“The Great Nutrition

Therapy Debate:

The Mediterranean Diet”

Catherine Itsiopoulos PhD APD

Associate Professor

Head of Dietetics

La Trobe University

© Dr Catherine Itsiopoulos (2011)

DAA VIC Branch Event RMH 25 March 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)

1960s-current

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 DietFood Consumption of Greek Men from Crete in the

Seven Countries Study

(Greek men aged 40-59; years 1960-65)

Food group g/day

N 31 persons

Bread 380

Cereals 30

Potatoes 190

Legumes 30

Vegetables 191

Fruit 464

Meat 35

Fish 18

Eggs 25

Cheese 13

Milk 235

Sugars 20

Pastries 0

Alcohol 15

Other foods 107

Total Animal foods 326

Total plant foods 1285

Plant/Animal food ratio 3.94

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.

Plant/Animal Food

Ratio of

Australians

is approx. 1.5-2:1

Is this the typical

Greek diet?

No! This is festive food

The Healthy

Greek Mediterranean Diet is a

1960s Post WWII Peasant Diet

Ref: Simopoulos and Sidosis. What is so special about the Greek diet?

World Rev Nutr Diet 2000

Bioactive phytochemicals•Vit C

•Vit E

•Carotenoids

•Phytoestrogens

•Phenolics

•Allylthiosulfinates

•Flavonoids

•Selenium

•N3 fatty acids:

ALA and EPA DHA

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)

Pu

blis

he

d p

ap

ers

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 cross-

sectional) 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.

Shai: N Engl J Med, Volume 359(3).July 17, 2008.229–241

Med diet more

effective on

Glycaemic control

In T2DM subjects

Typical Cretan Daily Diet(Itsiopoulos et al. 2010)

• Breakfast: – slice wholegrain bread with chopped tomatoes/ red onion/ olive

oil and herbs

• Lunch:– Baked fish with boiled potatoes and boiled leafy green

vegetables (dandelion/ endive)

– Fresh fruit

– Red wine*

• Dinner:– Thick bean and vegetable soup

– Slice wholegrain bread

– Greek salad: tomato/ cucumber/onion/ olive oil/ herbs + sm piece feta cheese

– Fresh fruit

• Snacks:– 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 Cretan Diet

23g 106g

162g 466g

149g45g

6g 65g

Plant:Animal Food ratio: 1.3 vs 5.4

Changes in Nutrient Intake on Cretan Diet(Itsiopoulos et al., 2010)

Nutrient Control Diet Cretan Diet

Energy (MJ) 7.5 (6.2,8.8) 9.3 (8.1, 10.6)b

Protein (%E) 18.2 (16.6,19.7) 13.5 (12.8,14.1)a

Fat (%E) 31.5 (29.3,33.7) 39.0 (37.0,40.9)a

CHO (%E) 46.4 (43.8,48.9) 43.5 (40.8,46.2)g

Folate (mg) 273 (225,320) 453 (368,539)a

Fibre (g) 21.8 (18.2, 25.3) 36.2 (30.9, 41.6)a

Vitamin C (mg) 91 (71, 110) 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 Parkinson‟s & Alzheimer‟s;

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, 1982–2002 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

2005

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 pre 2,590 & post 60,820 AGE U/g PRO

– Duck skin 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

AGEs

Vascular stiffening

Myocardial dysfunction

Accelerated Diabetes Complications

Retinopathy Nephropathy Neuropathy

Renal Disease

Accelerated Ageing

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 O‟Dea, Catherine Itsiopoulos.

Randomised

to Low AGE

Randomised

to High AGE

Baseline

MeasurementsWeek 4 Week 12

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

Low AGE Diet High AGE Diet

Dish Cooking Method Dish Cooking Method

Chicken casserole with

broad beans/

onions/garlic/tomatoes/

olive oil/herbs

1011 kU AGE/serve

Moist slow cooking

(180oC)

Charcoal chicken

with potato chips

5418 kU

AGE/serve

Chicken (grilled),

potato chips

(fried/reheated in

oven)

Lamb risoni pasta bake Meat not braised, but

simmered followed

by moist slow baking

Lamb chops with

potato chips

Lamb chop

(fried/grilled), potato

chips (fried/reheated

in oven)

Beef casserole with peas,

carrots, onions, potatoes

and tomatoes

Meat not braised but

slowly simmered

Grilled/fried steak

with potato chips

Beef steak

(fried/grilled), potato

chips (fried/baked)

Fish with potatoes

827 kU AGE/serve

Slow baking (180oC)

without browning

Fried fish with

potato chips

7897 kU

AGE/serve

Fish (fried), potato

chips (fried/reheated

in oven)

Meatballs Slow moist cooking

(180oC in oven)

without browning

Meatballs Fried until strongly

browned

Red pepper Raw Red peppers Skin scorched over a

flame

Pita bread & cold cooked

beef (or fresh cooked

chicken)

Sliced Deli beef (no

charring) or poached

chicken

Souvlaki Meat charred on a

revolving spit

Almonds Raw Almonds Roasted

Eggs

182 kU AGE/serve

Boiled/poached/scra

mbled

Eggs

1287 kU

AGE/serve

Fried

Chicken and Broad Bean

Casserole

Low AGE: 1011 kU/ serve

Charcoal Chicken and Chips

High AGE: 5418 kU / serve

Serum AGE levels following Greek AGE diets

327

277298

336

0.00

50.00

100.00

150.00

200.00

250.00

300.00

350.00

400.00

Before LAGE End of LAGE Before HAGE End of HAGE

Diet

Seru

m A

GE

levels

(n

g/m

l)

Change in serum AGEs (as CML**)

following low and high AGE diets

*

*

*P < 0.05

** ELISA

PRELIMINARY DATANor 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 O’Dea2

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

“10 Commandments”

of the

Mediterranean diet

The following dietary principles were derived from our

experience with this dietary study :

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

8. Choose wholegrain breads

and cereals “moderate portions”

9. Consume wine in moderation and

always with meals

•1-2 glasses/day

•Always with meals

•Don‟t 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

Greek Salad

Bean salad

Red pepper

salad

Lettuce salad

Cauliflower salad

Small serve meat and

Risoni pasta

This is how to get ½ 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!

Acknowledgements• Dr Laima Brazionis (Uni

Adelaide)

• Professor Kerin O‟Dea (Uni SA)

• Theano Itsiopoulos my mum

• 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)