Presentation on theme: "Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013."— Presentation transcript:
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
Relationships between genes, environment, and development are dynamic GenotypeEnvironment Phenotype Development Childs, B. (1990). Genetic Variation and Nutrition. World Rev Nutr Diet, Vol 63.
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
The desaturation and elongation of ω3 and ω6 fatty acids (FADS 2) (FADS 1)
Ratios of dietary ω6:ω3 fatty acids in the late Paleolithic period and in current Western dietary patterns (g/d) a,b PaleolithicWestern LA:ALA AA+DTA:EPA+DPA+DHA Total a Data from Eaton et al. (1998), World Rev Nutr Diet. b Assuming an energy intake of 35:65 of animal:plant sources.
ω6:ω3 ratios in various populations Populationω6:ω3Reference Paleolithic0.79 a,b Eaton et al, 1998 Greece prior to Simopoulos, 1999 Current United States16.74Eaton et al, 1998 United Kingdom and northern Europe 15.00Sanders, 2000 Japan4.00Sugano and Hirahana, 2000 India rural5-6.1Pella et al, 2003 India urban 38-50Pella et al, 2003 a Data from Eaton et al. (1998), World Rev Nutr Diet. b Assuming an energy intake of 35:65 of animal: plant sources.
The Mediterranean Region
The Mediterranean Diets Although Greece and the Mediterranean countries are usually considered to be areas of medium-high death rates ( per 1000 inhabitants), death rates on the island of Crete have been below this level continuously since before 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 It was per 1000 inhabitants before World War II and about 10.6 in 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 Reference: Allbaugh LG. Crete: A case study of an underdeveloped area. Princeton, NJ: Princeton University Press, 1953.
The Seven Country Study Greece(Crete and Corfu)37% fat Yugoslavia(Adriatic Sea, Croatia) Italy Holland Finland U.S. Japan10% fat
GREECE SPAIN ITALY PORTUGAL U.S.EEC/OTHER OLIVE OIL CONSUMPTION PER PERSON
Life expectancy and disease rates in the United States and Greece in the 1960’s Life expectancy and disease rates GenderUnited StatesGreece Life expectancy at age 45M2731 F3334 Coronary heart diseaseM18933 F5414 Cerebrovascular diseasesM3026 F2423 Breast cancerF228 Stomach cancerM610 F36 Colorectal cancerM113 F103 Total cancersM10283 F8761
Dietary characteristics in the United States and Greece in the 1960s Dietary characteristicsUnited StatesGreece Fat (% energy)3937 Saturated fat (% energy)188 Vegetables (g/day) Fruits (g/day) Legumes (g/day)130 Breads and cereals (g/day) Potatoes (g/day) Meat* (g/day)27335 Fish (g/day)339 Eggs (g/day)4015 Alcohol (g/day)623 * Includes poultry
Reference: National Geographic, September 1969, Vol. 136, No. 3
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
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
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
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
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
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):
Fatty acid content of plants* Fatty acidPurslaneSpinachButtercrunch Lettuce Red Leaf Lettuce Mustard 14: : : :1ω :2ω :3ω :5ω :6ω Other Total fatty acid content *mg/g of wet weight Source: A.P. Simopoulos and N. Salem, Jr. New England Journal of Medicine, 315:833 (1986).
Summary: Nutritional value of purslane One serving of fresh leaves (100 g) contains: 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):
Melatonin concentrations in some edible plants Foodstuffpg/g wet wt Apple48 Carrot55 Corn, sweet1,366 Cucumber25 Onion31 Pineapple36 Purslane19,000 Spinach38 Strawberry12 Reference: Simopoulos AP, et al. J Pineal Res 2005;39:
Fatty acid levels in various chicken egg yolks (mg fatty acid/g hard-boiled egg yolk) FATTY ACIDGREEK EGG SUPERMARKET EGG Saturated fats 14: : : : : TOTAL Mono-unsaturated fats 16:1ω : :1ω :1ω9-- 24:1ω TOTAL FATTY ACIDGREEK EGG SUPERMARKET EGG Omega-6 fatty acids 18:2ω :3ω :2ω :3ω :4ω :4ω :5ω TOTAL Omega-3 fatty acids 18:3ω :3ω :5ω :5ω :6ω TOTAL P40.68= =0.44Omega = =19.4 S Omega Simopoulos AP and Salem N Jr: n-3 fatty acids in eggs from range-fed Greek chickens. N Engl J Med 321:1412, 1989.
Fatty acid composition of selected cheeses (amount in grams/100 grams, edible portion) 2% Milk CheddarAmericanSwiss Greek Myzithra Greek 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 mg10 mg Eicosapentaenoic Acid mg14 mg Docosapentaenoic Acid mg23 mg Docosahexaenoic Acid mg5.1 mg Simopoulos AP. Mediterranean Diets: What is So Special About the Diet of Greece? The Scientific Evidence. J Nutr 2001;131:3065S-3073S.
Fatty acid composition of snails Origin18:018:1(9)18:2(6)18:3(3)20:2(6)20:4(6)20:5(3) Crete Greece France Weight of a snail = 10 to 15 gLipids = 0.15 to 0.19 g
Fat content and fatty acid composition of wild and cultured salmon* Wild (n=2)Cultured (n=2)Significance Fat (g/100g) 10 ± ± 0.6p < 0.01 Fatty acids (g/100 g fatty acid) 18:3ω3 1 ± :5ω3 5 ± ± :6ω3 10 ± 2 7 ± 0.1p < 0.05 Other ω3 1 3 ± ± :2ω6 1 ± ± 0.1 Other ω ± ± 0.1 Sum of ω3 20 ± 2 17 ± 0.2 Sum of ω6 2 ± ± 0.1p < 0.01 ω3:ω6 11 ± 2 6 ± 0.1p < 0.05 * X ± SD; n = number of lots; each lot consisted of one to two salmon 1 18:4ω3 + 20:3ω3 + 22:5ω3 2 20:4ω6 + 22:4ω6
Fatty acid composition of serum cholesterol esters (Percent, X ± SD) Crete (n = 92)Zutphen (n = 97)Significance 16: ± ± 0.1p < :0 0.7 ± ± 0.0p < :1ω ± ± 0.4p < :2ω ± ± 0.7p < :3ω3 0.9 ± ± 0.0p < Reference: Sandker GW et al. Serum lipids in elderly in Crete and The Netherlands. Eur J Clin. Nutr 1993;47:
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.
Cretan Mediterranean diet for prevention of coronary heart disease Renaud S et al. Am J Clin Nutr Jun;61(6 Suppl):1360S-1367S..
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: ,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
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.
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:
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.
The Components of the Metabolic Syndrome Abdominal Obesity waist circumference > 102 cm in Men and > 88 cm in Women Dyslipidemia Increase Trigylcerides > 150 mg/dl Decrease HDL < 40 mg/ dl in Men and < 50 mg/dl in Women Hypertension Blood Pressure > 130/85 mmHg Fasting Hyperglycemia 100 mg/dl
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.
ω-6/ω-3 ratio in chronic diseases Simopoulos, AP. Exp Biol Med (Maywood) Jun; 233(6): 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.
ω-6/ω-3 ratio in chronic diseases Simopoulos, AP. Exp Biol Med (Maywood) Jun; 233(6): 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.
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 Jan;111:39-44) important in visual and cognitive development
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.
ω -3’s in Healthy Subjects 33 healthy subjects, 13 M, 20 F, 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 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) :
ω -3’s in Healthy Subjects Olive Oil Fish Oil Day 1: AA/EPA = ± 8.32 mean value vs ± Day 35: AA/EPA = ± 8.87 mean value vs ± 2.60 P>0.0001
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 Before ω-3 After ω-3
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.
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):
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:
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.
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.
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.
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.
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 The Greek column food guide. The guide is based on genetic individuality, the principals of moderation, variety, proportionality, and energy intake = energy expenditure.
Reference: Minoans and Mycenaenans: Flavours of their time. Athens, Greece: Greek Ministry of Culture, National Archaeological Museum, 1999.
Interrelationships of aging: Omega-3 fatty acids and exercise AgingOmega-3’sExercise Bone Mass (Osteoporosis) ↓↑↑ Fat Mass ↑↓↓ Lean Body Mass ↓─↑ Basal Metabolic Rate ↓↑↑ Insulin Sensitivity ↓↑↑ Blood Pressure ↑↓↓ Bleeding Time ↓↑↑ Fibrinogen ?↓↓ Platelet Aggregation ?↓↓ ↑ increase↓decrease─ no change
Adequate intakes (AI) for adults Fatty AcidGrams/day (2000 kcal diet)% Energy LA (Upper Limit) LNA DHA + EPA DHA to be at least EPA to be at least TRANS-FA (Upper limit) SAT (Upper limit) 4 --< 8.0 MONOs 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.
Adequate intake (AI) for infant formula/ diet Fatty AcidPercent of Fatty Acids LA LNA1.50 AA DHA0.35 EPA 3 (Upper Limit)< 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.
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
Bernard Gesch, September 25, 2009, Volume 325, Science Magazine
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.
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.
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 5 th Century BC.