Mediterranean diet primary prevention of cvd journal club
Interesting Fad Diets in History
1820 lord Byron Vinegar and water
Early 1900’s Tapeworm diet, fell
out of favor quickly
1930 Grapefruit diet
1950 Cabbage soup diet
1970 Cookie diet, Dr. Sanford Siegal
(one meal daily and multiple
1992 Dr. Atkins diet publishes book
2000 Macrobiotic diet popular in
2011 HCG diet + 500-800 calorie a
History of Mediterranean Diet
Based on food patterns Crete,
Greece, southern Italy
High in plant foods, fresh fruit,
olive oil, low fat dairy, fish,
poultry, red wine
Low in red meat, processed foods
First made public by Ancel Keys
1st objective study Seven
Countries Study 1958 looked at
13,000 men found Cretan men
had lower death rates from heart
disease despite high intake of fat
Meta Analysis of prospective
observational studies published
by Sofi 2008. Looked at 12
studies 1,574,299 patients for 318 years. Showed adherence to
Mediterranean diet associated
with reduced overall mortality
(9%) mortality from CV disease
(9%) incidence or mortality from
cancer (6%) incidence or
Parkinson's and or Alzheimer's
Lyon heart study 1994 showed
lower mortality in the group
who’s diet was enriched with
Alpha-linolenic Acid. (found in
No Randomized controlled trials
• Randomly assigned in 1:1:1 ratio to one of three groups.
Started in 2003. Multicenter in Spain
• Group 1: Mediterranean diet with extra-virgin olive oil
• Group 2: Mediterranean diet with nuts (walnuts,
• Group 3: control diet instructed to follow low fat diet
• No caloric restriction or physical activity promoted in any
• Olive oil and nuts were donated. Non food gift items
given to control group.
Control Group Diet Handout
BUY LOW-FAT FOODS
• Bread, Cereals and pasta, Rice, Potatoes
• Fruit and vegetables
• Beans, lentils, chick-peas
• Low-fat milk, cheese, and other dairy
• Lean fish and seafood, Chicken and duck
meat with the skin removed
• Meat cuts low in fat instead of high-fat
ones such as beacon, beef and lamb
COOK WITH LESS FAT
• Avoid using oil, butter or fat-based sauces
• Dress dishes with the least possible oil
• Employ simple cooking methods, such as
boiling, baking or broiling. Avoid stewing,
frying, breading and use of “sofrito”
• Use the least possible amount of oil in the
frying pan, enough to avoid sticking of food
• Do not smear bread or toast with butter,
margarine, oil or other fat spreads
• Remove all visible fat from meat before
• Cool soups and broths to remove fat
layer on top before heating
WHICH FOODS CONTAIN MOST FAT AND
SHOULD NOT BE CONSUMED?
• Oils and oil-based dressings
• Butter, margarine, lard
• Fat-enriched dairy products, heavy
cream, custard, ice cream
• Fatty meats, sausages, cold cuts,
• Liver, kidney and offal in general, Fried
• Commercial sauces, mayonnaise,
Commercially cooked foods
• Tree nuts and peanuts
• Sunflower seeds, French fries and other
• Cakes, pies, pastries, cookies, crackers
• 2 Mediterranean groups had dietary training sessions at the start
and quarterly thereafter. A 14 item dietary screener was used to
• Control group had dietary training at baseline. They only had visits
once per year in the first 3 years. Then changed to same protocol
as Mediterranean group in 2006. Used a 9 item dietary screener.
• All groups underwent general medical and 137 item validated
food-frequency questionnaire, as well as Minnesota Leisure-time
physical activity questionnaire.
• Biomarkers of compliance were measured at random at 1,3 and 5
yrs. Urinary hydroxytyrosol levels (confirm EVOO) plasma alphalinolenic acid level (confirm mixed nut intake)
14 Item Mediterranean Questionnaire
1. Do you use olive oil as main culinary fat?
2. How much olive oil do you consume in a given
day (including oil used for frying, salads, out of
house meals, etc.)?
3. How many vegetable servings do you
consume per day?
4. How many fruit units (including natural fruit
juices) do you consume per day?
5. How many servings of red meat, hamburger,
or meat products (ham, sausage, etc.) do you
consume per day? (1 serving = 100-150 g)
6. How many servings of butter, margarine, or
cream do you consume per day? (1 serving = 12
7. How many sweet/carbonated beverages do
you drink per day?
8. How much wine do you drink per week? 7 or
9. How many servings of legumes do you
consume per week? (1 serving = 150 g)
•10. How many servings of fish or shellfish do
you consume per week?
•(1 serving: 100-150 g fish, or 4-5 units or 200
•11. How many times per week do you
consume commercial sweets or pastries (not
homemade), such as cakes, cookies, biscuits,
•12. How many servings of nuts (including
peanuts) do you consume per week?
•(1 serving = 30 g)
•13. Do you preferentially consume chicken,
turkey or rabbit meat instead of veal, pork,
hamburger or sausage?
•14. How many times per week do you
consume vegetables, pasta, rice, or other
dishes seasoned with sofrito (sauce made with
tomato and onion, leek, or garlic, simmered
with olive oil)?
• Men aged 55-80
• Women aged 60-80
• No CV disease at enrollment, Needed to have
type 2 diabetes or three of the below risk factors
• Current Smoking, HTN, elevated LDL (>160), low
HDL, overweight or obese (25-40) or family
history of premature CAD.
• Exclusion criteria: Documented MI, stroke, PVD,
medical condition prohibit from following diet
(nut allergy, difficulty swallowing), HIV +,
problematic Etoh use, BMI >40.
• Primary: composite of myocardia infarction ,
stroke and death from CV causes.
• Secondary end points: stroke, MI, death from
CV causes and death from any cause.
• Between 2003-2010
• Sources of info included, repeated contact w/
subjects, family physicians, yearly review of
medical records and National death Index
• Sample size first calculated at 9000 then recalculated to 7400
w/ assumption of 6 year f/u and event rates of 8.8% and 6.6%
in control and intervention groups respectively. (for 80%
power to detect 20% risk reduction)
• Yearly analysis began after two years. All analyses performed
with intention to treat basis. Time to event data analyzed w/
cox models with two dummy variables to obtain hazard ratio.
• Trial stopped in 2011 on results from interim analysis
• Cox regression models were used to adjust for sex, age and
risk factors to account for differences between groups.
7447 total participants, Followed for a median 4.8 years.
After 1st assessment 209 dropped out, by 2010 523 lost to follow up. Drop
out rate higher in control group 11.3% vs 4.9% in Mediterranean group.
Those who dropped out were younger, higher BMI, lower adherence to
Mediterranean diet. (P<0.05 for all comparisons)
Participants in three groups had similar adherence to Mediterranean diet
at baseline and similar food intake. Scores on 14 item Mediterranean
diet screener increased for those in Mediterranean group compared to
Subjects in med group increased intake of weekly servings of Fish 0.3
servings legumes 0.4 compared to control.
Biomarkers showed good compliance with those in both Mediterranean
• Median Follow up 4.8 years. 228 primary outcome events
• 96 in EVOO group 3.8%, 83 in mixed nut group 3.4%, 109 in
control group 4.4%.
• Rates once adjusting for accrual of person years 8.1, 8.0 and
11.2 per 1000 person years. Hazard ratios 0.70 (95% CI, 0.530.91) 0.70 (95% CI, 0.53-0.94) for med diet with olive oil and
med diet with nuts compared to control (P=0.015)
• For Secondary end point only Stroke was statistically
Kaplan-Meier Estimates of
the incidence of outcome
events in the total study
Mediterranean diet had an absolute risk reduction of 3 CV events per
1000 person-years, relative risk reduction of 30%.
Risk of stroke significantly reduced in Mediterranean groups but not for
myocardial infarction or all cause mortality.
Control group did not undergo same counseling/dietary advice for first 3
More losses to follow up in control group (but those who dropped out had
more CV risk factors at baseline than those who remained in the study)
Is the study generalizable as conducted on Mediterranean individuals
with high risk of cardiovascular disease?
Results could be exaggerated as early termination trial can spuriously
inflate estimated benefit.
• Subjects on either of the two Med-Diets consumed more
EVOO, nuts, and slightly more legumes and fish. The assigned
diets resulted in a slight increase in total fat (from about 39%
to 41%) in both Med-Diet arms, versus a slight decrease (3937%) in the control group.
• Control group was supposed to follow a low fat diet but did
not adhere to this.
• Would a different control diet have yielded different results?
• Would recommend to my patients, reduced
risk of CV disease and stroke which is cause of
significant morbidity in the US
• Fairly easy to follow and sustainable.
• May decrease amount of wine recommended.
Recent article in Annals of Internal Medicine , prevention of diabetes with
Mediterranean diets. A subgroup analysis Jan 7 th, 2014
Mediterranean diet with Extra virgin olive oil reduced risk of diabetes
(40% relative risk reduction)
Study had some limitations, diabetes not primary end point of study.
Secondary analysis conducted on the subgroup w/o diabetes.
Prospective Northern Manhattan study looking at risk of CKD and
prevention with Mediterranean diet. 50% reduction in risk of stage 3 CKD.
• Ramon Estruch, M.D, Ph.D., Emilio Ros, M.D., Ph. D.,
Jordi Salas-Salvado, M.D., Ph. D. Primary Prevention of
Cardiovascular Disease with a Mediterranean Diet.
April 4, 2013, Vol 368 NO 14.
• Jordi Salas-Salvdo, MD, PhD, Monica Bullo, PhD;Ramon
Estruch, MD, PhD. Prevention of diabetes with
Mediterranean Diets. Jan 07, 2014. Volume 160 N 1.
• Willett WC, Sacks F, Trichopoulou A, Et al.
Mediterranean Diet pyramid: a cultural model for
healthy eating. Am J Clin Nutr 1995;61: suppl:1402S1406S