > or =3 CVD risk factors to 3 dietary intervention groups: Med-Diet with supplemental virgin olive oil (VOO), Med-Diet with supplemental nuts, and low-fat diet. Changes from baseline in cellular and serum inflammatory biomarkers were assessed at 3 mo. RESULTS One hundred six participants (43% women; average age: 68 y) completed the study. At 3 mo, monocyte expression of CD49d, an adhesion molecule crucial for leukocyte homing, and of CD40, a proinflammatory ligand, decreased (P < 0.05) after both Med-Diets but not after the low-fat diet. Serum interleukin-6 and soluble intercellular adhesion molecule-1, inflammatory mediators crucial in firm adhesion of leukocytes to endothelial surfaces, decreased (P < 0.05) in both Med-Diet groups. Soluble vascular cellular adhesion molecule-1 and C-reactive protein decreased only after the Med-Diet with VOO (P < 0.05), whereas interleukin-6, soluble vascular cellular adhesion molecule-1, and soluble intercellular adhesion molecule-1 increased (P < 0.05) after the low-fat diet. CONCLUSIONS Med-Diets supplemented with VOO or nuts down-regulate cellular and circulating inflammatory biomarkers related to atherogenesis in subjects at high risk of CVD. The results support the recommendation of the Med-Diet as a useful tool against CVD.

Mediterranean Diet and Age-Related Cognitive Decline: A Randomized Clinical Trial

IMPORTANCE Oxidative stress and vascular impairment are believed to partly mediate age-related cognitive decline, a strong risk factor for development of dementia. Epidemiologic studies suggest that a Mediterranean diet, an antioxidant-rich cardioprotective dietary pattern, delays cognitive decline, but clinical trial evidence is lacking. OBJECTIVE To investigate whether a Mediterranean diet supplemented with antioxidant-rich foods influences cognitive function compared with a control diet. DESIGN, SETTING, AND PARTICIPANTS Parallel-group randomized clinical trial of 447 cognitively healthy volunteers from Barcelona, Spain (233 women [52.1%]; mean age, 66.9 years), at high cardiovascular risk were enrolled into the Prevención con Dieta Mediterránea nutrition intervention trial from October 1, 2003, through December 31, 2009. All patients underwent neuropsychological assessment at inclusion and were offered retesting at the end of the study. INTERVENTIONS Participants were randomly assigned to a Mediterranean diet supplemented with extravirgin olive oil (1 L/wk), a Mediterranean diet supplemented with mixed nuts (30 g/d), or a control diet (advice to reduce dietary fat). MAIN OUTCOMES AND MEASURES Rates of cognitive change over time based on a neuropsychological test battery: Mini-Mental State Examination, Rey Auditory Verbal Learning Test (RAVLT), Animals Semantic Fluency, Digit Span subtest from the Wechsler Adult Intelligence Scale, Verbal Paired Associates from the Wechsler Memory Scale, and the Color Trail Test. We used mean z scores of change in each test to construct 3 cognitive composites: memory, frontal (attention and executive function), and global. RESULTS Follow-up cognitive tests were available in 334 participants after intervention (median, 4.1 years). In multivariate analyses adjusted for confounders, participants allocated to a Mediterranean diet plus olive oil scored better on the RAVLT (P = .049) and Color Trail Test part 2 (P = .04) compared with controls; no between-group differences were observed for the other cognitive tests. Similarly adjusted cognitive composites (mean z scores with 95% CIs) for changes above baseline of the memory composite were 0.04 (-0.09 to 0.18) for the Mediterranean diet plus olive oil, 0.09 (-0.05 to 0.23; P = .04 vs controls) for the Mediterranean diet plus nuts, and -0.17 (-0.32 to -0.01) for the control diet. Respective changes from baseline of the frontal cognition composite were 0.23 (0.03 to 0.43; P = .003 vs controls), 0.03 (-0.25 to 0.31), and -0.33 (-0.57 to -0.09). Changes from baseline of the global cognition composite were 0.05 (-0.11 to 0.21; P = .005 vs controls) for the Mediterranean diet plus olive oil, -0.05 (-0.27 to 0.18) for the Mediterranean diet plus nuts, and -0.38 (-0.57 to -0.18) for the control diet. All cognitive composites significantly (P < .05) decreased from baseline in controls. CONCLUSIONS AND RELEVANCE In an older population, a Mediterranean diet supplemented with olive oil or nuts is associated with improved cognitive function. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN35739639.