The Medi-RIVAGE study: reduction of cardiovascular disease risk
factors after a 3-mo intervention with a Mediterranean-type diet or a
low-fat diet1–3
Stephanie Vincent-Baudry, Catherine Defoort, Mariette Gerber, Marie-Christine Bernard, Pierre Verger, Olfa Helal,
Henri Portugal, Richard Planells, Pascal Grolier, Marie-Josephe Amiot-Carlin, Philippe Vague, and Denis Lairon
ABSTRACT
Background: Epidemiologic studies link Mediterranean-type diets
to a low incidence of cardiovascular disease; however, few dietary
intervention studies have been undertaken, especially in primary
prevention.
Objectives: In the Mediterranean Diet, Cardiovascular Risks and
Gene Polymorphisms (Medi-RIVAGE) study, the effects of a
Mediterranean-type diet (Med group) or a low-fat diet (low-fat
group) on risk factors were evaluated in 212 volunteers (men and
women) with moderate risk factors for cardiovascular disease.
Design: After the 3-mo dietary intervention, changes in many risk
factors were evaluated. Dietary questionnaires and plasma nutri-
tional markers were used to test compliance.
Results: Although the dietary goals were only partially reached,
changes in dietary habits were observed in both groups (n ҃ 169):
protein, carbohydrate, and fiber intakes increased and fat quality
(decreased saturated fat and increased monounsaturated or polyun-
saturated fat) improved. BMI, total and triacylglycerol-rich lipopro-
tein (TRL) cholesterol, triacylglycerols, TRL triacylglycerols, apo-
lipoproteins A-I and B, insulinemia, glycemia, and the homeostasis
model assessment score were significantly lower after 3 mo. The
reductions in total cholesterol, triacylglycerols, and insulinemia re-
mained significant after adjustment for BMI. There was a trend for
a diet-by-time interaction for LDL cholesterol (P ҃ 0.09). Our data
predicted a 9% reduction in cardiovascular disease risk with the
low-fat diet and a 15% reduction with this particular Mediterranean
diet.
Conclusion: After a 3-mo intervention, both diets significantly re-
duced cardiovascular disease risk factors to an overall comparable
extent. Am J Clin Nutr 2005;82:964 –71.
KEY WORDS Intervention trial, primary prevention, blood
pressure, lipid metabolism, apolipoproteins
INTRODUCTION
Cardiovascular disease (CVD) is one of the leading causes of
death in the Western world and is the third cause of mortality in
developing countries, accounting for 앒25% of all deaths (1).
Many studies have already shown the effect of specific nutrients
or diets on cardiovascular disease risk factors or mortality. The
Seven Countries Study by Keys et al in the 1960s showed a
relation between saturated fat intake, fasting blood cholesterol
concentrations, and coronary heart disease (CHD) mortality in
964 Am J Clin Nutr 2005;82:964 –71. Printed in USA. © 2005 American Society for Nutrition
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various populations (2, 3), which suggests the protective effect of
traditional Mediterranean-type diets. The more recent MONICA
survey, conducted in Europe, confirmed the South-North gra-
dient in CHD mortality and its relation to dietary habits (4).
Even more recently, 3 cohort studies in Spain and Greece have
provided data supporting a cardiovascular protective effect of
Mediterranean diets (5-7). These studies, together with other
reliable epidemiologic studies (8), provide the basis for the
well-known traditional Mediterranean diet pyramid and
healthy eating model (9).
Nevertheless, drastic changes in food habits in Mediterranean
populations have recently occurred, and the traditional Mediter-
ranean model now seems restricted to elderly people and rural
areas (10). Indeed, even in Crete, the progressive upward trend in
total and saturated fat intakes is concomitant with a marked
increase in obesity and cardiovascular disease mortality (11).
Although individual nutrients common in the traditional Med-
iterranean diet have been individually tested in some studies
(12–14), very few intervention studies have looked at a global
diet (15). The Lyon Heart Study for secondary prevention of
CHD (16, 17) showed the positive effect of a Mediterranean-type
1
From the Human Nutrition and Lipids Joint Research Unit 476-
INSERM, National Institute of Health and Medical Research/1260-National
Institute of Agronomic Research, Faculty of Medicine Timone, Université de
la Méditerranée, Marseille, France (SV-B, CD, OH, RP, M-JA-C, and DL);
the Analytical Chemistry Laboratory, Faculty of Pharmacy, Marseille,
France (CD and HP); the Cancer Research Centre, INSERM-CRLC Val
d’Aurelle, Montpellier, France (MG); the Centre for Detection and Preven-
tion of Arteriosclerosis, Timone University Hospital, Marseille, France
(M-CB and PV); the Health Regional Observatory, Epidemiology and Social
Sciences Applied to Medical Innovation Unit-379-INSERM, Marseille,
France (PV); and the UMMM Metabolic Disease and Macronutrients Lab-
oratory, Clermont-Ferrand, France (PG).
2
Supported by the French Research Ministry (AQS grant, SV’s salary),
INSERM (IDS grant), the Provence-Alpes-Côte d’Azur Regional Council,
the Bouches du Rhône General Council, the CRITT-PACA, and the follow-
ing companies: Rivoire & Carret Lustucru, Jean Martin, Le Cabanon, Bou-
langerie Coagulation Surgelés, Distplack Mariani, and Minoterie Giraud.
3
Reprints not available. Address correspondence to D Lairon, UMR 476-
INSERM/1260-INRA, Human Nutrition and Lipids, Faculty of Medicine
Timone, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 5, France. E-
mail: denis.lairon@medecine.univ-mrs.fr.
Received January 5, 2005.
Accepted for publication July 2, 2005.
 THE MEDI-RIVAGE STUDY
diet enriched with ␣-linolenic acid (mainly in the form of mar-
garine), the survival rate after a first myocardial infarction in-
creasing markedly compared with that for the control group
(low-fat diet). Moreover, the Indo-Mediterranean Diet Heart
Study (18) showed that a Mediterranean-type diet (rich in
␣-linolenic acid from fruit, vegetables, and nuts) was also of
benefit for secondary prevention of CHD in non-Mediterranean
populations. The Mediterranean Alpha-linolenic Enriched
Groningen Dietary Intervention (MARGARIN) Study (19,
20), a primary prevention study in hypercholesterolemic sub-
jects, showed the benefit of the ␣-linolenic acid contained in
a Mediterranean diet. Finally, a recently published trial in
patients with the metabolic syndrome shows that a
Mediterranean-type diet decreases insulin resistance and im-
proves endothelial function (21).
As the only other primary intervention study in this field (21),
the Mediterranean Diet, Cardiovascular Risks and Gene Poly-
morphisms (Medi-RIVAGE) intervention study is based on an
overall daily diet instead of on a specific nutrient. In this study,
we aimed to evaluate the effect of a Mediterranean-type diet
compared with that of a low-fat (prudent) diet on CVD risk
factors in subjects at moderate CVD risk. It should be pointed out
that the 2 diets differed somewhat in food types and quality but
that the expected macronutrient contents were not markedly dif-
ferent. Extensive biological investigations were performed with
a special focus on lipid and lipoprotein variables. In this article
we report the effects of the 3-mo Medi-RIVAGE dietary inter-
vention on clinical and biochemical risk markers.
SUBJECTS AND METHODS
Subjects
The design and methods of the Medi-RIVAGE study were
recently reported (22) in detail. Briefly, the participants were
men and women aged 18-70 y who were visiting the Center for
Detection and Prevention of Arteriosclerosis (CPDA) at La
Timone University Hospital (Marseille, France) and who met at
least one of the following eligibility criteria: fasting plasma cho-
lesterol concentration of 6.5–7.7 mmol/L; triacylglycerol con-
centration of 2.1– 4.6 mmol/L; glycemia (glucose concentration
of 6.1– 6.9 mmol/L); systolic and diastolic blood pressure be-
tween 140 –180 and 90 –105 mm Hg, respectively; body mass
index [BMI (in kg/m2)] 쏜27; smoking; sedentary; or family
history of CVD (22). Subjects treated by hypolipemic or hypo-
glycemic drugs were excluded. Eligible volunteers provided
signed informed consent as approved by the institution’s ethics
committee (ethics committee number 98/25).
Nutritional strategy
Details of diet composition at baseline and of dietary inter-
vention strategy were previously described (22). Briefly, the
participants were consuming a Western-type diet at entry. They
were provided with nutritional recommendations by physicians
and dietitians and received a booklet presenting either the rec-
ommended Mediterranean diet adapted from the traditional
model (Med) or a commonly prescribed low-fat American Heart
Association–type diet adapted by the CDPA (low-fat diet). The
Med diet recommended nuts, whole-meal bread, cereals, and a
variety of raw or cooked, fresh, or dried fruit and vegetables and
legumes,. Olive oil was recommended as the main source of
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965
added fat. Fish was recommended 4 times/wk and red meat only
1 time/wk. Sheep and poultry were to provide the main source of
meat, whereas cheeses were mainly to be from sheep and goats.
Oat-bran– enriched pasta, tomato sauce, and olive oil were pro-
vided. In the low-fat group, recommendations were to eat more
poultry than mammal meat, to avoid offal and saturated fat–rich
animal products, and to eat fish 2–3 times/wk. The consumption
of raw and cooked fruit and vegetables, low-fat dairy products,
and vegetable oils was recommended.
In terms of nutrients, the quantity and quality of lipid intakes
were the major differences between the 2 recommended diets.
The Med diet recommendations accepted up to 35–38% of total
energy as fat, whereas the low-fat diet recommendations limited
fat intake to 30% of total energy. Moreover, in the Med diet, 50%
of the energy provided by lipids was to come from monounsat-
urated fatty acids, 25% from polyunsaturated fatty acids, and
25% from saturated fatty acids; in the low-fat diet, 33% of energy
was provided by each of the 3 lipid subclasses. Cholesterol was
restricted to 200 –300 mg/d in both diets. The recommended fiber
intake was higher in the Med group (25 g/d) than in the low-fat
group (20 g/d). The Med diet made specific mention of carot-
enoid intake (7 mg/d), a marker of fruit and vegetable intakes,
whereas there was no specific recommendation concerning these
micronutrients in the low-fat diet. Furthermore, to limit dairy
food intake as in the traditional Mediterranean diet, the Med
group subjects were instructed not to exceed a calcium intake of
800 mg/d. In the Med diet, 2 glasses of red wine/d were allowed
for men and 1 glass/d for women; however, alcohol was to be
avoided, especially for hypertriglyceridemic subjects, in the low-
fat diet.
To ensure adequate compliance with dietary recommenda-
tions, dietitians used 3-d food records (at inclusion and after 3
mo) and 24-h unscheduled dietary recalls (once a month). The
GENI program nutritional database was used (Micro6, Nancy,
France), which is based on the French REGAL food database.
The physical activity of the participants was recorded on ques-
tionnaires. It did not differ between groups at inclusion (22) and
did not change noticeably during the 3-mo intervention period, as
was recommended (data not shown).
Endpoints
The endpoints were observed changes in the risk factors (clin-
ical variables and biological markers) after 3 mo of dietary in-
tervention. A DNA bank was also built to determine the poly-
morphisms of genes involved in lipoprotein metabolism or
arteriosclerosis and to search for interactions between gene poly-
morphisms and responses to diets.
Weight and blood pressure were checked at entry and at the
end of 3 mo. After the subjects fasted overnight, plasma concen-
trations of glucose, insulin, total cholesterol, LDL cholesterol,
HDL cholesterol, TRL cholesterol, triacylglycerols, TRL tria-
cylglycerols, fatty acids, carotenoids, vitamin B-12, folates, and
apolipoprotein (apo) E, apo A-I, apo B, and apo C-III were
measured at entry and at the end of 3 mo with the use of methods
previously described (22). Insulin resistance was estimated by
the homeostasis model assessment (HOMA) (22).
Statistical analysis
A sample size of 80 subjects in each group was calculated to
have 90% statistical power to detect a difference of 0.5 mmol/L
 966 VINCENT-BAUDRY ET AL
FIGURE 1. Mean intakes (g/d) of important food items at baseline and after a 3-mo dietary intervention in subjects fed a Mediterranean-type diet (Med group;
n ҃ 88) or a low-fat diet (low-fat group; n ҃ 81) at baseline and at 3 mo.
in blood cholesterol, with a 5% level of significance (two-tailed
test).
The intention-to-treat principle was used to compare the Med
and low-fat groups. The groups were defined according to the
initial random assignment rather than according to reported com-
pliance with the protocol (n ҃ 169 at 3 mo). Continuous data are
expressed as mean (앐SD) values. Variables not normally dis-
tributed were tested with the Mann-Whitney U test. Associations
were examined by using Pearson’s (parametric data) and Spear-
man’s (non parametric data) correlation analysis.
The data were analyzed by using repeated-measures 2-factor
analysis of covariance. Time effect and diet interaction were
determined as reported in the tables (P values for time and time-
by-group interactions, respectively). The results were adjusted
for baseline values if they were different and also for age, sex,
tobacco, and BMI variation. Comparisons within groups were
made by using the paired-samples t test. Comparisons between
groups, at baseline, were made by using the independent-samples
t test. Two-tailed P values 쏝 0.05 were judged significant. SPSS
for WINDOWS version 12.0 (SPSS Inc, Chicago, IL) was used
for the statistical analysis.
RESULTS
A total of 232 subjects were invited to participate in the study
(22); 212 (91.4%) subjects were included in the study (n ҃ 102
in the Med group and 110 in the low-fat group). During the first
3 mo, 43 subjects dropped out [n ҃ 14 (15.9%) in the Med group
and 29 (35.8%) in the low-fat group]. The characteristics of the
dropouts were not significantly different from those of the other
subjects. Of the subjects (n ҃ 169) followed at month 3, 42%
were men and 58% women in the Med group, and 39.5% were
men and 60.5% were women in the low-fat group. The mean age
of the subjects was 50.8 (앐 10.8) and 51.6 (앐 10.3) in the 2
groups, respectively. Overall, 35% of the subjects were over-
weight (BMI: 25-30), 38% were obese (BMI 쏜 30), 93% were
hypercholesterolemic, 46% were hypertriacylglycerolemic, and
21% were hypertensive. There was no significant difference
between the Med (n ҃ 88) and low-fat (n ҃ 81) groups with
regard to energy intake and demographic, anthropometric, and
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clinical baseline data, with the exception of smoking [more
smokers in the Med group (27.3%) than in the low-fat group
(17.3%); P ҃ 0.07] and LDL cholesterol (4.4 mmol/L in the Med
group and 4.1 mmol/L in the low-fat group; P 쏝 0.05) as previ-
ously reported (22).
Nutritional data
As illustrated in Figure 1, the subjects noticeably altered their
food consumption pattern in line with recommendations to the 2
groups. For almost all dietary variables, there were no significant
time-by-group interactions; dietary changes in the Med group
were not significantly different from those in the low-fat group
(Table 1). Both groups decreased energy intake over the 3-mo
study period. Alcohol intake decreased significantly in both
groups, but the decrease was greater in the low-fat group than in
the Med group (P for interaction ҃ 0.02). In both groups, the
percentage of energy provided by proteins and carbohydrates
increased significantly, whereas that provided by total fat de-
creased. The percentage of energy provided by saturated fat
decreased over time, whereas that provided by polyunsaturated
fat increased. There was a significant interaction for percentage
of fat provided by monounsaturated fat, which increased with the
Med diet and decreased with the low-fat diet (P for interaction ҃
0.012). Ingested cholesterol decreased in both groups over the
3-mo period. Total, soluble, and nonsoluble dietary fiber intakes
did not increase significantly in either group. In both groups,
there was no variation in ␤-carotene, folate, vitamin C, and vi-
tamin B-12 intakes. Calcium intake decreased in both groups.
There was a significant interaction for vitamin B-6 and vitamin
E intakes (P for interaction ҃ 0.011 and 0.027, respectively);
vitamin B-6 increased with the Med diet and decreased with the
low-fat diet, whereas vitamin E showed the reverse trend. Iron
intake decreased in both groups, and there was a significant
interaction for iron (P for interaction ҃ 0.032).
Nutritional biomarkers
Changes in plasma nutritional biomarkers after the 3-mo diet
are shown in Table 2. After adjustment for BMI variation, we
observed a tendency for increased plasma ␤-carotene and lyco-
pene concentrations over time (P ҃ 0.10). Total plasma phenolic
 THE MEDI-RIVAGE STUDY 967
TABLE 1
Daily nutrient intakes of the sample by treatment group at baseline and after the 3-mo diet1

Med group Low-fat group

(n ҃ 88) (n ҃ 81) P for interaction2

Baseline 3 mo Mean change Baseline 3 mo Mean change Time Group Time ҂ group

Total energy (kJ) 8471.2 앐 2406.8 6280.4 앐 1714.6

3
Ҁ2190.8 8489.5 앐 2875.4 6408.2 앐 2060.5 Ҁ2081.3 쏝 0.001 NS NS
Alcohol
(g) 9.0 앐 12.84 6.4 앐 12.3 Ҁ2.6 11.2 앐 14.1 4.9 앐 6.65 Ҁ6.3 0.08 0.045 0.02
(kJ) 264.5 앐 377.6 187.5 앐 359.8 Ҁ77.0 330.3 앐 412.9 141.9 앐 192.65 Ҁ188.4 0.08 0.045 0.02
Energy without 8216.4 앐 2326.4 6075.6 앐 1540.0 Ҁ2140.8 8201.1 앐 2742.3 6245.9 앐 1796.6 Ҁ1955.2 쏝 0.001 NS NS
alcohol (kJ)
Protein
(g) 88.3 앐 23.1 70.5 앐 19.8 Ҁ17.8 92.5 앐 27.3 77.8 앐 19.3 Ҁ14.7 쏝 0.001 NS NS
(% of energy) 18.4 앐 3.5 19.6 앐 3.2 1.2 19.4 앐 4.0 21.3 앐 3.6 1.9 쏝 0.001 NS NS
Carbohydrates
(g) 208.9 앐 63.6 166.5 앐 45.3 Ҁ42.5 203.5 앐 74.6 168.3 앐 58.7 Ҁ35.2 쏝 0.001 NS NS
(% of energy) 42.6 앐 6.1 45.9 앐 5.1 3.3 41.6 앐 7.1 44.8 앐 6.7 3.2 쏝 0.001 NS NS
Fat
(g) 86.3 앐 32.0 56.2 앐 17.3 Ҁ30.1 86.5 앐 38.7 56.7 앐 20.5 Ҁ29.8 쏝 0.001 NS NS
(% of energy) 39.0 앐 6.1 34.6 앐 6.9 Ҁ4.4 39.0 앐 6.9 33.9 앐 6.4 Ҁ4.9 쏝 0.001 NS NS
Saturated fat
(g) 32.4 앐 15.6 16.3 앐 6.3 Ҁ16.1 31.6 앐 15.7 17.2 앐 7.7 Ҁ14.4 쏝 0.001 NS NS
(% of energy) 14.4 앐 3.7 10.0 앐 2.6 Ҁ4.4 14.3 앐 3.7 10.3 앐 3.1 Ҁ4.0 쏝 0.001 NS NS
Monounsaturated fat
(g) 31.3 앐 11.7 25.3 앐 8.8 Ҁ6.0 31.8 앐 14.3 22.4 앐 8.8 Ҁ9.4 쏝 0.001 0.066 NS
(% of energy) 14.3 앐 3.3 15.6 앐 3.95 1.3 14.4 앐 3.2 13.4 앐 3.25 Ҁ1.0 쏝 0.001 0.001 0.012
Polyunsaturated fat
(g) 11.5 앐 5.3 9.4 앐 4.2 Ҁ1.9 12.0 앐 6.7 10.5 앐 5.6 Ҁ1.5 쏝 0.001 NS NS
(% of energy) 5.4 앐 2.2 5.8 앐 2.2 0.4 5.4 앐 1.9 6.3 앐 2.7 0.9 쏝 0.001 NS NS
Polyunsaturated: 0.4 앐 0.23 0.6 앐 0.3 0.2 0.42 앐 0.24 0.7 앐 0.3 0.28 쏝 0.001 NS NS
saturated fat
Cholesterol (mg) 311.7 앐 138.6 180.2 앐 88.1 Ҁ131.5 338.6 앐 158.7 199.3 앐 94.5 Ҁ139.3 0.002 NS NS
Total fiber (g) 20.2 앐 7.2 22.3 앐 7.9 2.1 19.7 앐 8.1 20.6 앐 8.0 0.9 NS NS NS
Soluble fiber (g) 4.3 앐 2.1 4.9 앐 2.1 0.6 4.0 앐 1.9 4.4 앐 2.0 0.4 NS NS NS
Nonsoluble fiber (g) 15.8 앐 5.7 17.4 앐 6.0 1.6 15.8 앐 6.6 16.4 앐 6.5 0.6 NS NS NS
␤-Carotene (mg) 3.9 앐 2.7 5.0 앐 3.0 1.1 4.1 앐 3.6 5.1 앐 3.4 1.0 NS NS NS
Folic acid (␮g) 302.9 앐 110.6 333.4 앐 124.1 30.5 316.3 앐 144.8 345.5 앐 146.2 29.2 NS NS NS
Vitamin C (mg) 117.7 앐 68.6 137.1 앐 60.3 19.4 103.3 앐 61.2 134.3 앐 55.4 31.0 NS NS NS
Vitamin B-6 (mg) 1.7 앐 0.5 1.9 앐 0.6 0.2 1.8 앐 0.6 1.7 앐 0.6 Ҁ0.1 NS 0.005 0.011
Vitamin B-12 (␮g) 5.1 앐 3.5 4.5 앐 3.3 Ҁ0.6 6.3 앐 7.5 5.0 앐 3.8 Ҁ1.3 NS NS NS
Vitamin E (mg) 11.1 앐 5.2 9.5 앐 3.45 Ҁ1.6 11.1 앐 6.3 11.8 앐 5.9 0.7 0.059 0.017 0.027
Calcium (mg) 967.2 앐 333.3 689.1 앐 202.3 Ҁ278.1 981.4 앐 381.1 815.6 앐 284.1 Ҁ165.8 쏝 0.001 NS NS
Iron (mg) 12.2 앐 3.9 11.0 앐 3.75 Ҁ1.2 12.7 앐 4.2 10.5 앐 3.05 Ҁ2.2 0.035 0.097 0.032
1
Med, Mediterranean-type diet.
2
Adjusted for age, sex, tobacco use, and BMI variation; P values were obtained by using a 2-factor repeated-measures ANOVA.
3
x៮ 앐 SD (all such values).
4
Significantly different from low-fat group, P 쏝 0.05 (independent-samples t test).
5
Significantly different from baseline within single diet group for nutrient density [nutrient (g)/energy intake (kJ)], P 쏝 0.05 (paired-samples t test).

compounds showed a time-by-group interaction, with a signifi- Clinical endpoints

cant increase in the Med group after 3 mo.
For plasma fatty acids, we observed a significant time-by-
group interaction for palmitoleic (16:1nҀ9) and stearic (18:0)
acids. Docosahexaenoic acid (22:6nҀ3) significantly increased
after 3 mo in both the Med and the low-fat groups (0.7% and
0.3%, respectively). Fish consumption (69.7 앐 48.7 and 72.4 앐
56.7 g/d in the Med and the low-fat group at 3 mo) was positively
correlated with plasma eicosapentaenoic acid (r ҃ 0.30, P 쏝
0.01) and docosahexaenoic acid (r ҃ 0.19, P 쏝 0.05) concen-
trations. In both groups, no significant change was observed for
plasma folate or vitamin B-12 concentrations after 3 mo.
A small but significant decrease in BMI was observed after a
3-mo diet, in line with the moderate reduction in total energy
intake (Table 3). A significant, although weak, increase was
observed in diastolic blood pressure after 3 mo.
Biochemical variables
After the 3-mo diet (Table 4), plasma total cholesterol signif-
icantly decreased, with a tendency for a group effect (P ҃ 0.082)
in the Med group (Ҁ0.4 mmol/L, or Ҁ7.5%) and in the low-fat
group (Ҁ0.3 mmol/L, or Ҁ4.5%). There was a trend (P ҃ 0.09)

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 968 VINCENT-BAUDRY ET AL

TABLE 2
Plasma nutritional markers of the sample by treatment group at baseline and after the 3-mo diet1

Med group (n ҃ 88) Low-fat group (n ҃ 81) P for interaction2

Baseline3 3 mo Mean change Baseline3 3 mo Mean change Time Group Time ҂ group

␤-Carotene (␮g/mL) 0.26 앐 0.21 0.43 앐 0.49

4
0.17 0.34 앐 0.30 0.46 앐 0.35 0.12 NS NS NS
␣-Carotene (␮g/mL) 0.09 앐 0.08 0.13 앐 0.3 0.04 0.10 앐 .06 0.12 앐 0.1 0.02 NS NS NS
␤-Cryptoxanthin (␮g/mL) 0.15 앐 0.12 0.18 앐 0.13 0.03 0.17 앐 0.14 0.21 앐 0.16 0.04 NS NS NS
Lycopene (␮g/mL) 0.19 앐 0.10 0.33 앐 0.23 0.14 0.24 앐 0.13 0.30 앐 0.19 0.06 NS NS NS
Lutein (␮g/mL) 0.26 앐 0.15 0.24 앐 0.15 Ҁ0.02 0.27 앐 0.16 0.27 앐 0.17 0 NS NS NS
Zeaxanthin (␮g/mL) 0.06 앐 0.03 0.06 앐 0.04 0 0.06 앐 0.03 0.06 앐 0.04 0 NS NS NS
Phenolic compound (mmol/L) 0.28 앐 0.14 0.33 앐 0.175 0.05 0.26 앐 0.14 0.27 앐 0.18 0.01 NS NS 0.043
Plasma fatty acid (%)
16:0 24.8 앐 3.4 23.4 앐 2.8 Ҁ1.4 23.8 앐 3.4 23.4 앐 2.9 Ҁ0.4 NS 0.018 NS
16:1nҀ9 2.7 앐 1.1 2.2 앐 1.05 Ҁ0.5 2.3 앐 0.8 2.4 앐 1.05 0.1 NS 쏝 0.001 0.004
18:0 6.4 앐 1.6 6.5 앐 1.5 0.1 7.0 앐 1.6 6.8 앐 1.35 Ҁ0.2 NS 0.056 0.05
18:1nҀ9 20.7 앐 3.1 21.3 앐 3.4 0.6 20.2 앐 3.2 20.6 앐 3.3 0.4 NS NS NS
18:2nҀ6 28.0 앐 4.4 27.6 앐 4.4 Ҁ0.4 28.4 앐 4.0 27.7 앐 4.3 Ҁ0.7 NS NS NS
18:3nҀ3 0.31 앐 0.22 0.36 앐 0.3 0.05 0.38 앐 0.25 0.35 앐 0.2 Ҁ0.3 NS 0.055 NS
18:4 0.07 앐 0.12 0.07 앐 0.2 0 0.07 앐 0.14 0.05 앐 0.09 Ҁ0.02 NS NS NS
20:3nҀ6 1.5 앐 0.7 1.5 앐 0.6 0 1.6 앐 0.7 1.5 앐 0.7 Ҁ0.1 NS NS NS
20:4nҀ6 7.1 앐 1.8 7.1 앐 1.8 0 7.2 앐 1.8 7.1 앐 1.8 Ҁ0.1 NS NS NS
20:5nҀ3 0.8 앐 0.6 1.2 앐 1.0 0.4 1.0 앐 1.1 1.1 앐 0.8 0.1 NS NS NS
22:6nҀ3 2.4 앐 0.9 3.1 앐 1.0 0.7 2.7 앐 1.2 3.0 앐 1.2 0.3 0.013 NS NS
Folate (␮g/L) 5.64 앐 1.95 7.18 앐 2.89 1.54 5.95 앐 2.48 6.62 앐 2.74 0.67 NS NS NS
Vitamin B-12 (ng/L) 500.0 앐 177.5 527.8 앐 181.0 27.8 513.4 앐 160.2 535.8 앐 164.9 22.4 NS NS NS
1
Med, Mediterranean-type diet.
2
Adjusted for age, sex, tobacco use, and BMI variation; P values were obtained by using a 2-factor repeated-measures ANOVA.
3
No significant differences at baseline between groups, P 쏝 0.05 (independent-samples t test).
4
x៮ 앐 SD (all such values).
5
Significantly different from baseline within single diet group, P 쏝 0.05 (paired-samples t test).

for a time-by-group interaction in LDL cholesterol and a trend for
a main effect of group (P ҃ 0.074): Med group (Ҁ0.5 mmol/L)
and low-fat group (Ҁ0.2 mmol/L). After 3 mo, no change in HDL
cholesterol was observed, whereas TRL cholesterol decreased
significantly in both groups.
In both groups Apo-AI and Apo-B were significantly lower
over the 3-month period with no time-by-group interactions.
Apo-E and Apo-CIII did not change after 3 mo. Plasma triacyl-
glycerol and TRL-triacylglycerol concentrations significantly
decreased after 3 mo.
Glycemia, insulinemia, and HOMA score decreased signifi-
cantly after 3 mo, with no time-by-group interactions (Table 4).
Moreover, significant effects of BMI were found on total cho-
lesterol, triacylglycerols, glycemia, insulinemia, and HOMA
score: P ҃ 0.028, ҃ 0.014, 쏝 0.001, 쏝 0.001, and 쏝 0.001 by
using a 2-factor (time and BMI) repeated-measures analysis of
covariance. After adjustment for BMI variation, the time effect
remained significant for total cholesterol (P ҃ 0.032), triacylg-
lycerols (P ҃ 0.039), and insulinemia (P ҃ 0.014).
DISCUSSION
The Medi-RIVAGE study aimed to determine the effect of a
Mediterranean diet and of a commonly prescribed low-fat diet on
risk factors for cardiovascular disease. Aimed at a reduction in
cardiovascular disease risks in our population, the study strategy
was to globally modify dietary habits without particular focus on
any specific nutrient, as is usual in intervention studies. This
strategy was evaluated by using dietary questionnaires and mea-
suring plasma nutritional markers. In both diet groups, we ob-
served noticeable changes in food intake (Figure 1). The most
important changes in the Med group were increases in fruit,

TABLE 3
Mean BMI and blood pressure of the sample by treatment group at baseline and after the 3-mo diet1

Med group (n ҃ 88) Low-fat group (n ҃ 81) P for interaction2

Baseline3 3 mo Mean change Baseline3 3 mo Mean change Time Group Time ҂ group

BMI (kg/m ) 2
28.7 앐 4.6 4
27.2 앐 4.2 Ҁ1.5 28.7 앐 5.4 27.5 앐 5.1 Ҁ1.2 0.010 NS NS
Systolic blood pressure (mm Hg) 128 앐 17 127 앐 12 Ҁ1 126 앐 17 124 앐 11 Ҁ2 NS NS NS
Diastolic blood pressure (mm Hg) 78 앐 11 80 앐 8 2 79 앐 21 79 앐 8 0 0.049 NS NS
1
Med, Mediterranean-type diet.
2
Adjusted for age, sex, tobacco use, and BMI variation; P values were obtained by using a 2-factor repeated-measures ANOVA.
3
No significant differences at baseline between groups, P 쏝 0.05 (independent-samples t test).
4
x៮ 앐 SD (all such values).

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 THE MEDI-RIVAGE STUDY 969
TABLE 4
Cardiovascular disease risk factors of the sample by treatment group at baseline and after the 3-mo diet1

Med group (n ҃ 88) Low-fat group (n ҃ 81) P for interaction2

Baseline 3 mo Mean change Baseline 3 mo Mean change Time Group Time ҂ group

Cholesterol (mmol/L) 6.6 앐 1.0 3

6.2 앐 1.0 Ҁ0.4 6.4 앐 0.9 6.1 앐 0.9 Ҁ0.3 쏝 0.001 0.082 NS
HDL cholesterol (mmol/L) 1.5 앐 0.4 1.5 앐 0.5 0 1.6 앐 0.5 1.6 앐 0.5 0 NS NS NS
LDL cholesterol (mmol/L) 4.4 앐 1.04 3.9 앐 0.85 Ҁ0.5 4.1 앐 0.9 3.9 앐 0.85 Ҁ0.2 NS 0.074 0.09
TRL cholesterol (mmol/L) 1.28 앐 0.97 1.13 앐 1.00 Ҁ0.12 1.18 앐 1.33 1.15 앐 1.15 Ҁ0.03 0.010 NS NS
Triacylglycerols (mmol/L) 1.6 앐 1.0 1.4 앐 0.9 Ҁ0.2 1.5 앐 1.0 1.3 앐 0.6 Ҁ0.2 0.042 NS NS
TRL triacylglycerols (mmol/L) 1.03 앐 0.82 0.87 앐 0.69 Ҁ0.16 0.88 앐 0.93 0.79 앐 0.61 Ҁ0.09 쏝 0.001 NS NS
Apolipoprotein B (g/L) 1.28 앐 0.25 1.22 앐 0.25 Ҁ0.06 1.20 앐 0.22 1.15 앐 0.23 Ҁ0.05 쏝 0.001 NS NS
Apolipoprotein A-I (g/L) 1.43 앐 0.29 1.37 앐 0.24 Ҁ0.06 1.55 앐 0.28 1.48 앐 0.29 Ҁ0.07 쏝 0.001 NS NS
Apolipoprotein E (mg/L) 41.9 앐 12.4 39.9 앐 9.9 Ҁ1.0 42.1 앐 12.8 39.4 앐 14.2 Ҁ2.7 NS NS NS
Apolipoprotein C-III (mg/L) 27.7 앐 7.9 27.6 앐 8.8 Ҁ0.1 28.9 앐 8.0 28.7 앐 8.0 Ҁ0.2 NS NS NS
Glucose (mmol/L) 5.3 앐 0.6 5.1 앐 0.6 Ҁ0.2 5.2 앐 0.7 5.0 앐 0.6 Ҁ0.2 쏝 0.001 NS NS
Insulin (mmol/L) 10.6 앐 5.8 8.3 앐 4.4 Ҁ2.6 10.6 앐 7.8 8.9 앐 5.9 Ҁ1.7 쏝 0.001 NS NS
HOMA score 2.5 앐 1.6 1.9 앐 1.2 Ҁ0.6 2.6 앐 2.2 2.0 앐 1.4 Ҁ0.6 쏝 0.001 NS NS
1
Med, Mediterranean-type diet; TRL, triacylglycerol-rich lipoprotein; HOMA, homeostasis model assessment.
2
Adjusted for age, sex, and tobacco use; P values were obtained by using a 2-factor repeated-measures ANOVA.
3
x៮ 앐 SD (all such values).
4
Significantly different from low-fat group, P 쏝 0.05 (independent-samples t test).
5
Significantly different from baseline within single diet group, P 쏝 0.05 (paired-samples t test).

vegetables (including legumes), olive oil, nuts, and fish and re-
ductions in other vegetable oils, dairy products, and meat. In the
low-fat group, the main changes observed were increases in fruit,
vegetables, and fish and decreases in meat and dairy products.
These changes in food intake had the effects of reducing protein
intake, of increasing the relative proportion of carbohydrates, of
decreasing ingested cholesterol, and of reducing total fat with a
marked improvement in fat quality (Table 1). For some fatty
acids we found a significant variation after a 3-mo diet in the Med
and low-fat groups, and the increase in fish consumption ob-
served was corroborated by higher plasma docosahexaenoic ac-
ids. Fiber intakes tended to increase after a 3-mo diet, especially
in the Med group (2.1 g/d), as consistent with recommendations
to increase intakes of whole-grain food products and legumes.
We observed a trend toward increases in total carotenoids in-
gested, which was confirmed by the measurement of the plasma
nutritional markers, which reflected the increase in vegetable and
fruit intakes. To summarize, whereas the 2 diets compared were
based on somewhat different consumption patterns of some
foodstuffs (especially olive oil, whole grains, legumes, and nuts),
they did not generate markedly different supplies of macro- or
micronutrients.
Although we observed noticeable changes in dietary habits in
both groups, the objectives set for the subjects were not fully met.
Indeed, dietary records and nutritional markers showed insuffi-
cient intakes of several nutrients. Lipid intakes, especially mono-
unsaturated fatty acids, remained insufficient in the Med group,
whereas lipid intakes remained too high in the low-fat group;
fiber intake did not reach the intake recommended for the Med
group (25 g/d). This can be explained by the fact that subjects in
both groups did not fully follow the dietary recommendations. It
is difficult to recruit subjects who will be strictly compliant with
dietary recommendations. Moreover, because the subjects lived
in the Mediterranean area, those in the low-fat group may have
unintentionally altered the recommended low-fat diet toward a
kind of “moderate” Mediterranean diet pattern, which resulted in
a reduction in differences between the 2 groups. It is noteworthy
that we observed a 2-fold lower dropout rate in the Med group
after 3 mo, which highlighted a better compliance with the Med-
iterranean diet pattern, as recently checked by others (23).
Nevertheless, changes in risk factors in the low-fat group were
comparable and even more satisfactory than those reported by
others during short-term intervention studies with the low-fat
American Heart Association–recommended diet (24). In the
Medi-RIVAGE study, several variables were significantly dif-
ferent after a 3-mo dietary intervention, such as total and TRL
cholesterol, triacylglycerols, TRL triacylglycerols, apo A-I, apo
B, glucose, insulin, and HOMA score. Interestingly, the reduc-
tion in LDL cholesterol after 3 mo tended to be greater with the
Med diet (P ҃ 0.09 for time-by-group interaction) than with the
low-fat diet, which agreed with the observations of the MAR-
GARIN (20) and the Indo-Mediterranean (18) studies. Con-
versely, the biochemical variables did not change noticeably
during the Lyon Diet Heart study (16). Dietary factors may ex-
plain these results. The Med diet provided greater intakes of
soluble fibers (from fruit, vegetables, legumes, and cereals) and
monounsaturated fatty acids (oleic acid from olive oil), which are
known independently to have a cholesterol- and LDL cholester-
ol–lowering effect (25–28). Olive oil intake was recently shown
to be related to reduced rates of myocardial infarction (29). Fiber-
rich diets (28) and a high consumption of fruit and vegetables
have been related to a reduced occurrence of CHD (5, 6).
The beneficial changes in total and LDL-cholesterol that we
observed in both groups agree with those reviewed by Sacks and
Katan (30), for both a low-fat and a Mediterranean-type diet.
However, we found no increase in fasting triacylglycerols, as
observed with high-carbohydrate, low-fat diets (30), which was
likely due to the limited nature of the modification observed in
dietary intakes and with the limited reduction in dietary energy
and related weight loss, all of which are limiting factors for
carbohydrate-induced hypertriglyceridemia. The reduction in
plasma triacylglycerol (mainly in the form of TRLs) observed
only in the Med group may have been due mainly to a high intake
of fish and long-chain nҀ3 fatty acids (31, 32) and more probably

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 970 VINCENT-BAUDRY ET AL
to changes in postprandial lipoprotein metabolism induced by
meals rich in olive oil (33) or dietary fibers (34).
An important point to consider in data interpretation is body
weight and BMI reduction, which, although moderate, may im-
prove some cardiovascular disease risk factors (35). After ad-
justment for BMI variation for variables showing an interaction
with BMI, decreases in total cholesterol, triacylglycerols, and
insulin after 3 mo remained significant. This suggests that the
significant changes still observed for these variables, after ad-
justment for weight loss, result from an independent effect of diet
quality alteration. This agrees with the recent observation that the
Mediterranean diet is associated with decreased insulin resis-
tance in patients with metabolic syndrome (21).
We observed no improvement in systolic or diastolic blood
pressure with the dietary interventions. It is possible that the large
number of normotensive subjects present (79% of total) or the
limited duration of the interventions prevented such an observa-
tion, because several epidemiologic studies have reported re-
duced blood pressure linked to Mediterranean dietary patterns
(36, 37).
In conclusion, the diets tested during the Medi-RIVAGE
study, a Mediterranean-type diet or commonly prescribed low-
fat diet, show measurable efficiency in reducing key cardiovas-
cular risk factors. In line with most recent theories on optimal
eating patterns for prevention of CHD (38) and according to
Law’s concept (39), the observed lowering in plasma cholesterol
actually indicates a reduction in cardiovascular risk of 9% with
the low-fat diet and 15% with the Mediterranean-type diet. The
Medi-RIVAGE intervention study thus provides support to early
(2– 4) or recent (5–7, 21) observational studies linking adherence
to the traditional Mediterranean diet and reduced cardiovascular
disease mortality and reinforces the notion of its efficacy in
primary as well as secondary prevention.
We are indebted to N Rousset and S Loviconi (CDPA dietitians); MF
Alliaud and AM Lorec (laboratory supervisors); M Senft, J Leonardi, B Lyan,
C Bideau, D Iniesta, N Peyrol, and JF Lesgard (laboratory technicians); and
A Lanteaume and A Loundou (statisticians).
DL, MG, and PV coordinated the study. SV-B, CD, and DL wrote the
manuscript. MG was responsible for the nutritional strategy. M-CB recruited
the subjects and conducted the clinical evaluations. CD, SV-B, PG, and
M-JA-C were involved in the laboratory work and data interpretation. PV,
OH, and SV-B were involved in the statistical analyses. HP and RP were
involved in the blood analyses. All authors contributed to the final report.
None of the authors declared a conflict of interest.
REFERENCES
1. Lopez AD. Assessing the burden of mortality from cardiovascular dis-
eases. World Health Stat Q 1993;46:91– 6.
2. Keys A, Menotti A, Karvonen MJ, et al. The diet and 15-year death rate
in the seven countries study. Am J Epidemiol 1986;124:903–15.
3. Keys A, Blackburn HW, Menotti A, et al. Coronary heart disease in
seven countries. Summary. Circulation 1970;41:I186 –95.
4. Thom TJ, Epstein FH, Feldman JJ, Leaverton PE. Trends in total mor-
tality and mortality from heart disease in 26 countries from 1950 to 1978.
Int J Epidemiol 1985;14:510 –20.
5. Martinez-Gonzalez MA, Fernandez-Jarne E, Serrano-Martinez M,
Marti A, Martinez JA, Martin-Moreno JM. Mediterranean diet and re-
duction in the risk of a first acute myocardial infarction: an operational
healthy dietary score. Eur J Nutr 2002;41:153– 60.
6. Trichopoulou A, Costacou T, Bamia C, Trichopoulos D. Adherence to a
Mediterranean diet and survival in a Greek population. N Engl J Med
2003;348:2599 – 608.
7. Panagiotakos DB, Pitsavos C, Chrysohoou C, et al. Impact of lifestyle
Downloaded from https://academic.oup.com/ajcn/article-abstract/82/5/964/4607676
by guest
on 01 August 2018
habits on the prevalence of the metabolic syndrome among Greek adults
from the ATTICA study. Am Heart J 2004;147:106 –12.
8. Hu FB, Willett WC. Diet and coronary heart disease: findings from the
Nurses’ Health Study and Health Professionals’ Follow-up Study. J Nutr
Health Aging 2001;5:132– 8.
9. Willett WC, Sacks F, Trichopoulou A, et al. Mediterranean diet pyramid:
a cultural model for healthy eating. Am J Clin Nutr 1995;61(suppl):
1402S– 6S.
10. Scali J, Richard A, Gerber M. Diet profiles in a population sample from
Mediterranean southern France. Public Health Nutr 2001;4:173– 82.
11. Ferro-Luzzi A, James WP, Kafatos A. The high-fat Greek diet: a recipe
for all? Eur J Clin Nutr 2002;56:796 – 809.
12. Haban P, Klvanova J, Zidekova E, Nagyova A. Dietary supplementation
with olive oil leads to improved lipoprotein spectrum and lower nҀ6
PUFAs in elderly subjects. Med Sci Monit 2004;10:PI49 –54.
13. Perez DD, Strobel P, Foncea R, et al. Wine, diet, antioxidant defenses,
and oxidative damage. Ann NY Acad Sci 2002;957:136 – 45.
14. Gerber MJ, Scali JD, Michaud A, et al. Profiles of a healthful diet and its
relationship to biomarkers in a population sample from Mediterranean
southern France. J Am Diet Assoc 2000;100:1164 –71.
15. Trichopoulou A. Mediterranean diet: the past and the present. Nutr
Metab Cardiovasc Dis 2001;11:1– 4.
16. de Lorgeril M, Salen P, Martin JL, Monjaud I, Delaye J, Mamelle N.
Mediterranean diet, traditional risk factors, and the rate of cardiovascular
complications after myocardial infarction: final report of the Lyon Diet
Heart Study. Circulation 1999;99:779 – 85.
17. de Lorgeril M, Renaud S, Mamelle N, et al. Mediterranean alpha-
linolenic acid-rich diet in secondary prevention of coronary heart dis-
ease. Lancet 1994;343:1454 –9.
18. Singh RB, Dubnov G, Niaz MA, et al. Effect of an Indo-Mediterranean
diet on progression of coronary artery disease in high risk patients (Indo-
Mediterranean Diet Heart Study): a randomised single-blind trial. Lan-
cet 2002;360:1455– 61.
19. Bemelmans WJ, Broer J, Feskens EJ, et al. Effect of an increased intake
of alpha-linolenic acid and group nutritional education on cardiovascular
risk factors: the Mediterranean Alpha-linolenic Enriched Groningen
Dietary Intervention (MARGARIN) study. Am J Clin Nutr 2002;75:
221–7.
20. Bemelmans WJ, Broer J, de Vries JH, Hulshof KF, May JF, Meyboom-De
Jong B. Impact of Mediterranean diet education versus posted leaflet on
dietary habits and serum cholesterol in a high risk population for cardiovas-
cular disease. Public Health Nutr 2000;3:273– 83.
21. Esposito K, Marfella R, Ciotola M, et al. Effect of a Mediterranean-style
diet on endothelial dysfunction and markers of vascular inflammation in
the metabolic syndrome: a randomized trial. JAMA 2004;292:1440 – 6.
22. Vincent S, Gerber M, Bernard MC, et al. The Medi-RIVAGE study
(Mediterranean Diet, Cardiovascular Risks and Gene Polymorphisms):
rationale, recruitment, design, dietary intervention and baseline charac-
teristics of participants. Public Health Nutr 2004;7:531– 42.
23. Sanchez-Villegas A, Martinez JA, De Irala J, Martinez-Gonzalez MA.
Determinants of the adherence to an “a priori” defined Mediterranean
dietary pattern. Eur J Nutr 2002;41:249 –57.
24. Walden CE, Retzlaff BM, Buck BL, McCann BS, Knopp RH. Lipopro-
tein lipid response to the National Cholesterol Education Program step II
diet by hypercholesterolemic and combined hyperlipidemic women and
men. Arterioscler Thromb Vasc Biol 1997;17:375– 82.
25. Mensink RP, Katan MB. Effect of dietary fatty acids on serum lipids and
lipoproteins. A meta-analysis of 27 trials. Arterioscler Thromb 1992;12:
911–9.
26. Perez-Jimenez F, Lopez-Miranda J, Mata P. Protective effect of dietary
monounsaturated fat on arteriosclerosis: beyond cholesterol. Athero-
sclerosis 2002;163:385–98.
27. Mekki N, Dubois C, Charbonnier M, et al. Effects of lowering fat and
increasing dietary fiber on fasting and postprandial plasma lipids in
hypercholesterolemic subjects consuming a mixed Mediterranean-
Western diet. Am J Clin Nutr 1997;66:1443–51.
28. Rimm EB, Ascherio A, Giovannucci E, Spiegelman D, Stampfer MJ,
Willett WC. Vegetable, fruit, and cereal fiber intake and risk of coronary
heart disease among men. JAMA 1996;275:447–51.
29. Fernandez-Jarne E, Martinez-Losa E, Prado-Santamaria M, Brugarolas-
Brufau C, Serrano-Martinez M, Martinez-Gonzalez MA. Risk of first non-
fatal myocardial infarction negatively associated with olive oil consump-
tion: a case-control study in Spain. Int J Epidemiol 2002;31:474 – 80.
30. Sacks FM, Katan M. Randomized clinical trials on the effects of dietary
 THE MEDI-RIVAGE STUDY
fat and carbohydrate on plasma lipoproteins and cardiovascular disease.
Am J Med 2002;113(suppl):13S–24S.
31. Holub DJ, Holub BJ. Omega-3 fatty acids from fish oils and cardiovas-
cular disease. Mol Cell Biochem 2004;263:217–25.
32. Buckley R, Shewring B, Turner R, Yaqoob P, Minihane AM. Circulating
triacylglycerol and apoE levels in response to EPA and docosahexaenoic
acid supplementation in adult human subjects. Br J Nutr 2004;92:477– 83.
33. Roche HM, Zampelas A, Knapper JM, et al. Effect of long-term olive oil
dietary intervention on postprandial triacylglycerol and factor VII me-
tabolism. Am J Clin Nutr 1998;68:552– 60.
34. Cara L, Dubois C, Borel P, et al. Effects of oat bran, rice bran, wheat
fiber, and wheat germ on postprandial lipemia in healthy adults. Am J
Clin Nutr 1992;55:81– 8.
35. Nanchahal K, Morris JN, Sullivan LM, Wilson PW. Coronary heart
Downloaded from https://academic.oup.com/ajcn/article-abstract/82/5/964/4607676
by guest
on 01 August 2018
971
disease risk in men and the epidemic of overweight and obesity. Int J
Obes Relat Metab Disord 2005;29:317–23.
36. Panagiotakos DB, Pitsavos CH, Chrysohoou C, et al. Status and man-
agement of hypertension in Greece: role of the adoption of a Mediter-
ranean diet: the Attica study. J Hypertens 2003;21:1483–9.
37. Psaltopoulou T, Naska A, Orfanos P, Trichopoulos D, Mountokalakis T,
Trichopoulou A. Olive oil, the Mediterranean diet, and arterial blood
pressure: the Greek European Prospective Investigation into Cancer and
Nutrition (EPIC) study. Am J Clin Nutr 2004;80:1012– 8.
38. Hu FB, Willett WC. Optimal diets for prevention of coronary heart
disease. JAMA 2002;288:2569 –78.
39. Law MR, Wald NJ, Thompson SG. By how much and how quickly does
reduction in serum cholesterol concentration lower risk of ischaemic
heart disease? BMJ 1994;308:367–72.