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Systematic Review of the Mediterranean Diet for Long-Term Weight Loss

  • Joseph G. Mancini
    Affiliations
    Division of Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital/McGill University, Montreal, Quebec, Canada
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  • Kristian B. Filion
    Affiliations
    Division of Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital/McGill University, Montreal, Quebec, Canada

    Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
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  • Renée Atallah
    Affiliations
    Division of Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital/McGill University, Montreal, Quebec, Canada
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  • Mark J. Eisenberg
    Correspondence
    Requests for reprints should be addressed to Mark J. Eisenberg, MD, MPH, Divisions of Cardiology and Clinical Epidemiology, Jewish General Hospital/McGill University, 3755 Côte Ste-Catherine Road, Suite H-421.1, Montreal, QC H3T 1E2, Canada.
    Affiliations
    Division of Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital/McGill University, Montreal, Quebec, Canada

    Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada

    Division of Cardiology, Jewish General Hospital, Montreal, Quebec, Canada
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Published:December 22, 2015DOI:https://doi.org/10.1016/j.amjmed.2015.11.028

      Abstract

      Background

      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.

      Methods

      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.

      Results

      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.

      Conclusion

      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.

      Keywords

      Clinical Significance
      • The long-term efficacy of the Mediterranean diet for weight loss in overweight or obese individuals was previously unclear.
      • The Mediterranean diet is superior to low-fat diets for long-term weight loss.
      • 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.
      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.
      • Menotti A.
      • Puddu P.E.
      How the Seven Countries Study contributed to the definition and development of the Mediterranean diet concept: a 50-year journey.
      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.
      • Willett W.C.
      • Sacks F.
      • Trichopoulou A.
      • et al.
      Mediterranean diet pyramid: a cultural model for healthy eating.
      • Bach-Faig A.
      • Berry E.M.
      • Lairon D.
      • et al.
      Mediterranean Diet Foundation Expert Group
      Mediterranean diet pyramid today. Science and cultural updates.
      Observational studies have associated this Mediterranean diet with good overall health.
      • Bach-Faig A.
      • Berry E.M.
      • Lairon D.
      • et al.
      Mediterranean Diet Foundation Expert Group
      Mediterranean diet pyramid today. Science and cultural updates.
      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.

      Methods

      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.
      • Moher D.
      • Liberati A.
      • Tetzlaff J.
      • Altman D.G.
      PRISMA Group
      Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.

      Search Strategy

      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 2, 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.
      • Wilczynski N.L.
      • McKibbon K.A.
      • Haynes R.B.
      Enhancing retrieval of best evidence for health care from bibliographic databases: calibration of the hand search of the literature.
      We hand-searched the references of relevant RCTs, reviews, and meta-analyses retrieved by our database searches to identify additional RCTs.

      Study Selection

      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 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.

      Data Extraction and Synthesis

      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.
      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.
      The quality of included trials was assessed using the Cochrane Collaboration's tool for assessing risk of bias in RCTs.
      • Higgins J.P.
      • Altman D.G.
      • Gøtzsche P.C.
      • et al.
      Cochrane Bias Methods GroupCochrane Statistical Methods Group
      The Cochrane Collaboration's tool for assessing risk of bias in randomised trials.
      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.

      Results

      Search Results

      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.

      Study Characteristics

      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.
      • Tuttle K.R.
      • Shuler L.A.
      • Packard D.P.
      • et al.
      Comparison of low-fat versus Mediterranean-style dietary intervention after first myocardial infarction.
      • Shai I.
      • Schwarzfuchs D.
      • Henkin Y.
      • et al.
      Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet.
      Table 1Baseline Characteristics of Participants for Included Trials
      Studies are listed in descending order of number of participants included in analyses of each trial.
      Study (First Author)ParticipantsFollow-Up (mo)PopulationArmsNutritional CounselingExercise PrescriptionAge (y)Female (%)Weight (kg)BMI (kg/m2)
      RandomizedAnalyzed
      This represents the number of participants included in the analysis of outcomes at maximum follow-up.
      Shai 2008
      • Shai I.
      • Schwarzfuchs D.
      • Henkin Y.
      • et al.
      Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet.
      322322
      All 322 participants were included in the primary analyses, and the most recent values for weight and blood pressure were used.
      24BMI ≥27, type 2 diabetes mellitus or coronary heart diseaseMediterranean diet (Calorie-restricted)Low-fat diet (Calorie-restricted)Low-carbohydrate dietYesNo521491.430.9
      Esposito 2009
      • Esposito K.
      • Maiorino M.I.
      • Ciotola M.
      • 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.
      215215
      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.
      48Overweight, newly diagnosed type 2 diabetes mellitus
      The timeframe by which a diagnosis of type 2 diabetes mellitus was considered “new” was not specified.
      Mediterranean dietLow-fat dietYesYes5250.785.929.7
      Elhayany 2010
      • Elhayany A.
      • Lustman A.
      • Abel R.
      • Attal-Singer J.
      • Vinker S.
      A low carbohydrate Mediterranean diet improves cardiovascular risk factors and diabetes control among overweight patients with type 2 diabetes mellitus: a 1-year prospective randomized intervention study.
      259179
      Only participants who attended follow-up were analyzed.
      12Aged 30-65 y, type 2 diabetes mellitus, BMI 27-34Traditional Mediterranean dietLow-carbohydrate Mediterranean dietAmerican Diabetes Association dietYesYes554886.731.4
      Tuttle 2008
      • Tuttle K.R.
      • Shuler L.A.
      • Packard D.P.
      • et al.
      Comparison of low-fat versus Mediterranean-style dietary intervention after first myocardial infarction.
      10177
      Only participants who attended follow-up were analyzed.
      24<6 wk after first myocardial infarctionMediterranean-style dietLow-fat dietYesNo5826NR30
      McManus 2001
      • McManus K.
      • Antinoro L.
      • Sacks F.
      A randomized controlled trial of a moderate-fat, low-energy diet compared with a low fat, low-energy diet for weight loss in overweight adults.
      10161
      Only participants who attended follow-up were analyzed.
      18Overweight, nonsmokingMediterranean-style moderate fat dietLow-fat dietYesNo4490.19133.5
      BMI = body mass index; NR = not reported.
      Studies are listed in descending order of number of participants included in analyses of each trial.
      This represents the number of participants included in the analysis of outcomes at maximum follow-up.
      All 322 participants were included in the primary analyses, and the most recent values for weight and blood pressure were used.
      § 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.
      Only participants who attended follow-up were analyzed.
      The timeframe by which a diagnosis of type 2 diabetes mellitus was considered “new” was not specified.
      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 RCT
      • Tuttle K.R.
      • Shuler L.A.
      • Packard D.P.
      • et al.
      Comparison of low-fat versus Mediterranean-style dietary intervention after first myocardial infarction.
      was deemed to have a high risk of selective outcome reporting. Moreover, 2 RCTs
      • Elhayany A.
      • Lustman A.
      • Abel R.
      • Attal-Singer J.
      • Vinker S.
      A low carbohydrate Mediterranean diet improves cardiovascular risk factors and diabetes control among overweight patients with type 2 diabetes mellitus: a 1-year prospective randomized intervention study.
      • McManus K.
      • Antinoro L.
      • Sacks F.
      A randomized controlled trial of a moderate-fat, low-energy diet compared with a low fat, low-energy diet for weight loss in overweight adults.
      were 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).

      Participant Characteristics

      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/m2 and 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.
      • McManus K.
      • Antinoro L.
      • Sacks F.
      A randomized controlled trial of a moderate-fat, low-energy diet compared with a low fat, low-energy diet for weight loss in overweight adults.
      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%).
      • Tuttle K.R.
      • Shuler L.A.
      • Packard D.P.
      • et al.
      Comparison of low-fat versus Mediterranean-style dietary intervention after first myocardial infarction.
      • Shai I.
      • Schwarzfuchs D.
      • Henkin Y.
      • et al.
      Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet.
      The distribution of male and female participants was balanced in 2 RCTs.
      • Elhayany A.
      • Lustman A.
      • Abel R.
      • Attal-Singer J.
      • Vinker S.
      A low carbohydrate Mediterranean diet improves cardiovascular risk factors and diabetes control among overweight patients with type 2 diabetes mellitus: a 1-year prospective randomized intervention study.
      • Esposito K.
      • Maiorino M.I.
      • Ciotola M.
      • 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.

      Weight Loss and Change in Other Anthropometric Measures

      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.
      • Shai I.
      • Schwarzfuchs D.
      • Henkin Y.
      • et al.
      Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet.
      • McManus K.
      • Antinoro L.
      • Sacks F.
      A randomized controlled trial of a moderate-fat, low-energy diet compared with a low fat, low-energy diet for weight loss in overweight adults.
      • Esposito K.
      • Maiorino M.I.
      • Ciotola M.
      • 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.
      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).
      • Shai I.
      • Schwarzfuchs D.
      • Henkin Y.
      • et al.
      Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet.
      • Elhayany A.
      • Lustman A.
      • Abel R.
      • Attal-Singer J.
      • Vinker S.
      A low carbohydrate Mediterranean diet improves cardiovascular risk factors and diabetes control among overweight patients with type 2 diabetes mellitus: a 1-year prospective randomized intervention study.
      Table 2Change in Body Weight and Other Anthropometric Measures at 12 Months and Maximum Follow-up
      Studies are listed in descending order of number of participants included in the analyses of each trial.
      Study
      n is the number of participants analyzed for each arm of the trial at a specific point of follow-up (shown in Table 1).
      (First Author)
      Follow-Up (Mo)WeightBody Mass IndexWaist Circumference
      Baseline (kg)Mean Change (kg)Baseline (kg/m2)Mean Change (kg/m2)Baseline (cm)Mean Change (cm)
      Shai 2008
      • Shai I.
      • Schwarzfuchs D.
      • Henkin Y.
      • et al.
      Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet.
       Mediterranean diet (n = 109)1291.1 ± 13.6−4.7
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      Reported in the publication without discernable standard deviation.
      31.2 ± 4.1NR106.2 ± 9.1NR
       Low-fat diet (n = 104)91.3 ± 12.3−3.6
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      Reported in the publication without discernable standard deviation.
      30.6 ± 3.2105.3 ± 9.2
       Low-carbohydrate diet (n = 109)91.8 ± 14.3−5.3
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      Reported in the publication without discernable standard deviation.
      30.8 ± 3.5106.3 ± 9.1
       Mediterranean diet (n = 109)2491.1 ± 13.6−4.4 ± 6.0
      P <.05 vs low-fat diet.
      31.2 ± 4.1−1.5 ± 2.2106.2 ± 9.1−3.5 ± 5.1
       Low-fat diet (n = 104)91.3 ± 12.3−2.9 ± 4.230.6 ± 3.2−1.0 ± 1.4105.3 ± 9.2−2.8 ± 4.3
       Low-carbohydrate diet (n = 109)91.8 ± 14.3−4.7 ± 6.5
      P <.05 vs low-fat diet.
      30.8 ± 3.5−1.5 ± 2.1106.3 ± 9.1−3.8 ± 5.2
      Esposito 2009
      • Esposito K.
      • Maiorino M.I.
      • Ciotola M.
      • 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.
       Mediterranean diet (n = 108)1286.0 ± 10.4−6.2 ± 3.2
      P <.05 vs low-fat diet.
      29.7 ± 3.4−2.4 ± 1.6
      P <.05 vs low-fat diet.
      98 ± 10.1−4.8 ± 3.0
      P <.05 vs low-fat diet.
       Low-fat diet (n = 107)85.7 ± 9.9−4.2 ± 3.529.5 ± 3.6−1.4 ± 0.998 ± 10−3.5 ± 2.8
       Mediterranean diet (n = 108)2486.0 ± 10.4−4.9 ± 2.5
      P <.05 vs low-fat diet.
      29.7 ± 3.4−1.9 ± 0.9
      P <.05 vs low-fat diet.
      98 ± 10.1−4.4 ± 2.8
      P <.05 vs low-fat diet.
       Low-fat diet (n = 107)85.7 ± 9.9−3.7 ± 2.129.5 ± 3.6−1.1 ± 0.698 ± 10−3.3 ± 2.5
      Elhayany 2010
      • Elhayany A.
      • Lustman A.
      • Abel R.
      • Attal-Singer J.
      • Vinker S.
      A low carbohydrate Mediterranean diet improves cardiovascular risk factors and diabetes control among overweight patients with type 2 diabetes mellitus: a 1-year prospective randomized intervention study.
       Mediterranean diet (n = 63)1285.5 ± 10.6−7.4
      Reported in the publication without discernable standard deviation.
      31.1 ± 2.8−2.6 ± 4.0
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      111.1 ± 9.1−9.3 ± 12.0
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
       Low-carbohydrate Mediterranean diet (n = 61)86.7 ± 14.3−10.1
      Reported in the publication without discernable standard deviation.
      31.4 ± 2.8−3.3 ± 4.0
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      112.7 ± 9.6−10.4 ± 14.1
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
       ADA diet (n = 55)87.9 ± 13.7−7.7
      Reported in the publication without discernable standard deviation.
      31.8 ± 3.3−2.8 ± 4.6
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      113.4 ± 10−9.1 ± 14.1
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      Tuttle 2008
      • Tuttle K.R.
      • Shuler L.A.
      • Packard D.P.
      • et al.
      Comparison of low-fat versus Mediterranean-style dietary intervention after first myocardial infarction.
       Mediterranean-style diet (n = 47)12NRNR30 ± 5−2.0
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      Reported in the publication without discernable standard deviation.
      NRNR
       Low-fat diet (n = 46)31 ± 6−1.0
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      Reported in the publication without discernable standard deviation.
       Mediterranean-style diet (n = 37)24NRNR30 ± 5−1.0
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      Reported in the publication without discernable standard deviation.
      NRNR
       Low-fat diet (n = 34)31 ± 60.0
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      Reported in the publication without discernable standard deviation.
      McManus 2001
      • McManus K.
      • Antinoro L.
      • Sacks F.
      A randomized controlled trial of a moderate-fat, low-energy diet compared with a low fat, low-energy diet for weight loss in overweight adults.
       Mediterranean-style moderate fat diet (n = 27)1293 ± 32−4.8 ± 5.234 ± 5−2.0 ± 2.1104 ± 12−7.3 ± 6.3
       Low-fat diet (n = 13)89 ± 30−5.0 ± 7.333 ± 3−1.8 ± 2.9101 ± 11−1.6 ± 9.2
       Mediterranean-style moderate fat diet (n = 31)1893 ± 32−4.1 ± 6.5
      P <.05 vs low-fat diet.
      34 ± 5−1.6 ± 2.5
      P <.05 vs low-fat diet.
      104 ± 12−6.9 ± 9.1
      P <.05 vs low-fat diet.
       Low-fat diet (n = 30)89 ± 302.9 ± 7.733 ± 31.4 ± 3.3101 ± 112.6 ± 10.5
      Values are reported as: mean ± standard deviation, unless otherwise specified.
      ADA = American Diabetes Association; NR = not reported.
      Studies are listed in descending order of number of participants included in the analyses of each 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).
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      § P <.05 vs low-fat diet.
      Reported in the publication without discernable standard deviation.
      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/m2 vs 1.4 to −1.8 kg/m2), but similar to all other comparator diets (range of mean changes: −1.5 to −2.8 kg/m2). Similar trends were observed when examining waist circumference (Table 2).

      Other Cardiovascular Risk Factor Levels

      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.
      • Tuttle K.R.
      • Shuler L.A.
      • Packard D.P.
      • et al.
      Comparison of low-fat versus Mediterranean-style dietary intervention after first myocardial infarction.
      • Shai I.
      • Schwarzfuchs D.
      • Henkin Y.
      • et al.
      Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet.
      • Elhayany A.
      • Lustman A.
      • Abel R.
      • Attal-Singer J.
      • Vinker S.
      A low carbohydrate Mediterranean diet improves cardiovascular risk factors and diabetes control among overweight patients with type 2 diabetes mellitus: a 1-year prospective randomized intervention study.
      • Esposito K.
      • Maiorino M.I.
      • Ciotola M.
      • 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 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.
      Table 3Glycemic Control Measures of Participants at 12 Months and Maximum Follow-Up
      Studies are listed in descending order of number of participants included in the analyses of each trial. The randomized controlled trial by McManus et al10 did not report glycemic control measures and was therefore not included in this Table.
      Study
      n is the number of participants analyzed for each arm of the trial at a specific point of follow-up (shown in Table 1).
      Randomized controlled trials by Shai et al8 and Tuttle et al7 reported glycemic control measures among diabetic and nondiabetic participants. Please see Appendix 6.
      (First Author)
      Follow-Up (mo)Fasting GlucoseFasting InsulinHOMAHbA1c
      Baseline (mmol/L)Mean Change (mmol/L)Baseline (μU/mL)Mean Change (μU/mL)BaselineMean ChangeBaseline (%)Mean Change (%)
      Esposito 2009
      • Esposito K.
      • Maiorino M.I.
      • Ciotola M.
      • 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.
       Mediterranean diet (n = 108)129.0 ± 1.9−2.3 ± 1.9
      P <.05 for difference between groups.
      15.6 ± 6.2−2.0 ± 2.05.2 ± 1.7−1.9 ± 0.5
      P <.05 for difference between groups.
      7.8 ± 0.9−1.2 ± 1.0
      P <.05 for difference between groups.
       Low-fat diet (n = 107)8.8 ± 1.8−1.1 ± 1.116.6 ± 7.2−1.9 ± 1.95.3 ± 1.8−1.5 ± 1.07.7 ± 0.9−0.6 ± 0.6
       Mediterranean diet (n = 108)489.0 ± 1.9−1.7 ± 1.1
      P <.05 for difference between groups.
      15.6 ± 6.2−1.41 ± 1.285.2 ± 1.7−1.5 ± 1.0
      P <.05 for difference between groups.
      7.8 ± 0.9−0.9 ± 0.6
      P <.05 for difference between groups.
       Low-fat diet (n = 107)8.8 ± 1.8−0.8 ± 0.816.6 ± 7.2−0.8 ± 0.625.3 ± 1.8−0.9 ± 0.67.7 ± 0.9−0.5 ± 0.4
      Elhayany 2010
      • Elhayany A.
      • Lustman A.
      • Abel R.
      • Attal-Singer J.
      • Vinker S.
      A low carbohydrate Mediterranean diet improves cardiovascular risk factors and diabetes control among overweight patients with type 2 diabetes mellitus: a 1-year prospective randomized intervention study.
       Mediterranean diet (n = 63)1210.1 ± 1.8−3.5 ± 2.2
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      12.1 ± 6.51.2 ± 9.1
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      5.0 ± 2.9−1.3 ± 3.5
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      8.3 ± 1.0−1.8 ± 1.3
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      P <.05 vs ADA diet.
       Low-carbohydrate Mediterranean diet (n = 61)10.5 ± 2.0−4.3 ± 2.2
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      13.5 ± 5.72.3 ± 10.2
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      5.9 ± 4.0−1.7 ± 4.4
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      8.3 ± 1.0−2.0 ± 1.7
      P <.05 vs ADA diet.
       ADA diet (n = 55)10.3 ± 1.7−3.1 ± 2.5
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      12.7 ± 6.20.9 ± 8.5
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      5.8 ± 3.3−1.5 ± 3.9
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      8.3 ± 0.8−1.6 ± 1.2
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      Values are reported as: mean ± standard deviation, unless otherwise specified.
      ADA = American Diabetes Association; HOMA = Homeostatic Model Assessment; HbA1c = glycated hemoglobin.
      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
      • McManus K.
      • Antinoro L.
      • Sacks F.
      A randomized controlled trial of a moderate-fat, low-energy diet compared with a low fat, low-energy diet for weight loss in overweight adults.
      did not report glycemic control measures and was therefore not included in this Table.
      n is the number of participants analyzed for each arm of the trial at a specific point of follow-up (shown in Table 1).
      Randomized controlled trials by Shai et al
      • Shai I.
      • Schwarzfuchs D.
      • Henkin Y.
      • et al.
      Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet.
      and Tuttle et al
      • Tuttle K.R.
      • Shuler L.A.
      • Packard D.P.
      • et al.
      Comparison of low-fat versus Mediterranean-style dietary intervention after first myocardial infarction.
      reported glycemic control measures among diabetic and nondiabetic participants. Please see Appendix 6.
      § P <.05 for difference between groups.
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      P <.05 vs ADA diet.
      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).
      Table 4Lipid Profiles of Participants at 12 months and Maximum Follow-Up
      Studies are listed in descending order of number of participants included in the analyses of each trial. The randomized controlled trial by McManus et al10 did not report changes in lipid profiles throughout follow-up and was therefore not included in this Table.
      Study
      n is the number of participants analyzed for each arm of the trial at a specific point of follow-up (shown in Table 1).
      Follow-Up (mo)Total CholesterolLow-Density Lipoprotein CholesterolHigh-Density Lipoprotein CholesterolTriglycerides
      Baseline (mmol/L)Mean Change (mmol/L)Baseline (mmol/L)Mean Change (mmol/L)Baseline (mmol/L)Mean Change (mmol/L)Baseline (mmol/L)Mean Change (mmol/L)
      Shai 2008
      • Shai I.
      • Schwarzfuchs D.
      • Henkin Y.
      • et al.
      Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet.
      Reported with no discernable standard deviation.
       Mediterranean diet (n = 109)24NRNR3.18 ± 0.89−0.14
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      1.02 ± 0.240.16
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      1.96 ± 0.76−0.25
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
       Low-fat diet (n = 104)3.03 ± 0.92−0.001
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      1.00 ± 0.250.17
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      1.77 ± 0.70−0.03
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
       Low-carbohydrate diet (n = 109)3.03 ± 0.89−0.08
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      0.97 ± 0.220.22
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      P <.05 vs low-fat diet.
      2.05 ± 1.32−0.27
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      P <.05 vs low-fat diet.
      Esposito 2009
      • Esposito K.
      • Maiorino M.I.
      • Ciotola M.
      • 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.
       Mediterranean diet (n = 108)125.7 ± 0.9−0.39 ± 0.38
      P <.05 vs low-fat diet.
      NRNR1.1 ± 0.20.1 ± 0.12
      P <.05 vs low-fat diet.
      1.9 ± 0.8−0.44 ± 0.57
      P <.05 vs low-fat diet.
       Low-fat diet (n = 107)5.6 ± 0.9−0.25 ± 0.201.1 ± 0.20.025 ± 0.021.9 ± 0.8−0.22 ± 0.45
       Mediterranean diet (n = 108)245.7 ± 0.9−0.46 ± 0.32
      P <.05 vs low-fat diet.
      NRNR1.1 ± 0.20.12 ± 0.12
      P <.05 vs low-fat diet.
      1.9 ± 0.8−0.47 ± 0.57
      P <.05 vs low-fat diet.
       Low-fat diet (n = 107)5.6 ± 0.9−0.20 ± 0.201.1 ± 0.20.00 ± 0.021.9 ± 0.8−0.28 ± 0.42
      Elhayany 2010
      • Elhayany A.
      • Lustman A.
      • Abel R.
      • Attal-Singer J.
      • Vinker S.
      A low carbohydrate Mediterranean diet improves cardiovascular risk factors and diabetes control among overweight patients with type 2 diabetes mellitus: a 1-year prospective randomized intervention study.
       Mediterranean diet (n = 63)125.5 ± 0.8−1.00 ± 1.09
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      3.2 ± 0.8−0.57 ± 1.01
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      1.1 ± 0.20.00 ± 0.27
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      3.0 ± 0.7−1.50 ± 0.76
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      P <.05 vs ADA diet.
       Low-carbohydrate Mediterranean diet (n = 61)5.4 ± 0.9−0.90 ± 1.29
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      3.1 ± 0.8−0.64 ± 1.08
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      P <.05 vs ADA diet.
      1.1 ± 0.20.11 ± 0.02
      P <.05 vs ADA diet.
      P <.05 vs Mediterranean diet.
      3.2 ± 0.8−1.30 ± 0.86
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      P <.05 vs ADA diet.
       ADA diet (n = 55)5.4 ± 0.9−0.90 ± 1.14
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      3.0 ± 0.9−0.32 ± 1.20
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      1.1 ± 0.2−0.1 ± 0.29
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      3.1 ± 0.8−0.70 ± 1.38
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      Tuttle 2008
      • Tuttle K.R.
      • Shuler L.A.
      • Packard D.P.
      • et al.
      Comparison of low-fat versus Mediterranean-style dietary intervention after first myocardial infarction.
      Reported with no discernable standard deviation.
       Mediterranean-style diet (n = 47)12NRNR3.08 ± 0.96−0.54
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      0.96 ± 0.260.15
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      1.90 ± 1.29−0.53
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
       Low-fat diet (n = 46)3.10 ± 1.11−0.31
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      0.93 ± 0.280.13
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      1.55 ± 1.03−0.02
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
       Mediterranean-style diet (n = 37)24NRNR3.08 ± 0.96−0.47
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      0.96 ± 0.260.07
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      1.90 ± 1.29−0.45
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
       Low-fat diet (n = 34)3.10 ± 1.11−0.57
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      0.93 ± 0.280.10
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      1.55 ± 1.03−0.26
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      Values are reported as: mean ± standard deviation, unless otherwise specified.
      ADA = American Diabetes Association; NR = not reported.
      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
      • McManus K.
      • Antinoro L.
      • Sacks F.
      A randomized controlled trial of a moderate-fat, low-energy diet compared with a low fat, low-energy diet for weight loss in overweight adults.
      did not report changes in lipid profiles throughout follow-up and was therefore not included in this Table.
      n is the number of participants analyzed for each arm of the trial at a specific point of follow-up (shown in Table 1).
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      § P <.05 vs low-fat diet.
      P <.05 vs ADA diet.
      P <.05 vs Mediterranean diet.
      ∗∗ Reported with no discernable standard deviation.
      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).
      • Tuttle K.R.
      • Shuler L.A.
      • Packard D.P.
      • et al.
      Comparison of low-fat versus Mediterranean-style dietary intervention after first myocardial infarction.
      • Shai I.
      • Schwarzfuchs D.
      • Henkin Y.
      • et al.
      Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet.
      • Esposito K.
      • Maiorino M.I.
      • Ciotola M.
      • 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.
      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.
      • Esposito K.
      • Maiorino M.I.
      • Ciotola M.
      • 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.
      In the second trial,
      • Tuttle K.R.
      • Shuler L.A.
      • Packard D.P.
      • et al.
      Comparison of low-fat versus Mediterranean-style dietary intervention after first myocardial infarction.
      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,
      • Shai I.
      • Schwarzfuchs D.
      • Henkin Y.
      • et al.
      Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet.
      no difference was observed between groups, though blood pressure decreased slightly in the 3 groups during follow-up.
      Table 5Blood Pressure of Participants at 12 months and Maximum Follow-Up
      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.
      Study
      n is the number of participants analyzed for each arm of the trial at a specific point of follow-up (shown in Table 1).
      (First Author)
      Follow-Up (mo)Systolic Blood PressureDiastolic Blood Pressure
      Baseline (mm Hg)Mean Change (mm Hg)Baseline (mm Hg)Mean Change (mm Hg)
      Shai 2008
      • Shai I.
      • Schwarzfuchs D.
      • Henkin Y.
      • et al.
      Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet.
       Mediterranean diet (n = 109)24133.1 ± 14.1−5.5 ± 14.380.6 ± 9.2−2.2 ± 9.5
       Low-fat diet (n = 104)129.6 ± 13.2−4.3 ± 11.879.1 ± 9.1−0.9 ± 8.1
       Low-carbohydrate diet (n = 109)130.8 ± 15.1−3.9 ± 12.879.4 ± 9.1−0.8 ± 8.7
      Esposito 2009
      • Esposito K.
      • Maiorino M.I.
      • Ciotola M.
      • 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.
       Mediterranean diet (n = 108)12139.0 ± 12.0−5.1 ± 4.2
      P <.05 vs low-fat diet.
      87.0 ± 8.0−4.0 ± 3.0
      P <.05 vs low-fat diet.
       Low-fat diet (n = 107)140.0 ± 12.0−2.0 ± 1.986.0 ± 8.0−3.0 ± 4.0
       Mediterranean diet (n = 108)24139.0 ± 12.0−4.5 ± 3.787.0 ± 8.0−3.2 ± 2.8
       Low-fat diet (n = 107)140.0 ± 12.0−1.4 ± 1.786.0 ± 8.0−2.5 ± 2.3
      Tuttle 2008
      • Tuttle K.R.
      • Shuler L.A.
      • Packard D.P.
      • et al.
      Comparison of low-fat versus Mediterranean-style dietary intervention after first myocardial infarction.
       Mediterranean-style diet (n = 47)12118.0 ± 12.02.0 ± 20.871.0 ± 9.02.0 ± 12.7
       Low-fat diet (n = 46)119.0 ± 12.05.0 ± 20.071.0 ± 8.02.0 ± 12.0
       Mediterranean-style diet (n = 37)24118.0 ± 12.05.0 ± 20.071.0 ± 9.03.0 ± 12.7
       Low-fat diet (n = 34)119.0 ± 12.04.0 ± 17.071.0 ± 8.01.0 ± 11.3
      Values are reported as: mean ± standard deviation, unless otherwise specified.
      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.
      n is the number of participants analyzed for each arm of the trial at a specific point of follow-up (shown in Table 1).
      P <.05 vs low-fat diet.

      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.
      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 review
      • 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.
      of 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 diets
      • Atkins R.C.
      Dr. Atkins' New Diet Revolution.
      • Sears B.
      A Week in the Zone.
      • Agatston A.
      The South Beach Diet.
      about the elevated consumption of carbohydrates associated with the Mediterranean diet.
      • Willett W.C.
      • Sacks F.
      • Trichopoulou A.
      • et al.
      Mediterranean diet pyramid: a cultural model for healthy eating.
      The similar weight loss achieved across diets suggests that there is no optimal macronutrient composition for achieving sustained weight loss.
      Rather, it has been suggested that a “3-stepped intensification of care approach” is more likely to yield clinically significant weight loss.
      • Kushner R.F.
      Weight loss strategies for treatment of obesity.
      The first step is evidence-based lifestyle modification through diet, behavioral therapy, and physical activity.
      • Kushner R.F.
      Weight loss strategies for treatment of obesity.
      Combining diet with physical activity has been found to increase weight loss compared with each of these interventions used alone,
      • 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.
      • 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.
      • Curioni C.C.
      • Lourenco P.M.
      Long-term weight loss after diet and exercise: a systematic review.
      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.
      • 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.
      The second step is the concurrent use of weight loss pharmacotherapies.
      • Kushner R.F.
      Weight loss strategies for treatment of obesity.
      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.
      • Kushner R.F.
      Weight loss strategies for treatment of obesity.
      The Mediterranean diet has been the focus of many epidemiological studies, but the diet itself originated inauspiciously during the early to mid-20th 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.
      • Bach-Faig A.
      • Berry E.M.
      • Lairon D.
      • et al.
      Mediterranean Diet Foundation Expert Group
      Mediterranean diet pyramid today. Science and cultural updates.
      Individuals in these communities enjoyed numerous health benefits, including reduced rates of cardiovascular disease, which were first described by the Seven Countries Study.
      • Widmer R.J.
      • Flammer A.J.
      • Lerman L.O.
      • Lerman A.
      The Mediterranean diet, its components, and cardiovascular disease.
      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,
      • 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.
      an increase in levels of biomarkers associated with healthy aging,
      • Crous-Bou M.
      • Fung T.T.
      • Prescott J.
      • et al.
      Mediterranean diet and telomere length in Nurses' Health Study: population based cohort study.
      and a reduced risk of mortality over 20 years.
      • 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 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.
      • Estruch R.
      • Ros E.
      • Martinez-Gonzalez M.A.
      Mediterranean diet for primary prevention of cardiovascular disease.
      • Martinez-Gonzalez M.A.
      • Salas-Salvado J.
      • Estruch R.
      • et al.
      Benefits of the Mediterranean Diet: Insights From the PREDIMED Study.
      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.
      • Martinez-Gonzalez M.A.
      • Salas-Salvado J.
      • Estruch R.
      • et al.
      Benefits of the Mediterranean Diet: Insights From the PREDIMED Study.
      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.
      • Martinez-Gonzalez M.A.
      • Salas-Salvado J.
      • Estruch R.
      • et al.
      Benefits of the Mediterranean Diet: Insights From the PREDIMED 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,
      • 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.
      • 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.
      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 studies
      • 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.
      • 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.
      • Sofi F.
      • Cesari F.
      • Abbate R.
      • Gensini G.F.
      • Casini A.
      Adherence to Mediterranean diet and health status: meta-analysis.
      focused 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.
      • 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.
      Although previous knowledge syntheses have examined the Mediterranean diet for weight loss, many had several important methodological limitations. These include recent meta-analyses,
      • 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.
      • Esposito K.
      • Kastorini C.M.
      • Panagiotakos D.B.
      • Giugliano D.
      Mediterranean diet and weight loss: meta-analysis of randomized controlled trials.
      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-analyses
      • 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.
      • Esposito K.
      • Kastorini C.M.
      • Panagiotakos D.B.
      • Giugliano D.
      Mediterranean diet and weight loss: meta-analysis of randomized controlled trials.
      • Schwingshackl L.
      • Hoffmann G.
      Adherence to Mediterranean diet and risk of cancer: a systematic review and meta-analysis of observational studies.
      • Rees K.
      • Hartley L.
      • Flowers N.
      • et al.
      ‘Mediterranean’ dietary pattern for the primary prevention of cardiovascular disease.
      included RCTs that involved preferential nutritional counseling in Mediterranean diet treatment arms, which has been previously shown to increase 12-month weight loss.
      • Dansinger M.L.
      • Tatsioni A.
      • Wong J.B.
      • Chung M.
      • Balk E.M.
      Meta-analysis: the effect of dietary counseling for weight loss.
      The inclusion of such trials may partially explain the positive findings of these previous reviews and meta-analyses.
      • 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.
      • Esposito K.
      • Kastorini C.M.
      • Panagiotakos D.B.
      • Giugliano D.
      Mediterranean diet and weight loss: meta-analysis of randomized controlled trials.
      • Schwingshackl L.
      • Hoffmann G.
      Adherence to Mediterranean diet and risk of cancer: a systematic review and meta-analysis of observational studies.
      • Rees K.
      • Hartley L.
      • Flowers N.
      • et al.
      ‘Mediterranean’ dietary pattern for the primary prevention of cardiovascular disease.
      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.

      Limitations

      Our systematic review has several potential limitations. First, it was designed to focus on high-quality evidence from long-term RCTs. Consequently, only 5 RCTs were included, and these trials included a total of <1000 patients. With heterogeneity in design, population, and comparator, we were unable to statistically pool data across trials. However, this finding highlights the dearth of rigorous trials in this area. Second, with 89.9% of included participants having established cardiovascular disease or type 2 diabetes, the generalizability of our results to the general population of overweight or obese individuals trying to lose weight is unclear. Nonetheless, the high proportion of such individuals allowed for the assessment of the Mediterranean diet in individuals with obesity-associated comorbidities. Finally, our review was restricted to RCTs that explicitly mentioned the Mediterranean diet as a dietary intervention. This may have resulted in the exclusion of some RCTs that investigated diets with the alimentary and macronutrient composition of the Mediterranean diet without describing the intervention as such. However, this ensured that included RCTs studied the diet of interest.

      Conclusion

      Our systematic review was designed to investigate the effect of the Mediterranean diet on weight loss and cardiovascular risk factor levels among overweight or obese individuals trying to lose weight. Our results suggest that the Mediterranean diet results in greater weight loss than a low-fat diet, but similar weight loss as other comparator diets. The Mediterranean diet may also improve triglyceride levels as well as produce similar changes in blood pressure and other lipids as comparator diets. Although following the Mediterranean diet may result in some weight loss, and it likely has other health benefits, it does not appear to be superior to other diets when followed by overweight or obese individuals trying to lose weight.

      Acknowledgment

      The authors thank Ms. Caroline Franck and Natalie Zacchia for their help with data extraction. KBF holds a Canadian Institutes of Health Research New Investigator Award.

      Supplementary Data

      Appendix 1Description of Literature Search on MEDLINE
      Database contains references from 1946 to January 7, 2015.
      (Through Ovid) for Trials Comparing the Mediterranean Diet to Control Diets
      NumberSearch Term(s)Results
      1exp Diet, Mediterranean/1722
      2mediterranean*.ti,ab,mp.27,942
      3exp diet/ or diet*.ab,ti,mp.592,889
      42 AND 33876
      51 OR 43876
      6([randomized controlled trial or controlled clinical trial].pt. or randomized.ab. or randomised.ab. or placebo.ab. or drug therapy.fs. or randomly.ab. or trial.ab. or groups.ab.) not (exp animals/ not humans.sh.)3,081,632
      75 AND 61035
      8Limit 7 to English or French987
      Database contains references from 1946 to January 7, 2015.
      Appendix 2Description of Literature Search on EMBASE + EMBASE Classic
      Database contains references from 1947 to January 5, 2015.
      (Through Ovid) for Trials Comparing the Mediterranean Diet with Control Diets
      NumberSearch Term(s)Results
      1exp Mediterranean diet/3388
      2mediterranean*.ti,ab,mp.33,408
      3exp diet/ or diet*.ab,ti,mp.762,245
      42 and 35674
      51 or 45674
      6crossover-procedure/ or double-blind procedure/ or randomized controlled trial/ or single-blind procedure/ or (random* or factorial* or crossover* or cross over* or placebo* or (doubl* adj blind*) or (singl* adj blind*) or assign* or allocat* or volunteer*).tw.1,519,774
      75 and 61046
      8limit 7 to (english or french)998
      Database contains references from 1947 to January 5, 2015.
      Appendix 3Description of Literature Search of the Cochrane Central Register of Controlled Trials
      Database contains references from 1898 to December 2014.
      for Trials Comparing the Mediterranean Diet with Control Diets
      NumberSearch Term(s)Results
      1MeSH descriptor: [Diet, Mediterranean] explode all trees196
      2mediterranean*871
      3MeSH descriptor: [Diet] explode all trees12,312
      4diet*45,108
      5#3 or #447,319
      6#2 and #5523
      7#1 or #6523
      8#1 or #6 in Trials447
      Database contains references from 1898 to December 2014.
      Figure thumbnail fx1
      Appendix 4Flow Diagram Describing Systematic Literature Search for Randomized Controlled Trials Examining the Mediterranean Diet.
      Appendix 5Risk of Bias of Trials Comparing the Mediterranean Diet with an Active Comparator Diet
      Each criterion has been evaluated as being “High,” “Low,” or “Unclear” regarding the risk of bias following the guidelines of the Cochrane Collaboration's tool for assessing risk of bias.
      Study
      Studies are listed in descending order of number of participants included in the analyses of each trial.
      (First Author)
      Sequence GenerationAllocation ConcealmentBlinding of Participants, Personnel, and Outcome AssessorsIncomplete Outcome DataSelective Outcome ReportingOther Sources of Bias
      Shai, 2008
      • Shai I.
      • Schwarzfuchs D.
      • Henkin Y.
      • et al.
      Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet.
      LowUnclearLowLowLowLow
      Esposito, 2009
      • Esposito K.
      • Maiorino M.I.
      • Ciotola M.
      • 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.
      LowLowLowLowLowLow
      Elhayany, 2010
      • Elhayany A.
      • Lustman A.
      • Abel R.
      • et al.
      A low carbohydrate Mediterranean diet improves cardiovascular risk factors and diabetes control among overweight patients with type 2 diabetes mellitus: a 1-year prospective randomized intervention study.
      UnclearUnclearUnclearHighHighHigh
      Tuttle, 2008
      • Tuttle K.R.
      • Shuler L.A.
      • Packard D.P.
      • et al.
      Comparison of low-fat versus Mediterranean-style dietary intervention after first myocardial infarction.
      UnclearLowUnclearLowHighLow
      McManus, 2001
      • McManus K.
      • Antinoro L.
      • Sacks F.
      A randomized controlled trial of a moderate-fat, low-energy diet compared with a low fat, low-energy diet for weight loss in overweight adults.
      LowHighHighHighHighLow
      Each criterion has been evaluated as being “High,” “Low,” or “Unclear” regarding the risk of bias following the guidelines of the Cochrane Collaboration's tool for assessing risk of bias.
      Studies are listed in descending order of number of participants included in the analyses of each trial.
      Appendix 6Glycemic Control Measures in Diabetics and Nondiabetics in 2 Randomized Controlled Trials
      Studies are listed in descending order of number of participants included in the analyses of each trial.
      Studyn
      n is the number of participants analyzed for each arm of the trial at a specific point of follow-up (shown in Table 1).
      StatusFollow-Up, moFasting GlucoseFasting InsulinHOMAHbA1c
      Mean Change, mmol/LMean Change, μU/mLMean ChangeMean Change, %
      Shai 2008
      • Shai I.
      • Schwarzfuchs D.
      • Henkin Y.
      • et al.
      Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet.
      Standard deviation could not be discerned (values were presented graphically).
       Mediterranean Diet13Diabetic24−1.82
      P <.05 vs low-fat diet.
      −4.0−2.3
      P <.05 vs low-fat diet.
      NR
       Low-Fat Diet11Diabetic0.67−1.5−0.3
       Low-Carbohydrate Diet12Diabetic0.07−2.2−1.0
       Mediterranean Diet79Nondiabetic240.17−1.8−0.3NR
       Low-Fat Diet79Nondiabetic0.17−1.4−0.2
       Low-carbohydrate Diet69Nondiabetic0.07−3.7−0.8
      Tuttle 2008
      • Tuttle K.R.
      • Shuler L.A.
      • Packard D.P.
      • et al.
      Comparison of low-fat versus Mediterranean-style dietary intervention after first myocardial infarction.
      Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
       Mediterranean Diet
      There were n = 10 diabetics in the Mediterranean diet group and n = 10 diabetics in the low-fat diet group at baseline. The number of diabetics and nondiabetics represented at this point of follow-up was not reported.
      Diabetic12−0.890NRNR
       Low-Fat DietDiabetic−0.44−14
       Mediterranean Diet
      There were n = 10 diabetics in the Mediterranean diet group and n = 10 diabetics in the low-fat diet group at baseline. The number of diabetics and nondiabetics represented at this point of follow-up was not reported.
      Nondiabetic12−0.113NRNR
       Low-Fat DietNondiabetic−0.062
       Mediterranean Diet
      There were n = 10 diabetics in the Mediterranean diet group and n = 10 diabetics in the low-fat diet group at baseline. The number of diabetics and nondiabetics represented at this point of follow-up was not reported.
      Diabetic24−1.105NRNR
       Low-Fat DietDiabetic−0.60−16
       Mediterranean Diet
      There were n = 10 diabetics in the Mediterranean diet group and n = 10 diabetics in the low-fat diet group at baseline. The number of diabetics and nondiabetics represented at this point of follow-up was not reported.
      Nondiabetic240.110NRNR
       Low-Fat DietNondiabetic−0.174
      HbA1c = glycated hemoglobin; HOMA = homeostatic model assessment.
      Studies are listed in descending order of number of participants included in the analyses of each 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).
      Standard deviation could not be discerned (values were presented graphically).
      § Mean change was calculated as difference of means from baseline to follow-up from data of the publication.
      P <.05 vs low-fat diet.
      There were n = 10 diabetics in the Mediterranean diet group and n = 10 diabetics in the low-fat diet group at baseline. The number of diabetics and nondiabetics represented at this point of follow-up was not reported.

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