Figure 1
PRISMA flow for study selection.
Table 1
Characteristics of included studies.
| Study | Country | Sample Size | Participants | Mean age (years) | % male | Intervention | Comparison | Follow-up duration |
|---|---|---|---|---|---|---|---|---|
| Athyros 2011 [33] | ? | 150 (100 for this review) | Mild hyper-cholesterolaemia | 54.7 | 49 | Trained dieticians encouraged participants to adhere to a Mediterranean dietary pattern, with efforts to increase adherence and 7-day menu plans with food that incorporated the salient characteristics of the Mediterranean diet. | Hypolipidaemic diet | 16 weeks |
| Bajerska 2018 [34] | Poland | 144 | Postmenopausal women with central obesity | 60.5 | 0 | Participants followed a food plan based on Mediterranean dietary recommendations. Typical Mediterranean food products were used providing approximately 37% energy from total fat, 20% from MUFAs, 9% from PUFAs, 8% from SFAs, 18% from protein and 45% energy from carbohydrates. Olive oil was used in every meal and 5 to 7 nuts were served once a day. | Central European diet | 4 months |
| Castagnetta 2002 [35] | Italy | 115 | Healthy postmenopausal women | 44 to 71 | 0 | MEDIET project - participants were invited to a weekly cooking course and a social dinner with chefs addressing the principles of the traditional Mediterranean diet. The proposed recipes were based on a traditional Sicilian diet including whole cereals, legumes, seeds, fish, fruits, vegetables, olive oil and red wine to consume on a daily basis at home. Women were asked to avoid refined carbohydrates, salt and additional animal fat. | Usual diet | 6 and 12 months |
| Chasapidou 2014 [36] | Greece | 384 | Know cardiometabolic diseases | ? | ? | Mediterranean healthy diet personalised in calories and nutrients according to the patient’s cardiometabolic disease, monthly follow-up by a dietitian. | No dietary counselling | 6 months |
| Clements 2017 [37] | UK | 120 | Healthy elderly participants | 70 | 39 | Dietary advice sheets and individual dietary advice to achieve the quantitative requirements for the Nu-AGE dietary intervention. Participants were given extra-virgin olive oil, whole grain pasta and low-fat margarine rich in MUFA and PUFA freely throughout the study. | Standard healthy living advice leaflet from the British Dietetic Association and asked to maintain habitual dietary intake. | 1 year |
| Colquhoun 2000 [38] | ? | 68 | Documented CHD | ? | ? | Mediterranean diet: 35% to 40% energy from fat with > 50% of fat being monounsaturated | Low-fat diet: 20% to 25% energy from fat with 8% to 10% saturated | 3 months |
| Davis 2017 [39] | Australia | 166 | Healthy elderly participants | 71 | 44 | Based on a traditional Mediterranean diet, with small adaptations to the Australian food supply. Resources were provided that included a recipe book, guidelines for eating out, serving sizes and the recommended number of servings, and participants also received foods (olive oil, nuts, legumes, tuna and Greek yogurt) to increase the likelihood of adherence. | Regular diet without change (seasonal variation permitted). Participants received a voucher to buy regularly consumed foods from supermarkets. | 6 months |
| Dinu 2017 [40] | ? | 117 | Overweight with at least an additional metabolic risk factor | 51 | 15 | Mediterranean diet of 3 different sizes (1400, 1600, 1800 Kcal/day), according to specific energy requirements. | Vegetarian diet of 3 different sizes (1400, 1600, 1800 Kcal/day), according to specific energy requirements. | 3 months in each phase (cross-over) |
| Djuric 2009 [41] | US | 69 | Healthy non-obese women | 44 | 0 | Greek Mediterranean exchange list diet with exchange goals determined by dieticians at baseline and focused on increasing fruit and vegetable intake and variety and increasing MUFA intake while maintaining the baseline energy intake and total fat intake. Participants were given 3 L of extra-virgin olive oil at baseline and at 3 months. | Usual diet with no counselling, but participants were given the National Cancer Institutes Action guide to healthy eating and written materials on nutritional deficiencies if below 67% RDA. | 6 months |
| Entwistle 2018 [42] | UK | 41 | Heart and lung transplant recipients | 58 | 70 | Information and encouragement to follow an eating pattern representative of a traditional Mediterranean diet. The key dietary recommendations were: daily mixed consumption of a range of vegetables, fruit, whole grains, fish/seafood, raw nuts and legumes; abundant use of extra-virgin olive oil (a free 5L container of extra-virgin olive oil was provided to each participant); moderate consumption of dairy products and red wine; low intake of red and processed meats, of sweets, sweet-baked pastries and sweetened beverages. | Modified British Heart Foundation low-fat guidelines, with an emphasis on consuming mainly plant-based whole foods similar to the Mediterranean diet, and advice to minimise high-fat foods. Each participant received a low-fat recipe book. | 12 months |
| Esposito 2004 [43] | Italy | 180 | Metabolic syndrome | 44 | 55 | Advice about a Mediterranean-style diet. Through a series of monthly small-group sessions, participants received education in reducing dietary calories (if needed), personal goal-setting and self-monitoring using food diaries. Behavioural and psychological counselling was also offered. Dietary advice was tailored to each participant on the basis of 3-day food records. Participants were in the programme for 24 months and had monthly sessions with the nutritionist for the first year and twice monthly sessions for the second year. | Oral and written information about healthy food choices. The general recommendation for macro-nutrient composition of the diet was similar to that for the intervention group. Participants had bimonthly sessions with study personnel. | 2 years |
| Konstantinidou 2010 [44] | Spain | 90 | Healthy adults | 20 to 50 | 28 | 1. Traditional Mediterranean diet with virgin olive oil 2. Traditional Mediterranean diet with washed virgin olive oil The dietician gave personalised advice during a 30-minute session to each participant following the traditional Mediterranean diets, with recommendations on the desired frequency of intake of specific foods. | Control group (30 participants): participants were advised by a dietician to maintain their habitual lifestyle | 3 months |
| Lapetra 2018 [45] | Spain | 180 | Hypertensive patients | 55 to 75 | 92 | Mediterranean-style diet Both groups received dietary advice (individual and group) every 3 months for at least 2 years. Participants attended educational talks about hypertension and healthy eating and were given a booklet that included essential information from the talks and a seasonal menu, tailored for each group. | Low-fat diet according to American Heart Association guidelines | 2 years |
| Lindman 2004 [46] | Norway | 219 in whole study, 98 for the arms of interest to this review | Longstanding hyper-cholesterolaemia | 69.7 | 100 | Dietary advice (‘Mediterranean-type’ diet) and placebo capsules. Diet counselling was given individually by a clinical nutritionist based on a food frequency questionnaire. Participants were supported with a margarine rich in PUFA and vegetable oils free of cost. 2 placebo capsules were taken twice daily corresponding to 2.4 g corn oil. | Usual care + placebo capsules. 2 placebo capsules were taken twice daily corresponding to 2.4 g corn oil. | 6 months |
| Mayr 2018 [47] | Australia | 73 | Documented CHD patients | 62 | 84 | Based on a traditional Cretan Mediterranean diet. Modelled a 2-week meal plan incorporating key dietary components of a Mediterranean diet with a mix of traditional and modified recipes considered to be realistic options for multi-ethnic Australians. Patients received a recipe book, shopping lists, a food pyramid, weekly dietary intake checklists and label reading information. Hampers were provided at baseline and 3 months to aide adherence (6 L extra-virgin olive oil, 1.2 kg nuts, tinned fish and legumes and Greek yogurt). | Low-fat diet - followed the standard diet recommendations for cardiac patients in Australia at the time. A one week meal plan was provided, resources for label reading, low-fat cooking and recommended food group serving sizes. Participants received a supermarket voucher at the 3 face-to-face meetings. | 6 months |
| Michalsen 2006 [48] | Germany | 101 | Documented CHD patients | 59 | 77 | A lifestyle modification group with the focus on Mediterranean diet: 3-day non-residential retreat, and regular group meetings thereafter. The lifestyle programme addressed diet and stress management. Participants were extensively informed about the Mediterranean diet by nutritional information, repetitive group discussions, cooking classes and group meals, and dietary instructions were tailored to individuals where necessary. | Patients in the control group received only written and less detailed information about the dietary principles of the Mediterranean diet, and some leaflets with general advice about stress reduction. | 1 year |
| Misciagna 2017 [49] | Italy | 98 | Non-alcoholic fatty liver disease | ? | 50 | Low glycaemic index Mediterranean diet (LGIMD). | Italian National Research Institute for Foods and Nutrition (INRAN) guidelines, with information provided in brochures using in a traffic-light format. | 6 months |
| Ng 2011 [50] | China (Hong Kong) | 48 | HIV patients | ? | ? | The dietitian designed an individualised meal plan for each participant, taking into account any specific requirements related to their HIV status. The Mediterranean diet was modified to suit the local culture, for example: replacing red meat with fish or chicken; using canola, rapeseed or olive oil in place of cooking oil to replace saturated fats; canola margarine in place of butter or other margarine; using dried legumes or tofu to replace meat; using low-fat dairy or soy drink instead of full fat dairy. | Low-fat and low-cholesterol diet prescribed according to the NCEP Adult Treatment Panel III guidelines. | 12 months |
| PREDIMED [51] | Spain | 7447 | Increased risk of CVD (either T2DM or 3 or more risk factors) | 67 | 42 | 1) Mediterranean diet + extra-virgin olive oil 2) Mediterranean diet + tree nuts Advice to adhere to a Mediterranean diet through tailored individual visits to dieticians and group sessions every 3 months. Group sessions included informative talks and discussion with review of dietary goals, menu planning and shopping lists appropriate for each dietary intervention and provision of supplemental extra-virgin olive oil or nuts. | Low-fat diet – advice to reduce all types of fat, and recommending the consumption of lean meats, low-fat dairy products, cereals, potatoes, pasta, rice, fruits and vegetables. The use of olive oil was discouraged. Tailored individual visits to dieticians and group sessions every 3 months (after year 3 to match intensity of intervention). Non-food incentives provided at group sessions. | 4.8 years |
| Properzi 2018 [52] | Australia | 56 | Non-alcoholic fatty liver disease | ? | ? | Mediterranean diet | Low-fat diet | 12 weeks |
| Singh 1992 [53] | India | 406 | Definite or possible acute MI and unstable angina | 51 | 90 | Diet A - meat, eggs, hydrogenated oils, butter and clarified butter were replaced with vegetarian meat substitutes and soya bean, sunflower and ground nut oils. Patients were also advised to eat fruit, vegetables, pulses, nuts and fish. Patients following diet A had the advice regularly reinforced. | Diet B- meat, eggs, hydrogenated oils, butter and clarified butter were replaced with vegetarian meat substitutes and soya bean, sunflower and ground nut oils. Initial advice only, with no further reinforcement. | 1 year (blood measures) and 2 years (clinical endpoints) |
| Singh 2002 [54] | India | 1000 | Risk factors for CVD | 48.5 | 90 | National Cholesterol Education Program (NCEP) step I prudent diet, plus Indo-Mediterranean diet - at least 400 to 500g of fruits, vegetables and nuts per day, 400g to 500g of whole grains, legumes, rice, maize and wheat daily, as well as mustard seed or soy bean oil, in 3 to 4 servings per day, which is consistent with recommendations from the Indian Consensus Group. | Control patients were given an information sheet on the National Cholesterol Education Program (NCEP) step I prudent diet. | 2 years |
| Skouroliakou 2017 [55] | Greece | 70 | Women with breast cancer | ? | 0 | Personalised dietary intervention based on the Mediterranean diet, conducted by 2 trained registered dietitians. The diet was enriched with olive oil and foods with specific health benefits for breast cancer survivors. They received a personalised dietary programme via e-mail as well as face-to-face appointments every 15 days for the first 3 months and phone calls at the end of months 4 and 5 with in-person meetings at the end of the study at 6 months. Specific meals, products, recipes and food portions, educational booklets, food diaries and individual nutritional advice was provided. | Received the updated American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention and ad libitum diet. Patients were contacted by phone every 15 days for the first 3 months, then at months 4 and 5 and in-person meetings at baseline, 3 and 6 months. | 6 months |
| Sofi 2018 [56] | Italy | 118 | Clinically healthy with low to moderate cardiovascular risk profile | Median age 50 (range 21 to 75) | 22 | Advice to follow a Mediterranean diet delivered through face-to-face individual counselling sessions. Participants were provided with a detailed 1-week menu plan as well as tips and information on the food groups that could be included and those that could not. | Advice to follow a lacto-ovo vegetarian diet delivered through face-to-face individual counselling sessions. Participants were provided with a detailed 1-week menu plan as well as tips and information on the food groups that could be included and those that could not. Included also recipes for preparing meals. | Cross-over at 3 months |
| Stradling 2018 [57] | UK | 60 | HIV patients on antiretroviral therapy with LDL >3mmol/L | ? | ? | Advice and support to adopt the Mediterranean diet, supplemented by additional functional foods with cholesterol-lowering properties. Motivational interviewing-style consultation.50 mL cholesterol-lowering drink at randomisation and subsequent sessions. Supplies of the functional foods (nuts, soy protein, plant stanols, oats and pulses) were given to participants to offset the additional cost of making dietary changes. | Wait-list control, with low saturated fat diet. Focus on reduction of saturated fat to < 10% of energy intake, in line with UK guidelines. Resources were provided, such as written information, recipes and online videos. | 12 months |
| The Lyon Diet Heart Study [58] | ? | 605 | MI within 6 months | 53.5 | 90 | Tailored advice during 1 hour session with research cardiologist and dietician to follow a Mediterranean-type diet. Further dietary counselling at each visit at 2 months and annually. A rapeseed (canola) oil-based margarine was supplied free for the whole family, as participants would not accept olive oil as the only fat. | No dietary advice apart from that of hospital dieticians or attending physicians as usual care. | 24 and 46 months |
| Tuttle 2008 [59] | ? | 101 | Recruited 6 within 6 weeks of first MI | 58 | 74 | Mediterranean-style diet, with emphasis on the increased consumption of cold-water fish (3 to 5 times/week) and oils from olives, canola and soybeans. Participants procured and prepared their own meals. Participants received individual dietary counselling sessions and group sessions focused on behavioural modification and practical aspects of their assigned diet, including recipes, grocery shopping and dining out. | Low-fat diet (the American Heart Association Step II diet). Participants received individual dietary counselling sessions and group sessions focused on behavioural modification and practical aspects of their assigned diet, including recipes, grocery shopping and dining out. | 2 years |
| Vincent-Baudry 2005 [60] | France | 212 | At least one cardiovascular risk factor | 51 | 41 | Mediterranean diet - dietary advice given by physicians and dieticians, and participants received a booklet with nutritional recommendations. In addition, participants were provided with oat-bran enriched pasta, tomato sauce and olive oil. | Low-fat American Heart Association–type diet was adapted for the low-fat diet group. | 3 months |
| Wardle 2000 [61] | UK | 117 | Mild to moderate hyper-cholesterolaemia | 53.5 | 43.5 | Advice to follow a Mediterranean diet delivered in 8 sessions during the 12-week intervention period using a combination of individual and group sessions with a dietician and psychologist. Advised to increase intake of fruit and vegetables, and oily fish and to reduce fat to 30% of energy with substitution of predominantly monounsaturated fat for saturated fat. Individualised advice to implement dietary changes based on their lifestyle and food preferences and group support in maintaining changes. Intervention participants were also given free spreading fats and oils high in monounsaturated fats. | Wait-list control with no specific dietary advice. | 12 weeks |
| Weber 2012 [62] | Brazil | 122 | Established or previous CVD within past 10 years at increased CVD risk | 63 | 66 | Group B Received the dietary therapy that was proposed by the Brazilian guidelines for cardiovascular diseases, customised by the integration of typical Mediterranean foods (e.g. olives, olive oil, chestnuts, walnuts, almonds, hazelnuts, peanuts and cold water fish). Weekly counselling sessions with dietitians (in person or by telephone). Group C Received the same dietary intervention as Group B, but the patients were counselled monthly in person. | Group A Brazilian Cardioprotective Diet Program, i.e. avoiding high energy density foods (> 1 kcal/g); prioritisation of regional foods that are culturally accepted by the patients (rice, bean, soy oil, and Brazilian fruits and vegetables). Weekly in-person sessions with dietitians - tips for eating in restaurants, instructions on label reading and a list of typical Brazilian recipes that were adjusted for nutrients and energy densities. | 12 weeks |
[i] Key: CHD (coronary heart disease), CVD (cardiovascular disease), HIV (human immunodeficiency virus), LDL (low-density lipoprotein), MI (myocardial infarction), MUFA (monounsaturated fatty acids), PUFA (polyunsaturated fatty acids), SFA (saturated fatty acids), T2DM (Type 2 Diabetes Mellitus).
Figure 2
Risk of bias assessment of included studies.
Table 2
Summary of Findings Table for primary outcomes for each of the four main comparison groups.
| Comparison | Primary outcomes | RCTs (n) | Participants (n) | Follow-up (years) | Anticipated absolute effects (95% CI) | Effect estimate (95% CI) | Certainty of the evidence (GRADE) | Interpretation | |
|---|---|---|---|---|---|---|---|---|---|
| Control (events per 1000) | Intervention (events per 1000) | ||||||||
| Mediterranean diet vs no or minimal intervention (primary prevention) | Cardiovascular mortality | Not reported | |||||||
| Total mortality | Not reported | ||||||||
| Mediterranean diet vs another dietary intervention (primary prevention) | Cardiovascular mortality | 1 | 7447 | 4.8 | 12 | 10 (6 to 16) | HR 0.81(0.50 to 1.32) | ●●○○ LOW | Little or no effect |
| Total mortality | 1 | 7447 | 4.8 | 47 | 47 (38 to 57) | HR 1.00(0.81 to 1.24) | ●●○○ LOW | Little or no effect | |
| Myocardial infarction | 1 | 7447 | 4.8 | 16 | 12 (9 to 17) | HR 0.79(0.57 to 1.10) | ●●○○ LOW | Little or no effect | |
| Stroke | 1 | 7447 | 4.8 | 24 | 14 (11 to 19) | HR 0.60(0.45 to 0.80) | ●●●○ MODERATE | Reduction | |
| Mediterranean diet vs usual care (secondary prevention) | Cardiovascular mortality | 1 | 605 | 3.8 | 63 | 22 (9 to 51) | RR 0.35(0.15 to 0.82) | ●●○○ LOW | Reduction |
| Total mortality | 1 | 605 | 4 | 79 | 35 (17 to 73) | RR 0.44(0.21 to 0.92) | ●●○○ LOW | Reduction | |
| Mediterranean diet vs another dietary intervention (secondary prevention) | Total cardiac endpoints | 1 | 101 | 2 | 160 | 157 (64 to 386) | RR 0.98(0.40 to 2.41) | ●○○○ VERY LOW | Uncertainty |
Table 3
Summary of Findings Table for secondary outcomes for each of the four main comparison groups.
| Comparison | Secondary outcomes, change from baseline | RCTs (n) | Participants (n) | Follow-up (months) | Mean change from baseline in control group (range) | Effect estimate (95% CI) | Certainty of the evidence (GRADE) | Interpretation |
|---|---|---|---|---|---|---|---|---|
| Mediterranean diet vs no or minimal intervention (primary prevention) | Total cholesterol (mmol/L) | 5 | 569 | 3 to 24 | –0.003 to –0.2 | MD –0.16 (–0.32 to 0.00) | ●●○○ LOW | Small reduction |
| LDL cholesterol (mmol/L) | 4 | 389 | 3 to 6 | –0.2 to 0.05 | MD –0.08 (–0.26 to 0.09) | ●○○○ VERY LOW | Little or no effect | |
| HDL cholesterol (mmol/L) | 5 | 659 | 3 to 24 | –0.07 to 0.03 | MD 0.02 (–0.04 to 0.08) | ●●○○ LOW | Little or no effect | |
| Triglycerides (mmol/L) | 4 | 480 | Not pooled | ●●○○ LOW | Little or no effect | |||
| Systolic blood pressure (mmHg) | 2 | 269 | 3 to 24 | –1 to 1.4 | MD –2.99 (–3.45 to –2.53) | ●●●○ MODERATE | Reduction | |
| Diastolic blood pressure (mmHg) | 2 | 269 | 3 to 24 | –1 to 1.7 | MD –2.00 (–2.29 to –1.71) | ●●●○ MODERATE | Reduction | |
| Mediterranean diet vs another dietary intervention (primary prevention) | Total cholesterol (mmol/L) | 7 | 939 | 3 to 58 | –0.29 to 0.51 | MD –0.13 (–0.30 to 0.04) | ●●○○ LOW | Little or no effect |
| LDL cholesterol (mmol/L) | 7 | 947 | 3 to 58 | –0.18 to 0.27 | MD –0.15 (–0.27 to –0.02) | ●●●○ MODERATE | Small reduction | |
| HDL cholesterol (mmol/L) | 6 | 891 | 3 to 58 | –0.02 to 0.16 | MD 0.02 (–0.01 to 0.04) | ●●●○ MODERATE | Little or no effect | |
| Triglycerides (mmol/L) | 7 | 939 | 3 to 58 | –0.44 to 1.32 | MB –0.09 (–0.16 to –0.01) | ●●●○ MODERATE | Small reduction | |
| Systolic blood pressure (mmHg) | 4 | 448 | 3 to 12 | –10.4 to 6.9 | MD – 1.50 (–3.92 to 0.92) | ●●○○ LOW | Little or no effect | |
| Diastolic blood pressure (mmHg) | 4 | 448 | 3 to 12 | –8.1 to 5.3 | MD –0.26 (–2.41 to 1.90) | ●●○○ LOW | Little or no effect | |
| Mediterranean diet vs usual care (secondary prevention) | Total cholesterol (mmol/L) | 2 | 441 | 12 to 48 | –0.22 to –0.31 | MD 0.07 (–0.19 to 0.33) | ●●○○ LOW | Uncertainty |
| LDL cholesterol (mmol/L) | 2 | 441 | 12 to 48 | –0.26 to –0.41 | MD 0.11 (–0.09 to 0.31) | ●●○○ LOW | Uncertainty | |
| HDL cholesterol (mmol/L) | 2 | 441 | 12 to 48 | 0 to 0.15 | MD –0.01 (–0.08 to 0.07) | ●●○○ LOW | Uncertainty | |
| Triglycerides (mmol/L) | 2 | 441 | 12 to 48 | –0.02 to –0.08 | MD –0.14 (–0.38 to 0.10) | ●●○○ LOW | Uncertainty | |
| Systolic blood pressure (mmHg) | 1 | 339 | 48 | 9 | MD –2.00 (–5.29 to 1.29) | ●○○○ VERY LOW | Uncertainty | |
| Diastolic blood pressure (mmHg) | 1 | 339 | 48 | 5 | MD –1.00 (–4.29 to 2.29) | ●○○○ VERY LOW | Uncertainty | |
| Mediterranean diet vs another dietary intervention (secondary prevention) | Total cholesterol (mmol/L)* | Not reported | ||||||
| LDL cholesterol (mmol/L)* | 1 | 71 | 24 | 0.13 | MD 0.08 (–0.26 to 0.42) | ●○○○ VERY LOW | Little or no effect | |
| HDL cholesterol (mmol/L)* | 1 | 71 | 24 | 0.10 | MD –0.05 (–0.17 to 0.06) | ●●○○ LOW | Little or no effect | |
| Triglycerides (mmol/L)* | 1 | 71 | 24 | –0.63 | MD 0.46 (–0.24 to 1.16) | ●○○○ VERY LOW | Little or no effect | |
| Systolic blood pressure (mmHg)* | 2 | 150 | 3 to 24 | 4 to –9.33 | MD 1.76 (–2.80 to 6.33) | ●○○○ VERY LOW | Little or no effect | |
| Diastolic blood pressure (mmHg)* | 2 | 150 | 3 to 24 | 1 to –9.23 | MD 0.98 (–1.97 to 3.93) | ●○○○ VERY LOW | Little or no effect | |
[i] *sensitivity analysis without Singh studies.
Figure 3
Total Cholesterol.
Figure 4
LDL Cholesterol.
Figure 5
HDL Cholesterol.
Figure 6
Triglycerides.
Figure 7
Systolic Blood Pressure.
Figure 8
Diastolic Blood Pressure.