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Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013
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Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

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Page 1: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Artemis P. Simopoulos, M.D.

President

The Center for Genetics, Nutrition and Health

Washington DC, USA

Athens, Greece

October 16, 2013

Page 2: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

The concept of positive health

Positive health requires a knowledge of man’s primary constitution (what today we would call genetics) and of the powers of various foods, both those natural to them and those resulting from human skill (today’s processed food). But eating alone is not enough for health. There must also be exercise, of which the effects must likewise be known. The combination of these two things makes regimen, when proper attention is given to the season of the year, the changes of the winds, the age of the individual and the situation of his home. If there is any deficiency in food or exercise the body will fall sick.

~Hippocrates

Page 3: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Relationships between genes, environment, and development are dynamic

Genotype Environment

Phenotype

Development

Childs, B. (1990). Genetic Variation and Nutrition. World Rev Nutr Diet, Vol 63.

Page 4: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Hypothetical scheme of fat, fatty acid (ω6 and ω3, trans and total) intake (as percent of calories from fat)

and intake of vitamins E and C (mg/d)

Simopoulos AP: Genetic variation and evolutionary aspects of diet. In: Antioxidant Status, Diet, Nutrition, and Health, Papas AM (Editor), CRC Press, Boca Raton, 1999, pp. 65-88.

Page 5: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

The desaturation and elongation of ω3 and ω6 fatty acids

(FADS 2)

(FADS 1)

Page 6: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Ratios of dietary ω6:ω3 fatty acids in the late Paleolithic period and in current Western

dietary patterns (g/d) a,b

Paleolithic Western

LA:ALA 0.70 18.75

AA+DTA:EPA+DPA+DHA 1.79 3.33

Total 0.79 16.74

aData from Eaton et al. (1998), World Rev Nutr Diet.

bAssuming an energy intake of 35:65 of animal:plant sources.

Page 7: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

ω6:ω3 ratios in various populations

Population ω6:ω3 Reference

Paleolithic 0.79 a,b Eaton et al, 1998

Greece prior to 1960 1.00-2.00 Simopoulos, 1999

Current United States 16.74 Eaton et al, 1998

United Kingdom and northern Europe

15.00 Sanders, 2000

Japan 4.00 Sugano and Hirahana, 2000

India rural 5-6.1 Pella et al, 2003

India urban

38-50 Pella et al, 2003aData from Eaton et al. (1998), World Rev Nutr Diet.

bAssuming an energy intake of 35:65 of animal: plant sources.

Page 8: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

The Mediterranean Region

Page 9: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

The Mediterranean Diets

Although Greece and the Mediterranean countries are usually considered to be areas of medium-high death rates (14.0-18.0 per 1000 inhabitants), death rates on the island of Crete have been below this level continuously since before 1930. No other area in the Mediterranean basin has had as low a death rate as Crete, according to data compiled by the United Nations in their demographic yearbook for 1948. It was 11.3-13.7 per 1000 inhabitants before World War II and about 10.6 in 1946-1948. Cancer and heart disease caused almost three times as many deaths proportionally in the United States as in Crete. The diet of Crete represents the traditional diet of Greece before 1960. Reference: Allbaugh LG. Crete: A case study of an underdeveloped area. Princeton, NJ: Princeton University Press, 1953.

Page 10: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

The Seven Country Study

Greece (Crete and Corfu) 37% fat

Yugoslavia (Adriatic Sea, Croatia)

Italy

Holland

Finland

U.S.

Japan 10% fat

Page 11: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

GREECE SPAIN ITALY PORTUGAL U.S. EEC/OTHER

OLIVE OIL CONSUMPTION PER PERSON

Page 12: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Olive Oil SamplesRegion Squalene (mg/100g) Omega-6/Omega-3

Gargaliani Messinias 412 9.21

Mani, Messinias 274 10.61

Mani, Messinias 300 9.70

Chania, Crete 436 9.33

Chania, Crete 380 10.60

Kalamata, Messinias 425 8.78

Peloponissos 435 8.84

Kalamata Area, Messinias 294 13.07

Androusa, Messinias 415 5.70

Ampelistra – Messinias-Mani 358 7.98

Messinia – Mani 446 7.44

Lesbos 299 8.37

Agora, Crete 289 10.46

Agoureleo, Crete 366 5.93

Meropi, Messinias 404 10.59

Italian 326 10.92

Italian Classic Olive Oil 300 10.46

Spanish Olive oil 512 10.29

Italian Olive oil 374 15.60

Page 13: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Fatty Acid Composition of Olive Oil

FATTY ACIDS C %

Palmitic (16) 10.8%

Palmitoleic (16) 0.3%

Stearic (18) 0.8%

Oleic (18) 81.6%

Linoleic (18) 6.1%

Linolenic (18) 0.3%

Ampelistra Olive Oil

Page 14: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Life expectancy and disease rates in the United States and Greece in the 1960’s

Life expectancy and disease rates

Gender United States Greece

Life expectancy at age 45 M 27 31

F 33 34

Coronary heart disease M 189 33

F 54 14

Cerebrovascular diseases M 30 26

F 24 23

Breast cancer F 22 8

Stomach cancer M 6 10

F 3 6

Colorectal cancer M 11 3

F 10 3

Total cancers M 102 83

F 87 61

Page 15: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Dietary characteristics in the United States and Greece in the 1960s

Dietary characteristics United States Greece

Fat (% energy) 39 37

Saturated fat (% energy) 18 8

Vegetables (g/day) 171 191

Fruits (g/day) 233 463

Legumes (g/day) 1 30

Breads and cereals (g/day) 123 453

Potatoes (g/day) 124 170

Meat* (g/day) 273 35

Fish (g/day) 3 39

Eggs (g/day) 40 15

Alcohol (g/day) 6 23

* Includes poultry

Page 16: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Reference: National Geographic, September 1969, Vol. 136, No. 3

Page 17: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.
Page 18: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Per capita consumption of the major food groups in 1962 and 1997 in Greece demonstrating important trends in the nutrition of Greeks over

a period of 35 years

Simopoulos AP, Sidossis L. What is so special about the traditional diet of Greece: the scientific evidence. In: Simopoulos AP, Visioli F (Eds). Mediterranean Diets. World Rev Nutr Diet, vol. 87, 2000, pp. 24-42.

Page 19: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Per capita consumption of meat from various sources from 1962 to 1997 in Greece showing a steady increase in meat consumption

Simopoulos AP, Sidossis L. What is so special about the traditional diet of Greece: the scientific evidence. In: Simopoulos AP, Visioli F (Eds). Mediterranean Diets. World Rev Nutr Diet, vol. 87, 2000, pp. 24-42.

Page 20: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Per capita consumption of fish and other marine products from 1962 to 1997 in Greece

Simopoulos AP, Sidossis L. What is so special about the traditional diet of Greece: the scientific evidence. In: Simopoulos AP, Visioli F (Eds). Mediterranean Diets. World Rev Nutr Diet, vol. 87, 2000, pp. 24-42.

Page 21: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Per capita calorie consumption from vegetable and animal products from 1962 to 1997 in Greece

Simopoulos AP, Sidossis L. What is so special about the traditional diet of Greece: the scientific evidence. In: Simopoulos AP, Visioli F (Eds). Mediterranean Diets. World Rev Nutr Diet, vol. 87, 2000, pp. 24-42.

Page 22: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Per capita consumption of oils from various sources from 1962 to 1997 in Greece

Simopoulos AP, Sidossis L. What is so special about the traditional diet of Greece: the scientific evidence. In: Simopoulos AP, Visioli F (Eds). Mediterranean Diets. World Rev Nutr Diet, vol. 87, 2000, pp. 24-42.

Page 23: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Nature’s nutrients: The purslane plant

Simopoulos AP et al . Common purslane: A source of omega-3 fatty acids and antioxidants. J Am College Nutr 1992;11(4):374-382.

Page 24: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Fatty acid content of plants*

Fatty acid Purslane Spinach Buttercrunch Lettuce

Red Leaf Lettuce

Mustard

14:0 0.16 0.03 0.01 0.03 0.02

16:0 0.81 0.16 0.07 0.10 0.13

18:0 0.20 0.01 0.02 0.01 0.02

18:1ω9 0.43 0.04 0.03 0.01 0.01

18:2ω6 0.89 0.14 0.10 0.12 0.12

18:3ω3 4.05 0.89 0.26 0.31 0.48

20:5ω3 0.01 0.00 0.00 0.00 0.00

22:6ω3 0.00 0.00 0.001 0.002 0.001

Other 1.95 0.43 0.11 0.12 0.32

Total fatty acid content

8.50 1.70 0.601 0.702 1.101

*mg/g of wet weight

Source: A.P. Simopoulos and N. Salem, Jr. New England Journal of Medicine, 315:833 (1986).

Page 25: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Summary: Nutritional value of purslane

One serving of fresh leaves (100 g) contains:

• 300-400 mg 18:3ω3• 12 mg alpha-tocopherol• 27 mg ascorbic acid• 2 mg beta-carotene• 15 mg glutathione

Simopoulos AP et al. Common purslane: A source of omega-3 fatty acids and antioxidants. J Am College Nutr 1992;11(4):374-382.

Page 26: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Melatonin concentrations in some edible plants

Foodstuff pg/g wet wt

Apple 48

Carrot 55

Corn, sweet 1,366

Cucumber 25

Onion 31

Pineapple 36

Purslane 19,000

Spinach 38

Strawberry 12

Reference: Simopoulos AP, et al. J Pineal Res 2005;39:331-332.

Page 27: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Fatty acid levels in various chicken egg yolks (mg fatty acid/g hard-boiled egg yolk)

FATTY ACID GREEK EGGSUPERMARKET

EGG

Saturated fats

14:0 1.10 0.70

15:0 -- 0.07

16:0 77.60 56.66

17:0 0.66 0.34

18:0 21.33 22.88TOTAL 100.66 80.65

Mono-unsaturated fats

16:1ω7 21.70 4.67

18:1 120.50 109.97

20:1ω9 0.58 0.68

22:1ω9 -- --

24:1ω9 -- 0.04

TOTAL 142.78 115.36

FATTY ACID GREEK EGGSUPERMARKET

EGG

Omega-6 fatty acids

18:2ω6 16.00 26.1418:3ω6 -- 0.2520:2ω6 0.17 0.3620:3ω6 0.46 0.4720:4ω6 5.40 5.0222:4ω6 0.70 0.3722:5ω6 0.29 1.20TOTAL 23.02 33.81

Omega-3 fatty acids

18:3ω3 6.90 0.52

20:3ω3 0.16 0.0320:5ω3 1.20 --22:5ω3 2.80 0.09

22:6ω3 6.60 1.09

TOTAL 17.66 1.73

P 40.68 = 0.4 35.55 = 0.44 Omega-6 23.02 = 1.3 33.81 = 19.4

S 100.66 80.65 Omega-3 17.66 1.73

Simopoulos AP and Salem N Jr: n-3 fatty acids in eggs from range-fed Greek chickens. N Engl J Med 321:1412, 1989.

Page 28: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Fatty acid composition of selected cheeses (amount in grams/100 grams, edible portion)

2% Milk

Cheddar American SwissGreek

MyzithraGreek

Feta

Total polyunsaturated fat

.07 g .94 g .99 g .62 g .80 g .58 g

18:2 .04 g .58 g .61 g .34 g .38 g .29 g

18:3 .03 g .36 g .38 g .28 g .30 g .20 g

Arachidonic Acid -- -- -- 14 mg 10 mg

Eicosapentaenoic Acid

-- -- -- 18 mg 14 mg

Docosapentaenoic Acid

-- -- -- 31 mg 23 mg

Docosahexaenoic Acid

-- -- -- 5.5 mg 5.1 mg

Simopoulos AP. Mediterranean Diets: What is So Special About the Diet of Greece? The Scientific Evidence. J Nutr 2001;131:3065S-3073S.

Page 29: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Fatty acid composition of snails

Origin 18:0 18:1(9) 18:2(6) 18:3(3) 20:2(6) 20:4(6) 20:5(3)

Crete 7.3 19.9 17.2 9.7 7.0 8.8 1.1

Greece 8.6 12.7 18.7 10.6 7.2 9.2 1.2

France 10.9 10.3 14.3 4.9 10.6 16.2 1.7

Weight of a snail = 10 to 15 g Lipids = 0.15 to 0.19 g

Page 30: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Fat content and fatty acid composition of wild and cultured salmon*

Wild (n=2) Cultured (n=2) Significance

Fat (g/100g) 10 ± 0.1 16 ± 0.6 p < 0.01

Fatty acids (g/100 g fatty acid) 18:3ω3 1 ± 0.1 1 ± 0.1 20:5ω3 5 ± 0.2 5 ± 0.1 22:6ω3 10 ± 2 7 ± 0.1 p < 0.05 Other ω31 3 ± 0.5 4 ± 0.1 18:2ω6 1 ± 0.1 3 ± 0.1 Other ω62 0.2 ± 0.1 0.5 ± 0.1 Sum of ω3 20 ± 2 17 ± 0.2 Sum of ω6 2 ± 0.1 3 ± 0.1 p < 0.01

ω3:ω6 11 ± 2 6 ± 0.1 p < 0.05

* X ± SD; n = number of lots; each lot consisted of one to two salmon1 18:4ω3 + 20:3ω3 + 22:5ω32 20:4ω6 + 22:4ω6

Page 31: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Fatty acid composition of serum cholesterol esters(Percent, X ± SD)

Crete (n = 92) Zutphen (n = 97) Significance

16:0

11.1 ± 0.1 11.9 ± 0.1 p < 0.001

18:0 0.7 ± 0.0 1.1 ± 0.0 p < 0.001

18:1ω9 31.0 ± 0.3 21.4 ± 0.4 p < 0.001

18:2ω6 41.9 ± 0.4 53.1 ± 0.7 p < 0.001

18:3ω3 0.9 ± 0.1 0.3 ± 0.0 p < 0.001

Reference: Sandker GW et al. Serum lipids in elderly in Crete and The Netherlands. Eur J Clin. Nutr 1993;47:201-208.

Page 32: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Omega-3 fatty acids in traditional diets

•In traditional diets, omega-3 fatty acids are found throughout the food chain

•Eggs have a ratio of omega-6:omega-3 of 1:1

•Pasta made with eggs and milk that is rich in omega-3 fatty acids is enriched in omega-3’s

•Pasta made with water and flour, or regular milk, is not enriched in omega-3’s.

Page 33: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Cretan Mediterranean diet for prevention of coronary heart disease

Renaud S et al. Am J Clin Nutr. 1995 Jun;61(6 Suppl):1360S-1367S.

.

Page 34: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Early protection against sudden death by ω3 polyunsaturated fatty acids after myocardial infarction:

Time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto

Miocardico (GISSI)-Prevenzione

Marchioli R., Barzi F., Bomba E. et al. Circulation 2002; 105: 1897-1903.

• 11,323 patients were randomly assigned to supplements of omega-3 PUFAs

• 850 mg/d- ratio of EPA:DHA = 2.1• Vitamin E = 300 mg/d• Both omega-3 and vitamin E• None (control)• On top of optimal pharmacological treatment, lifestyle advice• Survival curves for omega-3 PUFA treatment diverged early

after randomization and total mortality was significantly lowered after 3 months of treatment

• A similar significant, although delayed pattern after 6 to 8 months of treatment was observed for cardiovascular, cardiac and coronary death

Page 35: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

ω-3 PUFA + CVD

Early benefit of omega-3 polyunsaturated fatty acid (ω-3 PUFA) therapy on total mortality, sudden death, coronary heart disease (CHD) mortality, and cardiovascular mortality. Probability measurements represent relative risk (95% confidence interval). Reprinted, with permission, from Marchioli et al. MI = myocardial infarction.

Page 36: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Early protection against sudden death by ω3 polyunsaturated fatty acids after myocardial infarction: Conclusion

The early effect of low dose 850 mg/d omega-3 PUFAs on total mortality and sudden death supports the hypothesis of an antiarrhythmic effect of omega-3 fatty acids. Such a result is consistent with the wealth of evidence coming from laboratory experiments on isolated myocytes, animal models, epidemiological and clinical studies.

Marchioli R., Barzi F., Bomba E. et al. Circulation 2002; 105: 1897-1903.

Page 37: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.
Page 38: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Metabolic Syndrome

The prevalence of metabolic syndrome in the U.S. has been increasing and is particularly high for older adults and certain ethnic groups. Hispanics have the highest reported prevalence of metabolic syndrome, and are more likely to be affected by type 2 diabetes than non-Hispanic whites.

Page 39: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

The Components of the Metabolic Syndrome

•Abdominal Obesity waist circumference > 102 cm in Menand > 88 cm in Women

•DyslipidemiaIncrease Trigylcerides > 150 mg/dlDecrease HDL < 40 mg/ dl in Men and < 50 mg/dl in Women

•HypertensionBlood Pressure > 130/85 mmHg

•Fasting Hyperglycemia 100 mg/dl

Page 40: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Omega-3s and Insulin Sensitivity

Dietary intake of omega-3 fatty acids have insulin-sensitivity actions in adipose tissue and liver and improve insulin sensitivity. Genes involved in insulin sensitivity (PPAR), glucose transport (GLUT-2/GLUT-4) and insulin receptor signaling (IRS-1/IRS-2) are upregulated by omega-3 fatty acids. Moreover omega-3 fatty acids increase adiponectin, an anti-inflammatory and insulin-sensitizing adipokine, and induce AMPK phosphorylation, a fuel-sensing enzyme and a gate keeper of the energy balance.

Page 41: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

ω-6/ω-3 ratio in chronic diseases

Simopoulos, AP. Exp Biol Med (Maywood). 2008 Jun; 233(6):674-88

In the secondary prevention of cardiovascular disease, a ratio of 4/1 was associated with a 70% decrease in total mortality. A ratio of 2.5/1 reduced rectal cell proliferation in patients with colorectal cancer, whereas a ratio of 4/1 with the same amount of omega-3 PUFA had no effect. The lower omega-6/ omega-3 ratio in women with breast cancer was associated with decreased risk.

Page 42: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

ω-6/ω-3 ratio in chronic diseases

Simopoulos, AP. Exp Biol Med (Maywood). 2008 Jun; 233(6):674-88

A ratio of 2-3/1 suppressed inflammation in patients with rheumatoid arthritis, and a ratio of 5/1 had a beneficial effect on patients with asthma, whereas a ratio of 10/1 had adverse consequences. These studies indicate that the optimal ratio may vary with the disease under consideration. This is consistent with the fact that chronic diseases are multigenic and multifactorial. Therefore, it is quite possible that the therapeutic dose of omega-3 fatty acids will depend on the degree of severity of disease resulting from the genetic predisposition.

Page 43: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

ω-3’s in Development

• Maternal intake of W-3’s during pregnancy and lactation may favor the later mental development of children (Helland et al. Pediatrics. 2003 Jan;111:39-44)

• important in visual and cognitive development

Page 44: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Metabolic programming of long-term outcomes due to fatty acid nutrition in early life

Understanding of the importance of dietary fatty acids has grown beyond a simple source of energy to complex roles in regulating gene expression and cell and intracellular communication. This is important because the metabolic and neuroendocrine environment of the fetus and infant plays a key role in guiding the set point of neural receptors that regulate energy homeostasis and expression of genes that control energy storage and oxidation. Early deviations in these pathways have the potential to lead to lasting adaptations, termed metabolic programming, which may combine to increase the risk of metabolic syndrome in later life. The quality of fatty acids in human diets has undergone major changes in the last 50 years, characterized by an increase in ω-6 and decrease in ω-3 fatty acids. Evidence is accumulating to support the concept that the maternal intake of ω-6 and ω-3 fatty acids in gestation and lactation, possibly involving both excess ω-6 and inadequate ω-3 fatty acids, can impact the developing infant tissue lipids and neuroendocrine and metabolic pathways relevant to metabolic programming. Further work is needed to understand the needs for different ω-6 and ω-3 fatty acids during fetal and infant life, and their roles with respect to development of energy homeostasis and metabolism.

Page 45: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

ω-3’s in Healthy Subjects

• 33 healthy subjects, 13 M, 20 F, 22-51 yrs (mean =33 ±7yrs)

Subjects were tested at the beginning of the

experiment and after 35 days. Supplemented with 4

grams of fish oil (1.60g EPA + 0.80 DHA + 0.4g of other

W-3’s).

Control consisted of 4g olive oil (indistinguishable by

packaging, shape or taste).

Fontani et al. Eur J Clin Invest. Nov; 35 (11) : 691-699

Page 46: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

ω-3’s in Healthy Subjects

Olive Oil Fish Oil

Day 1: AA/EPA = 16.39 ± 8.32 mean value vs. 16.17 ± 10.63

Day 35: AA/EPA = 14.26 ± 8.87 mean value vs. 4.29 ± 2.60

P>0.0001

Page 47: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Profile of Mood States (POMS). Comparison before and after Omega-3 supplementation. Mean ± standard error (subjects n = 33). Paired samples t-test: **** P < 0·0001, *** P < 0·001, ** P < 0·01, * P < 0·04. Fontani et al 2005.

Before ω-3

After ω-3

Page 48: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

ω-3’s in Healthy Subjects

The mood profile improved after W-3’s with increased

vigor and reduced anger, anxiety and depression

states. An EEG frequency shift towards the theta and

alpha band were recorded in all tests after W-3’s

Conclusion W-3 supplementation is associated with an

improvement of attentional and physiological

functions, particularly those involving complex cortical

processing.

Page 49: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

25-year CHD mortality in the Seven Countries Study

Reference: de Lorgeril, M., Salen, P. Mediterranean type of diet for the prevention of coronary heart disease. A global perspective from the Seven Countries Study to the most recent dietary trials. Int J Vitam Nutr Res 2001; 71(3): 166-172.

Page 50: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Mediterranean-inspired diet: Conclusion

A Mediterranean-inspired diet (MID) reduces the number of platelets and leukocytes and VEGF concentrations in healthy subjects. This may be linked to higher serum concentrations of omega-3 fatty acids, which promote a favorable composition of phospholipids.

Ambring A, Johansson M, Axelsen M, et al., Am J Clin Nutr 2006; 83: 575-81.

Page 51: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

A Reduced Omega-6/Omega-3 Fatty Acid Dietary Ratio Increases Adiponectin Concentration and

Fatty Acid Oxidation in Healthy Subjects

Guebre-Egziabher et al. carried out a ten week dietary intervention in 17 healthy subjects. The dietary intervention decreased the LA/ALA ratio from 32.2 (s.d. 3.7) versus post-intervention 2.2 (s.d. 0.1).

Guebre-Egziabher F, et al. Nutritional intervention to reduce the n-6/n-3 fatty acid ratio increases adiponectin concentration and fatty acid oxidation in healthy subjects. Eur J Clin Nutr 2007.

Page 52: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

A Reduced Omega-6/Omega-3 Fatty Acid Dietary Ratio Increases Adiponectin Concentration and

Fatty Acid Oxidation in Healthy Subjects

Dietary intake, euglycemic hyperinsulinemic clamp, indirect calorimetry, lipid profile, hormones, inflammatory markers and erythrocyte membrane fatty acid composition were measured before and at the end of the intervention period. Comparisons are between baseline and post-intervention levels.

Guebre-Egziabher F, et al. Nutritional intervention to reduce the n-6/n-3 fatty acid ratio increases adiponectin concentration and fatty acid oxidation in healthy subjects. Eur J Clin Nutr 2007.

Page 53: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

A Reduced Omega-6/Omega-3 Fatty Acid Dietary Ratio Increases Adiponectin Concentration and

Fatty Acid Oxidation in Healthy Subjects

There were significant decreases in glucose oxidation rate, in LDL and TNF-a with a non significant decrease in IL-6 and CRP. Most importantly, there was a significant increase in adiponectin and fatty acid oxidation, which may explain the decrease in adipose tissue noted by Couet et al., and the weight loss noted by Hill et al. with increased intakes of dietary omega-3 fatty acids.

Guebre-Egziabher F, et al. Nutritional intervention to reduce the n-6/n-3 fatty acid ratio increases adiponectin concentration and fatty acid oxidation in healthy subjects. Eur J Clin Nutr 2007.

Page 54: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

A Reduced Omega-6/Omega-3 Fatty Acid Dietary Ratio Increases Adiponectin Concentration and

Fatty Acid Oxidation in Healthy Subjects

The Guebre-Egziabher et al. study showed that a decreased omega-6/omega-3 fatty acid ratio can be achieved with simple dietary counseling, resulting in multiple potentially favorable effects on the metabolic and inflammatory profiles of the subjects.

Guebre-Egziabher F, et al. Nutritional intervention to reduce the n-6/n-3 fatty acid ratio increases adiponectin concentration and fatty acid oxidation in healthy subjects. Eur J Clin Nutr 2007.

Page 55: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Greek Column Food Guide

Simopoulos AP, Sidossis L. What is so special about the traditional diet of Greece: the scientific evidence. In: Simopoulos AP, Visioli F (Eds). Mediterranean Diets. World Rev Nutr Diet, vol. 87, 2000, pp. 24-42.

The Greek column food guide. The guide is based on genetic individuality, theprincipals of moderation, variety, proportionality, and energy intake = energy expenditure.

Page 56: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Reference: Minoans and Mycenaenans: Flavours of their time. Athens, Greece: Greek Ministry of Culture, National Archaeological Museum, 1999.

Page 57: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Synergistic effects: Omega-3 fatty acids and exercise

Omega-3’s Exercise

Basal Metabolic Rate ↑↑ ↑↑

Insulin Sensitivity ↑↑ ↑↑

Fat Mass ↓↓ ↓↓

Blood Pressure ↓↓ ↓↓

Bleeding Time ↑↑ ↑↑

Fibrinogen ↓↓ ↓↓

Platelet Aggregation ↓↓ ↓↓

Plasma Viscosity ↓↓ ↓↓

Arrhythmias ↓↓ ↓↓

Nitric Oxide ↑↑ ↑↑

Depression ↓↓ ↓↓

Catecholamines ↓↓ ↓↓↑ increase ↓decrease

Page 58: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Interrelationships of aging: Omega-3 fatty acids and exercise

Aging Omega-3’s Exercise

Bone Mass (Osteoporosis)

↓ ↑ ↑

Fat Mass ↑ ↓ ↓Lean Body Mass ↓ ─ ↑Basal Metabolic Rate ↓ ↑ ↑Insulin Sensitivity ↓ ↑ ↑Blood Pressure ↑ ↓ ↓Bleeding Time ↓ ↑ ↑Fibrinogen ? ↓ ↓Platelet Aggregation ? ↓ ↓

↑ increase ↓decrease ─ no change

Page 59: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Adequate intakes (AI) for adults

Fatty Acid Grams/day (2000 kcal diet) % Energy

LA 4.44 2.0

(Upper Limit)1 6.67 3.0

LNA 2.22 1.0

DHA + EPA 0.65 0.3

DHA to be at least2 0.22 0.1

EPA to be at least 0.22 0.1

TRANS-FA

(Upper limit)3 2.00 1.0

SAT

(Upper limit)4 -- < 8.0

MONOs5 -- --

1. Although the recommendation is for AI, the Working Group felt that there is enough scientific evidence to also state an upper limit (UL) for LA of 6.67 g/d based on a 2000kcal diet or of 3.0% of energy. 2. For pregnant and lactating women, ensure 300 mg/d of DHA.3.Except for dairy products, other foods under natural conditions do not contain trans-FA. Therefore, the Working Group does not recommend trans-FA to be in the food supply as a result of hydrogenation of unsaturated fatty acids or high temperature cooking (reused frying oils).4.Saturated fats should not comprise more than 8% of energy.5. The Working Group recommended that the majority of fatty acids are obtained from monounsaturates. The total amount of fat in the diet is determined by the culture and dietary habits of people around the world (total fat ranges from 15-40% of energy) but with special attention to the importance of weight control and the reduction of obesity.

Page 60: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Adequate intake (AI) for infant formula/ diet

Fatty Acid Percent of Fatty Acids

LA1 10.00

LNA 1.50

AA2 0.50

DHA 0.35

EPA3

(Upper Limit) < 0.10

1. The Working Group recognizes that in countries like Japan, the breast milk content of LA is 6-10% of fatty acids and the DHA is higher, about 0.6%. The formula/ diet comparison described here is patterned on infant formula studies in Western countries.

2. The Working Group endorsed the addition of the principal long chain polyunsaturates, AA and DHA, to all infant formulas.

3. EPA is a natural constituent of breast milk, but in amounts more than 0.1% in infant formula may antagonize AA and interfere with infant growth.

Page 61: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.
Page 62: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.
Page 63: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

How to get 2 grams of alpha-linolenic acid (ALA) from foods

• 100 grams of canola oil = 8 grams of ALA• 2 tablespoons of canola oil = 2 grams of ALA• 100 grams of canola oil based margarine = 5 grams

of ALA• 6 teaspoons of canola oil based margarine = 35

grams of margarine = 2 grams of ALA• 4 to 5 English walnuts = 2 grams of ALA• Eat walnuts and olive oil daily• 100 grams of ground flaxseed = 23 grams ALA• 1 tablespoon of ground flaxseed = 2 grams ALA• 100 grams of purslane = 400 mg ALA• 500 grams of purslane = 2 grams of ALA

Page 64: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.
Page 65: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Bernard Gesch, September 25, 2009 , Volume 325, Science Magazine

Page 66: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Recommendations

The time has come for Greeks to return to their traditional composition of the food supply. The scientific evidence for a balanced omega-6/omega-3 fatty acid ratio as it was prior to 1960 is robust.

Page 67: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Recommendations

Changing from the French or Swedish diets to one that is similar to the traditional diet of Greece (Greek Mediterranean diet) has been shown to be possible and to decrease cardiometabolic risk factors and inflammation.

Page 68: Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013.

Recommendations

Greece should take a leadership position in establishing 1 or 2 Centers on Genetics Nutrition and Fitness for Health to combat obesity and chronic non-communicable diseases and define the healthy diet for the Greek population through studies on Genetics, Physiology, Metabolism, Nutrition and Physical Activity, thus implementing the Concept of Positive Health as articulated by Hippocrates in 5th Century BC.