Evolutionary Medicine Frankfurt

Mismatch between Modern Lifestyle and Ancient Genes as the key for Western Diseases Pedro Bastos Frankfurt, October 16, 2009

The Modern World

CVD
Epithelial Cell Cancers
Hypertension
T2 Diabetes & Metabolic Syndrome
Osteoporosis
Autoimmune diseases
Karim-Kos HE, et al. Eur J Cancer . 2008 Jul;44(10):1345-89. Funada S, et al. Prev Med . 2008 Jul;47(1):66-70. Cordain L et al. Am J Clin Nutr . 2005 Feb;81(2):341-54. Gu Q, et al. Ann Epidemiol .2008 Apr;18(4):302-9. Callow AD. Vascul Pharmacol . 2006 Nov;45(5):302-7. American Heart Association. Heart Disease and Stroke Statistics -- 2009 Update. WHO. Global Database on Body Mass Index . http://www.who.int/bmi/index.jsp. Accessed 2008/12/09 Rose N R, Mackay IR. The auto-immune diseases . Academic Press, 2006. Müller-Nordhorn J, et al. Eur Heart J . 2008 May;29(10):1316-26. Kanis, J.A., et al. J Bone Miner Res 2002;17(7):1237-44 Chronic Degenerative Diseases Reach epidemic proportions

“ Nothing in biology makes sense except in the light of evolution.”
— Theodosius Dobzhansky
Dobzhansky TG: Nothing in biology makes sense except in the light of evolution. Am Biol Teacher 35:125-129, 1973

Exercise, sleep, sun exposure and dietary needs of every living organism are genetically determined.
Cordain L et al. Am J Clin Nutr . 2005 Feb;81(2):341-54 Booth FW, Lees SJ. Physiol Genomics . 2007 Jan 17;28(2):146-57. Parra EJ. Am J Phys Anthropol . 2007;Suppl 45:85-105

Evolutionary template
Similar to all species, contemporary humans are genetically adapted to the environment that their ancestors survived in and that consequently conditioned their genetic makeup.
Cordain L et al. Am J Clin Nutr . 2005 Feb;81(2):341-54

Hominin lineage Wood B. Nature 2002:418:133-35 Palaeolithic

During the Paleolithic:
Increase in the amount of animal foods
 PUFA for Brain Development ( DHA, AA )
Cordain L, Watkins BA, Mann NJ. World Rev Nutr Diet . 2001;90:144-61. Cunnane SC, et al. Am J Hum Biol . 2007 Jul-Aug;19(4):578-81. Savannah hypothesis vs Aquatic hypothesis

160 to 195,000 y ago:
Appear in Africa the first hominins anatomically identical to modern humans
McDougall I, et al. Nature 2005;433:733–736 White TD, et al. Nature 2003;423:742–747 Ethiopia From Liu H, et al., 2006

All humans living in Europe, Asia, Oceania and America share a common
African origin
Less genetic diversity as we move away from Africa
Relethford JH. Heredity. 2008 Jun;100(6):555-63. Manica A, et al. Nature ; 2007; 448(7151):346-8 Liu H, et al. Am J Hum Genet . 2006 Aug;79(2):230-7 Conrad D, et al. Nat Genet 2006; 38: 1251–1260 RAY N, et al. Genome Res 2005; 15:1161–1167 Macaulay V, et al. Science 2005; 308(5724):1034-6 Currat M, Excoffier L. PLoS Biology 2004; 2: 2264–2274 Jakobsson M, et al. Nature 2008; 451(7181):998-1003 Hellenthal G, Auton A, Falush D. PLoS Genet . 2008 May 23;4(5):e1000078 Ramachandran S, et al. Proc Natl Acad Sci U S A . 2005 Nov 1;102(44):15942-7 Prugnolle F, Manica A, Balloux F. Current Biology 2005; 15:R159–R160 Cavalli-Sforza LL, Feldman MW. Nat Genet 2003; 33:266–275 Tishkoff S, Williams S. Nat Rev Genet 2002; 3: 611–621 Harpending, H, Rogers, AR. Annu Rev Genomics Hum Genet 2000; 1:361–385 Ethiopia From Liu H, et al., 2006

Liu H, et al. Am J Hum Genet . 2006 Aug;79(2):230-7 Population of Homo Sapiens of ~1,000 individuals emigrated for Eurasia ~56,000 years ago and then inhabit the entire planet

Pre-agricultural diets & lifestyles
No universal diet or lifestyle existed!
It varied due to differences in
Geography
Ecologic niche
Season
Glaciations
Cordain L et al. Am J Clin Nutr . 2005 Feb;81(2):341-54

Obligate Physical Activity Cordain L, et al. Int J Sport Med 1998;19:328-335. Vital for survival

Sleep-Wake Cycle Wiley TS, Formby B, Lights Out – Sleep, Sugar and Survival . Pocket Books, New York, 2000 Virtually everyone on the planet until the development of artificial light, slept in sync with the daily variation in light exposure .

Regular sun exposure Chaplin G, Jablonski NG. Am J Phys Anthropol 2009 Aug;139(4):451-61 Optimal cutaneous generation of Vit D-3 Equator 20 N 20 S

Pre-agricultural diets

Plants
Roots and tubers
Berries
Fruits
Nuts
Cordain L et al. Am J Clin Nutr . 2005 Feb;81(2):341-54 Vegetable sources

Wild terrestrial animals
(muscle tissue, fat and organs)
Fowl
Insects
Fish & Seafood
Cordain L et al. Am J Clin Nutr . 2005 Feb;81(2):341-54 Animal sources

What Prehistoric Hunter-Gatherers didn’t eat

Cereal grains Isolated sugar (except honey) Salt Milk & Dairy Vegetable oils Cordain L. Implications of Plio-Pleistocene Hominin Diets for Modern Humans. In: Early Hominin Diets: The Known, the Unknown, and the Unknowable . Ungar, P (Ed.), Oxford University Press, Oxford, 2006, pp 363-83 Alcohol Fatty Domestic meat Legumes

Cordain L et al. Am J Clin Nutr . 2005 Feb;81(2):341-54. Dubreuil L. Journal of Archaeological Science 2004; 31(11): 1613-1629. Bar-Yosef O. Evol Anthropol 1998;6:159 –77. ~ 10,000 years ago "Agricultural Revolution" occurred in the Near East and then spread to northern Europe by ~ 5,000 years ago.

Neolithic (10,000 to 5,500 yrs ago) Food Introductions Years ago 0 66 100 133 167 200 233 267 300 333 Human Generations (30 yrs) present 33 SUCROSE WHEAT, BARLEY & RICE DOMESTICATED ~10,000 YRS AGO FIRST DAIRYING EVIDENCE & MAIZE DOMESTICATED ~9,000 YRS AGO SHEEP, GOATS, COWS DOMESTICATED WINE & BEER FIRST SALT MINES Cordain L et al. Am J Clin Nutr . 2005 Feb;81(2):341-54 Evershed RP, et al. Nature . 2008 Sep 25;455(7212):528-31 From Cordain L, with permission

Industrial Revolution (~200 yrs ago) Year 0 2 3 4 5 6 7 Human Generations (30 yrs) 2008 1 REFINED GRAINS HFCS HYDROGENATED OILS SUCROSE REFINED VEGETABLE OILS FEEDLOT PRODUCED MEATS Cordain L. Implications of Plio-Pleistocene Hominin Diets for Modern Humans. In: Early Hominin Diets: The Known, the Unknown, and the Unknowable . Ungar, P (Ed.), Oxford University Press, Oxford, 2006, pp 363-83 From Cordain L, with permission

Industrial Revolution Processed Foods – The 20 th Century Year O 2 3 4 Human Generations (30 yrs) 2008 1 1900: HERSHEY’S CHOCOLATE BAR 1902: PEPSI 1906: KELLOGS CORN FLAKES 1911: CRISCO 1913: OREO COOKIE 1921: WONDERBREAD 1928: RICE KRISPIES 1932: CORN CHIPS 1941: M&M’s 1952: SUGAR FROSTED FLAKES 1969: PRINGLES CHIPS Cordain L. Implications of Plio-Pleistocene Hominin Diets for Modern Humans. In: Early Hominin Diets: The Known, the Unknown, and the Unknowable . Ungar, P (Ed.), Oxford University Press, Oxford, 2006, pp 363-83 From Cordain L, with permission

What are we currently eating?

USA Cordain L et al. Am J Clin Nutr . 2005 Feb;81(2):341-54

Cew INE, December, 2006 Portugal Cereal Grains & tubers Dairy

Generations in the Evolution of Humanity
Generations % Total
Homo habilis (1 st Homo species ) 76,667 100.0
Homo erectus (modern body size) 60,000 78.2
Modern Homo sapiens (cranial size) 6,666 8.7
Agricultural Revolution (cereals) 333 0.4
Advent of Dairying (milk, cheese etc) 200 0.26
Industrial Revolution (refined sugars, 7 0.009
refined cereals, oils, canned food)
Food Processing Industry (junk food) 4 0.005
Conclusion : 99.6% of all Homo generations had no evolutionary experience with commonly consumed modern foods introduced during the Neolithic! Cordain L. Potential Therapeutic Characteristics of Pre-agricultural Diets in the Prevention and Treatment of Multiple Sclerosis. Direct MS (Multiple Sclerosis) of Canada Conference. Calgary, Canada, October 2007 From Cordain L, with permission

"Survival will be neither to the strongest of the species, nor to the most intelligent, but to those most adaptable to change." C. Darwin

Human Activity Patterns Following the Development of Agriculture

For most early farmers energy intake was still obligatorily linked to activity levels
Agriculture allowed for societal stratification
ENERGY IN ENERGY OUT Cordain L. How Much Exercise Is Enough? An Evolutionary Perspective . PNI Master Program, Girona, Spain, May, 2009 From Cordain L, with permission A few privileged elite did not have to work to obtain food

Evolution of Human Activity Neolithic Labor Saving Inventions Years ago O 67 100 133 167 200 233 267 300 333 Human Generations present 33 ~2,000 YRS FIRST WATER MILL FIRST BRONZE TOOLS ~6,5000 YRS AGO WHEEL ~5,500 YRS AGO COWS/OX DOMESTICATED – DRAFT ANIMAL HORSE DOMESTICATED ~6,000 YRS AGO ~3,000 YRS AGO FIRST IRON TOOLS The Beginning of the Agricultural “Revolution” Cordain L. How Much Exercise Is Enough? An Evolutionary Perspective . PNI Master Program, Girona, Spain, May, 2009 From Cordain L, with permission

Evolution of Human Activity: Labor Saving Devices (Industrial Revolution) Year O 3 4 5 6 7 Human Generations 2 TELEPHONE (1876) MODEL T FORD (1908) AIRPLANE (1903) STEAM ENGINE (1775) COMMERCIAL ELECTRICITY (1882) FIRST LOMOTIVE SERVICE (1829) 1 FIRST TV (1927) 1974 FIRST PC Cordain L. How Much Exercise Is Enough? An Evolutionary Perspective . PNI Master Program, Girona, Spain, May, 2009 From Cordain L, with permission

Modern Exercise Habits

Estimated Hominin Energy Expenditures Since the Appearance of the Human Genus Kcal/kg/day 2.2 MYA 1.7 MYA 0.6 MYA Modern Modern Cordain L, et al. Int J Sport Med 1998;19:328-335.

Modern Sleep Habits

Virtually every human being in industrialized countries is exposed to light at atypical biologic times Disrupting the normal circadian rhythm . A significant percentage of westernized populations sleeps less than 7 hours per night. The New way The Old way

Number of Months that UVB from sunshine cannot produce vitamin D3 in skin Vit D all year Theoretical skin colour Vit D all year Number of Months that UVB from sunshine cannot produce vitamin D3 in skin Number of Months that UVB from sunshine cannot produce vitamin D3 in skin Number of Months that UVB from sunshine cannot produce vitamin D3 in skin Number of Months that UVB from sunshine cannot produce vitamin D3 in skin Months with no Vitamin D synthesis Wavelengths of UVB for maximal synthesis of Vit D = 290-315 nanometers, which occurs below 35º latitude Chaplin G, Jablonski NG. Am J Phys Anthropol 2009 Aug;139(4):451-61 No Vit D for 6 mo/year No Vit D for 6 mo/year No Vit D for 1-6 mo/year No Vit D for 1-6 mo/year

Consequences

Nutritional Consequences

Macronutrient composition

Eaton SB. Proc Nutr Soc. 2006 Feb;65(1):1-6.
Cordain L et al. Am J Clin Nutr . 2005 Feb;81(2):341-54.
.
O'Keefe JH Jr, Cordain L. Mayo Clin Proc 2004 Jan;79(1):101-8.
Bastos, P . Unpublished data
Carbs (%) Lipids (%) Protein (%) Fiber (g) USA 51,8 32,8 15,4 15,1 Lisbon 49 35 16 14 Palaeolithic 22-40 28-58 19-35 > 30 Atkins Diet 4-26 51-78 18-23 Low Ornish Diet 80 <10 <15 High Mediterranean diet 50 27-34 16-23 High American Heart Association 55-60 < 30 15 25-30 Institute of Medicine 45-65 20-35 10-35 25 (M) 38 (H) WHO - 15-30 10-15 27-40

Decrease in Fiber intake

Fiber content of food groups Total Fiber (grams) 1000 kcal sample (n = 3) (n = 8) (n = 20) (n = 20) Cordain L et al. Am J Clin Nutr . 2005 Feb;81(2):341-54.

Consequences of Low Fiber Diet
Constipation,
Appendicitis,
Hemorrhoids,
Deep vein Thrombosis,
Varicoses veins
Diverticulitis,
Hiatal hernia,
Gastro- esophageal reflux,
Increased glycemic load,
Decreased satiety

Higher Glycemic Load

Glycemic Index Last AR, Wilson SA. Am Fam Physician 2006;73:1942-8

GL & GI tables Foster-Powell K, Holt SH, Brand-Miller JC. Am J Clin Nutr. 2002 Jul;76(1):5-56. Food GI Serving Carbs GL Sucrose 70 10 grs 10 grs 7 Yoghurt 36 200 ml 9 grs 3 Banana 52 120 grs 24 grs 12 Apple 38 120 grs 15 grs 6 Apricot 57 120 grs 9 grs 5 Kiwi 53 120 grs 12 grs 6 Mango 51 120 grs 17 grs 8 Orange 42 120 grs 11 grs 5 Grape 46 120 grs 18 grs 8

GL & GI tables Foster-Powell K, Holt SH, Brand-Miller JC. Am J Clin Nutr. 2002 Jul;76(1):5-56. Food GI Serving Carbs GL Papaya 59 120 grs 17 grs 10 Peach 42 120 grs 11 grs 5 Pear 38 120 grs 11 grs 4 Pineaple 59 120 grs grs13 7 Strawberries 40 120 grs 3 grs 1 Watermelon 72 120 grs 5.5 grs 4

GL & GI tables Foster-Powell K, Holt SH, Brand-Miller JC. Am J Clin Nutr. 2002 Jul;76(1):5-56. Food GI Serving Carbs GL Coca-Cola 63 250 ml 26 grs 16 Fanta 68 250 ml 33 grs 23 Aple Juice 40 250 ml 29 grs 12 Orange Juice 50 250 ml 26 grs 13 Tomato Juice 38 250 ml 9 grs 4 Pineaple Juice 46 250 ml 35 grs 16 Gatorade 78 250 ml 15 grs 12 Isostar 70 250 ml 18 grs 13

GL & GI tables Foster-Powell K, Holt SH, Brand-Miller JC. Am J Clin Nutr. 2002 Jul;76(1):5-56. Food GI Serving Carbs GL Pumpkin 75 80 grs 6 grs 4 Beet 64 80 grs 7 grs 4 Carrot 47 80 grs 6 grs 3 Potatoes with skin 60 150 grs 30 grs 18 Roasted Potatoe 85 150 grs 30 grs 27 Frozen French fries 85 150 grs 29 grs 22 Mash Potatoe 74 150 grs 20 grs 15 Sweet Potatoe 61 150 grs 28 grs 17 Cassava 70 150 grs 57 grs 40 Yams 37 150 grs 36 grs 13

GL & GI tables Foster-Powell K, Holt SH, Brand-Miller JC. Am J Clin Nutr. 2002 Jul;76(1):5-56. Food GI Serving Carbs GL White Bread 70 60 grs 30 grs 21 French bread 62 70 grs 42 grs 26 Rye Bread 50 60 grs 24 grs 12 Cheerios 74 30 grs 20 grs 15 Chocapic 84 30 grs 25 grs 21 CornFlakes 92 30 grs 26 grs 24 Golden Grahams 71 30 grs 25 grs 18 Special K 84 30 grs 24 grs 20 Bran Flakes 74 30 grs 16 grs 13 Cream Crackers 65 25 grs 17 grs 11 Alpen Muesli 55 30 grs 19 grs 10

GL & GI tables Foster-Powell K, Holt SH, Brand-Miller JC. Am J Clin Nutr. 2002 Jul;76(1):5-56. Food GI Serving Carbs GL White Rice Uncle Ben’s 10 min 68 150 grs 37 grs 25 Long White Rice 56 150 grs 41 grs 23 Basmati White Rice 58 150 grs 38 grs 22 Brown Rice 55 150 grs 33 grs 18 Millet 71 150 grs 36 grs 25 Bulgur 48 150 grs 26 grs 12 Corn Pasta (gluten free) 78 180 grs 42 grs 32 Fettucine with egg 40 180 grs 46 grs 18 Gnocchi 68 180 grs 48 grs 33 Linguini 46 180 grs 48 grs 22 Macarroni 47 180 grs 48 grs 23 Ravioli 40 180 grs 42 grs 32 Spaghetti, boiled for 5 minuts 38 180 grs 48 grs 18 Spaghetti, boiled for 20 minuts 61 180 grs 44 grs 27 Whole Pasta 37 180 grs 42 grs 16

Consequences of a Chronic High Glycemic Load diet

Hyperglycemia
Hyperinsulinemia
Increased ROS & CRP(hs)
Increased NFkb Activation
Increased Glycation
Gallstone disease
Dickinson S, et al. Am J Clin Nutr . 2008 May;87(5):1188-93 Cordain L et al. Am J Clin Nutr . 2005 Feb;81(2):341-54. Liu S et al. Am J Clin Nutr . 2002 Mar;75(3):492-8 Tsai CJ et al. Gut . 2005 Jun;54(6):823-8 Foster-Powell K, Holt SH, Brand-Miller JC. Am J Clin Nutr . 2002 Jul;76(1):5-56
Metabolic Syndrome
Type 2 Diabetes
Hypertension
Coronary Heart Disease
Dyslipidemia
Obesity
Gout

Other insulinotropic foods

Holt SH et al. An insulin index of foods: the insulin demand generated by 1000-kJ portions of common foods . Am J Clin Nutr. 1997 Nov;66(5):1264-76 Ostman EM, et al. Inconsistency between glycemic and insulinemic responses to regular and fermented milk products . Am J Clin Nutr 2001;74:96 –100. Food GI II Whole milk 30 90 Fermented milk (3% fat) 15 98 Lactose 68 50 White bread 100 100 Food GS IS White bread 100 100 Beef 21 51 Fish 28 59 Egg 42 31 Cheese 55 45 Ice-Cream 70 89 Yogurt 51 115

Consumption of milk induces a reactive hypoglycaemia similar to high glycaemic load carbohydrates
Even added to a low glycemic food increases the area under the insulin curve .
Milk’s insulin response Ostman EM, et al. Inconsistency between glycemic and insulinemic responses to regular and fermented milk products . Am J Clin Nutr 2001;74:96 –100. Hoyt G et al. Dissociation of the glycaemic and insulinaemic responses to whole and skimmed milk . Br J Nutr . 2005 Feb;93(2):175-7 Liljeberg Elmstahl H & Bjorck I. Milk as a supplement to mixed meals may elevate postprandial insulinaemia . Eur J Clin Nutr 2001; 55:994–999.

Whole vs low-fat milk Glucose Skimmed milk Whole milk Hoyt G, Hickey MS, Cordain L. . Dissociation of the glycaemic and insulinaemic responses to whole and skimmed milk . Br J Nutr. 2005 Feb;93(2):175-7

Intervention studies
Intensely milk fed calves experience insulin resistance, hyperglycemia and glucosuria.
24 8-yr boys consumed 53 g protein as milk or meat daily for 7-d .
Results:
Milk, but not meat
 I nsulin secretion and resistance
Hoppe C et al. High intakes of milk, but not meat increase s-insulin and insulin resistance in 8-year-old boys .
Eur J Clin Nutr. 2005 Mar;59(3):393-8
Hostettler-Allen RL et al. Insulin resistance, hyperglycemia, and glucosuria in intensively milk-fed calves. J Anim Sci . 1994 Jan;72(1):160-73.

Hyperinsulinemia Hepatic IGFBP-1 synthesis IGF-1 Growth Hormone Androgens SHBG PCOS Male Vertex Balding Circulating IGFBP-3 Alteration in Retinoid Receptor Activity Unregulated Tissue Growth Tissue Growth and/or Stature Early Menarche/Puberty Myopia Acne Epithelial cell cancer Promotion PCOS Skin Tags Acanthosis Nigricans Cordain L. et al. Comparative Biochemistry and Physiology Part A 2003; 136: 95–112 Insulin Resistance

Per Capita Percentages of Highly Glycemic and Highly Insulinemic Foods in the U.S. Diet (1990-99) 47.7 % of the energy in the typical U.S. diet comes from foods capable of promoting insulin resistance Cordain L et al. Am J Clin Nutr . 2005 Feb;81(2):341-54. From Cordain L, with permission

Higher Fructose Intake

Fructose & Insulin Resistance
Most ~ (50-60%) of fructose ingested is rapidly taken up by the liver
Fructose by-passes the major regulatory step (PFK) of glycolysis in liver allowing it:
1. To serve as an unregulated source of acetyl-CoA, and glycerol 3-P, necessary components of VLDL synthesis
Fructose increases hepatic de-novo lipogenesis whereas eucaloric glucose ingestion does not
Fructose Glucose Glucose 6-P Fructose 6-P Fructose 1,6 bisphosphate Dihydroxyacetone phosphate Glyceraldehyde 3-P Glyceraldehyde Fructose 1-P Glycerol 3-P Acetyl-CoA Acylglycerols VLDL Pyruvate Lactate Citrate Enzymes Glucokinase Glucose Phosphate Isomerase Phosphofructo- Kinase (PFK) Fructose 1,6 Bisphosphatase Fructokinase GLYCOLYSIS Elliott SS et al. Am J Clin Nutr 2002;76:911-22 From Cordain L, with permission

Fructose & elevation of Serum Uric Acid Concentrations
The enzymes of hepatic adenine degradation are normally inhibited by high concentrations of ATP and P(i)
The removal of this inhibition by lowered ATP & P(i) concentrations leads to increased generation of uric acid
Mayes PA. Am J Clin Nutr 1993;58:754S-65S. From Cordain L, with permission

Because fructose by-passes the major regulatory step (PFK) of glycolysis in liver , it elevates:
Lactate concentrations 1
Lactate is a potent inhibitor of uric acid excretion by liver 2
Consequently, fructose ingestion both enhances uric acid production and slows its excretion
Fructose & elevation of Serum Uric Acid Concentrations
Mayes PA. Am J Clin Nutr 1993;58:754S-65S.
2. Yamamoto T et al. Nephron 1993;65:73-6
From Cordain L, with permission

Higher Net Endogenous Acid Production

NEAP for some foods Net base yielding Net Acid yielding NEAP (mEq/100 kcal) PAEL (mEq/100 kcal) NEAP (mEq/100 kcal) NEUTROS Frassetto L.A. et al. J Nephrol . 2006 Mar-Apr;19 Suppl 9:S33-40. Fish 14,6 Meat 12,4 Poultry 7,8 Egg 7,3 Shellfish 7,3 Cheese 3,3 Milk 1,3 Cereals 1,1 Nuts -1,1 Fruit -5,2 Tubers -5,4 Mushrooms -11,2 Root vegetables -17,1 Tomato -17,5 Vegetables -23,4 Legumes -0,4

The displacement of fruits and vegetables by cereal grains, cheese & salt shifted hominin diets to net acid yielding
Diseases promoted by a net metabolic acidosis:
Osteoporosis
Hypertension
Kidney stones
Stroke
Sarcopenia
Sebastian A et al. Am J Clin Nutr 2002;76:1308-16 Frassetto LA, Morris RC Jr, Sebastian A. Am J Physiol Renal Physiol . 2007 Aug;293(2):F521-5.

Disruption of Dietary Fatty Acids Balance

Ramsden CE, Faurot KR, Carrera-Bastos P, Cordain L, De Lorgeril M, Sperling LS. Curr Treat Options Cardiovasc Med . 2009 Aug;11(4):289-301 Dietary fatty acids play critical regulatory roles in a host of biochemical processes implicated in various diseases
Inflammation, Endothelial activation, smooth muscle cell proliferation, thrombogenesis & plaque rupture ;
Arrythmogenesis;
Glucose and insulin metabolism;
Oxidative stress;
Adipogenesis

Increase in w6/w3 Ratio

W6/w3 Ratio in various populations Simopoulos, A. World Rev Nutr Diet . Basel, Karger, 2003, vol 92, pp 1–22.

Ω 3 Index
Von Schacky e Harris created & proposed a new risk factor for CVD
Ω 3 Index , which is calculated through the percentage of EPA & DHA in RBC membrane .
Ω 3 Index ≥ 8%  Risk of death by CVD 90% lower that an Ω 3 Index ≤ 4% .
von Schacky C, Harris WS. Cardiovascular benefits of omega-3 fatty acids . Cardiovasc Res. 2007 Jan 15;73(2):310-5.

Ω 6/ Ω 3 Ratio & CVD Okuyama H, Ichikawa Y, Sun Y, Hamazaki T, Lands WE. World Rev Nutr Diet. 2007;96:83-103.

High Ω 6/ Ω 3 Ratio may increase risk for Osteoporosis
Weiss LA, Barrett-Connor E, von Muhlen D. Am J Clin Nutr. 2005 Apr;81(4):934-8
Watkins BA, Li Y, Seifert MF. J Nutr Biochem . 2006 Apr;17(4):282-9
Bhattacharya A, et al. J Am Coll Nutr . 2005 Jun;24(3):200-9.
Hasturk H et al. FASEB J . 2006 Feb;20(2):401
Shen CL, et al. Br J Nutr . 2006 Mar;95(3):462-8
.

Epidemiologic & experimental studies sugest that:
High Ω 6/ Ω 3 Ratio may increase the risk for various types of cancer (prostate, breast, colon, pancreas & lung )
Ω 6/ Ω 3 Ratio & Cancer Chajes V, Bougnoux P. World Rev Nutr Diet . 2003;92:133-51. Okuyama H, Ichikawa Y, Sun Y, Hamazaki T, Lands WE. World Rev Nutr Diet . 2007;96:143-9.

Decrease in Micronutrient intake

Whole Whole Lean Grains Milk Fruits Veggies Seafood Meats Nuts/seeds Vitamin B12 (μg) 0.00 4 0.58 5 0.00 4 0.00 4 7.42 7 0.63 6 0.00 4 Vitamin B3 (mg) 1.12 4 0.14 1 0.89 3 2.73 5 3.19 6 4.73 7 0.35 2 Phosphorus (mg) 90 3 152 5 33 1 157 6 219 7 151 4 80 2 Vitamin B2 (mg) 0.05 2 0.26 6 0.09 3 0.33 7 0.09 4 0.14 5 0.04 1 Vitamin B1 (mg) 0.12 5 0.06 1 0.11 3 0.26 7 0.08 2 0.18 6 0.12 4 Folate (μg) 10.3 4 8.1 2 25.0 6 208.3 7 10.8 3 3.8 1 11.0 5 Vitamin C (mg) 0.0 1 1.5 4 74.2 6 93.6 7 1.9 5 0.1 2 0.4 3 Iron (mg) 0.90 4 0.08 1 0.69 2 2.59 7 2.07 6 1.10 5 0.86 3 Vitamin B6 (mg) 0.09 3 0.07 1 0.20 5 0.42 7 0.19 4 0.32 6 0.08 2 Vitamin A (RE) 2 2 50 5 94 6 687 7 32 4 1 1 2 3 Magnesium (mg) 32.6 4 21.9 2 24.6 3 54.5 7 36.1 6 18.0 1 35.8 5 Calcium (mg) 7.6 2 194.3 7 43.0 4 116.8 6 43.1 5 6.1 1 17.5 3 Zinc (mg) 0.67 4 0.62 3 0.25 1 1.04 5 7.6 7 1.9 6 0.6 2 Sum Rank Score 42 43 47 82 66 51 39 Nutrient Density for Food Groups (100 kcal samples) Superscripts are rank scores (7=highest;1=lowest) for each nutrient 13 Most Frequently Deficient Nutrients From Cordain L, with permission Cordain L et al. Am J Clin Nutr . 2005 Feb;81(2):341-54.

Total Antioxidants in Plant Foods – The FRAP assay (The reduction of Fe 3+ to Fe 2+ ) Mmol/100 g Mmol/100 g Adapted from Halvorsen BL et al. J Nutr 2002;132:461-71 n=8 n=17 n=4 n=9 n=22 n=31 n=11 n=4

Lifestyle Consequences

Decrease in Vitamin D status Ho lick MF, Chen TC. Am J Clin Nutr . 2008 Apr;87(4):1080S-6S

Sedentarism

Booth FW, Chakravarthy MV, Spangenburg EE. J Physiol . 2002 Sep 1;543(Pt 2):399-411.

CHD
Angina
Myocardial Infarction
Heart Failure
Hypertension
Stroke
T2D & Metabolic Syndrome
Obesity
Diseases of sedentarism
Sarcopenia
Dyslipidemia
Gallblader disease
Epithelial cell cancers
Immune dysfunction
Osteoporosis
Cognitive impairment
Booth FW, et al. J Appl Physiol. 2002 Jul;93(1):3-30

Disrupted sleep patterns

Impairs spatial learning & affects membrane excitability and mitochondrial protein in the hippocampus
Disrupts emotional brain reactivity
Insufficient Sleep Yang RH, et al. Brain Res . 2008 Sep 16;1230:224-32 Walker MP. Ann N Y Acad Sci . 2009 Mar;1156:168-97

Obese individuals sleep less than normal BMI individuals ( NHANES III data )
Sleep deprivation:
Ghrelin
Craving for high GL foods
Cortisol
Growth Hormone
Gangwisch JE et al. Sleep 2005 Oct 1;28(10):1289-96 Vorona RD et al. Arch Intern Med 2005;165:25-30 Insufficient Sleep

Associated with increased mortality from cardiovascular disease, noncardiovascular disease/noncancer, and all causes for both sexes
Insufficient Sleep Ikehara S, et al. Sleep 2009 Mar 1;32(3):295-301

Shift- and night-time work
Disruption of normal circadian rhythm may increase the risk of developing cance rs, especially breast cancer
Davis S, Mirick DK. Cancer Causes Control . 2006 May;17(4):539-45 Hansen J. Cancer Causes Control. 2006 May;17(4):531-7.

Are Primitive populations healthy ?????

Lower tricipital skinfold [mm] in hunter-gatherers compared to healthy americans Eaton SB, Konner M, Shostak M. Am J Med . 1988 Apr; 84(4): 739-49.

Lower Waist (cm)/height (m) in the Horticulturalists of Kitava (Papua-New Guinea) compared to healthy Swedish Lindeberg, S, Soderberg, S, Ahren, B, and Olsson, T. J Intern Med , 2001; 249: 553-8 Men Women Sweden

Lower fasting plasma insulin in the Horticulturalists of Kitava (Papua-New Guinea) compared to healthy Swedish Lindeberg S, Eliasson M, Lindahl B, Ahren B. Metabolism 1999; 48:1216-9

Lower blood levels of fasting leptin in the Horticulturalists of Kitava (Papua-New Guinea) compared to healthy Swedish Lindeberg, S, Soderberg, S, Ahren, B, and Olsson, T. J Intern Med , 2001; 249: 553-8

Lower blood levels of fasting leptin in the Ache Indians of Paraguay compared to North American runners Bribiescas RG, Hickey MS. Nutr Metab (Lond). 2006 Aug 30;3:34

Lower Total Blood Cholesterol in primitive populations versus Average Americans Eaton SB, Konner M, Shostak M. Am J Med . 1988 Apr; 84(4): 739-49. Lindeberg, S, et al. Am J Clin Nutr , 1997; 66: 845-52 O'Keefe JH, Cordain L, Harris, WH, Moe RM, Vogel R. J Am Coll Cardiol 2004;43: 2142-6

Low Blood Pressure amongst Yanomamö Indians Oliver WJ, Cohen EL, Neel JV. Circulation . 1975 Jul;52(1):146-51. National Heart, Lung, and Blood Institute. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure . NIH Publication No. 04-5230 (August, 2004) Age Men Women 0-9 93/59 96/62 10-19 108/67 105/65 20-29 108/69 100/63 30-39 106/69 100/63 40-49 107/67 98/62 50+ 100/64 106/64 Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Classification < 120 < 80 Optimal 120-139 80-89 Pre-Hipertension 140-159 90-99 Hipertension grade I ≥ 160 ≥ 100 Hipertension grade II

Higher Vo2 max in primitive populations versus Average Americans Eaton SB, Konner M, Shostak M. Am J Med . 1988 Apr; 84(4): 739-49.

Absence of Obesity and chronic degenerative diseases among primitive populations
Kitava Banock Indians (USA) San Bushmen (Kalahari Desert) Andaman e Nicobar Indigenous Eaton SB, Konner M, Shostak M. Am J Med . 1988 Apr; 84(4): 739-49. Lindeberg, S, et al. Am J Clin Nutr , 1997; 66: 845-52 . Cordain L, et al. Am J Clin Nutr . 2005 Feb;81(2):341-54

Thank you Special thanks to Prof. Loren Cordain , of Colorado State University For his mentorship & for generously allowing me to use some of his work

Pedro Bastos [email_address] www.nutriscience.pt

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Evolutionary Medicine Frankfurt

by Pedro Bastos on Dec 20, 2009

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Evolutionary Medicine Frankfurt — Presentation Transcript