Our findings suggest that the Mediterranean diet results in similar weight loss and cardiovascular risk factor level reduction as comparator diets in overweight or obese individuals trying to lose weight.

Five RCTs (n = 998) met our inclusion criteria. Trials compared the Mediterranean diet to a low-fat diet (4 treatment arms), a low-carbohydrate diet (2 treatment arms), and the American Diabetes Association diet (1 treatment arm). The Mediterranean diet resulted in greater weight loss than the low-fat diet at ≥12 months (range of mean values: −4.1 to −10.1 kg vs 2.9 to −5.0 kg), but produced similar weight loss as other comparator diets (range of mean values: −4.1 to −10.1 kg vs −4.7 to −7.7 kg). Moreover, the Mediterranean diet was generally similar to comparator diets at improving other cardiovascular risk factor levels, including blood pressure and lipid levels.

We systematically searched MEDLINE, EMBASE, and the Cochrane Library of Clinical Trials for RCTs published in English or French and with follow-up ≥12 months that examined the effect of the Mediterranean diet on weight loss and cardiovascular risk factor levels in overweight or obese individuals trying to lose weight.

Although the long-term health benefits of the Mediterranean diet are well established, its efficacy for weight loss at ≥12 months in overweight or obese individuals is unclear. We therefore conducted a systematic review of randomized controlled trials (RCTs) to determine the effect of the Mediterranean diet on weight loss and cardiovascular risk factor levels after ≥12 months.

Given the popularity of the Mediterranean diet and the importance of weight management in light of the current obesity epidemic, this review provides essential information for public health improvement.

The long-term efficacy of the Mediterranean diet for weight loss in overweight or obese individuals was previously unclear.

In the 1950s, the landmark Seven Countries Study identified a population in the Mediterranean region that enjoyed reduced rates of cardiovascular disease and cardiovascular mortality.These individuals adhered to a regional diet that consisted of a high consumption of fruits and vegetables, monounsaturated fats (primarily from olive oil), and cereals; a moderate consumption of poultry, fish, and dairy products; and little to no consumption of red meat.Observational studies have associated this Mediterranean diet with good overall health.Although the long-term health benefits of following the Mediterranean diet are well established, its efficacy for weight loss at ≥12 months in overweight or obese individuals is unclear. We therefore conducted a systematic review of randomized controlled trials (RCTs) to examine the long-term effects of the Mediterranean diet on weight loss and cardiovascular risk factor levels among overweight and obese individuals trying to lose weight.

How the Seven Countries Study contributed to the definition and development of the Mediterranean diet concept: a 50-year journey.

The quality of included trials was assessed using the Cochrane Collaboration's tool for assessing risk of bias in RCTs.Quality assessment was conducted by 2 independent reviewers, with disagreements resolved by consensus. Given the amount of heterogeneity that was present in the designs, populations, and comparators among the included RCTs, we were unable to statistically pool data across trials.

Our primary endpoint was sustained weight loss, reported as mean weight change in kilograms or as a mean percentage change, at ≥12 months or longest follow-up. Secondary endpoints included mean change in body mass index (BMI), body fat, waist circumference, waist-hip ratio, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, systolic blood pressure, diastolic blood pressure, fasting glucose, fasting insulin, homeostatic model assessment, and glycated hemoglobin (HbA1c) levels.

Data were extracted by 2 independent reviewers, with disagreements resolved by consensus. Extracted data included data on study characteristics, study population, demographic and clinical characteristics, intervention characteristics, and use of any co-interventions such as exercise or counseling. All outcome data were extracted at 12 months, as well as at 6 months and in 6-month increments beyond 12 months, if available, until maximum follow-up.

We excluded trials conducted in participants with malignancies or posttransplantation, as well as weight maintenance trials. We also excluded trials with a crossover design, unless the initial phase of the trial preceding the crossover was randomized, controlled, and lasted ≥12 months; the initial phase of such trials was included. Finally, nonrandomized trials, uncontrolled trials, and those that did not provide counseling or exercise interventions equally to ≥2 arms of the trial were designated as having an inappropriate control group and were thus excluded.

We included RCTs that examined the efficacy of the Mediterranean diet for weight loss and cardiovascular risk factor level reduction with follow-up ≥12 months. Inclusion was restricted to RCTs comparing a diet that was described explicitly as “Mediterranean,” “Mediterranean-Style,” or “Mediterranean-inspired” to any active comparator diet, including but not limited to low-fat diets, low-carbohydrate diets, calorie-restricted diets, and diets that are part of the usual care for certain medical conditions. Trials with an exercise prescription or nutritional counseling in intervention or comparator arms were eligible for inclusion provided that ≥2 arms of the trial received the same exercise prescription or nutritional counseling. This was done to isolate the effect of the Mediterranean diet.

We systematically searched MEDLINE (via Ovid), EMBASE (via Ovid), and the Cochrane Library of Clinical Trials from inception to January 2015 to identify RCTs that examined the effect of the Mediterranean diet on ≥12-month weight loss and cardiovascular risk reduction in overweight or obese individuals aged ≥18 years who were trying to lose weight. Our search terms consisted of medical subject headings, Emtree terms, and keywords for the Mediterranean diet ( Appendix 1 Appendix 3 , available online). The search was restricted to RCTs published in English or in French. Moreover, we limited our MEDLINE and EMBASE searches to RCTs using a modified version of the McMaster RCT hedge.We hand-searched the references of relevant RCTs, reviews, and meta-analyses retrieved by our database searches to identify additional RCTs.

Enhancing retrieval of best evidence for health care from bibliographic databases: calibration of the hand search of the literature.

Our systematic review was conducted according to a prespecified protocol and is described according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.

Only 3 RCTs reported changes in blood pressure, with available data suggesting that the Mediterranean diet has similar effects on systolic and diastolic blood pressure levels as comparator diets ( Table 5 ).Only one trial demonstrated a significantly greater reduction in systolic and diastolic blood pressure at 12 months with the Mediterranean diet compared with a low-fat diet.In the second trial,which consisted of participants with normal blood pressure at baseline, no difference between the Mediterranean diet and a low-fat diet was detected, with blood pressure increasing modestly in both groups during follow-up. In the third trial,no difference was observed between groups, though blood pressure decreased slightly in the 3 groups during follow-up.

Values are reported as: mean ± standard deviation, unless otherwise specified.

Effects of a Mediterranean-style diet on the need for antihyperglycemic drug therapy in patients with newly diagnosed type 2 diabetes: a randomized trial.

n is the number of participants analyzed for each arm of the trial at a specific point of follow-up (shown in Table 1 ).

Studies are listed in descending order of number of participants included in the analyses of each trial. Studies that did not report blood pressure changes throughout follow-up were not included in this Table.

∗ Studies are listed in descending order of number of participants included in the analyses of each trial. Studies that did not report blood pressure changes throughout follow-up were not included in this Table.

Effects of a Mediterranean-style diet on the need for antihyperglycemic drug therapy in patients with newly diagnosed type 2 diabetes: a randomized trial.

Effects of a Mediterranean-style diet on the need for antihyperglycemic drug therapy in patients with newly diagnosed type 2 diabetes: a randomized trial.

Changes in lipid levels were generally similar with the Mediterranean diet as with comparator diets ( Table 4 ). More specifically, the Mediterranean diet was similar to other diets with respect to changes in low-density and high-density lipoprotein cholesterol levels. However, the Mediterranean diet resulted in greater reductions in triglyceride levels than comparator diets at ≥12 months (range of mean changes: −0.25 to −1.50 mmol/L vs −0.03 to −0.70 mmol/L).

Values are reported as: mean ± standard deviation, unless otherwise specified.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Effects of a Mediterranean-style diet on the need for antihyperglycemic drug therapy in patients with newly diagnosed type 2 diabetes: a randomized trial.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

n is the number of participants analyzed for each arm of the trial at a specific point of follow-up (shown in Table 1 ).

Studies are listed in descending order of number of participants included in the analyses of each trial. The randomized controlled trial by McManus et al

The Mediterranean diet produced similar effects on measures of glycemic control as other diets but resulted in greater improvements in patients with type 2 diabetes ( Table 3 and Appendix 6 , available online). In particular, participants with type 2 diabetes demonstrated significant improvement from baseline in levels of fasting glucose, serum insulin, and the homeostatic model assessment with the Mediterranean diet.The Mediterranean diet resulted in greater reductions in fasting glucose levels in patients with type 2 diabetes than comparator diets at ≥12 months (range of mean changes: −0.89 to −4.30 mmol/L vs 0.67 to −3.10 mmol/L) and greater improvements in HbA1c levels.

Values are reported as: mean ± standard deviation, unless otherwise specified.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‖ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‖ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‖ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‖ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‖ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‖ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‖ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‖ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‖ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‖ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‖ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Effects of a Mediterranean-style diet on the need for antihyperglycemic drug therapy in patients with newly diagnosed type 2 diabetes: a randomized trial.

n is the number of participants analyzed for each arm of the trial at a specific point of follow-up (shown in Table 1 ).

Studies are listed in descending order of number of participants included in the analyses of each trial. The randomized controlled trial by McManus et al

Effects of a Mediterranean-style diet on the need for antihyperglycemic drug therapy in patients with newly diagnosed type 2 diabetes: a randomized trial.

The effect of the Mediterranean diet on BMI was similar to that for weight reduction ( Table 2 ). At ≥12 months, the Mediterranean diet was more efficacious than a low-fat diet at reducing BMI (range of mean changes: −1.0 to −3.3 kg/mvs 1.4 to −1.8 kg/m), but similar to all other comparator diets (range of mean changes: −1.5 to −2.8 kg/m). Similar trends were observed when examining waist circumference ( Table 2 ).

In general, the Mediterranean diet was modestly efficacious at reducing body weight (range of mean changes: −3.8 to −10.1 kg) at ≥12 months ( Table 2 ). In 3 RCTs, the Mediterranean diet was significantly more efficacious for weight loss than a low-fat diet at ≥12 months.However, the Mediterranean diet produced similar weight loss as other comparator diets at ≥12 months (range of mean changes: −4.7 to −7.7 kg).

Values are reported as: mean ± standard deviation, unless otherwise specified.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Effects of a Mediterranean-style diet on the need for antihyperglycemic drug therapy in patients with newly diagnosed type 2 diabetes: a randomized trial.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

‡ Mean change was calculated as difference of means from baseline to follow-up from data of the publication.

n is the number of participants analyzed for each arm of the trial at a specific point of follow-up (shown in Table 1 ).

Studies are listed in descending order of number of participants included in the analyses of each trial.

∗ Studies are listed in descending order of number of participants included in the analyses of each trial.

Effects of a Mediterranean-style diet on the need for antihyperglycemic drug therapy in patients with newly diagnosed type 2 diabetes: a randomized trial.

The average age of participants ranged from 44 to 67 years ( Table 1 ). On average, participants were borderline obese or obese, with mean BMIs ranging from 29.7 to 33.5 kg/mand mean body weights ranging from 85.9 to 91.4 kg. Moreover, only 1 RCT assessed the effects of the Mediterranean diet in overweight but otherwise healthy individuals, of whom 90.1% were women.The remaining 4 RCTs included participants with elevated cardiovascular disease risk, including participants with type 2 diabetes (3 trials), coronary heart disease (1 trial), or a recent myocardial infarction (1 trial). The 2 RCTs conducted in patients with cardiovascular disease consisted mainly of male participants (74%-86%).The distribution of male and female participants was balanced in 2 RCTs.

Effects of a Mediterranean-style diet on the need for antihyperglycemic drug therapy in patients with newly diagnosed type 2 diabetes: a randomized trial.

The 5 RCTs possessed varying degrees of bias, according to the Cochrane Collaboration's risk of bias assessment tool for RCTs. Most trials had a low or unclear risk of bias for sequence generation (5 trials), allocation concealment (4 trials), and blinding (4 trials). However, 1 RCTwas deemed to have a high risk of selective outcome reporting. Moreover, 2 RCTswere found to be high risk in 3 and 4 domains, respectively. In particular, these RCTs were at high risk of bias for incomplete outcome data and selective outcome reporting due to a high rate of loss to follow-up and incomplete outcome reporting, respectively ( Appendix 5 , available online).

The 5 included RCTs (n = 998) randomized participants to a Mediterranean diet (6 treatment arms; n = 492) or a low-fat diet (4 treatment arms; n = 312), a low-carbohydrate diet (1 treatment arm; n = 109), or the American Diabetes Association diet (1 treatment arm; n = 85) ( Table 1 ). Follow-up ranged from 12 to 48 months, with 2 studies also reporting 6-month outcomes.

The timeframe by which a diagnosis of type 2 diabetes mellitus was considered “new” was not specified.

¶ The timeframe by which a diagnosis of type 2 diabetes mellitus was considered “new” was not specified.

Risk factors and nutrient intake was compared by using a test based on the values at the end of follow-up and a t-test based on differences from baseline. Due to a low rate of loss to follow-up, a complete case analysis was used for secondary outcomes.

§ Risk factors and nutrient intake was compared by using a test based on the values at the end of follow-up and a t-test based on differences from baseline. Due to a low rate of loss to follow-up, a complete case analysis was used for secondary outcomes.

Effects of a Mediterranean-style diet on the need for antihyperglycemic drug therapy in patients with newly diagnosed type 2 diabetes: a randomized trial.

All 322 participants were included in the primary analyses, and the most recent values for weight and blood pressure were used.

‡ All 322 participants were included in the primary analyses, and the most recent values for weight and blood pressure were used.

This represents the number of participants included in the analysis of outcomes at maximum follow-up.

† This represents the number of participants included in the analysis of outcomes at maximum follow-up.

Studies are listed in descending order of number of participants included in analyses of each trial.

∗ Studies are listed in descending order of number of participants included in analyses of each trial.

Our search yielded 2432 potentially relevant publications ( Appendix 4 , available online). Following the removal of duplicates, 1069 publications underwent title and abstract screening. Of these, 78 were retrieved for full-text screening, and 5 were included in the systematic review.

Discussion

Our systematic review was designed to examine the long-term (≥12 months) effect of the Mediterranean diet on weight loss and cardiovascular risk factor levels among overweight and obese individuals trying to lose weight. We found that the Mediterranean diet is more efficacious for ≥12-month weight loss compared with low-fat diets, but not compared with other comparator diets. The Mediterranean diet also resulted in greater improvements in triglyceride levels but produced similar changes in other lipid levels and blood pressure. Furthermore, we found that it improved measures of glycemic control among patients with type 2 diabetes, but not in normoglycemic individuals. Taken together, our findings suggest that the Mediterranean diet is efficacious for weight loss and cardiovascular risk level reduction in overweight or obese individuals, but not more so than other diets.

12 Atallah R.

Filion K.B.

Wakil S.M.

et al. Long-term effects of 4 popular diets on weight loss and cardiovascular risk factors: a systematic review of randomized controlled trials. 13 Atkins R.C. Dr. Atkins' New Diet Revolution. , 14 Sears B. A Week in the Zone. , 15 Agatston A. The South Beach Diet. 2 Willett W.C.

Sacks F.

Trichopoulou A.

et al. Mediterranean diet pyramid: a cultural model for healthy eating. The findings from this systematic review add to the literature suggesting that there is no ideal diet for achieving sustained weight loss in overweight or obese individuals. This is consistent with the findings of our previous systematic reviewof popular commercial diets, in which we found that Atkins, Weight Watchers, and Zone all produced similar weight loss at ≥12 months. Importantly, the weight loss at ≥12 months with the Mediterranean diet in the present systematic review is consistent with that observed with these commercial diets in the previous one. The similar weight loss achieved with these diets reduces the concern raised by the creators of some of these commercial dietsabout the elevated consumption of carbohydrates associated with the Mediterranean diet.The similar weight loss achieved across diets suggests that there is no optimal macronutrient composition for achieving sustained weight loss.

16 Kushner R.F. Weight loss strategies for treatment of obesity. 16 Kushner R.F. Weight loss strategies for treatment of obesity. 17 Swift D.L.

Johannsen N.M.

Lavie C.J.

Earnest C.P.

Church T.S. The role of exercise and physical activity in weight loss and maintenance. , 18 Wu T.

Gao X.

Chen M.

van Dam R.M. Long-term effectiveness of diet-plus-exercise interventions vs. diet-only interventions for weight loss: a meta-analysis. , 19 Curioni C.C.

Lourenco P.M. Long-term weight loss after diet and exercise: a systematic review. 17 Swift D.L.

Johannsen N.M.

Lavie C.J.

Earnest C.P.

Church T.S. The role of exercise and physical activity in weight loss and maintenance. 16 Kushner R.F. Weight loss strategies for treatment of obesity. 16 Kushner R.F. Weight loss strategies for treatment of obesity. Rather, it has been suggested that a “3-stepped intensification of care approach” is more likely to yield clinically significant weight loss.The first step is evidence-based lifestyle modification through diet, behavioral therapy, and physical activity.Combining diet with physical activity has been found to increase weight loss compared with each of these interventions used alone,with physical activity unlikely to yield clinically significant weight loss unless it comprises a high level of aerobic exercise or is used in conjunction with a calorie-restricted diet.The second step is the concurrent use of weight loss pharmacotherapies.The third step is bariatric surgery for individuals for whom interventions from the prior steps have failed and who suffer from severe obesity or moderate obesity with comorbidities.

th century. The dietary pattern consisting of the elevated consumption of fruits and vegetables, legumes, cereals, and olive oil was followed, for the most part, in poor, rural regions of the Mediterranean. 3 Bach-Faig A.

Berry E.M.

Lairon D.

et al. Mediterranean Diet Foundation Expert Group

Mediterranean diet pyramid today. Science and cultural updates. 20 Widmer R.J.

Flammer A.J.

Lerman L.O.

Lerman A. The Mediterranean diet, its components, and cardiovascular disease. 21 Kesse-Guyot E.

Ahluwalia N.

Lassale C.

Hercberg S.

Fezeu L.

Lairon D. Adherence to Mediterranean diet reduces the risk of metabolic syndrome: A 6-year prospective study. 22 Crous-Bou M.

Fung T.T.

Prescott J.

et al. Mediterranean diet and telomere length in Nurses' Health Study: population based cohort study. 23 Prinelli F.

Yannakoulia M.

Anastasiou C.A.

et al. Mediterranean diet and other lifestyle factors in relation to 20-year all-cause mortality: a cohort study in an Italian population. The Mediterranean diet has been the focus of many epidemiological studies, but the diet itself originated inauspiciously during the early to mid-20century. The dietary pattern consisting of the elevated consumption of fruits and vegetables, legumes, cereals, and olive oil was followed, for the most part, in poor, rural regions of the Mediterranean.Individuals in these communities enjoyed numerous health benefits, including reduced rates of cardiovascular disease, which were first described by the Seven Countries Study.More recently, cohort studies have underscored the Mediterranean diet's impact on overall health, suggesting that adherence to the Mediterranean diet is associated with up to 50% reduced risk of developing the metabolic syndrome,an increase in levels of biomarkers associated with healthy aging,and a reduced risk of mortality over 20 years.

24 Estruch R.

Ros E.

Martinez-Gonzalez M.A. Mediterranean diet for primary prevention of cardiovascular disease. , 25 Martinez-Gonzalez M.A.

Salas-Salvado J.

Estruch R.

et al. Benefits of the Mediterranean Diet: Insights From the PREDIMED Study. 25 Martinez-Gonzalez M.A.

Salas-Salvado J.

Estruch R.

et al. Benefits of the Mediterranean Diet: Insights From the PREDIMED Study. 25 Martinez-Gonzalez M.A.

Salas-Salvado J.

Estruch R.

et al. Benefits of the Mediterranean Diet: Insights From the PREDIMED Study. The Prevencíon con Dieta Mediterránea (PREDIMED) RCT further highlighted the potential of the Mediterranean diet as an intervention for the primary prevention of cardiovascular disease. A total of 7447 individuals at high risk of developing cardiovascular disease were randomized to the Mediterranean diet supplemented with olive oil, the Mediterranean diet supplemented with nuts, or a low-fat diet, and followed for a median of 4.8 years. Compared with the low-fat diet, the Mediterranean diet was associated with an approximate 30% reduction in the primary, composite endpoint of myocardial infarction, stroke, or cardiovascular death, with similar benefits observed in both Mediterranean diet arms.Other cardiovascular health benefits observed with the Mediterranean diet included: decreases in incident type 2 diabetes, peripheral artery disease, and atrial fibrillation rates; metabolic syndrome reversion; decreases in blood pressure, hypertension risk, and carotid atherosclerosis.Many interactions were observed between Mediterranean diet and genetic determinants of intermediate and cardiovascular disease phenotypes. Often, the extent of these cardiovascular health benefits was correlated with the extent of adherence.

21 Kesse-Guyot E.

Ahluwalia N.

Lassale C.

Hercberg S.

Fezeu L.

Lairon D. Adherence to Mediterranean diet reduces the risk of metabolic syndrome: A 6-year prospective study. , 26 Chrysohoou C.

Panagiotakos D.B.

Pitsavos C.

Das U.N.

Stefanadis C. Adherence to the Mediterranean diet attenuates inflammation and coagulation process in healthy adults: the ATTICA study. 23 Prinelli F.

Yannakoulia M.

Anastasiou C.A.

et al. Mediterranean diet and other lifestyle factors in relation to 20-year all-cause mortality: a cohort study in an Italian population. , 26 Chrysohoou C.

Panagiotakos D.B.

Pitsavos C.

Das U.N.

Stefanadis C. Adherence to the Mediterranean diet attenuates inflammation and coagulation process in healthy adults: the ATTICA study. , 27 Sofi F.

Cesari F.

Abbate R.

Gensini G.F.

Casini A. Adherence to Mediterranean diet and health status: meta-analysis. 28 Hubert H.B.

Feinleib M.

McNamara P.M.

Castelli W.P. Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. There are several possible explanations for the differences in results between the aforementioned studies and our systematic review. In order to obtain the most rigorous form of evidence possible, we restricted inclusion to RCTs that compared the Mediterranean diet to active comparator diets. Much of the evidence for the Mediterranean diet's health benefits comes from observational studies,which often lack an appropriate comparator, and without the benefits of randomization, are prone to confounding and selection biases. In addition, several of these epidemiologic studiesfocused on the overall health benefits of the Mediterranean diet without focusing on its use among overweight and obese individuals trying to lose weight. Finally, we excluded short-term trials, which are more likely to show a favorable benefit with the Mediterranean diet, focusing on RCTs with longer-term follow-up data, as long-term weight loss represents a more important predictor of cardiovascular disease events.

29 Huo R.

Du T.

Xu Y.

et al. Effects of Mediterranean-style diet on glycemic control, weight loss and cardiovascular risk factors among type 2 diabetes individuals: a meta-analysis. , 30 Esposito K.

Kastorini C.M.

Panagiotakos D.B.

Giugliano D. Mediterranean diet and weight loss: meta-analysis of randomized controlled trials. 29 Huo R.

Du T.

Xu Y.

et al. Effects of Mediterranean-style diet on glycemic control, weight loss and cardiovascular risk factors among type 2 diabetes individuals: a meta-analysis. , 30 Esposito K.

Kastorini C.M.

Panagiotakos D.B.

Giugliano D. Mediterranean diet and weight loss: meta-analysis of randomized controlled trials. , 31 Schwingshackl L.

Hoffmann G. Adherence to Mediterranean diet and risk of cancer: a systematic review and meta-analysis of observational studies. , 32 Rees K.

Hartley L.

Flowers N.

et al. ‘Mediterranean’ dietary pattern for the primary prevention of cardiovascular disease. 33 Dansinger M.L.

Tatsioni A.

Wong J.B.

Chung M.

Balk E.M. Meta-analysis: the effect of dietary counseling for weight loss. 29 Huo R.

Du T.

Xu Y.

et al. Effects of Mediterranean-style diet on glycemic control, weight loss and cardiovascular risk factors among type 2 diabetes individuals: a meta-analysis. , 30 Esposito K.

Kastorini C.M.

Panagiotakos D.B.

Giugliano D. Mediterranean diet and weight loss: meta-analysis of randomized controlled trials. , 31 Schwingshackl L.

Hoffmann G. Adherence to Mediterranean diet and risk of cancer: a systematic review and meta-analysis of observational studies. , 32 Rees K.

Hartley L.

Flowers N.

et al. ‘Mediterranean’ dietary pattern for the primary prevention of cardiovascular disease. Although previous knowledge syntheses have examined the Mediterranean diet for weight loss, many had several important methodological limitations. These include recent meta-analyses,which pooled data across trials despite the presence of important heterogeneity in study design, durations of follow-up, and comparators. Moreover, previous reviews and meta-analysesincluded RCTs that involved preferential nutritional counseling in Mediterranean diet treatment arms, which has been previously shown to increase 12-month weight loss.The inclusion of such trials may partially explain the positive findings of these previous reviews and meta-analyses.With inclusion restricted to trials with appropriate comparators and synthesis focused on the qualitative assessment of the available data in light of the substantial heterogeneity of included trials, the present systematic review has thus overcome the limitations of many previous studies in this area.