Adherence to the mediterranean diet and risk of metabolic syndrome and its components
Nutrition, Metabolism & Cardiovascular Diseases (2009) 19, 563e570
Adherence to the Mediterranean diet and riskof metabolic syndrome and its components
´ ,, on behalf of the Nureta-PREDIMED investigators
a Human Nutrition Unit, Department of Biochemistry and Biotechnology, Faculty of Medicine and Health Sciences,Rovira i Virgili University, Spainb CIBER Fisiopatologı´a de la Obesidad y Nutricio´n CB06/03. Instituto de Salud Carlos III, Madrid, Spainc Direccio´ d’Atencio´ Prima`ria Tarragona-Reus. Institut Catala` de la Salut, Reus, Spaind Department of Preventive Medicine and Public Health, Medical School-Clı´nica Universitaria,University of Navarra, Pamplona, Spaine Preventive Medicine and Public Health Unit, Faculty of Medicine and Health Sciences,Rovira i Virgili University, Spain
Received 28 July 2008; received in revised form 24 October 2008; accepted 29 October 2008
Background and aims: The role of diet in the aetiology of metabolic syndrome
(MetS) is not well understood. The aim of the present study was to evaluate the relationship
between adherence to the Mediterranean diet (MedDiet) and MetS.
Methods and results: A cross-sectional study was conducted with 808 high cardiovascular risk
participants of the Reus PREDIMED Centre. MetS was defined by the updated National Choles-
terol and Education Program Adult Treatment Panel III criteria.
An inverse association between quartiles of adherence to the MedDiet (14-point score) and
the prevalence of MetS (P for trend < 0.001) was observed. After adjusting for age, sex, totalenergy intake, smoking status and physical activity, participants with the highest score ofadherence to the MedDiet (!9 points) had the lowest odds ratio of having MetS (OR [95% CI]of 0.44 [0.27e0.70]) compared to those in the lowest quartile.
Participants with the highest MedDiet adherence had 47 and 54% lower odds of having low HDL-c and
hypertriglyceridemia MetS criteria, respectively, than those in the lowest quartile. Some componentsof the MedDiet, such as olive oil, legumes and red wine were associated with lower prevalence of MetS. Conclusion: Higher adherence to a Mediterranean diet is associated with a significantly lower oddsratio of having MetS in a population with a high risk of cardiovascular disease. ª 2008 Elsevier B.V. All rights reserved.
* Corresponding author. Human Nutrition Unit, Department of Biochemistry and Biotechnology, Faculty of Medicine and Health Sciences,
Rovira i Virgili University, C/Sant Llorenc
0939-4753/$ - see front matter ª 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.numecd.2008.10.007
The MetS is a cluster of common cardiovascular risk factors,
including central obesity, hyperglycaemia, low HDL-cholesterol
A cross-sectional analysis on baseline data from the PRE-
triglyceridemia. The association of MetS with the risk of
DIMED trial centre in Reus was conducted. The PREDIMED is
developing diabetes and cardiovascular disease (CVD) is
a 5-year clinical trial and constitutes a randomized,
well documented, implying a greater risk of mortality .
parallel-group multicentre that aims to assess the effects of
In developed countries the MetS seems to affect around
the MedDiet on the primary prevention of CVD .
25% of the population , and there is evidence that MetS
Participants were men and women, without prior CVD and
has become more prevalent over the last decade
who fulfilled at least one of the following two criteria: (1)
probably influenced in part by increases in obesity.
type-2 diabetes or (2) !3 major cardiovascular risk factors
The aetiology of MetS, although largely unknown, is
(current smoking, hypertension [blood pressure ! 140/
considered to reside in a complex interaction between
90 mmHg or treatment with antihypertensive drugs], LDL-
genetic, metabolic, and environmental factors .
cholesterol level ! 160 mg/dL [or treatment with hypolipi-
Weight loss or gain can be considered to be one of the main
demic drugs], HDL-cholesterol level 40 mg/dL, body mass
environmental determinants of the MetS . Physical
index [BMI] ! 25 kg/m2, or a family history of premature
activity and diet have also been reported to be important
CVD). Other details have been reported elsewhere
Of the first 847 participants recruited in the Reus node,
Adherence to a healthy dietary pattern has been shown
39 were excluded because some of the MetS variables were
to be inversely associated with MetS some of its
missing. Our centre’s institutional review boards approved
components and type-2 diabetes[13]. In contrast,
the study protocol, and all the participants signed an
prospective finding have suggested that a Western dietary
pattern is directly associated with the risk of MetS . Clinical trials have also shown that behavioural programs
can be used to implement healthy dietary patterns anddecrease the prevalence of MetS .
The baseline examination included assessment of cardio-
In recent decades the Mediterranean Diet (MedDiet)
vascular risk factors, medical conditions and medication
has emerged as a healthy dietary pattern that protects
use. Height and weight were measured with light clothing
against CVD and other chronic conditions . The
and no shoes. Waist circumference was measured midway
MedDiet is characterized by a high consumption of
between the lowest rib and the iliac crest. Blood pressure
legumes, fruit and vegetables, grains and olive oil,
was measured (using a validated oscillometer [Omron HEM-
a moderate consumption of wine and dairy products and
705CP, Hoofddorp, Netherlands]) in triplicate with a 5-min
a low consumption of red and processed meat, cream and
interval between each measurement, and the mean of
these values was recorded. The validated Spanish version of
Few studies have analysed the relationship between
the Minnesota Leisure-Time Physical Activity Questionnaire
MedDiet adherence and the prevalence or incidence of
was used to estimate energy expenditure.
MetS and its components . With the exception ofthe cross-sectional study of Alvarez-Leo
who did not find any relationship between the adher-
ence to the MedDiet and MetS prevalence, other studies,conducted in samples of healthy participants do support
A previously validated 136-item food frequency question-
the beneficial effect of the MedDiet pattern on MetS
naire was used to appraise dietary habits. Spanish food
. Recent data from the SUN prospective study
composition tables were used to derive nutrient intake.
also show an inverse relationship between MedDiet adher-
A 14-point food-items questionnaire, an extension of a previ-
ence and the incidence of MetS . Finally, Esposito et al.
ously validated questionnaire , was used to assess adherence
by means of a feeding trial showed a decrease in the
to the traditional MedDiet (see Appendix 1).
prevalence of MetS in patients losing weight by adhering to
Previously applied scores were also used to
assess adherence to the MedDiet in secondary analyses. In
To the best of our knowledge, the association between
the Trichopoulou score, subjects whose consumption
MedDiet or its components and MetS has never been
was at or above the sex-specific median (monounsaturated-
explored in an elderly population with a high risk of CVD.
to-saturated fat ratio, legumes, cereals, vegetables, fruits
Likewise, no studies have analysed which of the compo-
and fish) or below the median (meat and dairy products)
nents of the MedDiet are most associated with MetS.
were assigned 1 point. Moderate alcohol consumption was
So, the aim of the present study was to assess the
also assigned 1 point. Therefore, the total Trichopoulou
relationship between adherence to the MedDiet and the
score had a potential range from 0 to 9 points.
prevalence of the MetS in participants of the PREDIMEDstudy, and to identify specific components of the MedDiet
associated with this syndrome that might support thebeneficial effects attributed to this overall healthy dietary
Centralized laboratory analyses were performed on frozen
serum samples obtained in fasting conditions. Serum
Mediterranean diet and metabolic syndrome
glucose, cholesterol, and triglyceride levels were measured
abnormal waist circumference and low level of HDL-
using standard enzymatic automated methods. HDL-
cholesterol features were significantly higher in women. No
cholesterol was measured by enzymatic procedure after
significant differences between women and men were
observed in relation to the MedDiet scores.
Association between Mediterranean diet andmetabolic syndrome
The updated criteria from the National Cholesterol Educa-tion Program’s Adult Treatment Panel III were used to
Multiple logistic regression models with polynomial contrast
define MetS. That is to say, subjects had to have !3 of the
showed an inverse association between adherence
following: (1) waist circumference > 102 cm in men and
to the MedDiet (14-point food-item score) and the preva-
>88 cm in women; (2) serum triglyceride ! 150 mg/dL; (3)
lence of the MetS (P for trend < 0.001). This association
HDL-cholesterol < 40 mg/dL in men and <50 mg/dL in
persisted after adjusting for age, sex, energy intake,
women; (4) blood pressure ! 130/85 mmHg; and (5) fasting
smoking status and physical activity, and even after
plasma glucose level ! 100 mg/dL. Participants who were
adjusting for BMI (P for trend Z 0.002). The category with
being treated with antidiabetic, antihypertensive or
the highest score of adherence to the MedDiet exhibited
triglyceride-lowering medications were considered as dia-
the lowest odds ratio of having MetS, (OR (95% CI) 0.44
betic, hypertensive or hypertriglyceridemic, respectively.
(0.27e0.70) for subjects on quartile 4 compared to those inquartile 1). No interaction between gender or age category(<65 and 65e80 years old) and the MedDiet score was
observed (P Z 0.537 for gender and P Z 0.321 for agecategory).
We built categories (approximately quartiles) of the
Significant inverse associations between adherence to
14-point food-item MedDiet or Trichopoulou score. A
MedDiet and MetS were observed only in men, even when
multiple logistic regression model was used to evaluate the
adjusted for all potential confounders. This association was
odds ratio for each of the three upper quartiles of adher-
ence to the MedDiet (compared with the lowest quartile)
trend Z 0.056). Men at the top quartile of adherence to the
and the prevalence of MetS or its components. Multiple
MedDiet had a statistically significant lower odds ratio of
logistic regression models with polynomial contrast were
having MetS in comparison with the lowest quartile. Higher
used to generate the P for trend. After the univariate
adherence to the MedDiet in men between 65 and 80 years
model, we built first a sex- and age-adjusted model (model
old was significantly associated to a lower prevalence of
1) and another model additionally adjusted for energy
intake, smoking and physical activity (model 2). Further
An inverse association between adherence to the Tri-
adjustments were made for BMI (model 3). We conducted
chopoulou score and MetS was observed in the unadjusted
the analyses first for the whole sample and then separately
model (Appendix 2). However, when we adjusted for
potential confounders the models were not statistically
In addition, a multiple logistic regression model was
significant. No significant association between MedDiet
fitted to evaluate which of the 14-point food items in the
score and MetS prevalence was observed when the Pan-
MedDiet were most strongly associated with the preva-
agiotakos MedDiet score was used (Appendix 3).
lence of the MetS, having previously adjusted for the
shows the results of the multiple logistic regres-
above-mentioned potential confounders and mutually
sion analysis evaluating which of the 14 elements used to
adjusted for the rest of the items of the score. Also,
define the MedDiet score were more strongly associated with
a multiple logistic regression model was fitted to evaluate
the prevalence of MetS. Even when mutually adjusted, no
which of the 14-point food MedDiet items were most
item in the score was significantly associated to MetS. When
strongly associated with the risk of having MetS, forcing
we used the forward method, the items ‘olive oil as culinary
the adjustment for non-dietary variables (sex, age, energy
fat’, ‘legumes consumption’ and ‘wine consumption’ were
intake, smoking [current smoker or not] and physical
selected in this order into an overall model as the highest
activity), but using the stepwise algorithm (forward
odds ratio of having MetS. There was no evidence of multi-
method) to allow the additional inclusion of each of the
colinearity when the items were simultaneously adjusted for
14 items included in the MedDiet adherence score
each other. No colinearity between the food item included in
the score was observed (VIF < 2). In separated models
The level of significance for all statistical tests was
stratified by sex, we found that ‘legumes consumption’ and
P < 0.05 for bilateral contrasts.
‘red meat consumption’, were significantly associated withthe MetS risk only among men.
Mediterranean diet adherence and metabolic
MetS was significantly more prevalent in women than in
The associations between the adherence to the MedDiet
men The prevalence of each ATP III component of
and each of the MetS criteria were considered separately
the MetS is summarized in The prevalence of
) using multiple logistic regression models with
4) was associated with a lower prevalence of hyper-
General characteristics of the subjects studied.
triglyceridemia criteria (P for trend Z 0.011).
When we stratified by sex, marginally significant differ-
ences across successively increasing quartiles of the score
were found for the high triglyceride criterion both among
Z 0.055) and men (P for trend Z 0.059).
This was also observed in men for the central obesity criteria
Although there is some evidence that the Mediterranean
dietary pattern protects against CVD few epidemio-
logic studies have assessed the relationship between
The present study is unique in assessing this relationship
in an elderly population with a high risk of CVD and also
a high baseline level of MetS risk factors (including diet).
Our main finding is that the highest adherence to MedDiet is
associated with a lower prevalence of MetS defined by the
Metabolic syndromeand its components, % (n)
ATP III criteria. It is important to note that this association
remained significant when the MetS criteria given by the
International Diabetes Federation (IDF) were used (data not
shown) and adjustments had been made for BMI.
To the best of our knowledge, only one longitudinal
study , two cross-sectional studies and one
clinical trial[15] have been conducted to assess the asso-
ciation between MedDiet and MetS. The longitudinal study,
including only university graduates at low cardiovascular
risk, reported an inverse association with the MetS (defined
by the IDF criteria) but only weak associations with most of
its defining criteria The two cross-sectional studies
found contradictory results. In both studies, in contrast to
our high risk participants, this association was analysed inpopulation samples with low cardiovascular risk. In
a sample of the general Greek population, individuals with
higher adherence to a MedDiet had a 20% lower odds ratio
of having MetS In contrast, in a cross-sectional study
performed on subjects from the general population of the
Canary Islands no significant relationship between MedDiet
In a Spanish cohort , after 6 years follow-up,
participants with the highest Trichopoulou score at base-
line presented the lowest cumulative incidence of MetS. In
our study we observed a better relationship between
MedDiet adherence and MetS when we used the 14-point
food-item score compared with the Trichopoulou score.
For this reason, the 14-item MetDiet score should be
evaluated in the future as a possible tool for analysing the
a The metabolic syndrome was defined by using the updated
relationship between MedDiet adherence and chronic
National Cholesterol Education program’s Adult Treatment
diseases. The advantage of the 14-item tool is that it is
assessed using only a short questionnaire and, therefore,the application of a full-length food frequency question-naire may not be needed to assess adherence to the
polynomial contrast and all the MetS components as
MedDiet. However, no significant relationship between
dependent variables. A higher adherence to the MedDiet
MedDiet adherence and MetS prevalence was observed
(quartile 4) was associated with a lower prevalence of the
when the Panagiotakos MedDiet score was used The
low HDL-cholesterol and high triglycerides criteria (47.0
cross-sectional design of our study and the space limits of
and 54%; P for trend Z 0.034 and 0.006 respectively) in
the manuscript precluded any analysis of specificity and
relation to the first quartile. After adjusting for BMI (data
sensitivity estimates such as that done by Panagiotakos in
not shown), only higher adherence to the MedDiet (quartile
Mediterranean diet and metabolic syndrome
Metabolic syndrome risk (odds ratio and their 95% confidence intervals) across quartiles of adherence to the Medi-
Multiple logistic regression was used to assess the association between MedDiet quartiles (dependent variables) and MetS (dependentvariable), and multiple logistic regression with polynominal contrast was used to generate the P for trend.
a Quartiles of Mediterranean diet score (0e14). b Adjusted for sex and age. c Adjusted for age. d Adjusted for sex, age, energy intake, smoking and physical activity. e Adjusted for age, energy intake, smoking and physical activity.
f Adjusted for sex, age, energy intake, smoking, physical activity and body mass index.
g Adjusted for age, energy intake, smoking, physical activity and body mass index.
Only one clinical trial has analysed the effect of the
pressure has been reported . A clinical trial did not
traditional MedDiet on the MetS. Esposito et al. showed
show any blood pressure effect after consumption of red wine
that an intervention using a Mediterranean-style diet seems
or de-alcoholized red wine. Moderate alcohol consumption
effective in reducing the prevalence of the MetS.
raises HDL-cholesterol levels and decreases plasma
Although Alvarez-Leon et al. found no relationship
concentrations of some inflammatory molecules. A meta-
between adherence to the MedDiet and lower MetS preva-
analysis indicated that the consumption of 30 g/day of alcohol
lence, they did observe that some components of the tradi-
increased HDL-cholesterol levels by a mean of 4 mg/dL, irre-
tional MedDiet (wine, fruit, vegetables and cereals) showed
spective of the alcoholic beverage consumed
an inverse association with MetS and its components. In fact,
High legume and low red meat consumption were
it has been suggested that not all the components of the
inversely associated in our study with MetS, but only among
MedDiet are likely to provide the same level of protection
men. Red meat is rich in saturated fat, which increases
In this sense, in our study, the use of olive oil as culinary
inflammation, LDL and TG-levels. Individuals adopting
fat, the high consumption of legumes and the moderate
a Western dietary pattern (characterized mainly by high red
consumption of wine were the principal components of the
or processed meat consumption) have an increased risk of
MedDiet associated with lower risk of MetS.
developing diabetes , whereas a MedDiet, low in meat
The inverse relationship observed between those typical
or meat products but rich in legumes was associated with
foods present in the MedDiet and MetS prevalence could be
a substantially lower diabetes risk Red meat intake
explained by many of the constituents of these foods. For
was also positively associated with the risk of hypertension
example olive oil is very rich in oxidation-resistant MUFA
in middle-aged and older men Furthermore, dietary
especially if the olive oil consumed is as the virgin
pattern analyses have shown that a dietary pattern char-
variety retaining all its polyphenol content Replacing
acterized by high red meat consumption is associated with
SFA by MUFA beneficially affects the plasma lipid profile
and improves insulin sensitivity . Olive oil consumption
Legumes are rich in fibre, magnesium and other
was reported to be associated with lower risk of developing
components that are associated with a better lipid profile,
hypertension, but only among men Virgin olive oil
and with improved glucose and inflammatory responses
or a diet rich in MUFA has been shown to reduce blood
. Subjects consuming legumes four or more times per
pressure more than an SFA-rich diet and, unlike a low-
week registered a lower risk of CVD Whole grain
fat, carbohydrate-rich diet, has no deleterious effect on
products and legumes protect against the development of
blood pressure in normotensive subjects .
diabetes . The viscous fibre content of legumes tends to
Some polyphenols present in red wine have beneficial
slow down carbohydrate digestion, decreasing the glycae-
endothelial and anti-inflammatory properties. An inverse
mic index of the diet, thus contributing to an increase in
association between red wine consumption and blood
the HDL-c levels and insulin sensitivity .
Metabolic syndrome risk (odds ratio and their 95% confidence intervals) in all subjects and Mediterranean diet food
Consumption ! 2 servings/day of vegetables
Consumption ! 3 fruit units/day (including natural fruit juices)
Consumption < 1 serving/day of red meat, hamburger or meat products
Consumption < 1 serving/day of butter, margarine or cream
Consumption < 1 serving/day of sweetened or carbonated beverages
Consumption ! 3 servings/week of fish or shellfish
Consumption < 3 times/week of commercial sweets or pastries (not
Consumption ! 1 servings/week of nuts (including peanuts)
Consumption preferentially of chicken, turkey, or rabbit meat instead of
Consumption ! 2 servings/week of vegetables, pasta, rice or other dishes
seasoned with sofrito (sauce made with tomato and onion, leek, or garlicand simmered with olive oil)
Multiple logistic regression models (enter method or forward method) including the presence or not of metabolic syndrome (dependentvariable) and the diet food items (independent variables), adjusted for sex, age, energy intake, smoking status and physical activity.
a Specific questions about these items are shown in Supplementary Appendix 1.
Metabolic syndrome components risk (odds ratio 95% confidence intervals) by quartiles of adherence to Mediterra-
nean diet in women (n Z 446) and men (n Z 362).
Waist circumference (>102 cm in men, >88 cm in women)All subjects
HDL-cholesterol (<40 mg/dL in men, <50 mg/dL in women)All subjects
Triglycerides (!150 mg/dL or hypotriglyceridemic treatment)All subjects
Glucose (>100 mg/dL or antidiabetic medication)All subjects
Blood pressure (systolic !130 mmHg, diastolic !85 or antihypertensive medication)All subjects
The multivariable logistic regression was adjusted for age, energy intake, smoking and physical activity. Multiple logistic regression wasused to assess the association between MedDiet quartiles (dependent variables) and each of the MetS components (dependent variable). Multiple logistic regression with polynominal contrast was used to generate the P for trend.
a Quartiles of Mediterranean diet score (0e14).
Mediterranean diet and metabolic syndrome
Finally, consistent with previous evidence regarding
outcomes other than MetS , a beneficial association of theoverall MedDiet pattern contrasts with the lack of evidence of
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