Mediterranean Diet For Obesity-Review-Curr Obes Rept-2022

Current Obesity Reports (2022) 11:287–304
https://doi.org/10.1007/s13679-022-00481-1
METABOLISM (M DALAMAGA, SECTION EDITOR)
Mediterranean Diet and Obesity‑related Disorders: What

is the Evidence?
Giovanna Muscogiuri1,2,3 · Ludovica Verde2 · Cem Sulu4 · Niki Katsiki5 · Maria Hassapidou5 · Evelyn Frias‑Toral6 ·
Gabriela Cucalón7 · Agnieszka Pazderska8 · Volkan Demirhan Yumuk4 · Annamaria Colao1,2,3 · Luigi Barrea2,9
Accepted: 16 April 2022 / Published online: 30 September 2022

© The Author(s) 2022
Abstract
Purpose of Review Obesity is a chronic disease, a major public health problem due to its association with non-communicable
diseases and all-cause mortality. Indeed, people with obesity are at increased risk for a variety of obesity-related disorders
including hypertension, dyslipidemia, type 2 diabetes mellitus, cardiovascular disease, and several cancers. Many popular
diets with very different macronutrient composition, including the Mediterranean diet (MD), have been used, proposed, and
studied for prevention and management of obesity. In particular, MD has been the subject of countless studies over the years
and now boasts a large body of scientific literature. In this review, we aimed to update current knowledge by summarizing
the most recent evidence on the effect of MD on obesity and obesity-related disorders.
Recent Findings The negative effects of obesity are partly reversed by substantial weight loss that can be achieved with
MD, especially when low-calorie and in combination with adequate physical activity. In addition, the composition of MD
has been correlated with an excellent effect on reducing dyslipidemia. It also positively modulates the gut microbiota and
immune system, significantly decreasing inflammatory mediators, a common ground for many obesity-related disorders.
Summary People with obesity are at increased risk for a variety of medical disorders including hypertension, dyslipidemia,
type 2 diabetes mellitus, and cardiovascular disease. Therefore, there is an inevitable need for measures to manage obesity
and its related disorders. At this point, MD has been proposed as a valuable nutritional intervention. It is characterized by a
high consumption of vegetables, fruit, nuts, cereals, whole grains, and extra virgin olive oil, as well as a moderate consump-
tion of fish and poultry, and a limited intake of sweets, red meat, and dairy products. MD proves to be the healthiest dietary
pattern available to tackle obesity and prevent several non-communicable diseases, including cardiovascular disease and
type 2 diabetes.
Keywords Mediterranean diet · Obesity · Obesity-related disorders · Cardiovascular diseases · Type 2 diabetes ·
Dyslipidemia
Introduction
The World Health Organization defines obesity as abnormal

or excessive fat accumulation that portends increased risk to
health status [1]. Despite this relatively simplistic definition,
it is a chronic disease, a major public health problem that
Giovanna Muscogiuri and Ludovica Verde contributed equally to
this work. adversely effects all aspects of mental and physical health.
Obesity has a growing worldwide prevalence irrespective of
This article is part of the Topical Collection on Metabolism age, sex, race, or socioeconomic status [2]. Nearly a third of
the world population is now suffering of overweight or obe-
* Giovanna Muscogiuri
[email protected] sity, which corresponds to one-fold increase since 1980 [3].
People with obesity are at increased risk for a variety
* Luigi Barrea
[email protected] of medical disorders including hypertension, dyslipidemia,
type 2 diabetes mellitus, cardiovascular disease (CVD),
Extended author information available on the last page of the article
13
Vol.:(0123456789)
288 Current Obesity Reports (2022) 11:287–304
and several cancers [4–6], all of which render obesity to supplemented with nuts, or a low-fat diet and followed for a
be consistently associated with increased mortality [7, 8]. median of 4.8 years [21]. The fat content in the two MD
Therefore, there is inevitable need for measures to manage arms accounted for 42% of daily energy. Calorie restriction
obesity and its related disorders. At this point, Mediterra- was not required in either intervention arm and physical
nean diet (MD) has been proposed to serve as a valuable activity was not encouraged, despite high prevalence of
nutritional intervention [9]. It is characterized by a high overweight and obesity in the study population. At the end
intake of vegetables, fruits, nuts, cereals, whole grains, of follow-up, participants in each of the three groups had
and extra-virgin olive oil, as well as a moderate consump- slightly reduced body weight and increased waist circumfer-
tion of fish and poultry, and a limited intake of sweets, red ence (WC). In comparison with low-fat diet, neither arm of
meat, and dairy products [10]. Indeed, the adherence to MD ad libitum MD demonstrated significant difference in body
dietary pattern is characterized by high intake of monoun- weight: −0.410 kg (95% CI −0.830 to 0.01; p = 0.056) for
saturated fat and fiber, and low in saturated fat with a bal- MD supplemented with olive oil and −0.016 kg (95% CI
anced ratio of omega-6/omega-3 essential fatty acids [11]. −0.453 to 0.421; p = 0.942) for MD supplemented with
The adherence to MD dietary pattern has been showed to nuts. There was evidence that MD was associated with less
be protective against the occurrence of several diseases, in gain of central adiposity as shown by the adjusted difference
particular obesity and CVD [12]. In particular, two previ- in WC after 5 years of −0.466 cm (95% CI −1.109 to 0.176;
ously conducted landmark randomized controlled trials p = 0.154) in MD with olive oil and −0.923 cm (95% CI
(RCT) provided sobering evidence concerning the potential −1.604 to −0.241; p = 0.008) in the nut group, compared
of MD for weight control and CVD prevention, which is not with low-fat diet group. In conclusion, high fat, unrestricted
available for any other dietary pattern [13, 14]. Furthermore, calories MD was associated with little weight changes and
Mediterranean dietary pattern compared to other diets has less central adiposity compared with low-fat diet long term
been reported as having proved to be the most effective in [21]. A systematic meta-analysis of 16 RCTs (n = 3436)
prevention of obesity and obesity-related diseases [15]. assessing MD interventions of duration between 4 weeks and
In this paper, we aimed to review the current knowledge 24 months concluded that consumption of MD is associated
regarding the effect of MD on obesity and obesity-related with a greater weight loss compared to control diets and that
disorders. the weight loss is more significant when energy restriction
and/or increased physical activity are recommended as part
of the intervention [22]. Another systematic analysis
Mediterranean Diet and Body Composition assessed the effects of calorie-restricted MD on weight loss
in individuals with overweight and obesity after 12 months
There is no single definition of what constitutes MD, but it or longer [23]. Five RCTs were included (n = 998). MD was
generally consists of little amounts of red meat, low to mod- somewhat superior in producing weight loss compared to
erate amounts of fish, poultry, and large quantities of fruit, low-fat diets (range of mean weight loss −4.1 to −10.1 kg
vegetables, whole grains, and pulses with unrestricted olive vs. −2.9 to −5.0 kg) but (similar to) same as low-carbohy-
oil as an important source of monounsaturated fatty acids drate diet and the American Diabetes Association (ADA)
(MUFA) [16]. This diet is generally considered to be rela- diet. The effects of MD on BMI and WC were similar to that
tively high in fat, and as such many health professionals may on body weight reduction [23]. The current recommendation
be reluctant to recommend it to individuals with overweight for lifestyle management of subjects with type 2 diabetes and
or obesity as high fat diets are perceived to promote weight overweight or obesity is to achieve and sustain a weight loss
gain. Contrary to that popular belief, epidemiological studies of ≥ 5% a target which is often difficult to reach in clinical
have described an inverse association of adherence to MD practice [24]. A meta-analysis incorporating 19 weight-loss
with Body Mass Index (BMI) and weight gain [17, 18]. intervention study groups (n = 2711) in type 2 diabetes dem-
Moreover, higher adherence to MD is associated with onstrated that energy restricted Mediterranean style diet
increased likelihood of weight loss maintenance [19]. How- combined with 175 min of physical activity weekly was one
ever, most of those studies did not include assessments of of only two interventions achieving the recommended 5%
physical activity or capture total energy intake, which could weight loss at 12 months [25]. This was associated with
serve as significant confounders. The evidence from inter- significant improvement in metabolic parameters [25].
ventional studies on MD suggest that the weight effect Emerging evidence suggests that MD can reduce central
depends more on energy content rather than macronutrient adiposity and visceral fat, both of which have been associ-
composition [20]. However, even when not energy restricted, ated with the risk of type 2 diabetes and CVD [26]. In cross-
this diet is not associated with weight gain. In the largest sectional studies, adherence to MD has been shown to be
RCT on MD conducted to date, 7447 individuals were ran- inversely associated with abdominal adiposity [17, 27, 28].
domized to MD supplemented with olive oil, MD The beneficial effect of MD on reducing central adiposity
13
Current Obesity Reports (2022) 11:287–304 289
and visceral fat could be related to its high content of poly- The reduction in central adiposity, albeit not universal, was
unsaturated fatty acids (PUFA) and MUFA and low intake observed irrespective of whether energy restriction was rec-
of saturated fatty acids (SFA) [11]. It has long been known ommended or not as part of the intervention. Interestingly,
that visceral adipose tissue comprises predominantly SFA, four of the five studies that did not observe improvement in
whereas subcutaneous fat has deposits of PUFA and MUFA measures of central adiposity were conducted in non-Med-
[29]. In line with this hypothesis, a short cross-over study in iterranean populations. It remains unclear if MD is more
patients with obesity (n = 11), individuals with insulin effective in reducing central adiposity compared to other
resistance demonstrated that an isocaloric MD rich in extra- dietary interventions given that MD showed superior effects
virgin olive oil prevented central body fat accumulation only in three studies included in the analysis [37•]. In con-
compared with a low-fat diet without effect on body weight clusion, MD is an effective tool in reducing body weight,
[30]. Reduction in visceral adipose tissue has been reported particularly when energy restricted and in combination with
in two interventional trials of MD after 2 months [31, 32]. increased exercise. Reassuringly, even when not energy-
Contrary to these findings, a small RCT of ad libitum MD restricted it is not associated with weight gain in the short or
(n = 35) compared to a low-fat diet (n = 31) for 6 months long term.
demonstrated that the former was associated with reduced MD has the potential to reduce abdominal adiposity, in
subcutaneous adipose tissue but not visceral adipose tissue particular metabolically detrimental visceral fat, indepen-
or other body composition parameters in patients with over- dently of weight loss, and can be recommended as a healthy
weight or obesity post coronary event [33]. However, the diet choice to individuals with obesity and overweight, par-
participants with more sustained adherence to MD had sig- ticularly at risk of cardiovascular and metabolic disease. MD
nificantly lower WC (−2.81 cm, p = 0.01). No change in may be more effective in Southern European populations
body weight, and a trend for reduction in total body fat, was due to better availability of specific food produce, cultural
observed despite the tendency for increased total energy and other factors.
intake in the MD group [33]. An intervention with calorie-
restricted protein-enriched MD of 8 weeks’ duration has
been shown to result in significant reduction in weight Mediterranean Diet and Type 2 Diabetes
(−16.7%), visceral fat (−27.4%), and fat mass (−28.1%) with
preservation of fat free mass (FFM) in men with obesity (n The International Diabetes Federation (IDF) estimated just
= 37) awaiting laparoscopic sleeve gastrectomy [32]. over 20 years ago that 151 million adults were affected by
Another short-intervention study of 6 weeks’ duration dem- T2D worldwide [38]. This has increased to 463 million in
onstrated that hypocaloric MD was superior in reducing 2019, suggesting a tripling of the global burden over this
body fat mass and preserving FFM compared to high-protein period [38].
diets in young, sedentary individuals [34••]. Preservation of Lifestyle measures remain the cornerstone for type 2 dia-
FFM may be of particular importance in preserving short- betes treatment as recommended by several scientific socie-
and long-term benefits of weight loss given that FFM has ties, including the ADA and the European Association for
been associated with decreased basal metabolic rate and the the Study of Diabetes (EASD) [39, 40]. In the latest (2021)
risk of developing sarcopenic obesity [35]. A meta-analysis ADA guidelines, recommendations for medical nutrition
of 50 studies including an overall population of nearly half therapy emphasize the implementation of a Mediterranean-
a million subjects concluded that MD had beneficial effects style eating pattern to improve both glucose and lipid metab-
on the risk of metabolic syndrome and its individual com- olism, thus minimizing individual’s cardiovascular risk [39].
ponents, including WC (mean difference −0.42 cm; 95% CI Such an eating pattern is characterized by reduced consump-
−0.81 to −0.02) [36]. Importantly, larger effects were seen tion of saturated and trans-fat, as well as an increased intake
in trials conducted in Mediterranean countries, possibly due of dietary PUFA n-3, viscous fiber, and plant sterols/stanols.
to better availability of the required food produce, although The plant-based components of MD (e.g., vegetables, fruits,
other confounders such as genetic or environmental factors whole grains, and nuts) contain polyphenols that have been
may have played a role [36]. A systematic review looked shown to reduce insulin resistance and improve cardiometa-
specifically at the effects of MD on central obesity outcomes. bolic risk factors [41]. Olive oil and low-to-moderate alcohol
The analysis of 18 interventional trials (7186 total subjects intake (especially red wine) also contribute to the benefits of
and 5168 subjects assigned to MD) concluded that MD MD via their polyphenol content [42, 43]. Overall, potential
could diminish abdominal adiposity as evidenced by reduc- mechanisms underlying the beneficial effects of MD include
tion in WC, waist-hip ratio, or visceral fat [37]. The most improvements in oxidative stress, inflammation, thrombosis,
consistent reductions were observed in WC and visceral fat, insulin sensitivity, lipid profile, endothelial dysfunction, and
although only two studies reported the effects on the latter. gut microbiota [44–46] (Fig. 1).
13
Fig. 1 The beneficial mechanisms of Mediterranean diet in obesity-related disorders
Mediterranean Diet and Type 2 Diabetes optimal macronutrient composition of the diet for long-term
Prevention management of type 2 diabetes [48]. Previous meta-analyses
showed that adherence to MD could prevent type 2 diabetes
Type 2 diabetes is considered one of the major obesity- development by 19–23% [49, 50]. In a more recent cohort
related comorbidities. The core pathophysiologic defect study (n = 25,317 female participants from the Women’s
which is at the base of obesity is insulin resistance in muscle Health Study), a higher MD intake was related to a 30%
and liver, predicting the onset of type 2 diabetes in suscep- relative risk decrease in type 2 diabetes incidence during a
tible subjects [47]. Although current dietary recommenda- 20-year follow-up [51]. Furthermore, an inverse association
tions focused on weight loss and overall dietary quality, to between adherence to MD and the prevalence of metabolic
date, in subjects with obesity, there is no consensus on the syndrome and prediabetes has been reported [52, 53].
13
Mediterranean Diet and Cardiometabolic −0.21), fasting insulin (M mean difference −0.55 μU/mL;
Risk Factors 95% CI −0.81 to −0.29), weight (mean difference −0.29 kg;
95% CI −0.55 to −0.04), BMI (mean difference −0.29 kg/
In patients with type 2 diabetes, MD can beneficially affect m2; 95% CI −0.46 to −0.12), TG (mean difference −0.29
glycemic control and cardiovascular risk [54, 55]. In this mmol/L; 95% CI −0.47 to −0.10), systolic BP (mean differ-
context, a cross-sectional study among 500 patients with ence −1.45 mmHg; 95% CI −1.97 to −0.94), and diastolic
type 2 diabetes investigated the impact of MD on glycated BP (mean difference −1.41 mmHg; 95% CI −1.84 to −0.97),
hemoglobin (HbA1c). Mean HbA1c was 8.57 (±standard as well as greater increases in HDL-C (mean difference 0.06
deviation, SD 1.94), 7.63 (±1.32), and 6.47 (±0.7) % in mmol/L; 95% CI 0.02 to 0.10) compared with control diets
patients with low, moderate, and high adherence to MD, [62]. These cardiometabolic effects of MD in patients with
respectively [56]. In another randomized trial (n = 215 type 2 diabetes were also summarized in a previous system-
newly diagnosed patients with type 2 diabetes), HbA1c was atic review [63].
significantly reduced by 1.2 and 0.9% at year 1 and 4, respec-
tively, in patients on MD [57]. Fasting plasma glucose,
serum insulin levels, and Homeostasis Model Assessment Mediterranean Diet and Diabetic
of Insulin Resistance (HOMA-IR) were also significantly Microvascular Complications
decreased. As a consequence, significantly less patients
needed antidiabetic drug therapy both at year 1 and year 4 Low adherence to MD was also linked to impaired renal
(hazard ratio, HR 0.70, 95% CI 0.59 to 0.90) [57]. Similar function and health-related quality of life in patients with
results were reported in a systematic review of 20 RCTs (> type 2 diabetes and chronic kidney disease [64, 65]. Among
6 months duration, n = 2223 patients with type 2 diabetes) women with type 2 diabetes, moderate and high MD scores
showing greater decreases in body weight and HbA1c lev- were related to significantly reduced rates of diabetic
els, as well as delayed requirement for antidiabetic drugs nephropathy by 62% (OR 0.38; 95% CI 0.20 to 0.73) and
in patients with type 2 diabetes following a MD compared 86% (OR 0.14; 95% CI 0.06 to 0.33), respectively, compared
with those on other low-fat or low-carbohydrate diets [58]. with a low MD score [66]. Of note, increases in MD score by
Apart from improvements in glucose metabolism and 1-point were associated with 10% lower risk of CKD (mean
body weight, MD can beneficially affect other cardiovascu- follow-up 20.6 ± 7.0 years) as shown in a meta-analysis (13
lar risk factors, including lipids as triglycerides (TG), low- studies, n = 27,618 individuals) [67]. Furthermore, imple-
density lipoprotein cholesterol (LDL-C) and high-density mentation of MD was associated with decreased rate of inci-
lipoprotein cholesterol (HDL-C), and blood pressure (BP), dent CKD during mean follow-up of 24 years among 12,155
in patients with type 2 diabetes [59]. For example, among participants (aged 45–64 years) from the Atherosclerosis
2568 patients with type 2 diabetes, those with a high MD Risk in Communities Study [68]. Even when CKD has been
score had significantly lower LDL-C (101.5 ± 31.2 vs. 105.1 developed, MD can exert nephroprotection. For example, in
± 31.9 mg/dL), TG (146.7 ± 71.0 vs. 156.2 ± 78.6 mg/ a cross-sectional analysis of the German Chronic Kidney
dL), systolic BP (133.3 ± 23.7 vs. 135.3 ± 14.9 mmHg), Disease Study (n = 2813 patients with CKD), a high MD
and diastolic BP (78.6 ± 8.5 vs. 80.7 ± 8.7 mmHg), as score correlated with higher estimated glomerular filtration
well as higher HDL-C (46.8 ± 12.4 vs. 45.3 ± 11.6 mg/ rate (eGFR) (β-coefficient 0.932, p = 0.007) [64]. Overall,
dL) than those with a low MD score [60]. Such findings MD has been shown to prevent CKD, as well as decrease
were confirmed in a network meta-analysis (10 RCTs, n = renal function decline and improve survival in patients with
921 patients with type 2 diabetes) reporting that MD was CKD [69].
superior to a low-fat diet in reducing HbA1c (mean dif- Increased adherence to MD has been associated with
ference −0.45%; 95% CI −0.55 to −0.34), fasting plasma lower risk of developing diabetic retinopathy (HR 0.34; 95%
glucose (mean difference −1.24 mmol/L; 95% CI −1.57 to CI 0.13 to 0.89; p = 0.001 for trend) among 3614 patients
−0.91), weight (mean difference −1.18 kg; 95% CI −1.99 with type 2 diabetes (aged 55–80 years) from the PREven-
to −0.37), WC (mean difference −0.73 cm; 95% CI −1.26 ción con DIeta MEDiterránea (PREDIMED) study [70].
to −0.19), and TG (mean difference −0.21 mmol/L; 95% CI Similar results have been reported in other studies [71–73].
−0.27 to −0.16), as well as in increasing HDL-C (mean dif- Few evidence supports a link between adherence to MD
ference 0.07 mmol/L; 95% CI 0.04 to 0.11) [61]. Similarly, and protection against diabetic neuropathy development
in another meta-analysis (9 RCTs, n = 1178 type 2 diabetes [72], but further research is needed to elucidate such associa-
patients), MD led to greater decreases in HbA1c (mean dif- tions. Similarly, there is data showing that MD may preserve
ference −0.30%; 95% CI −0.46 to −0.14), fasting plasma cognitive function and prevent dementia [74, 75], even in
glucose (mean difference −0.72 mmol/L; 95% CI −1.24 to patients with type 2 diabetes [76].
13
Mediterranean Diet and Diabetic Mediterranean Diet and Non‑alcoholic Fatty

Macrovascular Complications Liver Disease
A previous umbrella review of meta-analyses found that high Non-alcoholic fatty liver disease (NAFLD) has been associ-
adherence to MD was associated with a reduced risk of overall ated with type 2 diabetes and further increase of cardiovas-
mortality, CVD, coronary heart disease (CHD), myocardial cular risk [89–92]. NAFLD is regarded as the hepatic mani-
infarction (MI), overall cancer incidence, type 2 diabetes, festation of metabolic syndrome [93]. Currently, the global
and neurodegenerative diseases [77]. Furthermore, MD was NAFLD prevalence is reported to be 25%, being highest in
reported to protect against worse outcomes (heart failure hos- the Middle East (32%) and South America (31%) followed
pitalization, unstable angina, stroke, recurrent MI, all cause or by Asia (27%), the USA (24%), Europe (23%), and Africa
cardia death) up to 46 months following an MI [78]. Similarly, with the lowest prevalence (14%) [94].
data from the GISSI-Prevenzione clinical trial showed that MD has been proposed as an effective nutrition therapy
MD significantly decreased all-cause death in 11,323 patients for patients with type 2 diabetes and/or NAFLD, represent-
with MI [79]. Furthermore, among 23,232 participants of the ing the first-line treatment for these metabolic diseases
European Prospective Investigations into Cancer and Nutrition [93, 95•, 96]. In this context, MD was shown to improve
(EPIC) study, followed up for 17 years, stroke risk was signifi- biochemical and histological features of NAFLD [97, 98].
cantly reduced with a greater adherence to MD (HR 0.78; 95% Therefore, implementation of MD may protect liver struc-
CI 0.65 to 0.93) [80]. Low adherence to MD was also related ture and function in patients with type 2 diabetes. Of inter-
to a higher incident of stroke compared with moderate (HR est, in patients with of NAFLD, it has been reported the
1.32; 95% CI 1.05 to 1.66) and high adherence (HR 1.28; 95% enlargement of spleen which is the central organ in regulat-
CI 1.00 to 1.63) among 30,239 participants of the REasons for ing the inflammation-related immune response depicting the
Geographic And Racial Differences in Stroke (REGARDS) so called liver-spleen axis [99]. Healthy dietary patterns,
study, followed up for 6.5 years [81]. MD was shown to protect including MD, have been reported to improve immune and
against peripheral artery disease (PAD) development in the inflammatory responses by both reducing NAFLD and
PREDIMED study (n = 7435 participants, median follow-up: improving spleen function [100].
4.8 years) [82]. Overall, adherence to MD exerts several health benefits
In patients with type 2 diabetes, following MD led to sig- by improving cardiometabolic risk factors, including glucose
nificant reductions in CVD incidence (RR 0.62; 95% CI 0.5 and lipid metabolism, obesity indexes and NAFLD (Fig. 2).
to 0.78) [83]. A recent meta-analysis of 38 cohort studies and
3 RCTs (including patients with type 2 diabetes) found that Mediterranean Diet and Dyslipidemia
adherence to MD was associated with significantly lower inci-
dences of CHD (RR 0.73; 95% CI 0.62 to 0.86), MI (RR 0.73; Dyslipidemia is a primary cause of the atherosclerotic car-
95% CI 0.61 to 0.88), and stroke (RR 0.80; 95% CI 0.71 to diovascular disease (ASCVD) [101]. In particular, the most
0.90), as well as of CHD mortality (RR 0.83; 95% CI 0.75 atherogenic form has been associated with type 2 diabe-
to 0.92), stroke mortality (RR 0.87; 95% CI 0.80 to 0.96), tes and insulin resistance conditions [102]. Dyslipidemia
and total CVD death (RR 0.79; 95% CI 0.77 to 0.82) [84]. is characterized by elevated serum levels of LDL-C and
A higher MD score was also linked to a significantly lower TG and low levels of HDL-C [103]. In 2008, according to
risk (by 66%) of PAD incidence (OR 0.44; 95% CI 0.24 to the WHO Global Health Observatory, the prevalence of a
0.83) in patients with type 2 diabetes (n = 944) [85]. Similarly, plasma total cholesterol level ≥ 190 mg/dl was highest in
increased intake of fish and shellfish was reported to margin- Europe (54% for both sexes), followed by North and South
ally decrease PAD risk (HR per additional gram/week 0.99; America (48% for both sexes), while Africa and South-
95% CI 0.99 to 1.00, p = 0.051) in 1112 patients with type 2 East Asia had the lowest prevalence (22.6% and 29.0%,
diabetes followed for a median of 19.7 years in the Malmö Diet respectively) [104]. Between 1980 and 2018, globally, lit-
and Cancer study [86]. Nevertheless, further clinical data is tle or no change in total and non-HDL plasma cholesterol
needed in patients with type 2 diabetes to establish the effects was observed, but several regions experienced significant
of MD on cardiovascular morbidity and mortality. changes in some lipid parameters: high-income countries,
In sum, in patients with type 2 diabetes, MD may mini- which had the highest plasma cholesterol levels in 1980,
mize the risk of diabetic micro and macrovascular compli- experienced a substantial reduction in plasma cholesterol
cations, although further evidence is required. Therefore, levels, while low- and middle-income countries experienced
implementation of MD is recommended for both prevention large increases in both plasma cholesterol and plasma tri-
and treatment of prediabetes and type 2 diabetes [55, 87, 88]. glycerides [105].
13
Fig. 2 The beneficial effects of adherence to MD on cardiometabolic factors and diabetic complications in patients with type 2 diabetes
In recent years, several studies have investigated the role Also, MD favors the restriction of milk and dairy product
of diet and dyslipidemia. MD is a dietary pattern recom- consumption and limited intake of meat and meat-derived
mended for cardiovascular prevention and has been pro- products [16]. Moreover, high plant-based food intake, such
moted by the European Society of Cardiology/European as whole grains, vegetables, and fruits, is highly advisable.
Atherosclerosis Society (ESC/EAS) 2019 guidelines for MD suggests the consumption of seafood, regular consump-
the management of dyslipidemia in addition to other life- tion of olive oil, and increased physical activity. Finally, MD
style changes (Table 1) [103]. Ancel Keys designed MD recommends reducing simple sugar intake and eliminating
almost five decades ago, and it has been recognized as one alcohol. This dietary pattern is high on food groups such as
of the healthiest dietary patterns [16]. In addition, it has been fruits and vegetables, fibers, olive oil, fish, and red wine, that
negatively related to various chronic diseases, such as CVD are rich sources of several bioactive compounds, including
[106], cancer [107], obesity [108], type 2 diabetes [88], and antioxidants like carotenoids, flavonoids, resveratrol, and
other metabolic conditions [109]. other polyphenolic compounds [16].
Specifically for patients that suffer from hyperlipidemia, Studies have proven that consumption of foods causes
MD advocates for low intake of SFA, less than < 7% in modifications in the gut microbiota leading to an increase
patients with hypercholesterolemia, and high consumption of beneficial bacteria such as Lactobacillus, Bifidobacte-
of PUFA and micronutrients, including dietary vitamins and rium, and Prevotella, and a reduction of harmful bacteria
minerals, that rises the plasma antioxidant capacity [110]. like Clostridium [111]. This effect is positive for prevention
Table 1 Treatment targets/ Treatment Recommendation

goals 2019 European Society
of Cardiology/European Smoking No use in any form of tobacco
Atherosclerosis Society (ESC/
Diet Diet low in saturated fat with whole grain products, vegetables,
EAS) guidelines [103]
fruit, and fish
Physical activity 30–60 min moderately vigorous physical activity most days
Bodyweight BMI 20–25 kg/m2, and WC < 94 cm and < 80 cm (women)
Blood pressure < 140/90 mmHg
BMI body mass index, WC waist circumference
13
and treatment of chronic diseases like obesity [112], dyslipi- intake of SFA from dairy sources. However, the literature is
demia [113], and inflammation [114]. MD is also considered still controversial regarding the relationship between meat
a high fiber intake pattern, which can act on gut microbi- and dairy products intake and the effect on lipid profile [88,
ota by modulating its composition and the production of 121, 122]. The Prospective Urban and Rural Epidemiology
metabolites that regulate immune function [115]. MD leads study was a large study that helped understand the connec-
to an increase in the number of intestinal bacterial species tion between macronutrient intake and mortality, concluding
responsible for producing short-chain fatty acids (SCFAs) that SFA intake does not influence mortality rate [123]. At
such as acetate, propionate, and butyrate, essential for proper the same time, high consumption of carbohydrates has been
functioning in preventing metabolic diseases [115]. Also, associated with a higher mortality risk for CVD [123].
high consumption of PUFA n-3 from fish and vegetable Other studies have investigated the relationship between
sources and an adequate PUFA n-6/ PUFA n-3 ratio from SFA intake and cardiovascular mortality and did not observe
MD [116] promotes a better metabolic profile compared to an increased risk of ASCVD events in subjects with high
other dietary patterns that are high on PUFA n-6 and favors consumption of SFA compared with those with low con-
a higher production of proinflammatory substances and that sumption [124–126]. Consequently, ASCVD risk may be
increases the risk of chronic diseases like ASCVD [117]. influenced by the dietary source of SFA, mainly repre-
Dietary fiber has become a key mediator of the communica- sented by dairy and meat products. Meat consumption is
tion between the brain and the gut [118]. SCFAs exert their a dietary risk factor for atherogenic dyslipidemia [126]. de
beneficial effects directly by contributing to modulation of Oliveira et al. in the Multi-Ethnic Study of Atherosclerosis
host health through a range of tissue-specific mechanisms (n = 5209) reported that a higher intake of SFA from meat
related to gut barrier function, glucose homeostasis, immu- products is related to the development of ASCVD; on the
nomodulation, and appetite regulation [118]. Evidence on other hand, a lower ASCVD risk has been correlated to a
this effect has emerged from the modulation of gut microbial higher intake of SFA from dairy products [125]. However,
composition through administration of prebiotics, defined as studies are controversial regarding the relationship between
a non-digestible food ingredient that stimulates the growth meat and dairy products intake and the effect on lipid profile
and/or activity of one or a limited number of beneficial bac- [125, 126].
teria in the colon [119]. In 2021, Formisano et al. evaluated the influence of differ-
In addition to the gut microbiota modulation effects, the ent eating habits on the lipid profile of 106 patients suffering
beneficial impact of MD could also be due to immune sys- from different types of dyslipidemia [126]. They concluded
tem modulation [100, 120]. In an intervention study con- that a high intake of dairy products was associated with
ducted by Llorente-Cortés et al. in 2010 on a population hyperlipidemia (higher levels of total cholesterol and HDL-
with a high risk of ASCVD (n = 49), it was found that after C), while a diet with an excessive amount of meat products
3 months, subjects who followed MD integrated with virgin caused a form of dyslipidemia (higher total cholesterol and
olive oil or nuts showed not only a reduction in interleukin-6 TG levels and lower HDL-C levels) [126]. Therefore, dietary
and soluble intercellular adhesion molecule-1, significant recommendations should specify between SFA other than
inflammation mediators in the adhesion of leukocytes to the suggesting general reduction in SFA intake.
endothelial surface, but also a reduction in activation of bio- Adherence is primordial for treatment of chronic diseases
markers related to the atherosclerotic process [120]. There [88, 122, 127]. Some reports examine the adherence to MD
was a reduction of the proinflammatory ligand CD40 and the and have shown that individuals with obesity and with low
adhesion molecule CD49d on T lymphocytes and monocytes adherence to MD presented worse anthropometric measure-
after both MD [120]. ments and metabolic profile compared with subjects who
Different researchers have studied the relationship were good sleepers and with an average adherence, inde-
between SFA consumption, ASCVD risk and increased pendently of age and gender [88, 122, 127]. Also, the effect
LDL-C levels [121], while recent clinical studies support on gut microbiota includes the maintenance of presence of
the fact that SFA do not increase the risk of ASCVD. The Prevotella bacteria and other Firmicutes according to the
relationship between SFA intake and cardiovascular mortal- degree of adherence to MD [127–129]. On the contrary, low
ity has been discussed previously, and there was no higher adherence to MD has been associated with high levels of uri-
risk of ASCVD events in individuals with high consump- nary trimethylamine N-oxide, which is related to increased
tion of SFA than those with low consumption [121]. It has cardiovascular risk [130, 131]. Of interest, through inflam-
been concluded that ASCVD risk may be more influenced matory processes, TMAO would have a potential role in dif-
by the dietary source of SFA, mainly giving dairy and meat ferent chronic non-communicable diseases, including obe-
products more focus [121]. Therefore, a higher intake of sity [132], CVD [133], type 2 diabetes [134], NAFLD [134],
SFA from meat products is related to the development of and inflammatory diseases [135]. Also, obesity is associated
ASCVD, and that lower ASCVD risk is linked to a higher with reduced spontaneous and stimulated growth hormone
13
Table 2 Meta-analyses of studies regarding the effects of Mediterranean diet on obesity-associated disorders
Source No. and type of studies Subjects Aim Main findings
Esposito et al. [22] 16 RCTs 3436 subjects To evaluate the effect of MD on body MD had a significant effect on weight
weight (95% CI −2.86 to −0.64) and BMI
(95% CI −0.93 to −0.21). The effect
of MD on body weight was greater
in association with energy restriction
(mean difference, −3.88 kg, 95% CI
−6.54 to −1.21 kg), increased physical
activity (−4.01 kg, 95% CI −5.79 to
−2.23 kg), and follow-up longer than
6 months (−2.69 kg, 95% CI −3.99 to
−1.38 kg)
Franz et al. [25] 11 RCTs 6754 adults with overweight or obesity To evaluate the outcomes on HbA1c, 2 study groups reported a weight loss
and T2DM lipid (total cholesterol, LDL-C, of ≥ 5%: a Mediterranean-style diet
HDL-C, and TG) and BP (systolic implemented in newly diagnosed
and diastolic) from lifestyle weight- adults with T2DM, and an intensive
loss interventions resulting in weight lifestyle intervention implemented in
losses greater than or less than 5% at the Look AHEAD trial. Both included
12 months regular physical activity and frequent
To evaluate the weight and metabolic contact with health professionals and
outcomes from differing amounts reported significant beneficial effects
of macronutrients in weight-loss on HbA1c, lipids, and blood pressure
interventions
Kastorini et al. [36] 50 RCTs (35 clinical trials, 2 prospective 534,906 subjects To meta-analyze epidemiological studies Adherence to MD was associated with
and 13 cross-sectional) and clinical trials that have assessed the reduced risk of metabolic syndrome
effect of MD on metabolic syndrome (log HR −0.69; 95% CI −1.24 to
as well as its components −1.16). Results from clinical studies
revealed the protective role of MD on
components of metabolic syndrome,
like WC (mean difference −0.42 cm;
95% CI −0.82 to −0.02), HDL-C (mean
difference 1.17 mg/dl; 95% CI 0.38 to
1.96), TG (mean difference −6.14 mg/
dl; 95% CI −10.35 to −1.93), systolic
(mean difference −2.35 mm Hg; 95%
CI −3.51 to −1.18) and diastolic
BP (mean difference −1.58 mm Hg;
95% CI −2.02 to −1.13), and glucose
(mean difference −3.89 mg/dl; 95% CI
−5.84 to −1.95), whereas results from
epidemiological studies also confirmed
those of clinical trials
13
295
Table 2 (continued)
296
13
Koloverou et al. [49] 10 prospective studies (1 clinical trial, 136,846 subjects To meta-analyze prospective studies Higher adherence to MD was associated
9 prospective and 7 cross-sectional) that have evaluated the effect of MDwith 23% reduced risk of developing
on the development of T2DM T2DM (combined RR for upper vs
lowest available centile: 0.77; 95% CI
0.66 to 0.89). Subgroup analyses based
on region, health status of participants
and number of confounders controlling
for, showed similar results
Schwingshackl et al. [50] 1 RCT and 8 prospective cohort studies 122,810 subjects To meta-analyze the effects of MD For highest vs lowest adherence to MD
adherence on the risk of T2DM score, the pooled RR for T2DM was
0.81 (95% CI 0.73 to 0.90). Sensitivity
analysis including only long-term studies
confirmed the results of the primary
analysis (pooled RR 0.75; 95% CI 0.68
to 0.83)
Pan et al. [61] 10 RCTs 921 subjects with T2DM To comprehensively compare the Compared to low-fat diet, MD showed
differences between major dietary beneficial effects in glycemic control
patterns in improving glycemic (HbA1c 95% CI –0.55 to –0.34; fasting
control, cardiovascular risk, and plasma glucose 95% CI –1.57 to –0.91;
weight loss for patients with T2DM weight loss 95% CI –1.99 to –0.37;
WC 95% CI –1.26 to –0.19), and
cardiovascular risk factors (HDL-C
95% CI 0.04 to 0.11; total cholesterol
95% CI –0.26 to –0.08; TG 95% CI
–0.27 to –0.16)
Huo et al. [62] 9 RCTs 1178 subjects with T2DM To explore the effects of MD on Compared with control diets, MD led
glycemic control, weight loss and to greater reductions in HbA1c (mean
cardiovascular risk factors in T2DM difference, −0.30; 95% CI −0.46 to
patients −0.14), fasting plasma glucose (−0.72
mmol/l; 95% CI −1.24 to −0.21), fasting
insulin (−0.55 μU/ml; 95% CI −0.81
to −0.29), BMI (−0.29 kg/m2; 95% CI
−0.46 to −0.12) and body weight (−0.29
kg; 95% CI −0.55 to −0.04). Likewise,
concentrations of total cholesterol and
TG were decreased (−0.14 mmol/l; 95%
CI −0.19 to −0.09 and −0.29 mmol/l;
95% CI −0.47 to −0.10, respectively),
and HDL-C was increased (0.06 mmol/l;
95% CI 0.02 to 0.10). In addition, MD
was associated with a decline of 1.45
mm Hg (95% CI −1.97 to −0.94) for
systolic and 1.41 mm Hg (95% CI −1.84
to −0.97) for diastolic BP
Table 2 (continued)
Hansrivijit et al. [67] 4 prospective studies 8467 subjects ≥ 18 years of age To assess the association between MD With the mean follow-up duration of
without CKD adherence and CKD prevention 20.6 ± 7.0 years, the pooled OR for
CKD was 0.901 (95% CI 0.868 to
0.935) for each 1-point increment of
MD scale. The incidence of CKD was
0.026 events per person-year (95% CI
0.008 to 0.045)
Becerra-Tomás et al. [84] 3 RCTs and 38 prospective cohort Adults To evaluate the effect of MD on the Meta-analyses of RCTs revealed a
studies with type 1 diabetes or T2DM prevention of CVD incidence and beneficial effect of MD on total CVD
mortality (RR: 0.62; 95% CI 0.50 to 0.78) and
total myocardial infarction (RR: 0.65;

95% CI 0.49 to 0.88) incidence
Meta-analyses of prospective cohort
studies, which compared the highest
vs lowest categories of MD adherence,
revealed an inverse association with
total CVD mortality (RR 0.79; 95% CI
0.77 to 0.82), CHD incidence (RR 0.73;
95% CI 0.62 to 0.86), CHD mortality
(RR 0.83; 95% CI 0.75 to 0.92), stroke
incidence (RR 0.80; 95% CI 0.71
to 0.90), stroke mortality (RR 0.87;
95% C: 0.80 to 0.96) and myocardial
infarction incidence (RR 0.73; 95% CI
0.61 to 0.88)
Schwingshackl et al. [146] 2 RCTs, 51 cohort studies and 30 case– 2,130,753 subjects To evaluate the effects of adherence to Greater adherence to MD was associated
control studies MD on risk of overall cancer mortality, with a significantly lower risk of cancer
risk of different types of cancer, and mortality (RR 0.86; 95% CI 0.81 to
cancer mortality and recurrence risk in 0.91), colorectal cancer (RR 0.82; 95%
cancer survivors CI 0.75 to 0.88), breast cancer (RR 0.92;
95% CI 0.87 to 0.96), gastric cancer
(RR 0.72; 95% CI 0.60 to 0.86), liver
cancer (RR 0.58; 95% CI 0.46 to 0.73),
head and neck cancer (RR 0.49; 95% CI
0.37 to 0.66), and prostate cancer (RR
0.96; 95% CI 0.92 to 1.00)
RCT randomized controlled trial, MD Mediterranean diet, CI confidence interval, BMI body mass index, T2DM type 2 diabetes mellitus, LDL-C low-density lipoprotein cholesterol, HDL-C
high-density lipoprotein cholesterol, BP blood pressure, AHEAD Action for Health in Diabetes, HR hazard ratio, WC waist circumferences, RR risk ratio, CKD chronic kidney disease, CVD car-
diovascular disease, CHD coronary heart disease
13
297
secretion and basal insulin-like growth factor I levels [136] cancer were lower in the intervention groups with EVOO
which has been associated with increased risk of ASCVD or with nuts than in the control group with a low-fat diet.
[137]. The degree of adherence to MD and protein grams After multivariate adjustment, the group supplementing
intake was one of the most predictive factors of growth MD with EVOO had a significantly lower risk of devel-
hormone status in obesity, showing an association between oping breast cancer than the control group; for every 5%
adherence to MD and the clinical alterations of cardiometa- additional calories from EVOO, the risk was 28% lower
bolic status [136]. (95% CI, 0.57 to 0.90) [148]. A case–control study of 2396
Moreover, another critical nutrient that MD considers is women aged 25–74 years found that MD was associated
vitamin D, and the evidence suggests that vitamin D defi- with a 35% reduction in breast cancer risk [149]. The Four
ciency may represent a significant risk factor [138–140]. Corners Breast Cancer Study showed that Hispanic (n =
There is a close relationship between vitamin D and the 757 cases and 867 controls) and non-Hispanic (n = 1524
cardiovascular system by vitamin D receptors in vital tis- cases and 1598 controls) women who adopted MD had a
sues like endothelium, smooth muscle, and myocardium lower risk of breast cancer [150]. Two prospective studies of
[138–140]. Therefore, low vitamin D status has been associ- 91,779 American women [151] and 65,374 French women
ated with increased BP [139, 140], dyslipidemia [139, 140], [152] confirmed a protective association between adherence
impaired insulin metabolism [138], sleep disturbances [141, to MD and breast cancer incidence. The protective effect of
142], thus increasing the risk of cardiovascular atheroscle- MD on breast cancer risk was associated with a reduction
rosis [139, 140]. It has been studied that hypovitaminosis in circulating estrogen levels and increased intake of carot-
D might increase the cardiovascular risk in hypopituita- enoids, which are known antioxidants that reduce oxidative
rism patients, and it is a powerful predictor of prevalence stress. The protective associations were greater in women
of dyslipidemia and hypertension in individuals [138, 140]. with negative progesterone and estrogen receptor [152].
Hypovitaminosis D is commonly reported in patients with A lower risk of colon cancer has been associated with
obesity due to several mechanisms [143, 144]. Of interest, dietary patterns that are higher in vegetables, legumes,
very recently in a cross-sectional, observational study, it was fruits, whole grains, fish, lean meats, low-fat dairy prod-
reported that high adherence to MD was associated with ucts, moderate alcohol consumption, and lower consumption
low BMI in 617 individuals, probably through the antioxi- of red and/or processed meats, sugar-sweetened beverages,
dant and anti-inflammatory effects synergistically exerted and saturated fats [153]. In contrast, diets containing greater
by either high vitamin D levels or high adherence to MD on amounts of red/processed meat, sugars (i.e., desserts, sugar-
body weight [145••]. sweetened beverages, and sweets), potatoes, and chips are
associated with an increased risk of colorectal cancer [153].
Data from the Italian EPIC study involving 42,275 partici-
Mediterranean Diet and Cancer pants aged 25–70 years who did not have cancer at baseline
found that increased adherence to MD was associated with
To date, the important role of prevention in several cancer an 8–11% lower risk of colorectal cancer in men and women
settings is well known, and diet has a good place among [154]. The protective effect was observed mainly for distal
these prevention strategies. A meta-analysis including colon and rectal cancer, whereas it was lower for proximal
2,130,753 participants concluded that greater adherence to colon cancer [154].
MD was associated with a significantly lower risk of cancer In conclusion, all the above results suggest that adherence
mortality (RR 0.86; 95% CI 0.81 to 0.91), colorectal cancer to MD may contribute to the reduction of various cancers
(RR 0.82; 95% CI 0.75 to 0.88), breast cancer (RR 0.92; 95% and also of overall cancer-related mortality. Nevertheless,
CI 0.87 to 0.96), gastric cancer (RR 0.72; 95% CI 0.60 to further research is needed to determine which foods and
0.86), liver cancer (RR 0.58; 95% CI 0.46 to 0.73), head and nutrients are most effective for this outcome (Table 2).
neck cancer (RR 0.49; 95% CI 0.37 to 0.66), and prostate
cancer (RR 0.96; 95% CI 0.92 to 1.00) [146]. In addition,
data on the benefits of MD against incident cancers were
reported in the EPIC trial (n = 9669 incident cancers in men Conclusion
and 21,062 in women) [147]. Evidence of protection was
strongest for colorectal, gastric, and breast cancers, espe- The obesity pandemic is associated with high risk of mor-
cially after exclusion of alcohol from the score [147]. bidity and mortality from different non-communicable
Breast cancer has increased by more than 20% worldwide diseases. Of interest, the negative effects of obesity are
since 2008 and is the leading cause of cancer in women reversed in part with substantial weight loss. The composi-
[148]. Data from the PREDIMED study showed that after tion of MD has been related to an excellent effect on reduc-
a mean follow-up of 4.8 years, the observed rates of breast ing dyslipidemia. Additionally, it positively modulates the
13
gut microbiota and immune system, significantly decreasing an important role for lifestyle management. Curr Diab Rep.
inflammation mediators, common ground for many obesity- 2014;14(10):539.
7. Flegal KM, Kit BK, Orpana H, Graubard BI. Association of all-
related disorders. MD is the healthiest dietary pattern avail- cause mortality with overweight and obesity using standard body
able to prevent several non-communicable diseases, includ- mass index categories: a systematic review and meta-analysis.
ing cardiovascular disease and type 2 diabetes. JAMA. 2013;309(1):71–82.
8. Di Angelantonio E, Bhupathiraju SN, Wormser D, Gao P, Kaptoge
S, De Gonzalez AB, et al. Body-mass index and all-cause mortal-
ity: individual-participant-data meta-analysis of 239 prospective
Author Contribution Conceptualization: Giovanna Muscogiuri and studies in four continents. Lancet. 2016;388(10046):776–86.
Luigi Barrea; Literature search: Ludovica Verde, Cem Sulu, Niki 9. Estruch R, Ros E, Salas-Salvadó J, Covas M-I, Corella D, Arós F,
Katsiki, Maria Hassapidou, Evelyn Frias-Toral, Gabriela Cucalón and et al. Primary prevention of cardiovascular disease with a Medi-
Agnieszka Pazderska; Original draft preparation: Ludovica Verde, Cem terranean diet. N Engl J Med. 2013;368(14):1279–90.
Sulu, Niki Katsiki, Maria Hassapidou, Evelyn Frias-Toral, Gabriela 10. Bach-Faig A, Berry EM, Lairon D, Reguant J, Trichopoulou A,
Cucalón and Agnieszka Pazderska; Writing–review and editing: Vol- Dernini S, et al. Mediterranean diet pyramid today. Science and
kan Demirhan Yumuk, Ludovica Verde, Luigi Barrea and Giovanna cultural updates. Public Health Nutr. 2011;14(12):2274–84.
Muscogiuri; Supervision: Giovanna Muscogiuri, Annamaria Colao and 11. Marventano S, Kolacz P, Castellano S, Galvano F, Buscemi S,
Luigi Barrea. Mistretta A, et al. A review of recent evidence in human studies
of n-3 and n-6 PUFA intake on cardiovascular disease, cancer,
Funding Open access funding provided by Università degli Studi di and depressive disorders: does the ratio really matter? Int J Food
Napoli Federico II within the CRUI-CARE Agreement. Sci Nutr. 2015;66(6):611–22.
12. Sofi F, Abbate R, Gensini GF, Casini A. Accruing evidence on
Compliance with Ethical Standards benefits of adherence to the Mediterranean diet on health: an
updated systematic review and meta-analysis. Am J Clin Nutr.
2010;92(5):1189–96.
Conflict of Interest The authors have no competing interests to declare 13. Martínez-González MÁ, Corella D, Salas-Salvadó J, Ros E,
that are relevant to the content of this article. Covas MI, Fiol M, et al. Cohort profile: design and methods of
the PREDIMED study. Int J Epidemiol. 2012;41(2):377–85.
Human and Animal Rights and Informed Consent This article does not 14. Martínez-González MA, Buil-Cosiales P, Corella D, Bulló
contain any studies with human or animal subjects performed by any M, Fitó M, Vioque J, et al. Cohort profile: design and meth-
of the authors. ods of the PREDIMED-Plus randomized trial. Int J Epidemiol.
2019;48(2):387–8.
Open Access This article is licensed under a Creative Commons Attri- 15. Romaguera D, Norat T, Mouw T, May AM, Bamia C, Slimani
bution 4.0 International License, which permits use, sharing, adapta- N, et al. Adherence to the Mediterranean diet is associated with
tion, distribution and reproduction in any medium or format, as long lower abdominal adiposity in European men and women. J Nutr.
as you give appropriate credit to the original author(s) and the source, 2009;139(9):1728–37.
provide a link to the Creative Commons licence, and indicate if changes 16. Trichopoulou A. Mediterranean diet as intangible heritage of human-
were made. The images or other third party material in this article are ity: 10 years on. Nutr Metab Cardiovasc Dis. 2021;31(7):1943–8.
included in the article's Creative Commons licence, unless indicated 17. Sanchez-Villegas A, Bes-Rastrollo M, Martinez-Gonzalez MA,
otherwise in a credit line to the material. If material is not included in Serra-Majem L. Adherence to a Mediterranean dietary pattern
the article's Creative Commons licence and your intended use is not and weight gain in a follow-up study: the SUN cohort. Int J Obes.
permitted by statutory regulation or exceeds the permitted use, you will 2006;30(2):350–8.
need to obtain permission directly from the copyright holder. To view a 18. Schroder H, Marrugat J, Vila J, Covas MI, Elosua R. Adherence
copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. to the traditional mediterranean diet is inversely associated with
body mass index and obesity in a spanish population. J Nutr.
2004;134(12):3355–61.
19. Poulimeneas D, Anastasiou CA, Santos I, Hill JO, Panagiotakos
References DB, Yannakoulia M. Exploring the relationship between the Medi-
terranean diet and weight loss maintenance: the MedWeight study.
1. Organization WH. Obesity and overweight. Fact sheet N 311. Br J Nutr. 2020;124(8):874–80.
2012. http://w
ww.w ediac entre/f actsh eets/f s311/e n/. Last
ho.i nt/m 20. Kim JY. Optimal diet strategies for weight loss and weight loss
accessed 21 Jan 2022. maintenance. J Obes Metab Syndr. 2021;30(1):20–31.
2. Chooi YC, Ding C, Magkos F. The epidemiology of obesity. 21. Estruch R, Martinez-Gonzalez MA, Corella D, Salas-Salvado
Metabolism. 2019;92:6–10. J, Fito M, Chiva-Blanch G, et al. Effect of a high-fat Mediter-
3. Network GBoDC. Global Burden of Disease Study 2015 (GBD ranean diet on bodyweight and waist circumference: a prespeci-
2015) Obesity and Overweight Prevalence 1980–2015. IHME fied secondary outcomes analysis of the PREDIMED randomised
Seattle; 2017. controlled trial. Lancet Diabetes Endocrinol. 2019;7(5):e6–17.
4. Li Y, Pan A, Wang DD, Liu X, Dhana K, Franco OH, et al. 22. Esposito K, Kastorini CM, Panagiotakos DB, Giugliano D. Medi-
Impact of healthy lifestyle factors on life expectancies in the US terranean diet and weight loss: meta-analysis of randomized con-
population. Circulation. 2018;138(4):345–55. trolled trials. Metab Syndr Relat Disord. 2011;9(1):1–12.
5. Smith AD, Crippa A, Woodcock J, Brage S. Physical activity 23. Mancini JG, Filion KB, Atallah R, Eisenberg MJ. Systematic
and incident type 2 diabetes mellitus: a systematic review and review of the Mediterranean diet for long-term weight loss. Am
dose–response meta-analysis of prospective cohort studies. Dia- J Med. 2016;129(4):407–15.
betologia. 2016;59(12):2527–45. 24. American Diabetes Association. 8. Obesity management for the treat-
6. Valencia WM, Stoutenberg M, Florez H. Weight loss and ment of type 2 diabetes: standards of medical care in diabetes-2021.
physical activity for disease prevention in obese older adults: Diabetes Care. 2021;44(Suppl 1):S100–10.
13
25. Franz MJ, Boucher JL, Rutten-Ramos S, VanWormer JJ. Lifestyle 39. American Diabetes Association. 10. Cardiovascular disease and
weight-loss intervention outcomes in overweight and obese adults risk management: standards of medical care in diabetes-2021.
with type 2 diabetes: a systematic review and meta-analysis of ran- Diabetes Care. 2021;44(Suppl 1):S125–50.
domized clinical trials. J Acad Nutr Diet. 2015;115(9):1447–63. 40. Davies MJ, D’Alessio DA, Fradkin J, Kernan WN, Mathieu C,
26. Prasad DS, Kabir Z, Dash AK, Das BC. Abdominal obesity, an Mingrone G, et al. Management of hyperglycemia in Type 2
independent cardiovascular risk factor in Indian subcontinent: diabetes, 2018. A Consensus Report by the American Diabetes
a clinico epidemiological evidence summary. J Cardiovasc Dis Association (ADA) and the European Association for the Study
Res. 2011;2(4):199–205. of Diabetes (EASD). Diabetes Care. 2018;41(12):2669–701.
27. Bertoli S, Leone A, Vignati L, Bedogni G, Martinez-Gonzalez 41. Guasch-Ferre M, Merino J, Sun Q, Fito M, Salas-Salvado J.
MA, Bes-Rastrollo M, et al. Adherence to the Mediterranean diet Dietary polyphenols, Mediterranean diet, prediabetes, and type
is inversely associated with visceral abdominal tissue in Cauca- 2 diabetes: a narrative review of the evidence. Oxid Med Cell
sian subjects. Clin Nutr. 2015;34(6):1266–72. Longev. 2017;2017:6723931.
28. Martinez-Gonzalez MA, Garcia-Arellano A, Toledo E, Salas- 42. Katsiki N, Perez-Martinez P, Lopez-Miranda J. Olive oil intake
Salvado J, Buil-Cosiales P, Corella D, et al. A 14-item Mediter- and cardiovascular disease prevention: “seek and you shall find.”
ranean diet assessment tool and obesity indexes among high-risk Curr Cardiol Rep. 2021;23(6):64.
subjects: the PREDIMED trial. PLoS ONE. 2012;7(8):e43134. 43. Katsiki N, Tziomalos K, Mikhailidis DP. Alcohol and the car-
29. Calder PC, Harvey DJ, Pond CM, Newsholme EA. Site-specific diovascular system: a double-edged sword. Curr Pharm Des.
differences in the fatty acid composition of human adipose tissue. 2014;20(40):6276–88.
Lipids. 1992;27(9):716–20. 44. Ditano-Vazquez P, Torres-Pena JD, Galeano-Valle F, Perez-
30. Paniagua JA, de la Sacristana AG, Romero I, Vidal-Puig A, Caballero AI, Demelo-Rodriguez P, Lopez-Miranda J, et al.
Latre JM, Sanchez E, et al. Monounsaturated fat-rich diet pre- The fluid aspect of the mediterranean diet in the prevention and
vents central body fat distribution and decreases postprandial management of cardiovascular disease and diabetes: the role of
adiponectin expression induced by a carbohydrate-rich diet in polyphenol content in moderate consumption of wine and olive
insulin-resistant subjects. Diabetes Care. 2007;30(7):1717–23. oil. Nutrients. 2019;11(11):2833.
31. Buscemi S, Verga S, Tranchina MR, Cottone S, Cerasola G. 45. Gotsis E, Anagnostis P, Mariolis A, Vlachou A, Katsiki N, Karagiannis
Effects of hypocaloric very-low-carbohydrate diet vs. Mediter- A. Health benefits of the Mediterranean Diet: an update of research
ranean diet on endothelial function in obese women. Eur J Clin over the last 5 years. Angiology. 2015;66(4):304–18.
Invest. 2009;39(5):339–47. 46. Ismael S, Silvestre MP, Vasques M, Araujo JR, Morais J, Duarte
32. Schiavo L, Scalera G, Sergio R, De Sena G, Pilone V, Barbarisi MI, et al. A pilot study on the metabolic impact of Mediterra-
A. Clinical impact of Mediterranean-enriched-protein diet on liver nean diet in type 2 diabetes: is gut microbiota the key? Nutrients.
size, visceral fat, fat mass, and fat-free mass in patients undergoing 2021;13(4):1228.
sleeve gastrectomy. Surg Obes Relat Dis. 2015;11(5):1164–70. 47. Muscogiuri G, Barrea L, Caprio M, Ceriani F, Chavez AO, El
33. Mayr HL, Itsiopoulos C, Tierney AC, Kucianski T, Radcliffe J, Ghoch M, et al. Nutritional guidelines for the management of
Garg M, et al. Ad libitum Mediterranean diet reduces subcuta- insulin resistance. Crit Rev Food Sci Nutr. 2021;1–14.
neous but not visceral fat in patients with coronary heart dis- 48. Barrea L, Vetrani C, Caprio M, El Ghoch M, Frias-Toral E,
ease: a randomised controlled pilot study. Clin Nutr ESPEN. Mehta RJ, et al. Nutritional management of type 2 diabetes in
2019;32:61–9. subjects with obesity: an international guideline for clinical prac-
34.•• Feidantsis K, Methenitis S, Ketselidi K, Vagianou K, tice. Crit Rev Food Sci Nutr. 2021;1–13.
Skepastianos P, Hatzitolios A, et al. Comparison of short-term 49. Koloverou E, Esposito K, Giugliano D, Panagiotakos D. The
hypocaloric high-protein diets with a hypocaloric Mediterranean effect of Mediterranean diet on the development of type 2 dia-
diet: effect on body composition and health-related blood mark- betes mellitus: a meta-analysis of 10 prospective studies and
ers in overweight and sedentary young participants. Nutrition. 136,846 participants. Metabolism. 2014;63(7):903–11.
2021;91–92. In this randomised controlled trial, the authors 50. Schwingshackl L, Missbach B, Konig J, Hoffmann G. Adherence
demonstrated that among the three low-calorie diets (low- to a Mediterranean diet and risk of diabetes: a systematic review
calorie Mediterranean diet and two high-protein diets, with and meta-analysis. Public Health Nutr. 2015;18(7):1292–9.
and without whey protein supplementation), only the Mediter- 51. Ahmad S, Demler OV, Sun Q, Moorthy MV, Li C, Lee IM, et al.
ranean diet induced positive changes in body composition and Association of the Mediterranean diet with onset of diabetes in the
metabolic profile in overweight and sedentary individuals. women’s health study. JAMA Netw Open. 2020;3(11):e2025466.
35. Weinheimer EM, Sands LP, Campbell WW. A systematic review 52. Ortega E, Franch J, Castell C, Goday A, Ribas-Barba L, Soriguer
of the separate and combined effects of energy restriction and F, et al. Mediterranean diet adherence in individuals with pre-
exercise on fat-free mass in middle-aged and older adults: impli- diabetes and unknown diabetes: the [email protected] Study. Ann Nutr
cations for sarcopenic obesity. Nutr Rev. 2010;68(7):375–88. Metab. 2013;62(4):339–46.
36. Kastorini CM, Milionis HJ, Esposito K, Giugliano D, Goudevenos JA, 53. Viscogliosi G, Cipriani E, Liguori ML, Marigliano B, Saliola M,
Panagiotakos DB. The effect of Mediterranean diet on metabolic Ettorre E, et al. Mediterranean dietary pattern adherence: associ-
syndrome and its components: a meta-analysis of 50 studies and ations with prediabetes, metabolic syndrome, and related micro-
534,906 individuals. J Am Coll Cardiol. 2011;57(11):1299–313. inflammation. Metab Syndr Relat Disord. 2013;11(3):210–6.
37.• Bendall CL, Mayr HL, Opie RS, Bes-Rastrollo M, Itsiopoulos 54. Martin-Pelaez S, Fito M, Castaner O. Mediterranean diet effects
C, Thomas CJ. Central obesity and the Mediterranean diet: a on type 2 diabetes prevention, disease progression, and related
systematic review of intervention trials. Crit Rev Food Sci Nutr. mechanisms. A review. Nutrients. 2020;12(8):2236.
2018;58(18):3070–84 This systematic review highlights the 55. Pascual Fuster V, Perez Perez A, Carretero Gomez J, Caixas Pedragos
potential for a Mediterranean diet intervention to reduce A, Gomez-Huelgas R, Perez-Martinez P. Executive summary: updates
central obesity and in turn reduce obesity-related chronic to the dietary treatment of prediabetes and type 2 diabetes mellitus.
disease risk and associated public health burden. Endocrinol Diabetes Nutr (Engl Ed). 2021;68(4):277–87.
38. Federation ID. IDF diabetes atlas. 1st ed. Brussels, Belgium: 56. Mirahmadizadeh A, Khorshidsavar H, Seif M, Sharifi MH.
International Diabetes Federation; 2019. Adherence to medication, diet and physical activity and the
13
associated factors amongst patients with type 2 diabetes. Diabe- development of diabetic complications: a longitudinal study
tes Ther. 2020;11(2):479–94. from the nationwide diabetes report of the National Program
57. de Carvalho GB, Dias-Vasconcelos NL, Santos RKF, Brandao- for Prevention and Control of Diabetes (NPPCD 2016–2020).
Lima PN, da Silva DG, Pires LV. Effect of different dietary Maturitas. 2021;153:61–7.
patterns on glycemic control in individuals with type 2 dia- 73. Wong MYZ, Man REK, Fenwick EK, Gupta P, Li LJ, van Dam
betes mellitus: a systematic review. Crit Rev Food Sci Nutr. RM, et al. Dietary intake and diabetic retinopathy: a systematic
2020;60(12):1999–2010. review. PLoS ONE. 2018;13(1):e0186582.
58. Papamichou D, Panagiotakos DB, Itsiopoulos C. Dietary patterns and 74. Siervo M, Shannon OM, Llewellyn DJ, Stephan BC, Fontana L.
management of type 2 diabetes: a systematic review of randomised Mediterranean diet and cognitive function: from methodology to
clinical trials. Nutr Metab Cardiovasc Dis. 2019;29(6):531–43. mechanisms of action. Free Radic Biol Med. 2021;176:105–17.
59. Tosatti JAG, Alves MT, Gomes KB. The role of the Mediterranean 75. Soldevila-Domenech N, Forcano L, Vintro-Alcaraz C, Cuenca-
dietary pattern on metabolic control of patients with diabetes mel- Royo A, Pinto X, Jimenez-Murcia S, et al. Interplay between
litus: a narrative review. Adv Exp Med Biol. 2021;1307:115–28. cognition and weight reduction in individuals following a Medi-
60. Vitale M, Masulli M, Calabrese I, Rivellese AA, Bonora E, terranean diet: three-year follow-up of the PREDIMED-Plus
Signorini S, et al. Impact of a Mediterranean dietary pattern and trial. Clin Nutr. 2021;40(9):5221–37.
its components on cardiovascular risk factors, glucose control, 76. Kossler T, Weber KS, Wolwer W, Hoyer A, Strassburger K,
and body weight in people with type 2 diabetes: a real-life study. Burkart V, et al. Associations between cognitive performance
Nutrients. 2018;10(8):1067. and Mediterranean dietary pattern in patients with type 1 or type
61. Pan B, Wu Y, Yang Q, Ge L, Gao C, Xun Y, et al. The impact 2 diabetes mellitus. Nutr Diabetes. 2020;10(1):10.
of major dietary patterns on glycemic control, cardiovascular 77. Dinu M, Pagliai G, Casini A, Sofi F. Mediterranean diet and
risk factors, and weight loss in patients with type 2 diabetes: a multiple health outcomes: an umbrella review of meta-analyses
network meta-analysis. J Evid Based Med. 2019;12(1):29–39. of observational studies and randomised trials. Eur J Clin Nutr.
62. Huo R, Du T, Xu Y, Xu W, Chen X, Sun K, et al. Effects of 2018;72(1):30–43.
Mediterranean-style diet on glycemic control, weight loss and 78. Tuttle KR, Shuler LA, Packard DP, Milton JE, Daratha KB,
cardiovascular risk factors among type 2 diabetes individuals: a Bibus DM, et al. Comparison of low-fat versus Mediterranean-
meta-analysis. Eur J Clin Nutr. 2015;69(11):1200–8. style dietary intervention after first myocardial infarction (from
63. Sleiman D, Al-Badri MR, Azar ST. Effect of mediterranean diet The Heart Institute of Spokane Diet Intervention and Evaluation
in diabetes control and cardiovascular risk modification: a sys- Trial). Am J Cardiol. 2008;101(11):1523–30.
tematic review. Front Public Health. 2015;3:69. 79. Barzi F, Woodward M, Marfisi RM, Tavazzi L, Valagussa F,
64. Heindel J, Baid-Agrawal S, Rebholz CM, Nadal J, Schmid M, Marchioli R, et al. Mediterranean diet and all-causes mortality
Schaeffner E, et al. Association between dietary patterns and after myocardial infarction: results from the GISSI-Prevenzione
kidney function in patients with chronic kidney disease: a cross- trial. Eur J Clin Nutr. 2003;57(4):604–11.
sectional analysis of the German Chronic Kidney Disease Study. 80. Paterson KE, Myint PK, Jennings A, Bain LKM, Lentjes MAH,
J Ren Nutr. 2020;30(4):296–304. Khaw KT, et al. Mediterranean diet reduces risk of incident
65. Picard K, Senior PA, Adame Perez S, Jindal K, Richard C, stroke in a population with varying cardiovascular disease risk
Mager DR. Low Mediterranean Diet scores are associated with profiles. Stroke. 2018;49(10):2415–20.
reduced kidney function and health related quality of life but 81. Tsivgoulis G, Psaltopoulou T, Wadley VG, Alexandrov AV, Howard
not other markers of cardiovascular risk in adults with diabe- G, Unverzagt FW, et al. Adherence to a Mediterranean diet and
tes and chronic kidney disease. Nutr Metab Cardiovasc Dis. prediction of incident stroke. Stroke. 2015;46(3):780–5.
2021;31(5):1445–53. 82. Ruiz-Canela M, Estruch R, Corella D, Salas-Salvado J, Martinez-
66. Jayedi A, Mirzaei K, Rashidy-Pour A, Yekaninejad MS, Zargar Gonzalez MA. Association of Mediterranean diet with periph-
MS, Akbari Eidgahi MR. Dietary approaches to stop hyperten- eral artery disease: the PREDIMED randomized trial. JAMA.
sion, mediterranean dietary pattern, and diabetic nephropathy 2014;311(4):415–7.
in women with type 2 diabetes: a case-control study. Clin Nutr 83. Kahleova H, Salas-Salvado J, Rahelic D, Kendall CW, Rembert
ESPEN. 2019;33:164–70. E, Sievenpiper JL. Dietary patterns and cardiometabolic out-
67. Hansrivijit P, Oli S, Khanal R, Ghahramani N, Thongprayoon C, comes in diabetes: a summary of systematic reviews and meta-
Cheungpasitporn W. Mediterranean diet and the risk of chronic analyses. Nutrients. 2019;11(9):2209.
kidney disease: a systematic review and meta-analysis. Nephrol- 84. Becerra-Tomas N, Blanco Mejia S, Viguiliouk E, Khan T, Kendall
ogy (Carlton). 2020;25(12):913–8. CWC, Kahleova H, et al. Mediterranean diet, cardiovascular disease
68. Hu EA, Steffen LM, Grams ME, Crews DC, Coresh J, Appel LJ, and mortality in diabetes: a systematic review and meta-analysis of
et al. Dietary patterns and risk of incident chronic kidney disease: prospective cohort studies and randomized clinical trials. Crit Rev
the Atherosclerosis Risk in Communities study. Am J Clin Nutr. Food Sci Nutr. 2020;60(7):1207–27.
2019;110(3):713–21. 85. Ciccarone E, Di Castelnuovo A, Salcuni M, Siani A, Giacco A,
69. Chauveau P, Aparicio M, Bellizzi V, Campbell K, Hong X, Donati MB, et al. A high-score Mediterranean dietary pattern
Johansson L, et al. Mediterranean diet as the diet of choice for is associated with a reduced risk of peripheral arterial disease
patients with chronic kidney disease. Nephrol Dial Transplant. in Italian patients with Type 2 diabetes. J Thromb Haemost.
2018;33(5):725–35. 2003;1(8):1744–52.
70. Diaz-Lopez A, Babio N, Martinez-Gonzalez MA, Corella D, 86. Lilja E, Bergwall S, Sonestedt E, Gottsater A, Acosta S. The
Amor AJ, Fito M, et al. Mediterranean diet, retinopathy, nephrop- association between dietary intake, lifestyle and incident sympto-
athy, and microvascular diabetes complications: a post hoc analy- matic peripheral arterial disease among individuals with diabetes
sis of a randomized trial. Diabetes Care. 2015;38(11):2134–41. mellitus: insights from the Malmo Diet and Cancer study. Ther
71. Dow C, Mancini F, Rajaobelina K, Boutron-Ruault MC, Balkau Adv Endocrinol Metab. 2019;10:2042018819890532.
B, Bonnet F, et al. Diet and risk of diabetic retinopathy: a sys- 87. Milenkovic T, Bozhinovska N, Macut D, Bjekic-Macut J, Rahelic
tematic review. Eur J Epidemiol. 2018;33(2):141–56. D, Velija Asimi Z, et al. Mediterranean diet and type 2 diabe-
72. Ghaemi F, Firouzabadi FD, Moosaie F, Shadnoush M, Poopak tes mellitus: a perpetual inspiration for the scientific world. A
A, Kermanchi J, et al. Effects of a Mediterranean diet on the Review. Nutrients. 2021;13(4):1307.
13
88. Muscogiuri G, Barrea L, Di Somma C, Altieri B, Vecchiarini M, 105. Coll N. Repositioning of the global epicentre of non-optimal
Orio F, et al. Patient empowerment and the Mediterranean diet as cholesterol. Nature. 2020;582(7810):73–7.
a possible tool to tackle prediabetes associated with overweight 106. Migliaccio S, Brasacchio C, Pivari F, Salzano C, Barrea L,
or obesity: a pilot study. Hormones (Athens). 2019;18(1):75–84. Muscogiuri G, et al. What is the best diet for cardiovascular well-
89. Athyros VG, Tziomalos K, Katsiki N, Doumas M, Karagiannis A, ness? A comparison of different nutritional models. Int J Obes
Mikhailidis DP. Cardiovascular risk across the histological spec- Suppl. 2020;10(1):50–61.
trum and the clinical manifestations of non-alcoholic fatty liver 107. Laudisio D, Castellucci B, Barrea L, Pugliese G, Savastano S,
disease: an update. World J Gastroenterol. 2015;21(22):6820–34. Colao A, et al. Mediterranean diet and breast cancer risk: a nar-
90. Katsiki N, Athyros VG, Karagiannis A, Wierzbicki AS, Mikhailidis rative review. Minerva Endocrinol (Torino). 2021;46(4):441–52.
DP. Should we expand the concept of coronary heart disease equiva- 108. Barrea L, Pugliese G, Laudisio D, Colao A, Savastano S, Musco-
lents? Curr Opin Cardiol. 2014;29(4):389–95. giuri G. Mediterranean diet as medical prescription in menopau-
91. Katsiki N, Mikhailidis DP, Mantzoros CS. Non-alcoholic sal women with obesity: a practical guide for nutritionists. Crit
fatty liver disease and dyslipidemia: an update. Metabolism. Rev Food Sci Nutr. 2021;61(7):1201–11.
2016;65(8):1109–23. 109. Barrea L, Arnone A, Annunziata G, Muscogiuri G, Laudisio D,
92. Katsiki N, Perez-Martinez P, Anagnostis P, Mikhailidis DP, Salzano C, et al. Adherence to the Mediterranean diet, dietary
Karagiannis A. Is nonalcoholic fatty liver disease indeed the patterns and body composition in women with polycystic ovary
hepatic manifestation of metabolic syndrome? Curr Vasc Phar- syndrome (PCOS). Nutrients. 2019;11(10):2278.
macol. 2018;16(3):219–27. 110. Tosti V, Bertozzi B, Fontana L. Health benefits of the Mediter-
93. Gastaldelli A. Fatty liver disease: the hepatic manifestation of ranean diet: metabolic and molecular mechanisms. J Gerontol A
metabolic syndrome. Hypertens Res. 2010;33(6):546–7. Biol Sci Med Sci. 2018;73(3):318–26.
94. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, 111. Zmora N, Suez J, Elinav E. You are what you eat: diet, health and the
Wymer M. Global epidemiology of nonalcoholic fatty liver gut microbiota. Nat Rev Gastroenterol Hepatol. 2019;16(1):35–56.
disease-meta-analytic assessment of prevalence, incidence, and 112. Barrea L, Muscogiuri G, Annunziata G, Laudisio D, Pugliese
outcomes. Hepatology. 2016;64(1):73–84. G, Salzano C, et al. From gut microbiota dysfunction to obesity:
95.• Bakaloudi DR, Chrysoula L, Kotzakioulafi E, Theodoridis X, could short-chain fatty acids stop this dangerous course? Hor-
Chourdakis M. Impact of the level of adherence to Mediterra- mones (Athens). 2019;18(3):245–50.
nean diet on the parameters of metabolic syndrome: a system- 113. Marzullo P, Di Renzo L, Pugliese G, De Siena M, Barrea L,
atic review and meta-analysis of observational studies. Nutrients. Muscogiuri G, et al. From obesity through gut microbiota to
2021;13(5):1514 The authors conclude that high adherence cardiovascular diseases: a dangerous journey. Int J Obes Suppl.
to MD can have a positive impact on all parameters of Meta- 2020;10(1):35–49.
bolic Syndrome. In addition, there is sufficient evidence sug- 114. Al Bander Z, Nitert MD, Mousa A, Naderpoor N. The gut
gesting that long-term consumption of Mediterranean diet microbiota and inflammation: an overview. Int J Environ Res
can protect from obesity and improve cardiometabolic risk Public Health. 2020;17(20):7618.
markers, including the markers used for the diagnosis of 115. Merra G, Noce A, Marrone G, Cintoni M, Tarsitano MG,
Metabolic Syndrome. Capacci A, et al. Influence of Mediterranean diet on human
96. Pugliese N, Plaz Torres MC, Petta S, Valenti L, Giannini EG, gut microbiota. Nutrients. 2020;13(1):7.
Aghemo A. Is there an “ideal” diet for patients with NAFLD? 116. Casas R, Sacanella E, Estruch R. The immune protective effect of the
Eur J Clin Invest. 2021;52(3):e13659. Mediterranean diet against chronic low-grade inflammatory diseases.
97. Abenavoli L, Di Renzo L, Boccuto L, Alwardat N, Gratteri S, Endocr Metab Immune Disord Drug Targets. 2014;14(4):245–54.
De Lorenzo A. Health benefits of Mediterranean diet in nonal- 117. Schwingshackl L, Morze J, Hoffmann G. Mediterranean diet
coholic fatty liver disease. Expert Rev Gastroenterol Hepatol. and health status: active ingredients and pharmacological
2018;12(9):873–81. mechanisms. Br J Pharmacol. 2020;177(6):1241–57.
98. Saeed N, Nadeau B, Shannon C, Tincopa M. Evaluation of 118. Makki K, Deehan EC, Walter J, Backhed F. The impact of
dietary approaches for the treatment of non-alcoholic fatty liver dietary fiber on gut microbiota in host health and disease. Cell
disease: a systematic review. Nutrients. 2019;11(12):3064. Host Microbe. 2018;23(6):705–15.
99. Barrea L, Di Somma C, Muscogiuri G, Tarantino G, Tenore GC, 119. Holscher HD. Dietary fiber and prebiotics and the gastrointes-
Orio F, et al. Nutrition, inflammation and liver-spleen axis. Crit tinal microbiota. Gut Microbes. 2017;8(2):172–84.
Rev Food Sci Nutr. 2018;58(18):3141–58. 120. Llorente-Cortes V, Estruch R, Mena MP, Ros E, Gonzalez MA,
100. Barrea L, Muscogiuri G, Frias-Toral E, Laudisio D, Pugliese Fito M, et al. Effect of Mediterranean diet on the expression of
G, Castellucci B, et al. Nutrition and immune system: from the pro-atherogenic genes in a population at high cardiovascular
Mediterranean diet to dietary supplementary through the micro- risk. Atherosclerosis. 2010;208(2):442–50.
biota. Crit Rev Food Sci Nutr. 2021;61(18):3066–90. 121. Visioli F, Poli A. Fatty acids and cardiovascular risk. Evidence,
101. Descamps OS, Verhaegen A, Demeure F, Langlois M, Rietzschel lack of evidence, and diligence. Nutrients. 2020;12(12):3782.
E, Mertens A, et al. Evolving concepts on the management of 122. Barrea L, Tarantino G, Somma CD, Muscogiuri G, Macchia
dyslipidaemia. Acta Clin Belg. 2020;75(1):80–90. PE, Falco A, et al. Adherence to the Mediterranean diet and
102. Filippatos T, Tsimihodimos V, Pappa E, Elisaf M. Pathophysiology circulating levels of sirtuin 4 in obese patients: a novel associa-
of diabetic dyslipidaemia. Curr Vasc Pharmacol. 2017;15(6):566–75. tion. Oxid Med Cell Longev. 2017;2017:6101254.
103. Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon 123. Teo K, Chow CK, Vaz M, Rangarajan S, Yusuf S, Group PI-W.
L, et al. 2019 ESC/EAS Guidelines for the management of dyslipi- The Prospective Urban Rural Epidemiology (PURE) study:
daemias: lipid modification to reduce cardiovascular risk. Eur Heart examining the impact of societal influences on chronic non-
J. 2020;41(1):111–88. communicable diseases in low-, middle-, and high-income
104. WHO. Noncommunicable diseases: risk factors. The Global countries. Am Heart J. 2009;158(1):1–7.
Health Observatory. https://www.who.int/data/gho/data/themes/ 124. Antoniazzi L, Arroyo-Olivares R, Bittencourt MS, Tada MT,
topics/topic-details/GHO/ncd-risk-factors. Last accessed 21 Jan Lima I, Jannes CE, et al. Association of dietary components
2022. with dyslipidemia and low-grade inflammation biomarkers in
13
adults with heterozygous familial hypercholesterolemia from patients with growth hormone deficiency: is there a role for
different countries. Eur J Clin Nutr. 2019;73(12):1622–5. vitamin D? Endocrine. 2016;52(1):111–9.
125. de Oliveira Otto MC, Mozaffarian D, Kromhout D, Bertoni AG, 141. Muscogiuri G, Barrea L, Annunziata G, Di Somma C, Laudisio
Sibley CT, Jacobs DR Jr, et al. Dietary intake of saturated fat by D, Colao A, et al. Obesity and sleep disturbance: the chicken or
food source and incident cardiovascular disease: the Multi-Ethnic the egg? Crit Rev Food Sci Nutr. 2019;59(13):2158–65.
Study of Atherosclerosis. Am J Clin Nutr. 2012;96(2):397–404. 142. Muscogiuri G, Barrea L, Scannapieco M, Di Somma C, Scacchi
126. Formisano E, Pasta A, Cremonini AL, Di Lorenzo I, Sukkar M, Aimaretti G, et al. The lullaby of the sun: the role of vitamin
SG, Pisciotta L. Effects of a Mediterranean diet, dairy, and meat D in sleep disturbance. Sleep Med. 2019;54:262–5.
products on different phenotypes of dyslipidemia: a preliminary 143. Barrea L, Savastano S, Di Somma C, Savanelli MC, Nappi F,
retrospective analysis. Nutrients. 2021;13(4):1161. Albanese L, et al. Low serum vitamin D-status, air pollution
127. Muscogiuri G, Barrea L, Aprano S, Framondi L, Di Matteo R, and obesity: a dangerous liaison. Rev Endocr Metab Disord.
Laudisio D, et al. Sleep Quality in obesity: does adherence to the 2017;18(2):207–14.
Mediterranean diet matter? Nutrients. 2020;12(5):1364. 144. Savastano S, Barrea L, Savanelli MC, Nappi F, Di Somma C,
128. Antoniazzi L, Arroyo-Olivares R, Bittencourt MS, Tada MT, Orio F, et al. Low vitamin D status and obesity: role of nutrition-
Lima I, Jannes CE, et al. Adherence to a Mediterranean diet, ist. Rev Endocr Metab Disord. 2017;18(2):215–25.
dyslipidemia and inflammation in familial hypercholesterolemia. 145.•• Barrea L, Muscogiuri G, Laudisio D, Pugliese G, de
Nutr Metab Cardiovasc Dis. 2021;31(7):2014–22. Alteriis G, Colao A, et al. Influence of the Mediterranean
129. Barrea L, Altieri B, Muscogiuri G, Laudisio D, Annunziata G, diet on 25- hydroxyvitamin D levels in adults. Nutrients.
Colao A, et al. Impact of Nutritional Status on Gastroenteropancre- 2020;12(5):1439. The authors demonstrated that high adher-
atic Neuroendocrine Tumors (GEP-NET) Aggressiveness. Nutri- ence to the Mediterranean diet is associated with low BMI
ents. 2018;10(12):1854. and high 25OHD levels in both genders, probably through the
130. Barrea L, Annunziata G, Muscogiuri G, Di Somma C, Laudisio anti-inflammatory and antioxidant effects that are synergisti-
D, Maisto M, et al. Trimethylamine-N-oxide (TMAO) as novel cally exerted by the Mediterranean diet or vitamin D on body
potential biomarker of early predictors of metabolic syndrome. weight.
Nutrients. 2018;10(12):1971. 146. Schwingshackl L, Schwedhelm C, Galbete C, Hoffmann G.
131. Barrea L, Annunziata G, Muscogiuri G, Laudisio D, Di Somma Adherence to Mediterranean diet and risk of cancer: an updated
C, Maisto M, et al. Trimethylamine N-oxide, Mediterranean diet, systematic review and meta-analysis. Nutrients. 2017;9(10):1063.
and nutrition in healthy, normal-weight adults: also a matter of 147. Couto E, Boffetta P, Lagiou P, Ferrari P, Buckland G, Overvad K,
sex? Nutrition. 2019;62:7–17. et al. Mediterranean dietary pattern and cancer risk in the EPIC
132. Barrea L, Muscogiuri G, Annunziata G, Laudisio D, de Alteriis cohort. Br J Cancer. 2011;104(9):1493–9.
G, Tenore GC, et al. A new light on vitamin D in obesity: a novel 148. Toledo E, Salas-Salvado J, Donat-Vargas C, Buil-Cosiales P,
association with trimethylamine-N-Oxide (TMAO). Nutrients. Estruch R, Ros E, et al. Mediterranean diet and invasive breast
2019;11(6):1310. cancer risk among women at high cardiovascular risk in the
133. Thomas MS, Fernandez ML. Trimethylamine N-Oxide (TMAO), Diet PREDIMED trial: a randomized clinical trial. JAMA Intern Med.
and cardiovascular disease. Curr Atheroscler Rep. 2021;23(4):12. 2015;175(11):1752–60.
134. Leon-Mimila P, Villamil-Ramirez H, Li XS, Shih DM, Hui ST, 149. Wu AH, Yu MC, Tseng CC, Stanczyk FZ, Pike MC. Dietary
Ocampo-Medina E, et al. Trimethylamine N-oxide levels are patterns and breast cancer risk in Asian American women. Am
associated with NASH in obese subjects with type 2 diabetes. J Clin Nutr. 2009;89(4):1145–54.
Diabetes Metab. 2021;47(2):101183. 150. Murtaugh MA, Sweeney C, Giuliano AR, Herrick JS, Hines L,
135. Barrea L, Muscogiuri G, Pugliese G, de Alteriis G, Maisto M, Byers T, et al. Diet patterns and breast cancer risk in Hispanic
Donnarumma M, et al. Association of trimethylamine N-Oxide and non-Hispanic white women: the Four-Corners Breast Cancer
(TMAO) with the clinical severity of Hidradenitis Suppurativa Study. Am J Clin Nutr. 2008;87(4):978–84.
(Acne Inversa). Nutrients. 2021;13(6):1997. 151. Link LB, Canchola AJ, Bernstein L, Clarke CA, Stram DO, Ursin
136. Muscogiuri G, Barrea L, Laudisio D, Di Somma C, Pugliese G, G, et al. Dietary patterns and breast cancer risk in the California
Salzano C, et al. Somatotropic axis and obesity: is there any role Teachers Study cohort. Am J Clin Nutr. 2013;98(6):1524–32.
for the Mediterranean diet? Nutrients. 2019;11(9):2228. 152. Cottet V, Touvier M, Fournier A, Touillaud MS, Lafay L, Clavel-
137. Lombardi G, Di Somma C, Grasso LF, Savanelli MC, Colao Chapelon F, et al. Postmenopausal breast cancer risk and dietary
A, Pivonello R. The cardiovascular system in growth hormone patterns in the E3N-EPIC prospective cohort study. Am J Epide-
excess and growth hormone deficiency. J Endocrinol Invest. miol. 2009;170(10):1257–67.
2012;35(11):1021–9. 153. WCRF. Eat wholegrains, vegetables, fruit and beans. https://www.
138. Altieri B, Grant WB, Della Casa S, Orio F, Pontecorvi A, Colao wcrf.org/dietandcancer/eat-wholegrains-vegetables-fruit-and-beans/.
A, et al. Vitamin D and pancreas: the role of sunshine vitamin in Last accessed 21 Jan 2022.
the pathogenesis of diabetes mellitus and pancreatic cancer. Crit 154. Bamia C, Lagiou P, Buckland G, Grioni S, Agnoli C, Taylor AJ,
Rev Food Sci Nutr. 2017;57(16):3472–88. et al. Mediterranean diet and colorectal cancer risk: results from
139. Muscogiuri G, Barrea L, Altieri B, Di Somma C, Bhattoa HP, a European cohort. Eur J Epidemiol. 2013;28(4):317–28.
Laudisio D, et al. Calcium and vitamin D supplementation.
Myths and realities with regard to cardiovascular risk. Curr Vasc Publisher's Note Springer Nature remains neutral with regard to
Pharmacol. 2019;17(6):610–7. jurisdictional claims in published maps and institutional affiliations.
140. Savanelli MC, Scarano E, Muscogiuri G, Barrea L, Vuolo L,
Rubino M, et al. Cardiovascular risk in adult hypopituitaric
13
Authors and Affiliations
Giovanna Muscogiuri1,2,3 · Ludovica Verde2 · Cem Sulu4 · Niki Katsiki5 · Maria Hassapidou5 · Evelyn Frias‑Toral6 ·
Gabriela Cucalón7 · Agnieszka Pazderska8 · Volkan Demirhan Yumuk4 · Annamaria Colao1,2,3 · Luigi Barrea2,9
1 6
Dipartimento di Medicina Clinica e Chirurgia, School of Medicine, Universidad Católica Santiago
Endocrinology Unit, University Federico II, Naples, Italy de Guayaquil, Av. Pdte. Carlos Julio Arosemena Tola,
2 Guayaquil 090615, Ecuador
Centro Italiano per la cura e il Benessere del paziente
7
con Obesità (C.I.B.O), Department of Clinical Medicine Escuela Superior Politécnica del Litoral, ESPOL, Lifescience
and Surgery, Endocrinology Unit, University Medical School Faculty, ESPOL Polytechnic University, Campus Gustavo
of Naples, Naples, Italy Galindo Km. 30.5 Vía Perimetral, P.O. Box 09‑01‑5863,
3 Guayaquil, Ecuador
Cattedra Unesco “Educazione alla salute e allo sviluppo
8
sostenibile”, University Federico II, Naples, Italy Division of Endocrinology, Metabolism,
4 and Diabetes‑Department of Internal Medicine, Cerrahpasa
Division of Endocrinology, Metabolism and Diabetes,
Medical School, Istanbul University-Cerrahpasa,
Istanbul University-Cerrahpaşa, Cerrahpaşa Medical Faculty,
Istanbul 34098, Turkey
Istanbul, Turkey
9
5 Dipartimento di Scienze Umanistiche, Università Telematica
Department of Nutritional Sciences and Dietetics,
Pegaso, Naples 80143, Italy
International Hellenic University, Thessaloniki, Greece
13

Mediterranean Diet For Obesity-Review-Curr Obes Rept-2022

Uploaded by

Copyright:

Available Formats

Mediterranean Diet For Obesity-Review-Curr Obes Rept-2022

Uploaded by

Document Information

Original Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Mediterranean Diet For Obesity-Review-Curr Obes Rept-2022

Uploaded by

Copyright:

Available Formats

Current Obesity Reports (2022) 11:287–304

METABOLISM (M DALAMAGA, SECTION EDITOR)

Mediterranean Diet and Obesity‑related Disorders: What

Accepted: 16 April 2022 / Published online: 30 September 2022

The World Health Organization defines obesity as abnormal

Fig. 1 The beneficial mechanisms of Mediterranean diet in obesity-related disorders

Mediterranean Diet and Diabetic Mediterranean Diet and Non‑alcoholic Fatty

Table 1 Treatment targets/ Treatment Recommendation

BMI body mass index, WC waist circumference

Source No. and type of studies Subjects Aim Main findings

total myocardial infarction (RR: 0.65;

Authors and Affiliations

You might also like