Journal Club

Mediterranean Diet

Interesting Fad Diets in History • 1820 lord Byron Vinegar and water

diet • 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 cookies)

• 1992 Dr. Atkins diet publishes book Diet Revolution

• 2000 Macrobiotic diet popular in Hollywood

• 2011 HCG diet + 500-800 calorie a day regime

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

1945• 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

Prior studies • Meta Analysis of prospective

observational studies published by Sofi 2008. Looked at 12 studies 1,574,299 patients for 3-18 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 (13%)

• Lyon heart study 1994 showed lower mortality in the group who’s diet was enriched with Alpha-linolenic Acid. (found in walnuts)

• No Randomized controlled trials

Design

• 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,

hazelnuts, almonds) • Group 3: control diet instructed to follow low fat diet • No caloric restriction or physical activity promoted in any

group• Olive oil and nuts were donated. Non food gift items

given to control group.

The Diet

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

products• • 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

• REMOVE FAT• • Do not smear bread or toast with butter,

margarine, oil or other fat spreads• • Remove all visible fat from meat before

cooking• • 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,

beacon, cracklings• • Liver, kidney and offal in general, Fried

foods• • Commercial sauces, mayonnaise,

Commercially cooked foods• • Tree nuts and peanuts• • Sunflower seeds, French fries and other

salty snacks• • Cakes, pies, pastries, cookies, crackers

The Protocol • 2 Mediterranean groups had dietary training sessions at the start

and quarterly thereafter. A 14 item dietary screener was used to assess adherence.

• 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 alpha-linolenic 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 g)

• 7. How many sweet/carbonated beverages do you drink per day?

• 8. How much wine do you drink per week? 7 or more glasses

• 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 g shellfish)•11. How many times per week do you consume commercial sweets or pastries (not homemade), such as cakes, cookies, biscuits, or custard?•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)?

Subjects • 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.

End Points

• 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

Statistical Analysis

• 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.

Results • 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 control group.

• 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 groups.

End Point

• Median Follow up 4.8 years. 228 primary outcome events occurred.

• 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, 0.53-0.91) 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 significant.

Kaplan-Meier Estimates of the incidence of outcome events in the total study population

Discussion• 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

yrs. • 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.

Discussion cont

• 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 (39-37%) 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?

Conclusion

• 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.

Other studies• Recent article in Annals of Internal Medicine , prevention of diabetes with

Mediterranean diets. A subgroup analysis Jan 7th, 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.

Questions

References

• 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:1402S-1406S