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

2. The Modern World 3.

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. Mller-Nordhorn J, et al.Eur Heart J . 2008 May;29(10):1316-26.Kanis, J.A., etal.J Bone Miner Res2002;17(7):1237-44 Chronic Degenerative Diseases Reach epidemic proportions 4.

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 Teacher35:125-129, 1973 5.

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 6. 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 7. Hominin lineage Wood B.Nature2002:418:133-35 Palaeolithic 8.

During the Paleolithic:

Increase in the amount of animal foods

PUFA forBrain 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 hypothesisvs Aquatic hypothesis 9.

160 to 195,000 y ago:

Appear in Africa the first hominins anatomically identical to modern humans

McDougall I, et al. Nature2005;433:733736 White TD, et al.Nature2003;423:742747 Ethiopia From Liu H, et al., 2006 10.

All humans living in Europe, Asia, Oceania and America share a common

African origin

• Less genetic diversityas 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 Genet2006; 38: 12511260 RAY N, et al.Genome Res2005; 15:11611167 Macaulay V, et al.Science2005; 308(5724):1034-6 Currat M, Excoffier L.PLoS Biology2004; 2: 22642274 Jakobsson M, et al.Nature2008; 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 Biology2005; 15:R159R160 Cavalli-Sforza LL, Feldman MW.Nat Genet2003; 33:266275 Tishkoff S, Williams S.Nat Rev Genet 2002; 3: 611621 Harpending, H, Rogers, AR.Annu Rev Genomics Hum Genet2000; 1:361385 Ethiopia From Liu H, et al., 2006 11. Liu H, et al.Am J Hum Genet . 2006 Aug;79(2):230-7 Population ofHomo Sapiensof~1,000 individuals emigrated for Eurasia~56,000 years ago and then inhabit the entire planet 12. 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 13. Obligate Physical Activity Cordain L, et al.Int J Sport Med1998;19:328-335. Vital for survival 14. 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 . 15. Regular sun exposure Chaplin G, Jablonski NG.Am J Phys Anthropol2009Aug;139(4):451-61 Optimal cutaneous generation of Vit D-3 Equator 20 N 20 S 16. Pre-agricultural diets 17.

Plants

Roots and tubers

Berries

Fruits

Nuts

Cordain L et al.Am J Clin Nutr . 2005 Feb;81(2):341-54 Vegetable sources 18.

• 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 19. What Prehistoric Hunter-Gatherersdidnt eat 20. 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 363-83Alcohol Fatty Domestic meat Legumes 21. Cordain L et al. Am J Clin Nutr . 2005 Feb;81(2):341-54. Dubreuil L.Journal of Archaeological Science2004; 31(11): 1613-1629.Bar-Yosef O.Evol Anthropol1998;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. 22. Neolithic (10,000 to 5,500 yrs ago)Food IntroductionsYears 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 AGOSHEEP, 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 23. 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 24. Industrial RevolutionProcessed Foods The 20 thCentury Year O 2 3 4 Human Generations (30 yrs) 2008 1 1900: HERSHEYS CHOCOLATE BAR1902: PEPSI1906: KELLOGS CORN FLAKES1911: CRISCO1913: OREO COOKIE1921: WONDERBREAD1928: RICE KRISPIES1932: CORN CHIPS1941: M&Ms1952: SUGAR FROSTED FLAKES1969: PRINGLES CHIPSCordain 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 25. What are we currently eating? 26. USA Cordain L et al.Am J Clin Nutr . 2005 Feb;81(2):341-54 27. Cew INE, December, 2006 Portugal Cereal Grains & tubers Dairy 28. 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 allHomogenerationshad no evolutionary experience with commonly consumedmodern 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 29. "Survival will be neither to the strongest of the species, nor to the most intelligent, but to those most adaptable to change." C. Darwin 30. Human Activity Patterns Following the Development ofAgriculture 31.

For most early farmers energy intake was stillobligatorily linkedto activity levels

Agriculture allowed forsocietal 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 fewprivileged elitedid not have to work to obtain food 32. Evolution of Human Activity Neolithic Labor Saving InventionsYears ago O 67 100 133 167 200 233 267 300 333 Human Generations present 33 ~2,000 YRSFIRST 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 33. 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 34. Modern Exercise Habits 35. 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 Med1998;19:328-335. 36. Modern Sleep Habits 37. Virtually every human being in industrialized countries isexposed 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 38. 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 35 latitude Chaplin G, Jablonski NG.Am J Phys Anthropol2009Aug;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 39. Consequences 40. Nutritional Consequences 41. Macronutrient composition 42.

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 Proc2004 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