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The Great Nutrition Therapy Debate: The Mediterranean Diet

Catherine Itsiopoulos PhD APD

Associate Professor Head of Dietetics La Trobe University

DAA VIC Branch Event RMH 25 March 2011

Dr Catherine Itsiopoulos (2011)

Objectives of Seminar
1. Review of evidence of benefits of a Mediterranean diet in the dietary management of diabetes and cardiovascular disease;

2. The dietary recommendations for clients with diabetes and/or cardiovascular disease; 3. Three take home messages.

Mediterranean Diet: Which One?

There are many Mediterranean diets

7 Countries Study (Keys et al)

CHD mortality +ve association with SatF and -ve association with MonoFat

Cretan Cohort had lowest CHD Mortality linked to their diet (Med diet).

The Cretan Mediterranean Diet became the archetypal Mediterranean Diet

Food Consumption of Greek Men from Crete in the Seven Countries Study (Greek men aged 40-59; years 1960-65) Food group N Bread Cereals Potatoes Legumes Vegetables Fruit Meat Fish Eggs Cheese Milk Sugars Pastries Alcohol Other foods Total Animal foods Total plant foods Plant/Animal food ratio g/day 31 persons 380 30 190 30 191 464 35 18 25 13 235 20 0 15 107 326 1285 3.94

Plant/Animal Food Ratio of Australians is approx. 1.5-2:1

Source: Kromhout D., Keys A., Aravanis C. et al. Food Consumption patterns in the 1960s in seven countries. Am J Clin Nutr 1989;49:889-94.

Is this the typical Greek diet?

No! This is festive food

The Healthy Greek Mediterranean Diet is a 1960s Post WWII Peasant Diet

Bioactive phytochemicals
Vit C Vit E Carotenoids Phytoestrogens Phenolics Allylthiosulfinates Flavonoids Selenium N3 fatty acids: ALA and EPA DHA

Ref: Simopoulos and Sidosis. What is so special about the Greek diet? World Rev Nutr Diet 2000

Why are we still interested in the Mediterranean diet in Australia?

The Greek Migrant Paradox still exists!

Low All-Cause and CHD Mortality Rates (ABS, 2009):
Greek-born (4.5 deaths/1000 std popn.) Australian-born (6.0 deaths/1000 std popn.)

High Prevalence of CHD Risk Factors Obesity/ Hypertension/ Inactivity and Diabetes (Hodge et al, 2004; AIHW, 2006). Despite > 50 years since migration!

Published Evidence?
PubMed Search reveals 2142 published papers on Mediterranean diet (yrs:1961-2011)

Published papers

What are Health Benefits for Cardiovascular Disease?

Secondary Prevention AMI Trial

Lyon Diet-Heart Study:
605 people followed Mediterranean diet or standard treatment after heart attack. Those on Mediterranean diet had 70% reduction in risk of dying of heart disease in 2 yrs.
De Lorgeril et al, Circulation 1999

Anti-inflammatory effects MED

PREvencion con Dieta MEDiterranea (PREDIMED) trial
(5y multi-centre 1o prevention trial, 7500 participants)

Pilot of 772 subjects @ high risk of CVD:

2 MED diets (olive oil or nuts) vs low fat diet

Med diets down-regulate inflammatory biomarkers (CRP, IL-6, endothelial adhesion molecules) in addition to lowering BP, IR and dyslipidaemia.
Ref: Estruch, R. Proceedings Nutr Soc 2010;69:333-340.

What are Health Benefits for Diabetes?

Meta-Analysis of Mediterranean diet effects on Metabolic Syndrome

Systematic review of 50 studies (35 RCTs, 2 prospective and 13 crosssectional) with total 534,906 participants; Adherence to Med diet associated with:
31% risk of MetSyn RCTs showed significant improvements in MetSyn components:
-.42cm in waist; +1.17mg/dl HDL; -6.14 mg/dl TGs; -2.35 mmHg SBP & -1.58 mmHg DBP; -3.89 mg/dl Gluc

Ref: Kastorini et al. J Am Coll Cardiol. 2011 Mar 15:57(11): 1299-313.

Diabetes Prevention?: reversal of Metabolic Syndrome

Randomised trial investigating impact of the Med diet on MetabS; 180 patients with MetabS randomised to Med diet or prudent diet (LF, HCHO) At 2 yrs patients on Med diet had:
greater weight loss (-4kg vs -1kg) greater reduction in inflammatory markers (CRP, IL-6) greater reduction in IR

At 2 yrs 40/90 on Med diet still had MetabS whereas 78/90 on prudent diet still had MetabS
Esposito et al. JAMA 2004;292(12):1440-1446

Evidence from Diabetes Intervention Studies

Mediterranean diet: more sustainable weight loss and better for diabetes.

Med diet more effective on Glycaemic control In T2DM subjects

Shai: N Engl J Med, Volume 359(3).July 17, 2008.229241

Typical Cretan Daily Diet

(Itsiopoulos et al. 2010)
slice wholegrain bread with chopped tomatoes/ red onion/ olive oil and herbs

Baked fish with boiled potatoes and boiled leafy green vegetables (dandelion/ endive) Fresh fruit Red wine*

Thick bean and vegetable soup Slice wholegrain bread Greek salad: tomato/ cucumber/onion/ olive oil/ herbs + sm piece feta cheese Fresh fruit

Baklava* (*only once per week) Natural yoghurt Dried figs/ walnuts/ roasted chickpeas/ sultanas

All traditional foods provided for 12 week study period

* only for current consumers with meals, NHMRC guidelines

Food Preparation
Foods prepared in using traditional methods; Food preparation was conducted and supervised by Greek women; All foods prepared using fresh ingredients.

Theano and Anna making dolmades

Changes in Daily Food Intake on Cretan Diet

(Itsiopoulos et al., 2010)

Control Diet
23g 65g

Cretan Diet






Plant:Animal Food ratio: 1.3 vs 5.4

Changes in Nutrient Intake on Cretan Diet

(Itsiopoulos et al., 2010)
Nutrient Energy (MJ) Protein (%E) Fat (%E) CHO (%E) Folate (mg) Fibre (g) Vitamin C (mg) Control Diet 7.5 (6.2,8.8) 18.2 (16.6,19.7) 31.5 (29.3,33.7) 46.4 (43.8,48.9) 273 (225,320) 21.8 (18.2, 25.3) 91 (71, 110) Cretan Diet 9.3 (8.1, 10.6)b 13.5 (12.8,14.1)a 39.0 (37.0,40.9)a 43.5 (40.8,46.2)g 453 (368,539)a 36.2 (30.9, 41.6)a 191 (139, 243)a

a < 0.001; b <0.01; g <0.05

P = 0.012

Clinically significant change in HbA1c (of the order found in many clinical drug trials) Change of - 0.3 HbA1c% = 10% reduction in CHD Mortality in T2 diabetes

(Itsiopoulos et al., 2010)

Promotes Longevity?

Meta-Analysis of Mediterranean Diet Studies and Health Outcomes.

Systematic review of 12 international studies between 1966-2008 involving 1.5 Million people. Greater adherence to Mediterranean diet was associated with:
9% reduction in overall death; 9% reduction in cardiovascular death; 6% reduction in cancer death; 13% reduction in Parkinsons & Alzheimers;

Sofi et al, Adherence to Mediterranean diet and health status: meta-analysis. BMJ 2008:337:1344.

Mediterranean Diet impact on markers of Longevity and Oxidative Stress

192 overweight men randomly assigned to Med diet (with and without E restriction and exercise) or conventional wt loss (advice only); At 2 yrs subjects on med diets had greater changes in:
Weight Loss (-11.9kg; p<0.001) Insulin Sensitivity ( Homa) Adiponectin and 8-iso-PGF2a Other CVD risk factors ( Chol and BP)

(Esposito et al. Cardiology Research and Practice. 2011)

Wouldn't we all live longer if we lived here?

Is Genetics Important?
Greeks in Greece are becoming more Westernised and Heart Disease Risk factors are on the increase:
Kafatos et al. demonstrated significant changes in heart disease risk factors in the original Cretan Cohort at 30 years follow-up. AJCN 1997 Magkos et al investigated trends in cardiovascular risk factors among school-aged boys from Crete, Greece, 19822002 and found that boys were taller and heavier in 2002 and had a worse heart disease risk factors which may lead to early mortality. EJCN

Greek Migrants to Australia may hold the key to longevity!

Greek migrants continue to have lower all-cause and CHD mortality despite 50+ yrs since migration
(ABS, 2009).

Greek migrants have maintained important components of the traditional Greek Mediterranean diet since migration (high intakes of vegetables, cereals, nuts, legumes, fresh fruit and olive oil) but increased meat and dairy food intake (Kosmidis et al,
1980; McMichael, 1983; Powles, 1990; Kouris-Blazos, 1996).

Food Habits In Later Life study found that intake of legumes associated with 8% reduction in mortality (Blackberry, Kouris-Blazos,
Wahlqvist et al, 2004).

Adherence to Med-style diet associated with lower risk of CVD mortality (Harriss et al, 2007). MCCS

Conclusions: Prevalence of Diabetic Retinopathy was lower in Greek-born vs Australian-born men with diabetes - not explained by established risk factors. Protective effect of ethnicity may be attributed to consumption of Mediterranean diet.

Mediterranean Diet: The Low AGE Alternative

What are AGEs?

AGEs are classically formed by the Maillard Reaction (c1912) a non-enzymatic reaction between reducing sugars and proteins and fats endogenously OR exogenously; Endogenous AGEs: Early glycation of proteins e.g. HbA1c Early lipoxydation of lipids e.g. LDL, ApoB Later glycation of long lived proteins e.g. collagen, crystalline lens Endogenous AGE formation is accelerated with ageing and oxidative stress, renal failure and diabetes (hyperglycaemia)

AGEs in Foods
Exogenous AGEs: Formed in foods by Maillard reaction e.g. browning of foods through toasting/ BBQ/ grilling at high temperatures/ dry heat. Effect of cooking:
Doughnut Duck skin pre 2,590 & post 60,820 AGE U/g PRO pre 2,350 & post 236,180 AGE U/ g PRO (Koschinsky et al, 1997)

Why is the Mediterranean Diet Low in AGEs?

Low in saturated fat Moderately low in protein Focus on slow and moist method of cooking Highly plant based (low substrate)

Health Impact of AGEs

Vascular stiffening

Renal Disease

Accelerated Ageing

Myocardial dysfunction

Accelerated Diabetes Complications




The Impact of Cooking Method on the AGE Content of a Healthy Greek Diet
Authors: Nor Fadhilla Shahril, Karen Walker, Allison Hodge, Laima Brazionis, Tania Thodis, Melinda Coghlan, Josephine Forbes, Kerin ODea, Catherine Itsiopoulos.

RCT 16 healthy M and F with 4 weeks on both arms and 4 weeks washout

Randomised to Low AGE

Randomised to High AGE

Baseline Measurements

Week 4

Week 12

Low AGE Diet

Dish Chicken casserole with broad beans/ onions/garlic/tomatoes/ olive oil/herbs 1011 kU AGE/serve Cooking Method Moist slow cooking (180oC)

High AGE Diet

Dish Charcoal chicken with potato chips 5418 kU AGE/serve Cooking Method Chicken (grilled), potato chips (fried/reheated in oven)

Lamb risoni pasta bake

Meat not braised, but simmered followed by moist slow baking

Meat not braised but slowly simmered Slow baking (180oC) without browning

Lamb chops with potato chips

Lamb chop (fried/grilled), potato chips (fried/reheated in oven)

Beef steak (fried/grilled), potato chips (fried/baked) Fish (fried), potato chips (fried/reheated in oven) Fried until strongly browned Skin scorched over a flame Meat charred on a revolving spit

Beef casserole with peas, carrots, onions, potatoes and tomatoes Fish with potatoes 827 kU AGE/serve

Grilled/fried steak with potato chips Fried fish with potato chips 7897 kU AGE/serve Meatballs


Slow moist cooking (180oC in oven) without browning Raw Sliced Deli beef (no charring) or poached chicken

Red pepper Pita bread & cold cooked beef (or fresh cooked chicken)

Red peppers Souvlaki

Eggs 182 kU AGE/serve

Boiled/poached/scra mbled

Eggs 1287 kU AGE/serve


Chicken and Broad Bean Casserole

Low AGE: 1011 kU/ serve

Charcoal Chicken and Chips

High AGE: 5418 kU / serve

Change in serum AGEs (as CML**) following low and high AGE diets
Serum AGE levels following Greek AGE diets
Serum AGE levels (ng/ml)


350.00 300.00 250.00 200.00 150.00 100.00 50.00 0.00


336 298

Before LAGE

End of LAGE Diet

Before HAGE

End of HAGE

*P < 0.05 ** ELISA

Nor Fadhilla Shahril et al. (AMS Thesis)

Mighty Aphrodite

Greek Migrants Overweight but still long living?

Can the Mediterranean Diet Explain Metabolically Healthy Obesity?

Catherine Itsiopoulos1*, Laima Brazionis2, Allison Hodge3, Rachel Stoney4, Kevin Rowley5 and Kerin ODea2

432 Greek and Australian-born people aged 44-83yrs +/- type 2 diabetes Investigations included diet, body composition, blood chemistry, clinical measures and lifestyle

PCA identified 3 CVD risk factor clusters: diabetes, vascular risk, metabolically healthy obesity
In multivariate analyses, the metabolically healthy obesity factor was positively associated with Greek ethnicity (p<0.001), negatively associated with prevalent CHD (p<0.002) and positively associated with adherence to a traditional Greek Mediterranean diet (p<0.01).
Pre-diabetes and Metabolic Syndrome Conference, Spain 6-9 April 2011

The following dietary principles were derived from our experience with this dietary study :

10 Commandments of the Mediterranean diet

1. Use olive oil as the main added fat

60mls/day (3 tblsp/d)

2. Eat vegetables with every meal: include leafy greens and tomatoes

Include: 100g leafy greens

(1 cup cooked)

100g tomatoes
(1 whole med.)

200g other veggies

3. Include at least two legume meals per week

250g serve x 2/week

(1 cup cooked beans = serve)

4. Eat at least 2 serves of fish per week

150-200g serves 2 x per week Include oily fish

5. Eat Meat (beef, lamb, pork, chicken) less often (smaller portions)

6. Eat fresh fruit every day

Between meals as snacks or for dessert

7. Eat yoghurt everyday

Cheese in moderation


Choose wholegrain breads and cereals moderate portions

9. Consume wine in moderation and always with meals

1-2 glasses/day Always with meals Dont get drunk

10. Sweets for special occasions only!

small tastes

Difficult to Cook? No!

Fassoulada Fasolada Fill 5 litre pot with 3 litres cold water and add: 3 cups white canelli beans (canned OK) 2 whole finely chopped onions (300 g), 2 cloves finely chopped garlic (20 g), 3-4 stalks celery finely sliced (250g), 1 tin tomato puree (440g) and 6 tablespoons extra virgin olive oil (120ml). Simmer for 30 minutes. Add 3-4 whole diced carrots (250 g) and 1 tablespoon fresh parsley finely chopped and simmer for another 30 minutes. Add salt and pepper to taste.

A Typical Greek Meal

Bean salad
Greek Salad

Small serve meat and Risoni pasta Red pepper salad Lettuce salad

Cauliflower salad

This is how to get kilo vegetables per day!

Three take home messages

1. Prioritise improvements in metabolic profile in your patients, independent of weight loss! 2. Focus management on whole of diet cuisine approach to maximise benefits of total diet (e.g. Optimal macronutrient profile/ fatty acid profile/ antioxidant rich/ palatable and enjoyable!) 3. Empower your patients to make positive changes by focusing on simple steps (e.g. 10 step plan to Med diet....)

OR.... Put simply

1. Focus on improving metabolic health; 2. Sell a lifestyle concept; 3. Use KISS principle!

Dr Laima Brazionis (Uni Adelaide) Professor Kerin ODea (Uni SA) Theano Itsiopoulos my

Paraskevi Koutsis my
mother in law

Dr Antigone Kouris (LaTrobe) Tania Thodis (LaTrobe) Dr Karen Walker (Monash Uni) Dr Allison Hodge (Cancer Council Victoria) Mary Kaimakamis (formerly @Cancer Council Victoria) Melissa Cameron (Cancer Council)