Josep Basora

Primary Prevention of Cardiovascular Disease with a Mediterranean Diet

BACKGROUND Observational cohort studies and a secondary prevention trial have shown an inverse association between adherence to the Mediterranean diet and cardiovascular risk. We conducted a randomized trial of this diet pattern for the primary prevention of cardiovascular events. METHODS In a multicenter trial in Spain, we randomly assigned participants 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 individual and group 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 the rate of major cardiovascular events (myocardial infarction, stroke, or death from cardiovascular causes). On the basis of the results of an interim analysis, the trial was stopped after a median follow-up of 4.8 years. RESULTS A total of 7447 persons were enrolled (age range, 55 to 80 years); 57% were women. The two Mediterranean-diet groups had good adherence to the intervention, according to self-reported intake and biomarker analyses. A primary end-point event occurred in 288 participants. The multivariable-adjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.54 to 0.92) and 0.72 (95% CI, 0.54 to 0.96) for the group assigned to a Mediterranean diet with extra-virgin olive oil (96 events) and the group assigned to a Mediterranean diet with nuts (83 events), respectively, versus the control group (109 events). No diet-related adverse effects were reported. CONCLUSIONS Among persons at high cardiovascular risk, a Mediterranean diet supplemented with extra-virgin olive oil or nuts reduced the incidence of major cardiovascular events. (Funded by the Spanish governments Instituto de Salud Carlos III and others; Controlled-Trials.com number, ISRCTN35739639.).

Reduction in the Incidence of Type 2-Diabetes with the Mediterranean Diet: Results of the PREDIMED-Reus Nutrition Intervention Randomized Trial

OBJECTIVE To test the effects of two Mediterranean diet (MedDiet) interventions versus a low-fat diet on incidence of diabetes. RESEARCH DESIGN AND METHODS This was a three-arm randomized trial in 418 nondiabetic subjects aged 55–80 years recruited in one center (PREDIMED-Reus, northeastern Spain) of the Prevención con Dieta Mediterránea [PREDIMED] study, a large nutrition intervention trial for primary cardiovascular prevention in individuals at high cardiovascular risk. Participants were randomly assigned to education on a low-fat diet (control group) or to one of two MedDiets, supplemented with either free virgin olive oil (1 liter/week) or nuts (30 g/day). Diets were ad libitum, and no advice on physical activity was given. The main outcome was diabetes incidence diagnosed by the 2009 American Diabetes Association criteria. RESULTS After a median follow-up of 4.0 years, diabetes incidence was 10.1% (95% CI 5.1–15.1), 11.0% (5.9–16.1), and 17.9% (11.4–24.4) in the MedDiet with olive oil group, the MedDiet with nuts group, and the control group, respectively. Multivariable adjusted hazard ratios of diabetes were 0.49 (0.25–0.97) and 0.48 (0.24–0.96) in the MedDiet supplemented with olive oil and nuts groups, respectively, compared with the control group. When the two MedDiet groups were pooled and compared with the control group, diabetes incidence was reduced by 52% (27–86). In all study arms, increased adherence to the MedDiet was inversely associated with diabetes incidence. Diabetes risk reduction occurred in the absence of significant changes in body weight or physical activity. CONCLUSIONS MedDiets without calorie restriction seem to be effective in the prevention of diabetes in subjects at high cardiovascular risk.

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.

Prevention of Diabetes With Mediterranean Diets: A Subgroup Analysis of a Randomized Trial

Context Can changes in diet prevent diabetes in older adults? Contribution This subgroup analysis of a multicenter trial involved older adults with high risk for heart disease who were randomly assigned to a Mediterranean diet supplemented with either extra-virgin olive oil or mixed nuts or to a low-fat control diet. Neither energy restriction nor increased physical activity was advised. After 4 years of follow-up, fewer persons in the Mediterranean diet groups developed diabetes than in the control group. Implication Changes in dietary patterns that do not necessarily lead to weight loss or include energy restrictions could help prevent diabetes in some older adults. The Editors Type 2 diabetes mellitus represents a major health problem because worldwide prevalence has more than doubled in the past 3 decades, with nearly 347 million persons with diabetes in 2010 (1), and is a potent risk factor for cardiovascular disease (CVD), blindness, renal failure, and lower limb amputation (2). Compelling evidence shows that diabetes can be prevented with lifestyle changes. Intensive lifestyle modification promoting weight loss through energy-restricted diets together with increased physical activity can decrease incident diabetes to as low as 50% (3). Indeed, lifestyle modification has performed better than pharmacologic approaches (such as metformin or rosiglitazone) in diabetes prevention (46). Of interest, the benefit of lifestyle changes in decreasing diabetes risk seems to extend beyond the termination of active intervention (68). However, there is little information on whether changes in the overall dietary pattern, without energy restriction, increased physical activity, and ensuing weight loss, may also be effective to prevent diabetes. Prospective epidemiologic studies strongly suggest that dietary patterns characterized by high consumption of fruit, vegetables, whole grains, and fish and reduced consumption of red and processed meat, sugar-sweetened beverages, and starchy foods delay diabetes onset (9). In the last 6 years, the traditional Mediterranean diet has emerged as a healthy dietary pattern that is also associated with a decreased risk for diabetes (1012). The Mediterranean diet is moderately rich in fat (35% to 40% of energy), especially from vegetable sources (rich in olive oil and nuts), and relatively low in dairy products. Moderate consumption of alcohol, mostly wine, and frequent use of sauces with tomato, onions, garlic, and spices for meal preparation are also typical. Preliminary data from the PREDIMED (Prevencin con Dieta Mediterrnea) study (1317) showed that traditional Mediterranean diets enriched with high-fat foods of vegetable origin decreased the incidence of diabetes (18). However, that report studied participants only from 1 of the 11 PREDIMED recruiting centers. In this analysis, we provide the final results on diabetes incidence in the whole multicenter trial after a median follow-up of 4.1 years. Methods Design Overview The PREDIMED study is a parallel-group, randomized, primary cardiovascular prevention trial done in Spain in persons at high risk but without CVD at baseline. The protocol, design, objectives, and methods have been reported in detail elsewhere (13, 14). Briefly, participants were randomly assigned in a 1:1:1 ratio to 1 of 3 nutrition interventions: Mediterranean diet supplemented with extra-virgin olive oil (EVOO), Mediterranean diet supplemented with mixed nuts, or a control diet consisting of advice to reduce intake of all types of fat. A complete list of PREDIMED study investigators is available in Supplement 1. The local institutional review boards approved the protocol at each study location, and all participants provided written informed consent. Supplement. Original Version (PDF) Supplement 1. List of Prevencin con Dieta Mediterrnea Study Investigators Setting and Participants Eligible participants were community-dwelling men (aged 55 to 80 years) and women (aged 60 to 80 years) without CVD at baseline who had either type 2 diabetes or at least 3 or more cardiovascular risk factors, namely current smoking, hypertension, hypercholesterolemia, low high-density lipoprotein cholesterol levels, overweight or obesity, and family history of premature CVD. Exclusion criteria have previously been reported (13). Randomization and Intervention From October 2003 to June 2009, 7447 suitable candidates were enrolled in the trial. The study nurse from each recruiting center randomly assigned each participant to the corresponding intervention group following computer-generated random numbers for allocation contained in sealed envelopes, which were centrally prepared for each center by the coordinating unit. Four strata of randomization were built by sex and age (cutoff, 70 years) but not by baseline diabetes status. The primary care physicians did not participate in the randomization process. The study nurses were independent of the nursing staff of the primary care health centers. Therefore, they were not involved in the usual clinical care of participants, and their exclusive role was to collect data for the trial. Given the nature of the interventions (nutritional advice and provision of foods), only investigators assessing outcomes were blinded with respect to intervention assignment. This was done by providing them with coded data sets and medical records blinded with respect to the personal identity of the participant and without any information on treatment allocation. Because our main objective was to determine the effect of the 3 interventions on diabetes incidence, this report includes data only on participants who did not have diabetes at baseline and for whom we could ascertain the incidence of diabetes during follow-up (n= 3541) (Figure 1). Figure 1. Study flow diagram. EVOO = extra-virgin olive oil; MedDiet = Mediterranean diet. A behavioral intervention promoting the Mediterranean diet was implemented in the corresponding groups of the trial, as described (13). Dietitians gave personalized advice to participants about the amount and use of EVOO for cooking and dressing; weekly intake of nuts; increased consumption of vegetables, fruits, legumes, and fish; recommended intake of white meat instead of red or processed meat; avoidance of butter, fast food, sweets, pastries, or sugar-sweetened beverages; and the dressing of dishes with sofrito sauce (using tomato, garlic, onion, and spices simmered in olive oil). Reduction of alcoholic beverages other than wine was advised to all participants. Wine with meals was recommended with moderation only to habitual drinkers. At baseline and quarterly thereafter, dietitians conducted individual and group dietary training sessions to provide information on typical Mediterranean foods, seasonal shopping lists, meal plans, and recipes for each group. In each session, a 14-item questionnaire was used to assess adherence to the Mediterranean diet (13, 14) so that personalized advice could be provided to upgrade participants adherence. The same questionnaire was assessed yearly in the control group. Participants assigned to the 2 Mediterranean diet groups received allotments of either EVOO (50 mL/d) or mixed nuts (30 g/d: 15 g of walnuts, 7.5 g of almonds, and 7.5 g of hazelnuts) at no cost. Participants assigned to the control diet received recommendations to reduce intake of all types of fat (from both animal and vegetable sources) and received nonfood gifts (kitchenware, tableware, aprons, or shopping bags). Through October 2006, participants in the control group received only a leaflet describing the low-fat diet. Thereafter, participants assigned to the control diet also received personalized advice and were invited to group sessions with the same frequency and intensity as those in the Mediterranean diet groups. A separate 9-item dietary questionnaire (14) was used to assess adherence to the low-fat diet. Neither energy restriction nor increased physical activity was advised for any intervention group. At baseline examination and yearly during follow-up, we administered a 137-item validated semiquantitative food-frequency questionnaire (19); the validated Spanish version of the Minnesota Leisure-time Physical Activity Questionnaire (20); and a 47-item questionnaire about education, lifestyle, medical history, and medication use. At baseline, trained personnel performed electrocardiography and anthropometric and blood pressure measurements. Blood pressure was measured in triplicate by using a validated semiautomatic oscillometer with a 5-minute interval between measurements and the participant in a sitting position (Omron HEM-705CP, Omron, Hoofddorp, the Netherlands). Fasting blood and spot urine were sampled at baseline and follow-up years 1, 3, 5, and 7. After an overnight fast, tubes for EDTA plasma, citrate plasma, and serum and urine samples were collected and aliquots were coded and stored at 80C in the central laboratory until analysis. Serum glucose, cholesterol, and triglyceride levels were measured using standard enzymatic methods. High-density lipoprotein cholesterol was measured after precipitation with phosphotungstic acid and magnesium chloride. Biomarkers of adherence to the supplemental foods, including urine hydroxytyrosol levels and plasma -linolenic acid proportions, which are reliable biomarkers of EVOO and walnut intake, respectively, were measured in random subsamples of participants during the first 5 years of follow-up (by gas chromatographymass spectrometry and by gas chromatography, respectively). Laboratory technicians were blinded to intervention group. Outcomes and Follow-up Diabetes was a prespecified secondary outcome of the PREDIMED trial. IT was considered to be present at baseline by clinical diagnosis or use of antidiabetic medication. New-onset diabetes during follow-up was diagnosed using the American Diabetes Association criteria, namely fasting plasma glucose levels of 7.0 mmol/L or g

Adherence to the Mediterranean diet and risk of metabolic syndrome and its components

BACKGROUND AND AIMS The role of diet in the aetiology of metabolic syndrome (MetS) is not well understood. The aim of the present study was to evaluate the relationship between adherence to the Mediterranean diet (MedDiet) and MetS. METHODS AND RESULTS A cross-sectional study was conducted with 808 high cardiovascular risk participants of the Reus PREDIMED Centre. MetS was defined by the updated National Cholesterol and Education Program Adult Treatment Panel III criteria. An inverse association between quartiles of adherence to the MedDiet (14-point score) and the prevalence of MetS (P for trend<0.001) was observed. After adjusting for age, sex, total energy intake, smoking status and physical activity, participants with the highest score of adherence to the MedDiet (>/=9 points) had the lowest odds ratio of having MetS (OR [95% CI] of 0.44 [0.27-0.70]) compared to those in the lowest quartile. Participants with the highest MedDiet adherence had 47 and 54% lower odds of having low HDL-c and hypertriglyceridemia MetS criteria, respectively, than those in the lowest quartile. Some components of the MedDiet, such as olive oil, legumes and red wine were associated with lower prevalence of MetS. CONCLUSION Higher adherence to a Mediterranean diet is associated with a significantly lower odds ratio of having MetS in a population with a high risk of cardiovascular disease.

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.

Mediterranean diets and metabolic syndrome status in the PREDIMED randomized trial

Background: Little evidence exists on the effect of an energy-unrestricted healthy diet on metabolic syndrome. We evaluated the long-term effect of Mediterranean diets ad libitum on the incidence or reversion of metabolic syndrome. Methods: We performed a secondary analysis of the PREDIMED trial — a multicentre, randomized trial done between October 2003 and December 2010 that involved men and women (age 55–80 yr) at high risk for cardiovascular disease. Participants were randomly assigned to 1 of 3 dietary interventions: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with nuts or advice on following a low-fat diet (the control group). The interventions did not include increased physical activity or weight loss as a goal. We analyzed available data from 5801 participants. We determined the effect of diet on incidence and reversion of metabolic syndrome using Cox regression analysis to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Over 4.8 years of follow-up, metabolic syndrome developed in 960 (50.0%) of the 1919 participants who did not have the condition at baseline. The risk of developing metabolic syndrome did not differ between participants assigned to the control diet and those assigned to either of the Mediterranean diets (control v. olive oil HR 1.10, 95% CI 0.94–1.30, p = 0.231; control v. nuts HR 1.08, 95% CI 0.92–1.27, p = 0.3). Reversion occurred in 958 (28.2%) of the 3392 participants who had metabolic syndrome at baseline. Compared with the control group, participants on either Mediterranean diet were more likely to undergo reversion (control v. olive oil HR 1.35, 95% CI 1.15–1.58, p < 0.001; control v. nuts HR 1.28, 95% CI 1.08–1.51, p < 0.001). Participants in the group receiving olive oil supplementation showed significant decreases in both central obesity and high fasting glucose (p = 0.02); participants in the group supplemented with nuts showed a significant decrease in central obesity. Interpretation: A Mediterranean diet supplemented with either extra virgin olive oil or nuts is not associated with the onset of metabolic syndrome, but such diets are more likely to cause reversion of the condition. An energy-unrestricted Mediterranean diet may be useful in reducing the risks of central obesity and hyperglycemia in people at high risk of cardiovascular disease. Trial registration: ClinicalTrials.gov, no. ISRCTN35739639.

Olive oil intake and risk of cardiovascular disease and mortality in the PREDIMED Study

BackgroundIt is unknown whether individuals at high cardiovascular risk sustain a benefit in cardiovascular disease from increased olive oil consumption. The aim was to assess the association between total olive oil intake, its varieties (extra virgin and common olive oil) and the risk of cardiovascular disease and mortality in a Mediterranean population at high cardiovascular risk.MethodsWe included 7,216 men and women at high cardiovascular risk, aged 55 to 80 years, from the PREvención con DIeta MEDiterránea (PREDIMED) study, a multicenter, randomized, controlled, clinical trial. Participants were randomized to one of three interventions: Mediterranean Diets supplemented with nuts or extra-virgin olive oil, or a control low-fat diet. The present analysis was conducted as an observational prospective cohort study. The median follow-up was 4.8 years. Cardiovascular disease (stroke, myocardial infarction and cardiovascular death) and mortality were ascertained by medical records and National Death Index. Olive oil consumption was evaluated with validated food frequency questionnaires. Multivariate Cox proportional hazards and generalized estimating equations were used to assess the association between baseline and yearly repeated measurements of olive oil intake, cardiovascular disease and mortality.ResultsDuring follow-up, 277 cardiovascular events and 323 deaths occurred. Participants in the highest energy-adjusted tertile of baseline total olive oil and extra-virgin olive oil consumption had 35% (HR: 0.65; 95% CI: 0.47 to 0.89) and 39% (HR: 0.61; 95% CI: 0.44 to 0.85) cardiovascular disease risk reduction, respectively, compared to the reference. Higher baseline total olive oil consumption was associated with 48% (HR: 0.52; 95% CI: 0.29 to 0.93) reduced risk of cardiovascular mortality. For each 10 g/d increase in extra-virgin olive oil consumption, cardiovascular disease and mortality risk decreased by 10% and 7%, respectively. No significant associations were found for cancer and all-cause mortality. The associations between cardiovascular events and extra virgin olive oil intake were significant in the Mediterranean diet intervention groups and not in the control group.ConclusionsOlive oil consumption, specifically the extra-virgin variety, is associated with reduced risks of cardiovascular disease and mortality in individuals at high cardiovascular risk.Trial registrationThis study was registered at controlled-trials.com (http://www.controlled-trials.com/ISRCTN35739639). International Standard Randomized Controlled Trial Number (ISRCTN): 35739639. Registration date: 5 October 2005.

Frequency of nut consumption and mortality risk in the PREDIMED nutrition intervention trial

BackgroundProspective studies in non-Mediterranean populations have consistently related increasing nut consumption to lower coronary heart disease mortality. A small protective effect on all-cause and cancer mortality has also been suggested. To examine the association between frequency of nut consumption and mortality in individuals at high cardiovascular risk from Spain, a Mediterranean country with a relatively high average nut intake per person.MethodsWe evaluated 7,216 men and women aged 55 to 80 years randomized to 1 of 3 interventions (Mediterranean diets supplemented with nuts or olive oil and control diet) in the PREDIMED (‘PREvención con DIeta MEDiterránea’) study. Nut consumption was assessed at baseline and mortality was ascertained by medical records and linkage to the National Death Index. Multivariable-adjusted Cox regression and multivariable analyses with generalized estimating equation models were used to assess the association between yearly repeated measurements of nut consumption and mortality.ResultsDuring a median follow-up of 4.8 years, 323 total deaths, 81 cardiovascular deaths and 130 cancer deaths occurred. Nut consumption was associated with a significantly reduced risk of all-cause mortality (P for trend <0.05, all). Compared to non-consumers, subjects consuming nuts >3 servings/week (32% of the cohort) had a 39% lower mortality risk (hazard ratio (HR) 0.61; 95% CI 0.45 to 0.83). A similar protective effect against cardiovascular and cancer mortality was observed. Participants allocated to the Mediterranean diet with nuts group who consumed nuts >3 servings/week at baseline had the lowest total mortality risk (HR 0.37; 95% CI 0.22 to 0.66).ConclusionsIncreased frequency of nut consumption was associated with a significantly reduced risk of mortality in a Mediterranean population at high cardiovascular risk.Please see related commentary: http://www.biomedcentral.com/1741-7015/11/165.Trial registrationClinicaltrials.gov. International Standard Randomized Controlled Trial Number (ISRCTN): 35739639. Registration date: 5 October 2005.

Nut intake and adiposity: meta-analysis of clinical trials

BACKGROUND Epidemiologic studies have shown an inverse association between the frequency of nut consumption and body mass index (BMI) and risk of obesity. However, clinical trials that evaluated nut consumption on adiposity have been scarce and inconclusive. OBJECTIVE We performed a systematic review and meta-analysis of published, randomized nut-feeding trials to estimate the effect of nut consumption on adiposity measures. DESIGN MEDLINE and the Cochrane Central Register of Controlled Trials databases were searched for relevant clinical trials of nut intake that provided outcomes of body weight, BMI (in kg/m(2)), or waist-circumference measures and were published before December 2012. There were no language restrictions. Two investigators independently selected and reviewed eligible studies. The weighted mean difference (WMD) between nut or control diets was estimated by using a random-effects meta-analysis with 95% CIs. RESULTS Thirty-three clinical trials met our inclusion criteria. Pooled results indicated a nonsignificant effect on body weight (WMD: -0.47 kg; 95% CI: -1.17, 0.22 kg; I(2) = 7%), BMI (WMD: -0.40 kg/m(2); 95% CI: -0.97, 0.17 kg/m(2); I(2) = 49%), or waist circumference (WMD: -1.25 cm; 95% CI: -2.82, 0.31 cm; I(2) = 28%) of diets including nuts compared with control diets. These findings were remarkably robust in the sensitivity analysis. No publication bias was shown. CONCLUSION Compared with control diets, diets enriched with nuts did not increase body weight, body mass index, or waist circumference in controlled clinical trials.