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Mediterranean diet and health status: An updated meta-analysis and a proposal for a literature-based adherence score

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To update previous meta-analyses of cohort studies that investigated the association between the Mediterranean diet and health status and to utilize data coming from all of the cohort studies for proposing a literature-based adherence score to the Mediterranean diet. We conducted a comprehensive literature search through all electronic databases up to June 2013. Cohort prospective studies investigating adherence to the Mediterranean diet and health outcomes. Cut-off values of food groups used to compute the adherence score were obtained. The updated search was performed in an overall population of 4 172 412 subjects, with eighteen recent studies that were not present in the previous meta-analyses. A 2-point increase in adherence score to the Mediterranean diet was reported to determine an 8 % reduction of overall mortality (relative risk = 0·92; 95 % CI 0·91, 0·93), a 10 % reduced risk of CVD (relative risk = 0·90; 95 % CI 0·87, 0·92) and a 4 % reduction of neoplastic disease (relative risk = 0·96; 95 % CI 0·95, 0·97). We utilized data coming from all cohort studies available in the literature for proposing a literature-based adherence score. Such a score ranges from 0 (minimal adherence) to 18 (maximal adherence) points and includes three different categories of consumption for each food group composing the Mediterranean diet. The Mediterranean diet was found to be a healthy dietary pattern in terms of morbidity and mortality. By using data from the cohort studies we proposed a literature-based adherence score that can represent an easy tool for the estimation of adherence to the Mediterranean diet also at the individual level.
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Public Health Nutrition: page 1 of 14 doi:10.1017/S1368980013003169
Review Article
Mediterranean diet and health status: an updated meta-analysis
and a proposal for a literature-based adherence score
Francesco Sofi
1,2,3,
*, Claudio Macchi
3
, Rosanna Abbate
1
, Gian Franco Gensini
1,3
and Alessandro Casini
1,2
1
Department of Clinical and Experimental Medicine, University of Florence, Largo Brambilla 3, 50134 Florence,
Italy:
2
Agency of Nutrition, University Hospital of Careggi, Florence, Italy:
3
Don Carlo Gnocchi Foundation Italy,
IRCCS, Florence, Italy
Submitted 21 February 2013: Final revision received 5 July 2013: Accepted 15 October 2013
Abstract
Objective: To update previous meta-analyses of cohort studies that investigated
the association between the Mediterranean diet and health status and to utilize
data coming from all of the cohort studies for proposing a literature-based
adherence score to the Mediterranean diet.
Design: We conducted a comprehensive literature search through all electronic
databases up to June 2013.
Setting: Cohort prospective studies investigating adherence to the Mediterranean
diet and health outcomes. Cut-off values of food groups used to compute the
adherence score were obtained.
Subjects: The updated search was performed in an overall population of
4 172 412 subjects, with eighteen recent studies that were not present in the
previous meta-analyses.
Results: A 2-point increase in adherence score to the Mediterranean diet was
reported to determine an 8 % reduction of overall mortality (relative risk 50?92;
95 % CI 0?91, 0?93), a 10 % reduced risk of CVD (relative risk 50?90; 95 % CI 0?87,
0?92) and a 4 % reduction of neoplastic disease (relative risk 50?96; 95 % CI 0?95,
0?97). We utilized data coming from all cohort studies available in the literature
for proposing a literature-based adherence score. Such a score ranges from
0 (minimal adherence) to 18 (maximal adherence) points and includes three
different categories of consumption for each food group composing the
Mediterranean diet.
Conclusions: The Mediterranean diet was found to be a healthy dietary pattern in
terms of morbidity and mortality. By using data from the cohort studies we
proposed a literature-based adherence score that can represent an easy tool for
the estimation of adherence to the Mediterranean diet also at the individual level.
Keywords
Mediterranean diet
Meta-analysis
Update
Score
The Mediterranean diet has consistently been demonstrated
to have a beneficial influence on health and longevity
(1–3)
.
Two meta-analyses conducted by our group in 2008
and in 2010 clearly showed a significant protection for
greater adherence to the Mediterranean diet on mortality
and morbidity from several causes
(2,3)
. However, since
the publication of the earliest meta-analysis further
studies have been published, making an update of the
literature necessary. In addition, despite the vast amount
of literature available, one main issue remains yet to
be solved: how can we define one’s adherence to the
Mediterranean diet?
Over the past years, several attempts for estimating
adherence to the Mediterranean diet have been done,
mainly through the creation of diet quality indices
(4,5)
.
The usefulness of these measures, the most common
of which is certainly the Mediterranean dietary score
created by Trichopoulou et al.
(6)
, has been assessed in
several longitudinal studies in association with different
health outcomes
(3)
. Although significant associations
between such scores and mortality have been found in
different populations, the clinical application of such
scores is not easy to obtain since studies evaluating
different cohorts with different dietary behaviours present
Public Health Nutrition
*Corresponding author: Email francescosofi@gmail.com rThe Authors 2013
different cut-off values for consumption of food groups
and the quantification of each food component is
not always available. To the best of our knowledge, no
studies have been conducted that attempt to review
and analyse altogether the studies investigating the
Mediterranean diet score in relation to health outcomes,
with the aim of proposing an adherence score that could
be used not only as an epidemiological tool but also at an
individual level.
Hence, the aims of the present study were to: (i) perform
an updated systematic review and meta-analysis on studies
investigating adherence score to the Mediterranean diet
and health status, due to the high number of studies that
have been published since the release of the earliest meta-
analysis; and (ii) obtain from all of the available cohort
studies the cut-off value for consumption of each food
group, in order to propose a questionnaire for estimation of
adherence to the Mediterranean diet based on descriptive
data of the literature.
Methods
Updated systematic review
The databases MEDLINE (source: PubMed, 1966 to June
2013), Embase (1980 to June 2013), Web of Science, The
Cochrane Library (source: The Cochrane Database of
Systematic Review, 2013, issue 6), Clinicaltrials.org and
Google Scholar were systematically reviewed and updated
using a literature search strategy. Relevant keywords relating
to the Mediterranean diet in combination as MeSH (Medical
Subject Headings) terms and text words (‘Mediterranean
diet’, or ‘diet’ or ‘dietary pattern’ ‘Mediterranean’, or
‘adherence’ or ‘score’ and their variants) were used in
combination with words relating to health status (‘health’,
or ‘mortality’ or ‘morbidity’, or ‘cardiovascular diseases’,
or ‘neoplastic diseases’, or ‘cancer’, or ‘neoplasm’, or
‘degenerative diseases’, or ‘Alzheimer’s disease’, or
‘Parkinson’s disease’, or ‘cerebrovascular disease’, or ‘stroke’,
or ‘outcome’, or ‘prospective’, or ‘follow-up’, or ‘cohort’
and their variants). The search strategy had no language
restrictions and was supplemented by manually reviewing
the reference list of all retrieved articles.
Two investigators (F.S., A.C.) assessed potentially
relevant articles for eligibility. The decision to include or
exclude studies was hierarchical and initially made on the
basis of the study title, then of the study abstract and
finally of the complete study manuscript. We included
studies that assessed in a prospective way the possible
association between a Mediterranean dietary score and
health outcomes, as already reported in the previous
meta-analyses
(2,3)
. Two researchers independently com-
pleted searches, study identification, data abstraction and
tabulation, and discordances were resolved by discussion.
Outcomes of interests were overall mortality, mortality
from and/or incidence of cardio- and cerebrovascular
diseases, mortality from and/or incidence of cancer, as well
as incidence of neurodegenerative diseases.
Literature-based adherence score to the
Mediterranean diet
All cohort studies that investigated the association
between adherence to the Mediterranean diet and health
outcomes were collected. We summarize all the amounts
chosen as cut-offs for determining adherence to the
Mediterranean diet, together with the author, year of
publication, cohort analysed, country of the cohort,
number of subjects investigated and the age of subjects,
according to sex, in Tables 1 and 2.
Due to the wide distribution of median consumption of
some food groups in the included studies (e.g. see legumes,
whose consumption ranges from 2 to 75 g/d), data were
logarithmically transformed and back-transformed for data
presentation. Median (or mean) values for consumption of
food groups composing the Mediterranean diet adherence
score were weighted for the number of subjects enrolled in
each study. This was because of the large variability in
terms of subjects analysed and because the sample size of
the study was found to be the most significant contributor
to the robustness of results in our previous meta-analysis
(3)
.
After that, we calculated the mean value of all of the
weighted medians and the 2 SD for each food group. In
order to provide meaningful estimates for clinical practice
we finally rounded the resulting numbers close to the 2 SD
values for each measure, by obtaining three categories of
consumption for each food group.
Statistical analysis
We used RevMan version 5?0?18 for Macintosh and IBM
SPSS Statistics version 18?0 for Macintosh to pool and
analyse results from the individual studies. The methods
and results of all the recent identified cohort prospective
studies were added to the previous table and data were
formally combined
(3)
. Pooled results are reported as
relative risk (RR) and are presented with 95 % confidence
interval with two-sided Pvalues using a random-effects
model (DerSimonian and Laird method) and the general
variance-based method. A Pvalue less than 0?05 was
considered statistically significant. We used, when avail-
able, the results of the original studies from multivariate
models with the most complete adjustment for potential
confounders; the confounding variables included in this
analysis are shown in Table 3.
Statistical heterogeneity was evaluated using the I
2
statistic, which assesses the appropriateness of pooling
the individual study results. The I
2
value provides an
estimate of the amount of variance across studies due to the
heterogeneity rather than chance. Where I
2
was greater
than 50%, heterogeneity was considered substantial. Small
study bias and/or publication bias was appraised by visual
inspection of a funnel plot of effect size v. standard error
and, analytically, by Egger’s test.
Public Health Nutrition
2 F Sofi et al.
Public Health Nutrition
Table 1 Values of components of adherence score to the Mediterranean diet among men (g/d)
Author Year Cohort Country nAge (years) Disease Legumes Cereals Fruit Vegetables Fish Meat Dairy
Trichopoulou et al.
(25)
1995 Greek villages G 91 .70 OM 60 291 249 303 n.d. 109 201
Kouris-Blazos et al.
(26)
1999 Anglo-Celts;
Greek-Australian
A70.70 OM 50* 232?5* 291* 349?5* n.d. 246* 296*
Lasheras et al.
(27)
2000 Spanish volunteers S 49 65–95 OM 13?5 248?5211?5313?5 n.d. 139?5416
Knoops et al.
(28)
2004 SENECA B, D, F, G, H, I, N,
P, S, Sw
781 73* OM 7 248 228 306 26 130 313
Knoops et al.
(28)
2004 FINE F, I, N 726 77* OM 10 231 209 248 20 113 392
Trichopoulou et al.
(29)
2005 EPIC-Elderly D, F, Ge, G, I, N, S,
Swe, UK
24 545 .60 OM 3?3 212 176?7156?832?2 111?6285?7
Scarmeas et al.
(30)
2006 WHICAP USA 720 77?2* Al 57 184 472 197 20 85 182
Benetou et al.
(31)
2008 Greek-EPIC G 10 582 20–86 C 10?2* 187?2* 383?2* 578?6* 26?3* 126?2* 221?2*
Trichopoulou et al.
(32)
2009 Greek-EPIC G 9504 20–86 OM 9?1 178?3362?5548?623?7 121?1196?1
Buckland et al.
(33)
2009 Spanish-EPIC S 15 442 29–69 CHD 23?791?2109?990?723?358?791?4
Buckland et al.
(34)
2010 EPIC D, F, G, Ge, I, N,
No, S, Swe, UK
144 577 35–70 C 2?284?870?163?87?350?5116?9
Sjorgen et al.
(7)
2010 ULSAM Swe 924 71* OM, CVD 75 405 124 75 27 98 417
Martinez-Gonzalez et al.
(35)
2011 SUN S 5444 38* CVD 21 90 235 401 87 177 182
Tognon et al.
(8)
2011 GGPSG Swe 497 .70 OM 13?3 213 155?5239 53?7 109?1446
Agnoli et al.
(9)
2011 EPICOR Study I 12563 35–64 St 16 272 319 173 28 110 54
Buckland et al.
(10)
2011 EPIC-Spain S 15 324 49?3* OM, CVD, C 56 214 380 282?264?196?9198?5
van der Brandt
(11)
2011 NLCS N 1690 55–69 OM 6?5 n.d. 153?9202?611?5 124 n.d.
Gardener et al.
(12)
2011 NOMAS USA 931 68?6* CVD, St 16 68 149 77 12 40 104
Couto et al.
(13)
2011 EPIC D, F, Ge, G, I, N,
No, S, Swe, UK
142 605 25–70 C 14?6* 219 247?3211?237?298?7326?7
Dilis et al.
(17)
2012 Greek-EPIC G 9740 20–86 CHD 9 176 356 547 24 121 198
Hoevenaar-Blom et al.
(18)
2012 EPIC-NL N 8764 20–70 CVD, St 15 250 117 103 8 141 353
Misirli et al.
(19)
2012 Greek-EPIC G 9617 20–86 CBVD 8?9* 163?4* 382?2* 553?5* 23?7* 108?9* 220?2*
Martinez-Gonzalez et al.
(15)
2012 SUN S 6271 38* OM 21 85 245 412 86 174 164
Tognon et al.
(16)
2012 VIP Swe 37 546 30–60 OM n.d. 33?749?294?79?653206
Bamia et al.
(20)
2013 EPIC D, F, Ge, G, I, N,
No, S, Swe, UK
143 752 25–70 C 5?7 200?1199?6174?128 91?7276
SENECA, Survey in Europe on Nutrition and the Elderly: a Concerted Action; FINE, Finland, Italy, the Netherlands, Elderly study; EPIC, European Prospective Investigation into Cancer and Nutrition; WHICAP,
Washington Heights-Inwood Columbia Aging Project; ULSAM, Uppsala Longitudinal Study of Adult Men; SUN, Seguimiento Universidad de Navarra; GGPSG, Gerontological and Geriatric Population Studies in
Gothenburg; EPICOR Study, Italian Section of the European Prospective Investigation into Cancer and Nutrition; NLCS, Netherlands Cohort Study; NOMAS, Northern Manhattan Study; VIP, Va
¨sterbotten Intervention
Program; G, Greece; A, Australia; S, Spain; B, Belgium; D, Denmark; F, France; H, Hungary; I, Italy; N, The Netherlands; P, Portugal; Sw, Switzerland; Swe, Sweden; Ge, Germany; No, Norway; OM, overall mortality;
Al, Alzheimer’s disease; C, cancer; St, stroke; CBVD, cerebrovascular disease; n.d., not determined.
*Mean values.
Adherence score to Mediterranean diet and health 3
Public Health Nutrition
Table 2 Values of components of adherence score to the Mediterranean diet among women (g/d)
Author Year Cohort Country nAge (years) Disease Legumes Cereals Fruit Vegetables Fish Meat Dairy
Trichopoulou et al.
(25)
1995 Greek villages G 91 .70 OM 49 248 216 248 n.d. 91 194
Kouris-Blazos et al.
(26)
1999 Anglo-Celts;
Greek-Australian
A95.70 OM 50* 232?5* 291* 349?5* n.d. 246* 296*
Lasheras et al.
(27)
2000 Spanish volunteers S 112 65–95 OM 10?5 197 228 228 n.d. 105 352?5
Knoops et al.
(28)
2004 SENECA B, D, F, G, H, I, N,
P, S, Sw
832 73* OM 5 194 262 272 23 107 317
Trichopoulou et al.
(29)
2005 EPIC-Elderly D, F, Ge, G, I, N, S,
Swe, UK
50 062 .60 OM 5 168?4 245?7 183?826?982?2301?1
Lagiou et al.
(36)
2006 SWLHC Swe 42 237 30–49 OM, C 17?5183?3 136?961?922?784?4334?2
Scarmeas et al.
(30)
2006 WHICAP USA 1546 77?2* Al 57 184 472 197 20 85 182
Benetou et al.
(31)
2008 Greek-EPIC G 15 041 20–86 C 7?8144?6 375?6 531?121?893?7214?7
Trichopoulou et al.
(32)
2009 Greek-EPIC G 13 845 20–86 OM 6?7139?6 356?8 499?318?989?9191?4
Buckland et al.
(33)
2009 EPIC-Spain S 25 636 29–69 CHD 19?484?4 155?8 113 23?154155?9
Buckland et al.
(34)
2010 EPIC D, F, G, Ge, I, N,
No, S, Swe, UK
340 467 35–70 C 3 85 113?497?49?844?5147?2
Martinez-Gonzalez et al.
(35)
2011 SUN S 8165 38* CVD 21 81 300 501 86 170 143
Tognon et al.
(8)
2011 GGPSG Swe 540 .70 OM 2 165 176?4 209?545?289?7373?3
Agnoli et al.
(9)
2011 EPICOR Study I 28 118 35–64 St 17 185 319 173 28 83 50
Buckland et al.
(10)
2011 EPIC-Spain S 25 928 49?3* OM, CVD, C 56 214 380 282?264?196?9198?5
van der Brandt
(11)
2011 NLCS N 1886 55–69 OM 4?9 n.d. 212?9 218?78?8 106?1 n.d.
Gardener et al.
(12)
2011 NOMAS USA 1637 68?6* CVD, St 9 61 131 67 10 33 92
Couto et al.
(13)
2011 EPIC D, F, Ge, G, I, N,
No, S, Swe, UK
335 873 25–70 C 14?6* 219* 247?3* 211?2* 37?2* 98?7* 326?7*
Dilis et al.
(17)
2012 Greek-EPIC G 14 189 20–86 CHD 7 139 351 499 19 90 194
Hoevenaar-Blom et al.
(18)
2012 EPIC-NL N 25 944 20–70 CVD, St 12 165?5 174 118 7?594?5380
Misirli et al.
(19)
2012 Greek-EPIC G 13 984 20–86 CBVD 8?9* 163?4* 382?2* 553?5* 23?7* 108?9* 220?2*
Martinez-Gonzalez et al.
(15)
2012 SUN S 9264 38* OM 21 81 301 503 86 164 126
Tognon et al.
(16)
2012 VIP Swe 39 605 30–60 OM n.d. 38?6 109?1 148 11?652219
Bamia et al.
(20)
2013 EPIC D, F, Ge, G, I, N,
No, S, Swe, UK
336 556 25–70 C 5?7200?1 199?6 174?128 91?7276
Buckland et al.
(21)
2013 EPIC D, F, Ge, G, I, N,
No, S, Swe, UK
335 062 25–70 C 14* 172?3* 250?2* 218?8* 26?8* 87?4* 322?1*
Couto et al.
(22)
2013 SWLHC Swe 49 258 30–49 C 19?3* 195?6* 158?1* 70?4* 24?4* 87?7* 369?8*
SENECA, Survey in Europe on Nutrition and the Elderly: a Concerted Action; EPIC, European Prospective Investigation into Cancer and Nutrition; SWLHC, Scandinavian Women’s Lifestyle and Health Cohort; WHICAP,
Washington Heights-Inwood Columbia Aging Project; SUN, Seguimiento Universidad de Navarra; GGPSG, Gerontological and Geriatric Population Studies in Gothenburg; EPICOR Study, Italian Section of the
European Prospective Investigation into Cancer and Nutrition; NLCS, Netherlands Cohort Study; NOMAS, Northern Manhattan Study; VIP, Va
¨sterbotten Intervention Program; G, Greece; A, Australia; S, Spain;
B, Belgium; D, Denmark; F, France; H, Hungary; I, Italy; N, The Netherlands; P, Portugal; Sw, Switzerland; Swe, Sweden; Ge, Germany; No, Norway; OM, overall mortality; Al, Alzheimer’s disease; C, cancer; St, stroke;
CBVD, cerebrovascular disease; n.d., not determined.
*Mean values.
4 F Sofi et al.
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Table 3 Study characteristics of the recent prospective studies investigating adherence to the Mediterranean diet and health outcomes
Author, year (cohort) Country n/NOutcome
Follow-up
(years)
Age
(years) Sex
Components of the adherence
score Adjustment
Sjorgen et al.
(7)
, 2010
(ULSAM)
Swe 215/924 OM 10?1 71* M 1. High vegetables and legumes;
2. High cereals and potatoes;
3. High fruit; 4. High fish; 5.
High PUFA:SFA; 6. Moderate
alcohol; 7. Low meat and meat
products; 8. Low milk and milk
products
EI, smoking habit, social class,
diabetes, MetS, lipid-lowering
treatment, BP-lowering
treatment, WC, BP, insulin,
CRP
88/924 CVD mortality
Tognon et al.
(8)
, 2011
(GGPSG)
Swe 622/1037 OM 8?5.70 M/F 1. High legumes and nuts; 2. High
wholegrain cereals; 3. High
fruit; 4. High vegetables and
potatoes; 5. High fish and
fish products; 6. High
MUFA1PUFA:SFA;7.Moderate
alcohol; 8. Low meat, meat
products and eggs; 9. Low dairy
products
Sex, BMI, WC, PA, marital status,
smoking habit, education
Agnoli et al.
(9)
, 2011
(EPICOR Study)
I 178/40 681 St 7?9 35–74 F 1. High pasta; 2. High vegetables;
3. High fruit; 4. High legumes;
5. High fish; 6. High olive oil;
7. Low potatoes; 8. Low butter;
9. Moderate alcohol; 10. Low
red and processed meat;
11. Low soft drinks
Age, sex, smoking habit,
education, EI, BMI
Buckland et al.
(10)
, 2011
(EPIC-Spain)
S 1855/40 622 OM 13?4 29–69 M/F 1. High legumes; 2. High cereals;
3. High fruit and nuts; 4. High
vegetables; 5. High fish; 6. High
MUFA:SFA; 7. Moderate
alcohol; 8. Low meat and
poultry; 9. Low dairy products
Age, education, BMI, WC,
education, PA, smoking habit,
total energy
399/40 622 CVD mortality
913/40 622 C mortality
van den Brandt
(11)
, 2011
(NLCS)
Men
N 6329/58 279 OM 4?9 55–69 M 1. High legumes; 2. High cereals;
3. High fruit and nuts; 4. High
vegetables; 5. High fish; 6. High
MUFA:SFA; 7. Moderate
alcohol; 8. Low meat and
poultry; 9. Low dairy products
Age, smoking habit, cigarettes,
years of smoking, BMI, PA,
hypertension, education, EI
van der Brandt
(11)
, 2011
(NLCS)
Women
N 3362/62 573 OM 4?9 55–69 F 1. High legumes; 2. High cereals;
3. High fruit and nuts; 4. High
vegetables; 5. High fish; 6. High
MUFA:SFA; 7. Moderate
alcohol; 8. Low meat and
poultry; 9. Low dairy products
Age, smoking habit, cigarettes,
years of smoking, BMI, PA,
hypertension, education, EI
Adherence score to Mediterranean diet and health 5
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Table 3 Continued
Author, year (cohort) Country n/NOutcome
Follow-up
(years)
Age
(years) Sex
Components of the adherence
score Adjustment
Gardener et al.
(12)
, 2011
(NOMAS)
USA 518/2568 CVD 9 69 M/F 1. High legumes; 2. High cereals;
3. High fruit; 4. High vegetables;
5. High fish; 6. High
MUFA:SFA; 7. Moderate
alcohol; 8. Low meat and meat
products; 9. Low dairy products
Age, sex, race, education, PA, EI,
smoking habit, hypertension,
diabetes,
hypercholesterolaemia
Couto et al.
(13)
, 2011
(EPIC)
D, F, Ge,
G, I, N,
No, S,
Swe, UK
30 731/478 478 C 8?7 25–70 M/F 1. High legumes; 2. High cereals;
3. High fruit; 4. High vegetables;
5. High fish; 6. High
MUFA:SFA; 7. Moderate
alcohol; 8. Low meat and meat
products; 9. Low dairy products
Age, sex, smoking habit, duration
of smoking, education, height,
BMI, EI, PA, menopause, HRT
McNaughton et al.
(14)
, 2010
(BDNS)
UK 654/972 OM 14 .65 M/F 1. High legumes; 2. High cereals;
3. High fruit and nuts; 4. High
vegetables; 5. High fish; 6. High
MUFA:SFA; 7. Moderate
alcohol; 8. Low meat and meat
products; 9. Low dairy products
Age, sex, EI, social class, region,
smoking habit, PA, BMI
Martinez-Gonzalez et al.
(15)
,
2012
(SUN)
S 125/15 535 OM 6?8 38 M/F 1. High legumes; 2. High cereals;
3. High fruit and nuts; 4. High
vegetables; 5. High fish; 6. High
MUFA:SFA; 7. Moderate
alcohol; 8. Low meat and meat
products; 9. Low dairy products
Age, sex, years of education, BMI,
smoking habit, PA, h/d spent
watching TV, depression,
hypertension,
hypercholesterolaemia, EI, egg
and potatoes
Tognon et al.
(16)
,2012
(VIP)
Swe 1453/37 546 OM 10 30–70 M 1. High vegetables and potatoes;
2. High fruit and juices; 3. High
wholegrain cereals; 4. High fish
and fish products; 5. High fish;
6. High MUFA1PUFA:SFA;
7. Moderate alcohol; 8. Low
meat and meat products; 9. Low
dairy products
Age, obesity, PA, smoking habit,
education493/35 950 C
499/35 950 CVD
Tognon et al.
(16)
,2012
(VIP)
Swe 923/39 605 OM 10 30–70 F 1. High vegetables and potatoes;
2. High fruit and juices; 3. High
wholegrain cereals; 4. High fish
and fish products; 5. High fish;
6. High MUFA1PUFA:SFA;
7. Moderate alcohol; 8. Low
meat and meat products; 9. Low
dairy products
Age, obesity, PA, smoking habit,
education481/38 034 C
181/38 034 CVD
6 F Sofi et al.
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Table 3 Continued
Author, year (cohort) Country n/NOutcome
Follow-up
(years)
Age
(years) Sex
Components of the adherence
score Adjustment
Dilis et al.
(17)
, 2012
(Greek-EPIC)
Men
G 150/9740 CHD mortality 10 25–70 M 1. High legumes; 2. High cereals;
3. High fruit and nuts; 4. High
vegetables; 5. High fish; 6. High
MUFA:SFA; 7. Moderate
alcohol; 8. Low meat and meat
products; 9. Low dairy products
Age, BMI, height, PA, education,
smoking habit, hypertension, EI
Dilis et al.
(17)
, 2012
(Greek-EPIC)
Women
G 90/14 189 CHD mortality 10 25–70 F 1. High legumes; 2. High cereals;
3. High fruit and nuts; 4. High
vegetables; 5. High fish; 6. High
MUFA:SFA; 7. Moderate
alcohol; 8. Low meat and meat
products; 9. Low dairy products
Age, BMI, height, PA, education,
smoking habit, hypertension, EI
Hoevenaar-Blom et al.
(18)
,
2012
(EPIC-NL: MORGEN and
PROSPECT)
N 4881/34 708 CVD 12 20–70 M/F 1. High legumes; 2. High cereals;
3. High fruit; 4. High vegetables;
5. High fish; 6. High
MUFA:SFA; 7. Moderate
alcohol; 8. Low meat and meat
products; 9. Low dairy products
Age, sex, cohort, smoking habit,
PA, education, EI448/34 708 Stroke
Misirli et al.
(19)
, 2012
(EPIC-Greece)
Men
G 204/9617 CBVD 10?6 25–70 M 1. High legumes; 2. High cereals;
3. High fruit; 4. High vegetables;
5. High fish; 6. High
MUFA:SFA; 7. Moderate
alcohol; 8. Low meat and meat
products; 9. Low dairy products
Age, education, smoking habit,
BMI, PA, hypertension,
diabetes, EI
Misirli et al.
(19)
, 2012
(EPIC-Greece)
Women
G 191/13 984 CBVD 10?6 25–70 F 1. High legumes; 2. High cereals;
3. High fruit; 4. High vegetables;
5. High fish; 6. High
MUFA:SFA; 7. Moderate
alcohol; 8. Low meat and meat
products; 9. Low dairy products
Age, education, smoking habit,
BMI, PA, hypertension,
diabetes, EI
Bamia et al.
(20)
, 2013
(EPIC)
D, F, Ge,
G, I, N,
No, S,
Swe, UK
3724/397 641 Colorectal
cancer
11?6 25–70 M/F 1. High legumes; 2. High cereals;
3. High fruit and nuts; 4. High
vegetables; 5. High fish; 6. High
MUFA:SFA; 7. Low meat and
meat products; 8. Low dairy
products
Age, sex, BMI, PA, education,
smoking habit, EI
Buckland et al.
(21)
, 2013
(EPIC)
D, F, Ge,
G, I, N,
No, S,
Swe, UK
10 225/335 062 Breast cancer 11 25–70 F 1. High legumes; 2. High cereals;
3. High fruit and nuts; 4. High
vegetables; 5. High fish; 6. High
MUFA:SFA; 7. Low meat and
meat products; 8. Low dairy
products
Age, BMI, height, education, PA,
smoking habit, menopause, age
at menopause, oral
contraception, age at menarche,
age at first pregnancy, HRT,
SFA intake, EI
Adherence score to Mediterranean diet and health 7
Public Health Nutrition
Table 3 Continued
Author, year (cohort) Country n/NOutcome
Follow-up
(years)
Age
(years) Sex
Components of the adherence
score Adjustment
Couto et al.
(22)
, 2013
(SWLHC)
Swe 1278/49 285 Breast cancer 16 30–49 F 1. High legumes; 2. High cereals;
3. High fruit and nuts; 4. High
vegetables; 5. High fish; 6. High
MUFA:SFA; 7. Moderate
alcohol; 8. Low meat and meat
products; 9. Low dairy products
Age, BMI, height, education, PA,
smoking habit, history of breast
cancer, age at menarche, EI,
beverages, potatoes, sweets,
eggs
Agnoli et al.
(23)
, 2013
(EPIC)
Men
I 181/14 195 Colorectal
cancer
11?3 25–70 M 1. High pasta; 2. High vegetables;
3. High fruit; 4. High legumes;
5. High fish; 6. High olive oil;
7. Low potatoes; 8. Low butter;
9. Moderate alcohol; 10. Low
red and processed meat;
11. Low soft drinks
Age, non-alcoholic EI, BMI,
smoking habit, education, PA
Agnoli et al.
(23)
, 2013
(EPIC)
Women
I 254/31 080 Colorectal
cancer
11?3 25–70 F 1. High pasta; 2. High vegetables;
3. High fruit; 4. High legumes;
5. High fish; 6. High olive oil;
7. Low potatoes; 8. Low butter;
9. Moderate alcohol; 10. Low
red and processed meat;
11. Low soft drinks
Age, non-alcoholic EI, BMI,
smoking habit, education, PA
Bosire et al.
(24)
, 2013
(NIH-AARP)
USA 23 453/293 464 Prostate cancer 8?9 50–71 M 1. High legumes; 2. High
wholegrain cereals; 3. High fruit
and nuts; 4. High vegetables;
5. High fish; 6. High MUFA:SFA;
7. Moderate alcohol; 8. Low
meat and meat products; 9. Low
dairy products
Age, ethnicity, education, BMI,
smoking habit, PA, family
history of prostate cancer,
diabetes, EI, history of PSA
screening
ULSAM, Uppsala Longitudinal Study of Adult Men; GGPSG, Gerontological and Geriatric Population Studies in Gothenburg; EPICOR Study, Italian Section of the European Prospective Investigation into Cancer and
Nutrition; EPIC, European Prospective Investigation into Cancer and Nutrition; NLCS, Netherlands Cohort Study; NOMAS, Northern Manhattan Study; BDNS, British Diet and Nutrition Survey; SUN, Seguimiento
Universidad de Navarra; VIP, Va
¨sterbotten Intervention Program; SWLHC, Swedish Women’s Lifestyle and Health Cohort; NIH-AARP, National Institutes of Health-AARP Diet and Health Study; Swe, Sweden; I, Italy;
S, Spain; N, The Netherlands; D, Denmark; F, France; Ge, Germany; G, Greece; No, Norway; OM, overall mortality; St, stroke; C, cancer; CBVD, cerebrovascular disease; M, males, F, females; EI, energy intake;
MetS, metabolic syndrome; BP, blood pressure; WC, waist circumference; CRP, C-reactive protein; PA, physical activity; HRT, hormone replacement therapy; TV, television; PSA, prostate-specific antigen.
*Mean values.
8 F Sofi et al.
Results
Updated systematic review and meta-analysis
The updated search from recent years resulted in the
identification of eighteen additional prospective studies
published up to June 2013
(7–24)
. Characteristics of these
recent studies are displayed in Table 3. Of these, seven
cohorts presented overall mortality as clinical out-
come
(7,8,10,11,14–16)
, eight incidence and/or mortality from
cardio- and cerebrovascular diseases
(7,9,10,12,16–19)
, and
eight incidence and/or mortality from neoplastic dis-
eases
(10,13,16,20–24)
. No updated studies for the incidence
of neurodegenerative diseases have been found. On
the other hand, one study resulted to be an updated
analysis of a study already reported in the previous
meta-analyses for the overall mortality outcome, so
only the most updated study was added to this updated
final analysis
(13)
. Altogether with the studies previously
investigated, a total of thirty-five cohort prospective
studies were included and entered into the final
analysis. This updated analysis determined an increase of
the study population up to a total of 4 172 412 subjects
analysed.
Meta-analytic pooling under a random-effects model
showed the already reported significant association
between 2-point increased adherence to the Mediterranean
diet and reduced risk of mortality from all causes
(RR 50?92; 95 % CI 0?91, 0?93; P,0?00001; Fig. 1), with
little evidence of statistical heterogeneity across the
studies (I
2
547 %; P50?01). This heterogeneity seems
to be determined mainly by the study of van den
Brandt
(11)
. After exclusion of this latter study, the statistical
heterogeneity disappeared (I
2
535 %; P50?08), with
no modification of the association between adherence to
the Mediterranean diet and overall mortality (RR 50?92;
95 % CI 0?91, 0?93; P,0?00001).
Moreover, we found that a 2-point increase of adher-
ence to the Mediterranean diet still remained associated
with a reduced risk of mortality from and incidence of
CVD (RR 50?90; 95 % CI 0?87, 0?92; P,0?00001; Fig. 2),
showing no significant heterogeneity across the studies
(I
2
538 %; P50?07). Likewise, among studies investigating
mortality and incidence of neoplastic diseases (Fig. 3), a
greater adherence to the Mediterranean diet still deter-
mined a significant protection, to a similar extent as the
previous meta-analysis (RR 50?96; 95 % CI 0?95, 0?97;
P,0?00001), with evidence of significant heterogeneity
across the studies (I
2
565 %; P,0?0 0 1). The hetero-
geneity seems to be determined by the recent studies
investigating breast and colorectal cancer
(21–23)
.After
exclusion of these three studies, the statistical heterogeneity
disappeared (I
2
536 %; P50?10),withnomodication
Public Health Nutrition
Study RR (95 % CI)Weight (%)
0·3
0·2
0·1
6·5
10·3
3·0
17·1
15·7
5·3
0·4
4·2
10·1
5·1
7·0
2·7
0·9
6·7
4·4
100·0 0·91 (0·89, 0·93)
0·92 (0·85, 1·00)
0·92 (0·86, 0·98)
0·72 (0·58, 0·89)
0·88 (0·79, 0·99)
0·84 (0·79, 0·89)
0·94 (0·87, 1·02)
0·94 (0·90, 0·98)
0·86 (0·79, 0·94)
0·69 (0·49, 0·97)
0·86 (0·80, 0·93)
0·93 (0·91, 0·95)
0·92 (0·91, 0·94)
0·93 (0·83, 1·04)
0·93 (0·89, 0·97)
0·88 (0·82, 0·94)
0·48 (0·22, 1·03)
0·79 (0·50, 1·25)
0·69 (0·48, 0·99)Trichopoulou et al. (1995)(25)
Kouris-Blazos et al. (1999)(26)
Lasheras et al. (2000)(27)
Knoops et al. (2004)(28)
Trichopoulou et al. (2005)(29)
Lagiou et al. (2006)(36)
Mitrou et al. (2007) (M)
Mitrou et al. (2007) (F)
Trichopoulou et al. (2009)(32)
Sjorgen et al. (2010)(7)
Tognon et al. (2011)(8)
Buckland et al. (2011)(10)
van den Brandt (2011)(11) (M)
van den Brandt (2011)(11) (F)
McNaughton et al. (2012)(14)
Martinez-Gonzalez et al. (2012)(15)
Tognon et al. (2012)(16) (M)
Tognon et al. (2012)(16) (F)
Total (95% CI)
0·4 0·6
Reduced risk
RR (95 % CI)
Increased risk
0·8 1·0 1·2 1·4
Fig. 1 Forest plot for updated meta-analysis on greater adherence score to the Mediterranean diet (2-point increase) and overall
mortality risk. Plotted are the relative risk (RR; represented by , with the symbol size proportional to the weight in meta-analysis)
and the 95 % confidence interval (represented by horizontal bars), with the summary measure (represented by ----- and E, with
the associated 95 % confidence interval indicated by the symbol width) and the line of no effect (——)
Adherence score to Mediterranean diet and health 9
on the protection of the Mediterranean diet v. neoplastic
disease (RR 50?96; 95 % CI 0?95, 0?97; P,0?00001).
Literature-based adherence score to the
Mediterranean diet
Characteristics of the studies included for this analysis
are reported in Tables 1 and 2 for men and women,
respectively. For the purpose of this analysis some studies
previously included in the updated meta-analytic analysis
were excluded, due to the lack of information on amount
of consumption for the different food groups composing
the adherence score.
We were able to collect data from twenty-four cohort
studies for men
(7–13,15–20,25–35)
and twenty-six for
women
(8–13,15–22,25–36)
. It is interesting to note that values of
consumption for food groups composing adherence score
to the Mediterranean diet resulted to be, in some cases,
different across the studies. For instance, between two
cohorts of subjects coming from the same continent (e.g.
Spain and Greece) the median consumption of some food
groupsvariedfrom90to187g/d(e.g.cerealsformen
between Martinez-Gonzalez et al.
(35)
and Buckland et al.
(10)
).
More interestingly, vegetable consumption showed a wide
variability even between two cohorts of subjects coming
from the same country (e.g. vegetables: 75 g/d v.239g/dfor
Sjorgen et al.
(7)
and Tognon et al.
(8)
, respectively).
We utilized such data for proposing an adherence score
based on literature data. To this aim, we weighted all the
median (or mean) values for the sample size of each
study population and then we calculated the mean value
of all the weighted medians. Hence, we calculated the
2SD value and we rounded the number close to the 62SD,
determining three different categories of consumption for
each food group (e.g. for cereals: weighted mean 5162?7
(SD 34?6) g/d that determined three different categories
,130 g; 131–200 g; .200 g). For food groups typical of
the Mediterranean diet (fruit, vegetables, cereals, legumes
and fish) we gave 2 points to the highest category of
consumption, 1 point for the middle category and 0 point
for the lowest category. Conversely, for food groups not
typical of the Mediterranean diet (meat and meat pro-
ducts, dairy products) we gave 2 points for the lowest
category, 1 point for the middle category and 0 point for
the highest category of consumption. For alcohol, we
used the categories related to the alcohol unit (1 alcohol
unit 512 g of alcohol), by giving 2 points to the middle
category (1–2 alcohol units/d), 1 point to the lowest
category (,1 alcohol unit/d) and 0 point to the highest
category of consumption (.2 alcohol units/d). Finally,
we introduced olive oil as part of the proposed score due
to its importance in the typical Mediterranean diet and
the beneficial effect of its consumption on health and
Public Health Nutrition
Martinez-Gonzalez et al. (2011)(35)
Agnoli et al. (2011)(9) (Stroke)
Buckland et al. (2011)(10)
Gardener et al. (2011)(12)
Tognon et al. (2012)(16) (M)
Tognon et al. (2012)(16) (F)
Dilis et al. (2012)(17) (M)
Dilis et al. (2012)(17) (F)
Hoevenaar-Blom et al. (2012)(18) (CVD)
Hoevenaar-Blom et al. (2012)(18) (Stroke)
Misirli et al. (2012)(19) (M)
Misirli et al. (2012)(19) (F)
Total (95% CI)
Sjorgen et al. (2010)(7)
Buckland et al. (2010)(34)
Fung et al. (2009) (Stroke)
Fung et al. (2009) (CHD)
Mitrou et al. (2007) (F)
Mitrou et al. (2007) (M)
Knoops et al. (2004)(28)
Trichopoulou et al. (1995)(25)
0·4 0·6
Reduced risk Increased risk
0·8 1·0 1·2 1·4
Study RR (95 % CI)
RR (95 % CI)
Weight (%)
0·7 0·67 (0·47, 0·95)
0·84 (0·76, 0·94)
0·92 (0·89, 0·96)
0·93 (0·88, 0·99)
0·87 (0·82, 0·92)
0·95 (0·88, 1·01)
0·89 (0·81, 0·97)
0·86 (0·49, 1·53)
0·80 (0·62, 1·03)
0·60 (0·45, 0·82)
0·88 (0·81, 0·96)
0·90 (0·81, 1·01)
0·98 (0·86, 1·11)
0·81 (0·67, 0·98)
0·81 (0·66, 0·99)
0·75 (0·57, 0·99)
0·95 (0·91, 0·99)
0·88 (0·78, 0·99)
0·88 (0·74, 1·05)
0·81 (0·67, 0·98)
0·90 (0·87, 0·92)
5·3
13·2
10·0
10·5
9·0
6·4
0·3
1·2
0·9
7·1
5·0
4·1
2·1
1·8
1·0
12·6
4·3
2·4
2·0
100·0
Fig. 2 Forest plot for updated meta-analysis on greater adherence score to the Mediterranean diet (2-point increase) and cardiovascular
incidence and/or mortality risk. Plotted are the relative risk (RR; represented by , with the symbol size proportional to the weight in
meta-analysis) and the 95 % confidence interval (represented by horizontal bars), with the summary measure (represented by - - - - - and
E, with the associated 95 % confidence interval indicated by the symbol width) and the line of no effect (——)
10 F Sofi et al.
Public Health Nutrition
0·4 0·6
Reduced risk Increased risk
0·8 1·0 1·2 1·4
Study
Knoops et al. (2004)(28)
Lagiou et al. (2006)(36)
Fung et al. (2006)
Mitrou et al. (2007) (M)
Mitrou et al. (2007) (F)
Benetou et al. (2008)(31)
Buckland et al. (2010)(34)
Buckland et al. (2011)(10) (Spain)
Couto et al. (2011)(13)
Tognon et al. (2012)(16) (M)
Tognon et al. (2012)(16) (F)
Bamia et al. (2013)(20)
Buckland et al. (2013)(21)
Couto et al. (2013)(22)
Agnoli et al. (2013)(23) (M)
Agnoli et al. (2013)(23) (F)
Bosire et al. (2013)(24)
Total (95% CI)
RR (95 % CI)
RR (95 % CI)
Weight (%)
7·9 0·95 (0·90, 1·00)
0·89 (0·77, 1·03)
0·91 (0·82, 1·01)
0·94 (0·91, 0·97)
0·96 (0·92, 1·00)
0·88 (0·81, 0·96)
0·86 (0·78, 0·96)
0·98 (0·93, 1·03)
0·96 (0·95, 0·97)
0·85 (0·76, 0·95)
0·96 (0·85, 1·09)
0·96 (0·92, 1·00)
0·98 (0·96, 1·00)
1·08 (1·00, 1·17)
0·66 (0·45, 0·98)
0·60 (0·45, 0·79)
1·00 (0·95, 1·06)
0·95 (0·93, 0·97)
1·7
3·0
10·9
9·1
4·3
3·1
7·5
13·5
2·8
2·3
8·9
12·2
4·9
0·3
7·1
0·5
100·0
Fig. 3 Forest plot for updated meta-analysis on greater adherence score to the Mediterranean diet (2-point increase) and cancer
incidence and/or mortality risk. Plotted are the relative risk (RR; represented by , with the symbol size proportional to the weight
in meta-analysis) and the 95 % confidence interval (represented by horizontal bars), with the summary measure (represented by
----- and E, with the associated 95 % confidence interval indicated by the symbol width) and the line of no effect (——)
FRUIT
1 portion: 150 g
<1 portion/d >2 portions/d
0 2
VEGETABLES
1 portion: 100 g
LEGUMES
1 portion: 70 g
<1 portion/week >2 portions/week1–2 portions/week
CEREALS
1 portion: 130 g
FISH
1 portion: 100 g
MEAT AND MEAT PRODUCTS
1 portion: 80 g
DAIRY PRODUCTS
1 portion: 180 g
ALCOHOL
1 Alcohol Unit (AU) = 12 g
<1 U.A./d >2 U.A./d
1–2 U.A./d
OLIVE OIL
TOTAL:
0 21
1 02
1–1·5 portions/d
1
<1 portion/d >2·5 portions/d
0 2
1–2·5 portions/d
1
<1 portion/d >1·5 portions/d
0 2
1–1·5 portions/d
1
<1 portion/week >2·5 portions/week1–2·5 portions/week
0 21
<1 portion/d >1·5 portions/d
2 0
1–1·5 portions/d
1
<1 portion/d >1·5 portions/d
2 0
1–1·5 portions/d
1
Occasional use Regular useFrequent use
0 21
Fig. 4 Literature-based adherence score to the Mediterranean diet (range: 0–18 points). Portion sizes derive from the calculation of
mean value of weighted medians (or means) 62SD coming from all the cohort studies reported in Tables 1 and 2
Adherence score to Mediterranean diet and health 11
longevity (2 points 5regular use; 1 point 5frequent use;
0 point 5occasional use). The final adherence score
comprised nine food categories with a score ranging from
0 point (lowest adherence) to 18 points (highest adher-
ence). Since no relevant differences for proposed food
categories across men and women were obtained, a single
score was computed for both sexes (Fig. 4).
Discussion
In the present study we conducted an updated meta-
analysis on the association between adherence to the
Mediterranean diet and health outcomes, with the addi-
tional purpose of proposing an adherence score, based
on data from the literature, that can be used also at
an individual level and not only in an epidemiological
setting.
Greater adherence to the Mediterranean diet has long
been reported to be protective against the occurrence
of chronic degenerative disease
(1)
. Two previous
meta-analyses conducted by our group reported the
Mediterranean diet to be the optimal diet for preserving a
good health status
(2,3)
. Moreover, recently, the protective
role of the Mediterranean diet has been also demon-
strated in a dietary intervention study conducted in
Spanish middle-aged subjects. Over a follow-up period of
4?8 years, subjects following the Mediterranean diet
reported to have a protection of 30 % v. the occurrence of
CVD in a primary prevention setting
(37)
.
We decided to update the meta-analysis previously
published by our group because many studies have been
released in the last 3 years. This updated analysis was
conducted with the same methods used for the previous
meta-analysis
(3)
and allowed us to add eighteen pro-
spective studies to the final analysis
(7–24)
.Hence,wewere
able to extend the evidence to an overall study population
of more than 4 000 000 subjects and to other countries
such as Italy and Scandinavian countries
(7–9,16,22,23)
. From
this updated analysis we could report that a 2-point
increase in adherence score to the Mediterranean diet is
actually protective v. the occurrence of overall mortality,
incidence and/or mortality from cardiovascular and
neoplastic causes, with again similar results compared
with the previous analyses (28 % for overall mortality,
210 % for CVD and 24 % for cancer).
An additional purpose of the present article was to
obtain, from the most updated prospective cohort studies,
data regarding the amount of consumption for food groups
composing the adherence score to the Mediterranean diet
in order to propose a literature-based adherence score that
can be used to assess adherence to the Mediterranean diet
also at an individual level.
Over the last years, research on nutritional science and
on its relationship with disease has shifted from the study
of single nutrients to the evaluation of food patterns,
since subjects do not eat isolated nutrients and because
the complex interactions among different nutrients have
been reported to be extremely relevant for the healthy
aspects of diet. Some attempts for estimating the adherence
to the whole diet, and particularly to the Mediterranean
diet, have been conducted
(4,5)
. The first and most widely
used tool to assess adherence to the Mediterranean diet,
created by Trichopoulou et al.
(6)
, has been extremely
widely used for epidemiological research and is based
on the sex-based median amount of consumption of
food groups that are characteristic of the traditional
Mediterranean diet in the sample investigated. On one
hand, this score has many advantages because it helped
to introduce the concept of an adherence score to a
specific diet and allowed to estimate the association
between the adherence score and risk of disease in an
epidemiological setting. On the other hand, however, it
has the main disadvantage of being widely related to the
availability of data coming from a sample population,
differing substantially from one cohort to another, even
within the same country, and more importantly because it
does not give an amount of consumption for food groups
composing the score that can be used in everyday clinical
practice, at an individual level. This is the reason why
other indices have been created. One example is that
of Panagiotakos et al.
(38)
who created a simple ques-
tionnaire based on recommendations of the guidelines for
a healthy diet and characterized by a few questions used
for estimating the frequency of consumption (monthly or
daily) of food groups more or less characteristic of the
Mediterranean diet. Another example is the questionnaire
developed in the PREDIMED study and recently assessed
in the SUN (Seguimiento Universidad de Navarra)
cohort
(39)
. Both these questionnaires have the advantage
of being feasible for assessing adherence to the Medi-
terranean diet at an individual level but they are not based
on data from the literature.
That is why we decided to utilize all the available
data coming from the most relevant cohort studies for
proposing a new evidence-based score for assessing
adherence to the Mediterranean diet.
The approach we used, despite able to obtain all the
literature data available in this context, may present some
limitations. Different cohorts coming from the same
country reported to have different cut-offs of consump-
tion for the adherence to the Mediterranean diet, and
even among the same countries the range of consump-
tion within the same food group varied. Moreover, by
analysing data it became apparent that the median of
consumption was extremely related to the sample size of
the population investigated. To date, smaller cohorts had,
at the same time, higher consumption and vice versa.
Hence, we decided to calculate the mean value of all the
food groups by taking into account the sample size of the
population, i.e. estimating the weighted medians for
consumption of all of the food groups.
Public Health Nutrition
12 F Sofi et al.
Despite all these efforts, some limitations that are
intrinsic to the single studies still remain. One of these is
the lack of uniformity in data regarding the same food
group. Some studies report potatoes together with vege-
tables, while others include them as a single food group,
whereas some others include legumes with nuts and not
by themselves, and so on.
Nevertheless, the strength of this proposed adherence
score is that food group data come from the most updated
and comprehensive review of the literature in this context.
If confirmed and validated in other studies, the evidence-
based search strategy used for obtaining data from the
available studies will hopefully help the transferability of
such an adherence score into clinical practice.
Conclusion
We updated the results of our previous meta-analyses by
including eighteen cohort prospective studies published
in the last 3 years and we were able to show the beneficial
effects of a greater adherence to the Mediterranean diet in
terms of protection v. overall mortality and occurrence of
the most important chronic diseases. In addition, by using
data coming from the systematic review we proposed
an adherence score based on literature data that can be
also feasible for assessment of the adherence to the
Mediterranean diet at an individual level.
Acknowledgements
Sources of funding: This research received no specific
grant from any funding agency in the public, commercial
or not-for-profit sectors. Conflicts of interest: No conflicts
of interest to declare. Ethics: Ethical approval was not
required. Authors’ contributions: conception and design:
F.S. and G.F.G.; analysis and interpretation of the data:
F.S., C.M. and A.C.; drafting of the article: F.S. and R.A.;
critical revision of the article for important intellectual
content: A.C., C.M., R.A. and G.F.G.; final approval of the
article: F.S. A.C., R.A. and G.F.G.; statistical expertise: F.S.
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Public Health Nutrition
14 F Sofi et al.
... The traditional Mediterranean diet (MD) has long been acknowledged as one of the healthiest diets, capable of reducing the risk of developing chronic diseases and improve survival in numerous cohorts [11,12], possibly through a favourable modulation of several cardiovascular and cerebrovascular disease (CVD) risk factors [13] and inflammatory markers [14]. ...
... The health advantages of an MD are well-documented in a variety of population cohorts [11,12,32] and also supported by RCTs [36,37]; this diet is characterized by olive oil as a major source of unsaturated fat and high content of fibre and polyphenols, all acting on different, though complementary, health-promoting pathways. ...
Article
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Background/Objectives Unsaturated fats, fibre-rich foods and polyphenols are distinctive features of a traditional Mediterranean diet and have pleiotropic properties possibly contributing to reduce the long-term risk of non-communicable diseases and mortality associated with this diet. We aimed to evaluate whether changes over time in dietary fats, fibre and polyphenols consumption are associated with modifications in cardiovascular disease (CVD) risk factors. Methods The analytic sample consists of a sub-cohort of 2023 men and women enrolled in the Moli-sani Study (n = 24,325). Dietary and health data were obtained both at baseline (2005–2010) and at re-examination (2017–2020). The exposures were changes in dietary fats, fibre and polyphenols consumption measured after 12.7 years (median), and the outcome was change in a composite score including 13 modifiable CVD risk factors (e.g., blood lipids, C-reactive protein), measured both at enrolment and after the 12.7 years period. Results In multivariable-adjusted analysis including lifestyles, sociodemographic and clinical factors, an incremental intake of the ratio of monounsaturated to saturated fats or of fibre was associated with a reduction in the composite score of CVD risk factors (β = −0.086; 95%CI −0.150, −0.021 and β = −0.051; 95%CI −0.091, −0.012, respectively). Change in polyphenol intake was not associated with a substantial variation in the CVD risk score (p = 0.15). Conclusions An incremental consumption over time of monounsaturated versus saturated fats and of fibre was associated with an improvement in modifiable CVD risk factors as reflected by a composite score.
... Adherence to healthy diets is important to reduce the risk of illness throughout life. The Mediterranean diet (MED), which is rich in fruits and vegetables, whole grains, legumes, nuts, fish, and olive oil, is widely considered to beneficially impact health and longevity (4,5). Not only has MED been incorporated into the national dietary guidelines set forth by the United States Department of Agriculture (USDA) but it has also attracted attention as a lifestyle modification with significant potential to reduce risks of menopausal metabolic syndrome, polycystic ovary syndrome, type 2 diabetes and cognitive decline (6)(7)(8)(9). ...
... All dietary intake data from both 24-h recalls were aggregated as an average intake over 2 days for each participant. A MED index was subsequently calculated using the aMED score (4,5). The aMED . ...
Article
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The Mediterranean diet (MED), a dietary pattern rich in fruits and vegetables, whole grains, legumes, nuts, fish, and olive oil, has anti-oxidative and anti-inflammatory effects. Although some data suggest that MED adherence is associated with decreased manifestation of depressive symptoms, it remains necessary to further analyze this apparent non-linear association as well as the influence of different factors on the relationship between MED and depression. Here, we investigated associations between the alternate MED (aMED) score and depressive symptom via multivariate logistic regression, weighted generalized additive (GAM) and two-step linear regression models, analyzing data from the 2005–2018 National Health and Nutrition Examination Survey (NHANES). The most important factor relevant to aMED score that contributed to the prevalence of depressive symptom was assessed using random forest. Furthermore, we examined whether the relationship between aMED score and depressive symptom differs by age, race, sex, socioeconomic variables, lifestyle- and health-related variables, and chronic medical conditions, via subgroup analyses. A total of 19,477 participants (20–80 years of age) were included in this cross-sectional study. In crude and adjusted (1–5) multivariate logistic regression models, increased aMED score was noted to associate with non-depressive status, as defined using the Patient Health Questionnaire-9 (P < 0.05). Data analyses via GAM and two-piecewise linear regression revealed a non-linear association between aMED and depressive symptom, which had an inflection point of 3. Random forest results revealed that vegetable score contributes greatest to the relationship between aMED and depressive symptom. Subgroup analyses revealed that aMED score is significantly negatively related with depressive symptom in most different populations (P < 0.05) with the exception of high annual income, diabetes, borderline blood glucose level and Parkinson's disease (PD) (P > 0.05). In conclusion, we observed a non-linear association between aMED score and depressive symptom. Further studies are needed to validate our results.
... Cross-sectional and prospective cohort studies including several meta-analyses have related the MedDiet to a lower prevalence and incidence of numerous non-communicable chronic diseases and related conditions (e.g., dyslipidemias, obesity, metabolic syndrome, type 2 diabetes, cardiovascular diseases, cancer, and neurodegeneration). In addition, beneficial effects related to the MedDiet, including a reduced overall mortality, increased longevity, and improvement in quality of life, have also been reported [156][157][158]. Clinical intervention trials for primary and secondary prevention, in which the diet was modified by increasing their adherence to the MedDiet, have been shown to decrease the incidence of numerous chronic diseases [155,159]. ...
Article
Glycoxidative stress with the consequent generation of advanced glycation end products has been implied in the etiology of numerous non-communicable chronic diseases. During the postprandial state, the levels of 1,2-dicarbonyl compounds can increase, depending on numerous factors, including characteristics of the subjects mainly related to glucose metabolism disorders and nutritional status, as well as properties related to the chemical composition of meals, including macronutrient composition and the presence of dietary bioactive molecules and macromolecules. In this review, we examine the chemical, biochemical, and physiological pathways that contribute to postprandial generation of 1,2-dicarbonyl compounds. The modulation of postprandial 1,2-dicarbonyl compounds is discussed in terms of biochemical pathways regulating the levels of these compounds, as well as the effect of phenolic compounds, dietary fiber, and dietary patterns, such as Mediterranean and Western diets.
... No or uncommon intake of carbonated/sweetened drinks and alcoholic beverages was reported by the majority of patients. The MEDI-LITE score was originally developed through the analysis of data generated by numerous cohort studies that investigated the association between adherence to the Mediterranean diet and health outcomes [25]. In this system, nine food categories are considered. ...
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This paper presents a multi-professional integrated approach toward the recognition and management of the nutritional and psychological needs of cancer patients. In particular, the patients undertook a multi-professional, multistep process that included the collection of both personal and clinical data, the evaluation of anthropometric measures, nutritional status and psychometric indices, and an ensuing personalized nutritional prescription and psychological support, ultimately leading to combined nutritional and psychological interventions to control their adherence to a nutritional program and to consolidate motivation to change. Overall, 120 patients were recruited for the study. The majority (84.2%) were female. Breast cancer was by far the most frequent malignancy (52.5%), followed by colorectal (17.5%), pancreatic (9.2%), ovarian (9.2%) and lung (5.0%) cancers. The results of the nutritional and psychological screening at baseline indicated that only 35% of patients had a normal BMI, whilst a relatively high proportion (nearly 32%) was overweight or obese (25%). The INRAN and MEDI-LITE questionnaires, which were used to assess the eating habits and adherence to a Mediterranean diet, respectively, revealed a mixed prevalence of cereals/cereal-based, fresh/processed meat, and fish or fishery food, with a medium–low adherence to the Mediterranean diet in nearly 38% of patients. The BUT, HADS and SF-36 tests, which were used to assess psychological disturbances, showed that 37.5% of patients had disorders regarding body image, 29.2% had abnormal anxiety and 20.0% had a depressive state, while no significant association was observed between the SF-36 PCS and MCS and the patients′ characteristics. The results of the potential impact of this novel approach on the QoL of patients after completion of the course are awaited with expectation.
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Diet has long been identified as a major determinant of cardiovascular and other chronic diseases. In this study, we assess the relation between adherence to different dietary patterns and biochemical and metabolic parameters as well as the 10-year risk of major cardiovascular diseases (CVDs) in a community of blood donors in Northern Italy. We assess their adherence to four dietary patterns, namely, the Dietary Approach to Stop Hypertension (DASH) diet, the Mediterranean diet through the Greek and Italian Mediterranean Indices (GMI and IMI) and the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, using a validated semi-quantitative food frequency questionnaire (FFQ). We then assess their association with blood parameters and the 10-year risk of major CVD using a spline regression model. We found an inverse association between the DASH and MIND diets and total and LDL cholesterol, and triglyceride and HDL cholesterol values for the Mediterranean diets (IMI and GMI). Additionally, according to our sex-stratified analyses, men who have greater adherence to dietary patterns have a decreased risk of major CVD for all patterns. The results suggest that greater adherence to dietary patterns positively influences blood biochemical and metabolic parameters, thus reducing the risk of developing cardiovascular disease and delaying the use of drug treatments.
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Mediterranean populations enjoy the health benefits of a Mediterranean diet (MedDiet), but is it feasible to implement such a pattern beyond the Mediterranean region? The MedLey trial, a 6-month MedDiet intervention vs habitual diet in older Australians, demonstrated that the participants could maintain high adherence to a MedDiet for 6 months. The MedDiet resulted in improved systolic blood pressure (BP), endothelial dilatation, oxidative stress, and plasma triglycerides in comparison with the habitual diet. We sought to determine if 12 months after finishing the MedLey study, the participants maintained their adherence to the MedDiet principles and whether the reduction in the cardiovascular disease (CVD) risk factors that were seen in the trial were sustained. Participants completed a food frequency questionnaire, and a 15-point MedDiet adherence score (MDAS; greater score = greater adherence) was calculated. Home BP was measured over 6 days, BMI was assessed, and fasting plasma triglycerides were measured. The data were analysed using intention-to-treat linear mixed effects models with a group × time interaction term, comparing data at baseline, 2, 4, and 18 months (12 months post-trial). At 18 months (12 months after finishing the MedLey study), the MedDiet group had a MDAS of 7.9 ± 0.3, compared to 9.6 ± 0.2 at 4 months (p < 0.0001), and 6.7 ± 0.2 (p < 0.0001), at baseline. The MDAS in the HabDiet group remained unchanged over the 18-month period (18 months 6.9 ± 0.3, 4 months 6.9 ± 0.2, baseline 6.7 ± 0.2). In the MedDiet group, the consumption of olive oil, legumes, fish, and vegetables remained higher (p < 0.01, compared with baseline) and discretionary food consumption remained lower (p = 0.02) at 18 months. These data show that some MedDiet principles could be adhered to for 12 months after finishing the MedLey trial. However, improvements in cardiometabolic health markers, including BP and plasma triglycerides, were not sustained. The results indicate that further dietary support for behaviour change may be beneficial to maintaining high adherence and metabolic benefits of the MedDiet.
Article
Unhealthy diet is an important factor in the progression of non-alcoholic fatty liver disease (NAFLD). Previous studies showed the benefits of a Mediterranean diet (MedDiet) on Metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), and cardiovascular diseases, which usually have a pathophysiological relationship with NAFLD. To assess the effect of adherence to a MedDiet on NAFLD in MetS patients after lifestyle intervention, this multicentre (Mallorca and Navarra, Spain) prospective randomized trial, with personalized nutritional intervention based on a customized MedDiet, coupled with physical activity promotion was performed to prevent, and reverse NAFLD among patients with MetS. The current analysis included 138 patients aged 40 to 60 years old, Body Mass Index (BMI) 27–40 kg/m2, diagnosed with NAFLD using MRI, and MetS according to the International Diabetes Federation (IDF). A validated food frequency questionnaire was used to assess dietary intake. Adherence to Mediterranean diet by means of a 17-item validated questionnaire, anthropometrics, physical activity, blood pressure, blood biochemical parameters, and intrahepatic fat contents (IFC) were measured. The independent variable used was changes in MedDiet adherence, categorized in tertiles after 6 months follow-up. Subjects with high adherence to the MedDiet showed higher decreases in BMI, body weight, WC, SBP, DBP, and IFC. An association between improvement in adherence to the MedDiet and amelioration of IFC after 6-month follow-up was observed. High adherence to the MedDiet is associated with better status of MetS features, and better values of IFC.
Thesis
La polyarthrite rhumatoïde (PR) est une maladie rhumatismale de physiopathologie complexe, où l'interaction entre agents environnementaux et facteurs génétiques est susceptible de déclencher l'auto-immunité. A ce jour, seul le tabac, chez des patients génétiquement prédisposés, a été rapporté comme associé de façon reproductible au risque de PR. Bien que l'implication des hormones féminines soit vraisemblable, au vu des taux d'incidence plus élevés chez la femme que chez l'homme, les données de la littérature sont discordantes. Différentes études rapportent aussi une association entre excès pondéral et le risque de PR le plus souvent séronégative et chez les femmes. Dans ces études, seul l'indice de masse corporel est utilisé, bien qu'il ne représente pas la répartition corporelle du tissu adipeux qui semble être un élément plus important que l'excès de masse grasse lui-même.Les objectifs de ce projet doctoral étaient d'étudier les associations entre les expositions hormonales, les mesures anthropométriques et le risque de PR dans la cohorte prospective française E3N comptant 98 995 femmes dont 698 PR incidentes.Nos résultats suggèrent qu'un haut niveau d'expositions cumulées aux hormones féminines endogènes et exogènes tout au long de la vie des femmes est inversement associé au risque de survenue d'une PR après la ménopausées. Une trajectoire de silhouette constamment large de la puberté jusqu'à la péri-ménopause est associée à une augmentation de risque de PR chez les femmes non exposées au tabac.Ce projet a ainsi permis d'affiner les connaissances sur les impacts des expositions hormonales féminines cumulées et de la répartition du tissu adipeux sur le risque de PR. Nos résultats soutiennent aussi l'hypothèse selon laquelle les expositions, survenant tôt dans la vie, cumulées et persistantes sont impliquées dans la physiopathologie de la PR. Ces nouvelles données sur la distribution du tissu adipeux à des périodes charnières de la vie reproductive des femmes (puberté et ménopause) mettent en lumière les relations complexes entre fonctions adipocytaires, hormones sexuelles et réponses immunitaires.
Article
Importance: The Mediterranean diet may reduce the burden of Alzheimer disease and other associated dementias in Hispanic or Latino people. Objective: To investigate the association of a Mediterranean diet with cognitive performance among community-dwelling Hispanic or Latino adults. Design, setting, and participants: This cohort study analyzed data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA), an HCHS/SOL ancillary study. Cognition tests were administered in the HCHS/SOL from March 2008 to June 2011 (visit 1) and in the SOL-INCA from October 2015 to March 2018 (visit 2). Participants included in the present study had completed a diet assessment at visit 1 and neurocognitive evaluations at visits 1 and 2. Data were analyzed from September 2021 to May 2022. Exposures: Mediterranean diet adherence was ascertained using the Mediterranean diet score (MDS) and was categorized as low (MDS: 0-4 points), moderate (MDS: 5-6 points), or high (MDS: 7-9 points). The mean of two 24-hour dietary recalls was used to calculate the MDS. Main outcomes and measures: Cognitive change between visits 1 and 2 was calculated by subtracting the cognitive score at visit 2 from the cognitive score at visit 1 and adjusting by the time elapsed between visits and cognitive score at visit 1. Neurocognitive tests administered were Brief Spanish-English Verbal Learning Test (B-SEVLT) Sum, B-SEVLT Recall, word fluency, and Digit Symbol Substitution Test (DSST). Results of each test were z score-transformed and the means were averaged to create a global cognition score. Complex sample linear regression analysis was used to ascertain the association between MDS and neurocognitive performance at each visit and neurocognitive change. Results: A total of 6321 participants (mean [SE] age, 56.1 [0.18] years at visit 1; n = 4077 women [57.8%]) were included. Mediterranean diet adherence weighted frequencies were 35.8% (n = 2112 of 6321) for the low adherence group, 45.4% (n = 2795) for the moderate adherence group, and 18.8% (n = 1414) for the high adherence group. In the fully adjusted model, z score-transformed cognitive scores at visit 1 in the high vs low adherence groups were higher for B-SEVLT Sum (β = 0.11; 95% CI, 0.02-0.20), B-SEVLT Recall (β = 0.16; 95% CI, 0.07-0.25), and global cognition (β = 0.10; 95% CI, 0.04-0.16) tests. In the mean follow-up time of 7 years, cognitive change in the high vs low adherence groups was less pronounced for B-SEVLT Sum (β = 0.12; 95% CI, 0.05-0.20) and B-SEVLT Recall (β = 0.14; 95% CI, 0.05-0.23), but not for word fluency, DSST score, or global cognition score. Conclusions and relevance: Results of this cohort study suggested that high adherence to a Mediterranean diet was associated with better cognitive performance and decreased 7-year learning and memory decline among middle-aged and older Hispanic or Latino adults. Culturally tailored Mediterranean diet may reduce the risk of cognitive decline and Alzheimer disease in this population.
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Objective: To systematically review all the prospective cohort studies that have analysed the relation between adherence to a Mediterranean diet, mortality, and incidence of chronic diseases in a primary prevention setting. Design: Meta-analysis of prospective cohort studies. Data sources: English and non-English publications in PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials from 1966 to 30 June 2008. Studies reviewed Studies that analysed prospectively the association between adherence to a Mediterranean diet, mortality, and incidence of diseases; 12 studies, with a total of 1 574,299 subjects followed for a time ranging from three to 18 years were included. Results: The cumulative analysis among eight cohorts (514,816 subjects and 33,576 deaths) evaluating overall mortality in relation to adherence to a Mediterranean diet showed that a two point increase in the adherence score was significantly associated with a reduced risk of mortality (pooled relative risk 0.91, 95% confidence interval 0.89 to 0.94). Likewise, the analyses showed a beneficial role for greater adherence to a Mediterranean diet on cardiovascular mortality (pooled relative risk 0.91, 0.87 to 0.95), incidence of or mortality from cancer (0.94, 0.92 to 0.96), and incidence of Parkinson's disease and Alzheimer's disease (0.87, 0.80 to 0.96). Conclusions: Greater adherence to a Mediterranean diet is associated with a significant improvement in health status, as seen by a significant reduction in overall mortality (9%), mortality from cardiovascular diseases (9%), incidence of or mortality from cancer (6%), and incidence of Parkinson's disease and Alzheimer's disease (13%). These results seem to be clinically relevant for public health, in particular for encouraging a Mediterranean-like dietary pattern for primary prevention of major chronic diseases.
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Background Observational cohort studies and a secondary prevention trial have shown an inverse association between adherence to the Mediterranean diet and cardiovascular risk. We conducted a randomized trial of this diet pattern for the primary prevention of cardiovascular events. Methods In a multicenter trial in Spain, we randomly assigned participants who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly individual and group educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was the rate of major cardiovascular events (myocardial infarction, stroke, or death from cardiovascular causes). On the basis of the results of an interim analysis, the trial was stopped after a median follow-up of 4.8 years. Results A total of 7447 persons were enrolled (age range, 55 to 80 years); 57% were women. The two Mediterranean-diet groups had good adherence to the intervention, according to self-reported intake and biomarker analyses. A primary end-point event occurred in 288 participants. The multivariable-adjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.54 to 0.92) and 0.72 (95% CI, 0.54 to 0.96) for the group assigned to a Mediterranean diet with extra-virgin olive oil (96 events) and the group assigned to a Mediterranean diet with nuts (83 events), respectively, versus the control group (109 events). No diet-related adverse effects were reported. Conclusions Among persons at high cardiovascular risk, a Mediterranean diet supplemented with extra-virgin olive oil or nuts reduced the incidence of major cardiovascular events. (Funded by the Spanish government's Instituto de Salud Carlos III and others; Controlled-Trials.com number, ISRCTN35739639 .).
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BACKGROUND: Observational cohort studies and a secondary prevention trial have shown an inverse association between adherence to the Mediterranean diet and cardiovascular risk. We conducted a randomized trial of this diet pattern for the primary prevention of cardiovascular events. METHODS: In a multicenter trial in Spain, we randomly assigned participants who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly individual and group educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was the rate of major cardiovascular events (myocardial infarction, stroke, or death from cardiovascular causes). On the basis of the results of an interim analysis, the trial was stopped after a median follow-up of 4.8 years. RESULTS: A total of 7447 persons were enrolled (age range, 55 to 80 years); 57% were women. The two Mediterranean-diet groups had good adherence to the intervention, according to self-reported intake and biomarker analyses. A primary end-point event occurred in 288 participants. The multivariable-adjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.54 to 0.92) and 0.72 (95% CI, 0.54 to 0.96) for the group assigned to a Mediterranean diet with extra-virgin olive oil (96 events) and the group assigned to a Mediterranean diet with nuts (83 events), respectively, versus the control group (109 events). No diet-related adverse effects were reported. CONCLUSIONS: Among persons at high cardiovascular risk, a Mediterranean diet supplemented with extra-virgin olive oil or nuts reduced the incidence of major cardiovascular events. (Funded by the Spanish government's Instituto de Salud Carlos III and others; Controlled-Trials.com number, ISRCTN35739639.).
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