Predimed study is one of the few truly long term randomized trials with disease and mortality outcomes. It is unique in many ways and will have a strong and lasting impact

1. Predimed study
Primary Prevention of Cardiovascular
Disease with a Mediterranean Diet
Estruch J et al. NEJM February 25, 2013 DOI:
10.1056/NEJMoa1200303
Page 1

2. Introduction
• Systematic reviews of prospective cohort studies suggest that
Mediterranean Diet pattern (Med Diet) is linked to better
cardiovascular (Mente et al. 2009), cognitive (Daviglus et al.
2011), weight management outcomes (Esposito et al. 2011) &
cancer outcomes (Sofi et al 2010)
• Lyon Diet Heart Study is so far the only randomized trial with
morbidity and mortality outcomes on Med Diet. The study
delivered robust results favouring Med Diet vs usual French Diet
(de Lorgeril et al 1994).
• It may be argued that Oslo Diet Heart (1966) study was also Med
Diet study. It also delivered clear benefits in favor of Med Diet
• The effects of Med Diet as primary prevention strategy are not
known
2 www.pronutritionistblog.com

3. Methods 1/4
Note! Processed and red meat was restricted in both
groups and fish encouraged in both groups.
Estruch J et al. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet. NEJM February 25, 2013 DOI:
10.1056/NEJMoa1200303
Page 3

4. Methods 2/4
• High risk patients in primary care setting (Spain)
– A) Type 2 Diabetes OR
– B) Minimum 3 out of the following: Smoking, LDL>4,1 (or statin in
use), low HDL, hypertension, BMI>25 and CHD heritage
– Exclusion criteria: Not ready to the dietary change (Prochaska &
DiClemente Scale), MI, peripheral artery disease & allergy to nuts
• N=7447
• Diets
– A) American Heart Association diet (version from year 2000) without
any free delivery of food items
– B) Mediterranean Diet (Med Diet) with free extra virgin olive oil
(minimum use per day is 4 teaspoons)
– C) Mediterranean Diet with free nut mix , 30 g/day (walnuts 15 g,
almonds 7,5 g & hazelnuts 7.5 g)
– Diet were constructed and patients informed by study dietitians
– Adherence to diets is evaluated by Med Diet scores and AHA scores
Page 4 Marttinez-González et al. Cohort Profile: design and methods of the PREDIMED
study. International Journal of Epidemiology 2010;1–9

5. Methods 3/4
• Primary endpoints
– Composite endpoint of myocardial infarction, strokes and
cardiovascular deaths
• Secondary endpoints
– Deaths (any reason)
– Myocardial infarctions
– Strokes
– Dementia and other neurodegenerative diseases
– Cancers
– Surrogate markers like LDL, HDL, inflammation markers, glucose,
insulin …
Page 5 Marttinez-González et al. Cohort Profile: design and methods of the PREDIMED
study. International Journal of Epidemiology 2010;1–9

6. Methods 4/4
Randomization of patients
(High risk patients in primary
care, Spanish n = 7447)
A) Mediterranean diet including
free extra virgin olive oil daily
B) Mediterranean diet including
free nut mix daily
Year 2003 → Year 2012
C) Low fat diet (AHA diet early 2000), no
free delivery of any food items
Mean follow up ∼ 4,8 years
Drop out rates were very low. 11,4 % of participants were lost in
control group and 5,4 % in Med Diet groups
Page 6

7. Results /primary end point
Risk of composite cardiovascular end point was reduced by 30
% in both Med Diet groups vs controls.
Estruch J et al. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet. NEJM February 25, 2013 DOI:
10.1056/NEJMoa1200303

8. Results /myocardial infarctions
Incidence of myocardial infarctions was not significantly different
between groups (trend favouring Med Diet)
Estruch J et al. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet. NEJM February 25, 2013 DOI:
10.1056/NEJMoa1200303 (SUPPLEMENT MATERIAL)

9. Results /strokes
Strokes were reduced by nut enriched Med Diet by 49 % and by
extra virgin olive oil based 36 %
Estruch J et al. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet. NEJM February 25, 2013 DOI:
10.1056/NEJMoa1200303 (SUPPLEMENT MATERIAL)

10. Results / mortality end points
•Incidence of fatal cardiovascular events was not significantly
different between groups
•Total mortality was not significantly different between groups

11. Results / Diets
• There was no difference is the use of red and prosessed meat
bwetween the groups (disencouraged also in the control group)
• Control group used also a diet high in fish, fruits and vegetables
– More than 60 % of participants in control group used
veggies and fruits at least five servings per day
– 66 % of participants in control group used lean fish at least
three servings per week
– Intake of fiber was at the same level in between the groups
• Intake of saturated fat did not differ between the groups. Intake
of ALA (plant based PUFA) was higher in nut enriched Med Diet
group
• It seems that the biggest changes in diet happened in nut, olive
oil, sofrito and wine intake
11

12. Similarities & differences vs other Med
Diet trials
Predimed Lyon Heart Study Oslo Diet Heart
• Outcomes on dementia, cancer, strokes and myocardial
ACTIVE GROUPS ACTIVE GROUP ACTIVE GROUP
infarctions and deaths will N=584 (at end) soon
N=7447 (at start) be published N=412 (at start)
Fat used (provides for Extra virgin olive (Active Canola spread, canola Soy oil
free in all 3 trials) Group A only) oil & olive oil
Nuts Provided for free (Active Encouraged Encouraged
Group B only)
Fish (oily) Encouraged Encouraged Canned sardines in oil for free
Red & Processed To be restricted To be restricted To be restricted
meat
Whole grains Not stated (neutral) Encouraged Encouraged
Fruit/berries Encouraged Encouraged Encouraged
Vegetables Encouraged Encouraged Encouraged
Butter & milk fat Butter resticted, dairy To be restricted To be restricted
neutral
Alcohol Wine encouraged Wine encouraged Alcohol “allowed”

13. My discussion
• Thisis the largest randomized study ever on Mediterranean diet. Thus,
the results will have strong and lasting impact
• Done in modern era (vs fat replacement RCT during 1960’s)
• The results are in line with surrogate marker trials (short RCTs),
prospective cohort studies and ecological correlations. Thus,
mediterranean diet pattern has the most robust evidence supporting its
effect on cardiovascular health
• This is the first randomized trial on diet demonstrating a clear benefit in
terms of strokes
• Mechanism of action is not clear as the data on lipid ,inflammation,
blood pressure, sugar and other parameters was not disclosed at his
stage
13

14. Please read the whole paper
Estruch J et al. NEJM February 25, 2013
DOI: 10.1056/NEJMoa1200303
Page 14

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Reijo Laatikainen, M Sc, MBA,
Registered Dietitian
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