Anatomy of health effects of Mediterranean diet: Greek EPIC prospective cohort study.

Abstract

To investigate the relative importance of the individual components of the Mediterranean diet in generating the inverse association of increased adherence to this diet and overall mortality.
Prospective cohort study.
Greek segment of the European Prospective Investigation into Cancer and nutrition (EPIC).
23 349 men and women, not previously diagnosed with cancer, coronary heart disease, or diabetes, with documented survival status until June 2008 and complete information on nutritional variables and important covariates at enrolment.
All cause mortality.
After a mean follow-up of 8.5 years, 652 deaths from any cause had occurred among 12 694 participants with Mediterranean diet scores 0-4 and 423 among 10 655 participants with scores of 5 or more. Controlling for potential confounders, higher adherence to a Mediterranean diet was associated with a statistically significant reduction in total mortality (adjusted mortality ratio per two unit increase in score 0.864, 95% confidence interval 0.802 to 0.932). The contributions of the individual components of the Mediterranean diet to this association were moderate ethanol consumption 23.5%, low consumption of meat and meat products 16.6%, high vegetable consumption 16.2%, high fruit and nut consumption 11.2%, high monounsaturated to saturated lipid ratio 10.6%, and high legume consumption 9.7%. The contributions of high cereal consumption and low dairy consumption were minimal, whereas high fish and seafood consumption was associated with a non-significant increase in mortality ratio.
The dominant components of the Mediterranean diet score as a predictor of lower mortality are moderate consumption of ethanol, low consumption of meat and meat products, and high consumption of vegetables, fruits and nuts, olive oil, and legumes. Minimal contributions were found for cereals and dairy products, possibly because they are heterogeneous categories of foods with differential health effects, and for fish and seafood, the intake of which is low in this population.

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RESEARCH
AnatomyofhealtheffectsofMediterraneandiet:GreekEPIC
prospective cohort study
Antonia Trichopoulou, professor,1Christina Bamia, lecturer,1Dimitrios Trichopoulos, professor2
ABSTRACT
Objective To investigate the relative importance of the
individual components of the Mediterranean diet in
generating the inverse association of increased
adherence to this diet and overall mortality.
Design Prospective cohort study.
Setting Greek segment of the European Prospective
Investigation into Cancer and nutrition (EPIC).
Participants 23349 men and women, not previously
diagnosed with cancer, coronary heart disease, or
diabetes, with documented survival status until June
2008 and complete information on nutritional variables
and important covariates at enrolment.
Main outcome measure All cause mortality.
Results After a mean follow-up of 8.5 years, 652 deaths
from any cause had occurred among 12694 participants
with Mediterranean diet scores 0-4 and 423 among
10655 participants with scores of 5 or more. Controlling
for potential confounders, higher adherence to a
Mediterranean diet was associated with a statistically
significant reduction in total mortality (adjusted mortality
ratio per two unit increase in score 0.864, 95%
confidence interval 0.802 to 0.932). The contributions of
the individual components of the Mediterranean diet to
this association were moderate ethanol consumption
23.5%, low consumption of meat and meat products
16.6%, high vegetable consumption 16.2%, high fruit
and nut consumption 11.2%, high monounsaturated to
saturated lipid ratio 10.6%, and high legume
consumption 9.7%. The contributions of high cereal
consumption and low dairy consumption were minimal,
whereas high fish and seafood consumption was
associated with a non-significant increase in mortality
ratio.
Conclusion The dominant components of the
Mediterranean diet score as a predictor of lower mortality
are moderate consumption of ethanol, low consumption
of meat and meat products, and high consumption of
vegetables, fruits and nuts, olive oil, and legumes.
Minimal contributions were found for cereals and dairy
products, possibly because they are heterogeneous
categoriesoffoodswithdifferentialhealtheffects,andfor
fish and seafood, the intake of which is low in this
population.
INTRODUCTION
The Mediterranean diet was introduced to the scienti-
fic communityas ahealth protecting dietbythe classic
studiesofAncelKeysandcolleagues.1In1995asimple
score to assess adherence to the Mediterranean diet
was introduced,2and this score, or variants of it, has
beenusedtoevaluatetherelationoftheMediterranean
diet to overall mortality, as well as to specific health
outcomes, including Alzheimer’s disease, diabetes
mellitus, and cancer overall.3-5Most of these studies
have focused on overall survival, as this is a natural
priority.Arecentmeta-analysissummarisedtheresults
of nine cohort studies that evaluated the relation
between adherence to the Mediterranean diet and
overall mortality.6An inverse association was noted
in all these studies, with a pooled mortality ratio (rela-
tiverisk)of0.91(95%confidenceinterval0.89to 0.94)
for each two point increment in a scale ranging from 0
to 9. The reported associations were somewhat stron-
ger in studies done in Mediterranean countries and
somewhatweakerinstudiesdoneinwesternEuropean
countriesandSweden,27-10althoughnostatisticallysig-
nificant heterogeneity existed.6However, no attempt
has been made to investigate the relative importance
of the individual components of the Mediterranean
diet (and of the Mediterranean diet score) in the gen-
eration of the inverse association of increased adher-
ence to this diet and overall mortality.
We have evaluated the contribution of the nine
widely accepted components of the Mediterranean
diet(highintakeofvegetables,fruitsandnuts,legumes,
fish and seafood, and cereals; low intake of meat and
meat productsanddairyproducts;highratioof mono-
unsaturatedtosaturatedlipids;andmoderateintakeof
ethanol) in the inverse association of this diet with all
cause mortality in a population based cohort in
Greece.
METHODS
European Prospective Investigation into Cancer and
nutrition
The study population consisted of the participants in
theGreeksegmentoftheEuropeanProspectiveInves-
tigation into Cancer and nutrition (EPIC). EPIC is run
in 23 research centres across 10 European countries,
withthe purposeof investigatingthe roleofbiological,
1Department of Hygiene,
Epidemiology and Medical
Statistics, University of Athens,
Medical School, 115 27 Athens,
Greece
2Department of Epidemiology,
Harvard School of Public Health,
677 Huntington Avenue, Boston,
MA 02115, USA
Correspondence to: D
Trichopoulos
dtrichop@hsph.harvard.edu
Cite this as: BMJ 2009;338:b2337
doi:10.1136/bmj.b2337
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dietary, lifestyle, and environmental factors in causing
cancer and other chronic diseases.1112
In Greece, 28572 apparently healthy men and
women aged 20-86 years were recruited from the gen-
eral population throughout the country between 1994
and 1997. Trained interviewers administered dietary
and lifestyle questionnaires to participants at enrol-
ment, and trained health professionals made somato-
metric measurements.
Data on diet
Dietary intakes during the year preceding enrolment
were assessed with the use of a validated food fre-
quency questionnaire that includes approximately
150 foods and beverages commonly consumed in
Greece.13Standardportionsizeswereusedfortheesti-
mation of consumed quantities, and nutrient and etha-
nol intakes were calculated by using a food
composition database modified to accommodate the
particularitiesoftheGreekdiet.14Foreachparticipant,
grams per day of intake of various food groups and
nutrients, as well as total energy intake, were calcu-
lated.
Forthisanalysis,wefocusedonninenutritionalvari-
ables: vegetables, legumes, fruits and nuts, dairy pro-
ducts, cereals, meat and meat products, fish and
seafood, monounsaturated to saturated lipid ratio,
and ethanol.
Mediterranean diet score
We assessedtheconformityto thetraditionalMediter-
ranean diet with a 10 unit scale.7The scale relies on
nine dietary components that capture the essence of
the traditionalMediterranean
legumes, fruits and nuts, fish and seafood, and cereals
arepresumedtobebeneficialforhealth,whereasmeat
and meat products and dairy products are presumed
nottobebeneficial.Ahigherratioofmonounsaturates
to saturates is considered to be beneficial and reflects
the high olive oil consumption that characterises the
traditional Mediterranean diet. Ethanol is used as a
measure of the consumption of alcoholic beverages,
which in the Mediterranean countries are mostly con-
sumed during meals and mainly in the form of wine.
We assigned values of 0 or 1 to each of the above
indicated components (except for ethanol intake),
using the sex specific medians in the studied popula-
tion as cut-offs. We assigned a value of 0 to people
whose consumption was below the median values of
components with a presumably beneficial effect and a
value of 1 to people with consumption equal to or
above the median. In contrast, we assigned a value of
1 to people with below the median consumption of
components without a beneficial effect and a value of
0 to those whose consumption of these components
was above the corresponding median. For ethanol,
we gave value of 1 to men who consumed quantities
from 10 g (or one unit) a day to less than 50 g (or six
units)adayandavalueof0otherwise;thecorrespond-
ing cut-offs for women were 5 g (or half a unit) a day
and25g(orthreeunits)aday(intheUnitedKingdom,
a unit of alcohol is defined as 10 ml, or approximately
8 g, of ethanol). Thus, the total Mediterranean diet
score can take values from 0 (minimal conformity to
the traditional Mediterranean diet) to 9 (maximal con-
formity to the traditional Mediterranean diet).
diet. Vegetables,
Lifestyle, anthropometric, dietary, and medical history data
A section of the lifestyle questionnaire recorded the
frequency and duration of participation in occupa-
tional and leisure time physical activities. We assigned
a multiple of resting metabolic rate (metabolic equiva-
lent of task or MET value) to each of these activities.
We then multiplied time spent on each activity by the
MET value of the activity and summed the resulting
MET-hour products to produce an index of daily phy-
sicalactivity,expressingtheamountofenergyperkilo-
gram of body weight expended during an average
day.15
Information on smoking status was collected
through a smoking history questionnaire. We cate-
gorised participants as never, current, and former
Table 1 |Distribution of study participants without cancer, coronary heart disease, or diabetes
mellitus at enrolment, by sex and baseline sociodemographic, somatometric, lifestyle, and
medical characteristics. Values are numbers (percentages)
Characteristic Men (n=9504)Women (n=13 845)Total (n=23 349)
Age (years):
<453 479 (37)4 521 (33)8 000 (34)
45-542 361 (25)3 402 (25)5 763 (25)
55-64
≥65
1 923 (20)3 338 (24)5 261 (23)
1 741 (18)2 584 (19)4 325 (19)
Education:
None/elementary school
degree
4 471 (47)8 295 (60) 12 766 (55)
Secondary/technical
school degree
2 994 (32) 3 247 (23)6 241 (27)
University degree/higher 2 039 (21)2 303 (17)4 342 (19)
Smoking of cigarettes (at
enrolment):
Current 3 904 (41)2 543 (18) 6 447 (28)
Former2 964 (31)1 101 (8) 4 065 (17)
Never2 636 (28) 10 201 (74)12 837 (55)
Body mass index (kg/m2):
≤251 897 (20)3 545 (26) 5 442 (23)
>25-<30
≥30
5 006 (53) 5 152 (37)10 158 (44)
2 601 (27)5 148 (37)7 749 (33)
Waist:hip ratio:
≤0.902 082 (22) 11 948 (86)14 030 (60)
>0.90-<0.95
≥0.95
2 694 (28) 1 155 (8)3 849 (16)
4 728 (50) 742 (5)5 470 (23)
Physical activity (MET-
hours/day):
<34.996
≥34.996
5 109 (54) 6 567 (47)11 676 (50)
4 395 (46) 7 278 (53) 11 673 (50)
Ethanol intake*:
Low4 484 (47)10 900 (79)15 384 (66)
Moderate 4 200 (44)2 731 (20) 6 931 (30)
High 820 (9)214 (2)1 034 (4)
*Low: <10 g/day for men, <5 g/day for women; moderate: men ≥10 g/day and ≤50 g/day, women ≥5 g/day and
≤25 g/day; high: >50 g/day for men, >25 g/day for women.
RESEARCH
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smokers as of the date of enrolment. For current smo-
kers, we recorded the average number of cigarettes
smoked each day.16Standardised procedures were
used to make anthropometric measurements.17We
derived body mass index as the ratio of weight in kilo-
gramsdividedbythesquareoftheheightinmetresand
calculated the waist to hip ratio. Participants were also
asked whether they had ever had a medically docu-
menteddiagnosisofcertaindiseases—specifically,can-
cer, diabetes mellitus, myocardial infarction, and
angina pectoris.
Study participants and follow-up
Greek EPIC participants were actively followed up by
teamsledbytrainedphysiciansuntilJune2008.Ofthe
initial 28572 participants, 1073 (4%) did not respond
orwerenottracedduringfollow-upandwereexcluded
from further analysis. Of the remaining 27499 partici-
pants, 3554 reported at enrolment that they had had a
previousdiagnosisofcoronaryheartdisease(n=1371),
cancer (611), or diabetes mellitus (1921). For an addi-
tional 596 participants, information was missing for
one or more of the sociodemographic, dietary, medi-
cal, somatometric, or lifestyle variables used in this
investigation. Thus, the final sample used for the ana-
lyses reported in this paper consisted of 23349 partici-
pants who had not previously been diagnosed as
havingcancer,coronaryheartdisease,ordiabetesmel-
litus;forwhomvitalstatusatfollow-uphadbeenascer-
tained; and for whom all the required information was
available.
The mean length of follow-up for the 23349 study
participants was 8.5 years. The range was 10 days (a
participant who died soon after enrolment) to 14.
2 years.
Statistical analysis
We used Stata statistical software for all analyses. We
set statistical significance at two sided P<0.05.We pre-
sent descriptive sociodemographic data by simple
tabulationsanddietaryvariablesasmediansandinter-
quartile ranges.
We used proportional hazards (Cox) regression
models to analyse survival data. In these models, the
time variable was the interval between the date of
enrolment and the date of last follow-up or date of
death, whichever occurred first. Participants who
were alive as of the date of last follow-up or were lost
tofollow-upwereconsideredcensoredasofthedateof
last contact.
With the Cox regression models, we estimated the
association (“effect”) of a two unit increase in the Med-
iterranean diet score with all cause mortality. We also
evaluated the relative importance of each of the com-
ponents of the scale as follows. Firstly, we included all
nine components, considered as dichotomous (using
the sex specific medians as cut-offs), simultaneously
in a Cox regression. Subsequently, we evaluated the
influence of each of the dietary components on the
mortality ratio associated with the Mediterranean diet
score by subtracting alternately one component at a
time from the original score (thus reducing the 10
point score to nine point scores) and estimating the
nine mortality ratios associated with a two unit incre-
ment in the score minus vegetables, score minus
pulses,scoreminusfruitsandnuts,scoreminuscereals,
score minus fish and seafood, score minus lipid ratio,
score minus meat and meat products, score minus
dairy products, and score minus ethanol. To preserve
comparability, we multiplied the logarithm of the esti-
mated nine mortality ratios by 9/10 before exponen-
tiating them.
In another analysis, we successively removed from
the Mediterranean diet score each of the components
in descending order of importance (as assessed from
the model in which all nine components were simulta-
neously included) to evaluate the impact on the mor-
tality ratioof the sequentialremovalof the component
factors. Because successive removal of components
reducestherangeofthescore,andtopreservecompar-
ability, we multiplied each of the successively derived
log coefficients by 9/10, 8/10, 7/10, and so on before
exponentiating them.
Lastly,weevaluatedtheassociationwithmortalityof
the joint action of each two by two combination of the
individual components of the Mediterranean diet
score and examined whether the joint action of any
combination of two components was at least additive.
AstheMediterraneanscoreincludesninedietarycom-
ponents, we assessed 36 (9×(9−1)/2) two by two com-
binations. In these combinations, we dichotomised
each dietary component as indicated in the construc-
tion of the Mediterranean diet score.
In all analyses, we controlled for sex, age at enrol-
ment (<45, 45-54, 55-64, ≥65 years; categorically),
education(none/elementaryschooldegree,secondary
schoolortechnicalschooldegree,universitydegreeor
higher; categorically), smoking status (never, former,
and, current at enrolment with cigarettes per day,
1-10, 11-20, 21-30, 31-40, ≥41; ordered), MET-hours
(fifths; ordered), total energy intake (fifths; ordered),
waist to hip ratio (sex specific fifths; ordered), and
body mass index (sex specific fifths; ordered).
Table 2 |Daily intakes (g/day) of indicated dietary variables by sex. Values are median
(interquartile range)
Dietary variableMen Women
Vegetables548.60 (434.67-683.86) 499.33 (388.98-634.26)
Legumes9.13 (5.75-13.32) 6.66 (3.62-10.52)
Fruits and nuts362.52 (257.17-483.60)356.77 (257.15-471.46)
Cereals178.32 (135.24-232.98)139.59 (108.06-176.22)
Fish and seafood 23.67 (13.92-33.62)18.89 (12.51-27.73)
Dairy products196.11 (116.90-301.35) 191.41 (110.76-292.55)
Meat and meat products121.11 (86.83-163.69)89.88 (64.02-120.09)
Monounsaturated lipids56.04 (44.67-69.45) 46.62 (36.92-57.86)
Saturated lipids33.08 (25.19-42.06) 27.11 (20.62-34.83)
Monounsaturated/saturated lipids
(ratio)
1.72 (1.46-2.02)1.74 (1.45-2.07)
Ethanol11.07 (3.43-25.41) 1.17 (0.04-4.02)
RESEARCH
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Whenever we excluded one or more factors from the
Mediterranean diet score, we still adjusted for these
factors in the statistical analyses to control for possible
confounding. Moreover, when we evaluated the two
by two combinations, we controlled for the rest of the
componentsoftheoriginalscore.Wecheckedthepro-
portionality assumption with the log-log plots.
RESULTS
The 23349 study participants were followed up for
199726 person years, during which period 1075
deaths occurred. Table 1 shows the distribution of
study participants without a medically documented
history of major chronic diseases at enrolment. By
design, the Greek EPIC cohort contains more women
than men. The sampled age groups contain relatively
few people with university level education. As is well
knownfortheGreekpopulationingeneral,ahighpro-
portionofpeoplewereoverweightorobeseandahigh
proportion of men were ever smokers. Almost half of
men and a substantial fraction of women were
consumers of a moderate amount of alcoholic bev-
erages; few men and very few women were high con-
sumers.
Table 2 shows medians and interquartile ranges of
the daily intakes (by sex) of food groups that are char-
acteristics of the traditional Mediterranean diet
because they are consumed either in relatively high
or in relatively low amounts. The high consumption
of vegetables, legumes, fruits, and monounsaturated
lipids (mostly olive oil) is evident.
Table 3 shows associations, derived from Cox
regression, of the nine components of the Mediterra-
nean diet with mortality, assessed through mutually
adjusted ratios contrasting high with low consumption
(except for ethanol) and controlled for potential con-
founders as indicated in the footnote. All components
of the Mediterranean diet score have been simulta-
neously introduced in this model, allowingassessment
of the relative impact of each component. Compared
with moderate intake of ethanol, both low and high
intakes were associated with excess mortality to a sta-
tisticallysignificantdegree.Amongthepresumedben-
eficial components of the Mediterranean diet score,
highconsumptionofallbutfishandseafoodwasinver-
sely associated with mortality, although none of these
associations was statistically significant. For fish and
seafood, the mortality ratio for consumption above or
equal to the median compared with consumption
below the median was 1.078 (95% confidence interval
0.950 to 1.224; P=0.243). With respect to meat and
meat products and dairy products, as expected we
found positive associations, which for meat and meat
products approached statistical significance (P=0.06).
Because ethanol was introduced in the Mediterranean
diet score as a binary variable (moderate intake versus
other), we also calculated the corresponding mortality
ratio, which is 0.810 (0.706 to 0.931).
Afterameanfollow-upof8.5years,652deathsfrom
any cause had occurred among 12694 participants
with Mediterranean diet scores 0-4 and 423 among
10655 participants with scores 5 or more. Table 4
shows the mortality ratio associated with a two unit
increment in the Mediterranean diet score, as well as
how thisratio changes with alternateexclusionof each
of the nine components of the score. Because of the
construction of the score (in which one unitis assigned
when a beneficial component is consumed in high
quantities,ethanolisconsumedinmoderatequantities,
or a non-beneficial component is consumed in low
quantities), the benefit is expected to decrease (and
the mortality ratio is expected to increase towards the
null value of 1) after the alternate exclusion from the
score of each of the nine components. Table 4 also
shows the percentage reduction in the apparent effect
of the Mediterranean diet score. Thus, when vegeta-
bles are excluded from the score the mortality ratio,
properly adjusted for the change from a 10 point to a
ninepointscale,increasesfrom0.864to0.886—thatis,
the beneficial effect of the Mediterranean diet score is
reduced from 1−0.864=0.136 to 1−0.886=0.114 or by
16.2%. In the construction of the Mediterranean diet
Table 3 |Mutually adjusted mortality ratios associated with intake of components of
Mediterranean diet
Dietary variableMortality ratio* (95% CI)P value
Vegetables:
<Median
≥Median
Reference
0.901 (0.775 to 1.048)0.177
Legumes:
<Median
≥Median
Reference
0.942 (0.825 to 1.076)0.379
Fruits and nuts:
<Median
≥Median
Reference
0.931 (0.816 to 1.061)0.284
Cereals:
<Median
≥Median
Reference
0.989 (0.862 to 1.133) 0.869
Fish and seafood
<Median
≥Median
Reference
1.078 (0.950 to 1.224) 0.243
Monounsaturated/saturated lipids
(ratio):
<Median
≥Median
Reference
0.908 (0.792 to 1.042)0.171
Dairy products:
<Median
≥Median
Reference
1.069 (0.931 to 1.227)0.345
Meat and meat products:
<Median
≥Median
Reference
1.148 (0.992 to 1.329) 0.063
Ethanol intake†:
ModerateReference
Low intake1.193 (1.032 to 1.380)0.017
High intake 1.470 (1.132 to 1.907) 0.004
*Adjusted for sex, age (<45, 45-54, 55-64, ≥65, categorically), education (none/elementary school degree,
secondary or technical school degree, university degree or higher, categorically), smoking status (never, former,
and current at enrolment with cigarettes per day 1-10, 11-20, 21-30, 31-40, ≥41 ordered), waist:hip ratio (sex
specific fifths, ordered), body mass index (sex specific fifths, ordered), MET score (fifths, ordered), and total
energy intake (fifths, ordered).
†Low: <10 g/day for men, <5 g/day for women; moderate: men ≥10 g/day and ≤50 g/day, women ≥5 g/day and
≤25 g/day; high: >50 g/day for men, >25 g/day for women.
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score,fishandseafoodareexpectedtohaveaninverse
(beneficial) association, but in this particular dataset
the association turned out to be non-significantly posi-
tive(table 33).Forthis reason,wedidnotcalculatethe
mortality ratio corresponding to the exclusion of fish
and seafood from the Mediterranean diet score in
table 4.
Table 5 shows changes in the mortality ratios asso-
ciated with a two unit increment in the Mediterranean
diet score (properly adjusted for the sequential change
inscale),aftersuccessiveremovalofeachofitscompo-
nents, ranked according to the magnitude of effect in
the model in which the nine components were
mutuallyadjusted(table 3).Again,wedidnotconsider
fish and seafood in this analysis (except as a possible
confoundingvariable).Asexpected,themortalityratio
gradually approaches the null value of 1 after removal
firstlyofethanol,thenofmeatandmeatproducts,then
of vegetables, then of fruits and nuts, then of the lipid
ratio, and finally of legumes. Change in the order of
removal did not noticeably affect the pattern shown
in table 5.
Wealsoexaminedtheconsequencesofthejointpre-
senceofanytwobytwocombinationsoftheninecom-
ponents of the Mediterranean diet score, excluding
combinations of fish and seafood with the rest of the
components because of the unexpected (probably
owing to chance) positive association of this food
group with mortality. Of the 28 possible two by two
combinations, we found clear additive or super-
additive associations of the joint presence of any two
componentsin 13 instances (in none of these instances
was there a statistically significant interaction in the
multiplicative scale implicit in the Cox regression).
Moderate ethanol consumption, high lipid ratio, and
low intake of meat and meat products were each pre-
sent five times in the 26 (2×13) possible entries,
whereas high intakes of vegetable, fruits, and legumes
were each represented three times (the remaining two
entries were once for low intake of dairy products and
once for high cereal intake). In conjunction with the
results in table5, we interpret these findings as
suggesting that moderate ethanol intake, low intake
of meat and meat products, high lipid ratio, and high
intakeofplantfoodsaredrivingtheassociationofhigh
Mediterranean diet score with low mortality.
DISCUSSION
Main findings
In a prospective investigation based on the general
population,inwhich23349participantswerefollowed
upfor199726personyearsand1075deathsoccurred,
we found that people with closer adherence to the tra-
ditional Mediterranean diet, as indicated by the Medi-
terranean diet score, had lower overall mortality.
Specifically, increased adherence to the Mediterra-
nean diet score by two units, a realistic change, was
associated with a statistically significant 14% lower
overall mortality. In many studies assessing the health
effects of the Mediterranean diet, the authors have
speculated about the biological processes that mediate
its apparent effects, focusing on possible anti-
oncogenicactionsoftheoleicacidinoliveoil,18resver-
atrol and piceid mostly in wine,19and several other
antioxidants in olive oil and plant foods,20as well as
the widely accepted favourable effects of olive oil on
blood lipids.21
The contribution of the nine components to the
Mediterranean diet score was approximately additive
in thesense thatthe additionof theexcessesorthe def-
icits in the mortality ratios in table 3 divided by the
number of components (nine) would equal −0.07 and
wouldapproximatelycorrespondtothemortalityratio
of the Mediterranean diet score per one unit incre-
ment.Nevertheless,thecontributiontotheassociation
of adherence to the Mediterranean diet score with
lower mortality was larger for moderate (rather than
excessive or minimal) consumption of ethanol (24%),
followed by low consumption of meat and meat pro-
ducts (17%) and high consumption of vegetables
(16%);highconsumptionoffruitsandnuts,highmono-
unsaturatedtosaturatedlipidratio,andhighconsump-
tion of legumes each contributed about 10-11%. The
contributions of high consumption of cereals and low
Table 4 |Mortality ratios associated with two unit increment* in Mediterranean diet score (MDS) and after alternate
subtraction of each of its dietary components
Dietary variable Mortality ratio† (95% CI) P valueReduction in apparent effect (%)‡
MDS overall 0.864 (0.802 to 0.932)<0.0010
MDS minus vegetables0.886 (0.822 to 0.955)0.00216.2
MDS minus legumes 0.877 (0.815 to 0.944)<0.0019.7
MDS minus fruit and nuts 0.879 (0.818 to 0.946)0.00111.2
MDS minus cereals0.872 (0.814 to 0.935) <0.001 6.1
MDS minus monounsaturated/saturated lipids (ratio)0.878 (0.806 to 0.957)0.00310.6
MDS minus dairy products 0.870 (0.806 to 0.939)<0.001 4.5
MDS minus meat and meat products0.887 (0.825 to 0.953) 0.00116.6
MDS minus ethanol0.896 (0.835 to 0.962) 0.00223.5
*Originally estimated logarithms of mortality ratios were multiplied by 9/10 and then exponentiated to correct for nine point scale.
†Adjusted for sex, age (<45, 45-54, 55-64, ≥65, categorically), education (none/elementary school degree, secondary or technical school degree,
university degree or higher, categorically), smoking status (never, former, and current at enrolment with cigarettes per day 1-10, 11-20, 21-30, 31-40,
≥41 ordered), waist:hip ratio (sex specific fifths, ordered), body mass index (sex specific fifths, ordered), MET score (fifths, ordered), total energy
intake (fifths, ordered), and corresponding subtracted components (<median intake, ≥ median intake).
‡Estimated from original numbers.
RESEARCH
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