Evolutionary Medicine Frankfurt

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Exercise, sleep, sun exposure and dietary needs of every living organism are genetically determined, which is why it is being increasingly recognized that the profound changes in diet and lifestyle that occurred in the last 10,000 years are too recent, on an evolutionary time scale, for the human genome to have fully adapted, which underlies many of so-called diseases of civilization, such as coronary heart disease, obesity, hypertension, type 2 diabetes and metabolic syndrome, epithelial cell cancers and osteoporosis.

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  • Good afternoon. Thank you all for attending .   Before we begin, I would like to thank the Congress Organization for the cordial invitation & Dr. Michael Colgan for proposing my name. Last, but not least, special thanks to my mentor & friend Professor Loren Cordain of CSU. He was the one who introduced me to Evolutionary Medicine and as you will see, his work is quoted many times in this presentation. During this lecture I’ll try to show you that the profound changes in diet and lifestyle that occurred in the last 10,000 years and especially in the past 200 years are too recent, on an evolutionary time scale, for the human genome to have adapted, which underlies many of so-called diseases of civilization.
  • Today, in this modern age,
  • Indeed, as everyone is aware, today Chronic Degenerative Diseases (CVD, Epithelial Cell Cancers, Hypertension, T2 Diabetes & Metabolic Syndrome, Osteoporosis, Autoimmune diseases) reach epidemic proportions in virtually every industrialized country and diet and lifestyle has been repeatedly identified as a major risk factor for most of these chronic illnesses. So the question I would ask is how we got to where we are today????   To answer that, we need to go back to our distant past.   Why do we need to that????? Because …..
  • Exercise, sleep, sun exposure and dietary needs of every living organism are genetically determined
  • Similar to all species, contemporary humans are genetically adapted to the environment that their ancestors survived in and that consequently conditioned their genetic makeup. But What is the native human ecological niche?   To answer this, we need to take a brief look at the history of humanity itself…
  • In the 5-7 million-year period since the evolutionary emergence of hominins (bipedal primates within the taxonomic tribe, hominini) 20 or more species may have existed. You can see here that the first member of the human genus, Homo, was Homo habilis who has been dated to ~2.5 million years ago. At roughly the same time, stone tools appear in the fossil record and this marks the beginning of the Palaeolithic era.  
  • During the Palaeolithic there was an increase in the intake of animal foods, which provided the crucial nutrients for human brain development , such as iodine, zinc, selenium, iron and especially the long chain polyunsaturated fatty acids Docosahexaenoic acid and Arachidonic acid.   There is an going debate between the proponents of the savannah hypothesis who claim that terrestrial animal foods, such as brain, bone marrow and organ meats, would have supplied these necessary nutrients for the increase in hominid brain mass relative to body mass, and the aquatic hypothesis who argues that shore-based foods, such as fish, shellfish, turtles, frogs and also plants would have been essential for the hominin brain evolution.   I take no position on the different interpretations, but I’m absolutely convinced that the nutrients mentioned and probably others, such as choline, are crucial for normal brain development and functioning.
  • Anatomically modern Homo sapiens appear in the fossil record in Africa by about 160 to 195,000 years ago.
  • Anthropologic and genetic studies suggest that all human beings living in Europe, Asia, Australia and America share a common African origin, which is further backed up from the fact that there is less genetic diversity as we move away from Africa.
  • So, we know that Homo sapiens evolved in Africa approximately 200,000 years ago, and first left Africa about 100,000 years ago to briefly colonize the Levant   However, it was not until ~ 56,000 years ago that our species began to permanently leave Africa and inhabit the entire planet.
  • So during our time as hunter-gatherers, clearly no universal diet or lifestyle existed, but rather varied due to differences in geography, ecologic niche, season and glaciations (availability of edible foods).   Nevertheless, there are universal characteristics of pre-agricultural hominin lifestyles
  • First, all hunter-gatherers, except for the very young and very old are required to hunt, gather or fish for food. As so, they have obligate periods of physical activity, but also rest.
  • Our primitive ancestors and virtually everyone on the planet until the development of artificial light, slept in sync with the daily variation in light exposure.
  • Hunter-gatherers living below 20º latitude lived in a UVB rich environment, allowing optimal cutaneous generation of vitamin D-3 from its precursor 7-dehydrocholesterol
  • B efore the development of agriculture and animal husbandry hominin dietary choices would have been necessarily limited to minimally processed, wild plant and animal foods.  
  • As it is important to know what they might have eaten, it is also very important to look at what they didn’t ate
  • But about 10,000 years ago The so-called "Agricultural Revolution" (primarily the domestication of animals & cereal grains) occurred in the Near East and then spread to northern Europe by about 5,000 years ago.
  • With the advent of agriculture, novel foods were introduced as staples for which the hominin genome had little evolutionary experience, especially cereal grains, milk and dairy, alcohol, salt and later on cane sugar.  
  • More importantly, food-processing procedures were developed, particularly following the Industrial Revolution, which allowed for quantitative and qualitative food and nutrient combinations that had not previously been encountered over the course of hominin evolution.
  • And just for a bit of fun, here’s when some of those incredible foods were introduced.
  • But What are we currently eating
  • But What are we currently eating
  • The mechanization of agriculture starting 200 years ago with the Industrial Revolution Increasingly allowed the average citizen to break the ancient link between energy input and energy output
  • Compared to hunter-gatherers and other more primitive populations, most individuals in westernized countries do not engage in any form of physical activity
  • Virtually every human being in industrialized countries is exposed to light at atypical biologic times, disrupting the normal circadian rhythm. Moreover, a significant percentage of these individuals sleep less than 7 hours per night.
  • Populations living away from the equator have a poor Vitamin D status, because Optimal wavelengths of UVB for maximal synthesis of Vitamin D are 290-315 nanometers, which occurs below 35º latitude
  • Although there were other important changes in our lifestyle, I believe sleep, physical activity, UVB exposure & diet are the main ones that we have to understand and act upon if we want to really implement correct public health policies. So, let’s take a look at the consequences of these major changes:
  • SG – Score glicemico SI – Score de insulina Em ambos os casos, usou-se o pão branco como alimento de referência
  • Papilomas Cutâneos: Lesões da pele hiperproliferativas de origem idiopática que afectam o pescoço, axila e virilhas. Encontram-se, frequentemente em pacientes obesos e são marcadores cutâneos para Diabetes tipo 2 e insulinorresistência. Causas: IGF-1 actua directamente nestas células epiteliais Acanthosis Nigricans : Doença dermatológica__Hiperpigmentação e Hiperqueratose que afecta o pescoço, axilas, virilhas e nós dos dedos. IGF-1 liga-se a receptores (IGF-R) nos queratinócitos e fibroblastos dermais Insulina eleva ácidos gordos livres no plasma, o que aumenta o número de receprores de EGF (EGF-R). Doença associada a PCOS e Diabetes tipo 2.
  • Evolutionary Medicine Frankfurt

    1. 1. Mismatch between Modern Lifestyle and Ancient Genes as the key for Western Diseases Pedro Bastos Frankfurt, October 16, 2009
    2. 2. The Modern World
    3. 3. <ul><li>CVD </li></ul><ul><li>Epithelial Cell Cancers </li></ul><ul><li>Hypertension </li></ul><ul><li>T2 Diabetes & Metabolic Syndrome </li></ul><ul><li>Osteoporosis </li></ul><ul><li>Autoimmune diseases </li></ul>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
    4. 4. <ul><li>“ Nothing in biology makes sense except in the light of evolution.” </li></ul><ul><li>— Theodosius Dobzhansky </li></ul>Dobzhansky TG: Nothing in biology makes sense except in the light of evolution. Am Biol Teacher 35:125-129, 1973
    5. 5. <ul><li>Exercise, sleep, sun exposure and dietary needs of every living organism are genetically determined. </li></ul>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. 6. Evolutionary template <ul><li>Similar to all species, contemporary humans are genetically adapted to the environment that their ancestors survived in and that consequently conditioned their genetic makeup. </li></ul>Cordain L et al. Am J Clin Nutr . 2005 Feb;81(2):341-54
    7. 7. Hominin lineage Wood B. Nature 2002:418:133-35 Palaeolithic
    8. 8. <ul><li>During the Paleolithic: </li></ul><ul><li>Increase in the amount of animal foods </li></ul><ul><li> PUFA for Brain Development ( DHA, AA ) </li></ul>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
    9. 9. <ul><li>160 to 195,000 y ago: </li></ul><ul><li>Appear in Africa the first hominins anatomically identical to modern humans </li></ul>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
    10. 10. <ul><li>All humans living in Europe, Asia, Oceania and America share a common </li></ul><ul><li> African origin </li></ul><ul><ul><li>Less genetic diversity as we move away from Africa </li></ul></ul>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
    11. 11. 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
    12. 12. Pre-agricultural diets & lifestyles <ul><li>No universal diet or lifestyle existed! </li></ul><ul><li>It varied due to differences in </li></ul><ul><li>Geography </li></ul><ul><li>Ecologic niche </li></ul><ul><li>Season </li></ul><ul><li>Glaciations </li></ul>Cordain L et al. Am J Clin Nutr . 2005 Feb;81(2):341-54
    13. 13. Obligate Physical Activity Cordain L, et al. Int J Sport Med 1998;19:328-335. Vital for survival
    14. 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. 15. 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
    16. 16. Pre-agricultural diets
    17. 17. <ul><li>Plants </li></ul><ul><li>Roots and tubers </li></ul><ul><li>Berries </li></ul><ul><li>Fruits </li></ul><ul><li>Nuts </li></ul>Cordain L et al. Am J Clin Nutr . 2005 Feb;81(2):341-54 Vegetable sources
    18. 18. <ul><ul><li>Wild terrestrial animals </li></ul></ul><ul><ul><li>(muscle tissue, fat and organs) </li></ul></ul><ul><ul><li>Fowl </li></ul></ul><ul><ul><li>Insects </li></ul></ul><ul><ul><li>Fish & Seafood </li></ul></ul>Cordain L et al. Am J Clin Nutr . 2005 Feb;81(2):341-54 Animal sources
    19. 19. What Prehistoric Hunter-Gatherers didn’t eat
    20. 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 363-83 Alcohol Fatty Domestic meat Legumes
    21. 21. 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 &quot;Agricultural Revolution&quot; occurred in the Near East and then spread to northern Europe by ~ 5,000 years ago.
    22. 22. 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
    23. 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. 24. 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
    25. 25. What are we currently eating?
    26. 26. USA Cordain L et al. Am J Clin Nutr . 2005 Feb;81(2):341-54
    27. 27. Cew INE, December, 2006 Portugal Cereal Grains & tubers Dairy
    28. 28. Generations in the Evolution of Humanity <ul><li>Generations % Total </li></ul><ul><li>Homo habilis (1 st Homo species ) 76,667 100.0 </li></ul><ul><li>Homo erectus (modern body size) 60,000 78.2 </li></ul><ul><li>Modern Homo sapiens (cranial size) 6,666 8.7 </li></ul><ul><li>Agricultural Revolution (cereals) 333 0.4 </li></ul><ul><li>Advent of Dairying (milk, cheese etc) 200 0.26 </li></ul><ul><li>Industrial Revolution (refined sugars, 7 0.009 </li></ul><ul><li>refined cereals, oils, canned food) </li></ul><ul><li>Food Processing Industry (junk food) 4 0.005 </li></ul>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
    29. 29. &quot;Survival will be neither to the strongest of the species, nor to the most intelligent, but to those most adaptable to change.&quot; C. Darwin
    30. 30. Human Activity Patterns Following the Development of Agriculture
    31. 31. <ul><li>For most early farmers energy intake was still obligatorily linked to activity levels </li></ul><ul><li>Agriculture allowed for societal stratification </li></ul>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
    32. 32. 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
    33. 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. 34. Modern Exercise Habits
    35. 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 Med 1998;19:328-335.
    36. 36. Modern Sleep Habits
    37. 37. 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
    38. 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 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
    39. 39. Consequences
    40. 40. Nutritional Consequences
    41. 41. Macronutrient composition
    42. 42. <ul><li>Eaton SB. Proc Nutr Soc. 2006 Feb;65(1):1-6. </li></ul><ul><li>Cordain L et al. Am J Clin Nutr . 2005 Feb;81(2):341-54. </li></ul><ul><li>. </li></ul><ul><li>O'Keefe JH Jr, Cordain L. Mayo Clin Proc 2004 Jan;79(1):101-8. </li></ul><ul><li>Bastos, P . Unpublished data </li></ul>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
    43. 43. Decrease in Fiber intake
    44. 44. 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.
    45. 45. Consequences of Low Fiber Diet <ul><li>Constipation, </li></ul><ul><li>Appendicitis, </li></ul><ul><li>Hemorrhoids, </li></ul><ul><li>Deep vein Thrombosis, </li></ul><ul><li>Varicoses veins </li></ul>Cordain L et al. Am J Clin Nutr . 2005 Feb;81(2):341-54. <ul><li>Diverticulitis, </li></ul><ul><li>Hiatal hernia, </li></ul><ul><li>Gastro- esophageal reflux, </li></ul><ul><li>Increased glycemic load, </li></ul><ul><li>Decreased satiety </li></ul>
    46. 46. Higher Glycemic Load
    47. 47. Glycemic Index Last AR, Wilson SA. Am Fam Physician 2006;73:1942-8
    48. 48. 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
    49. 49. 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
    50. 50. 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
    51. 51. 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
    52. 52. 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
    53. 53. 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
    54. 54. Consequences of a Chronic High Glycemic Load diet
    55. 55. <ul><li>Hyperglycemia </li></ul><ul><li>Hyperinsulinemia </li></ul><ul><li>Increased ROS & CRP(hs) </li></ul><ul><li>Increased NFkb Activation </li></ul><ul><li>Increased Glycation </li></ul><ul><li>Gallstone disease </li></ul>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 <ul><li>Metabolic Syndrome </li></ul><ul><li>Type 2 Diabetes </li></ul><ul><li>Hypertension </li></ul><ul><li>Coronary Heart Disease </li></ul><ul><li>Dyslipidemia </li></ul><ul><li>Obesity </li></ul><ul><li>Gout </li></ul>
    56. 56. Other insulinotropic foods
    57. 57. 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
    58. 58. <ul><li>Consumption of milk induces a reactive hypoglycaemia similar to high glycaemic load carbohydrates </li></ul><ul><li>Even added to a low glycemic food increases the area under the insulin curve . </li></ul>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.
    59. 59. 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
    60. 60. Intervention studies <ul><li>Intensely milk fed calves experience insulin resistance, hyperglycemia and glucosuria. </li></ul><ul><li>24 8-yr boys consumed 53 g protein as milk or meat daily for 7-d . </li></ul><ul><ul><li>Results: </li></ul></ul><ul><ul><ul><li>Milk, but not meat </li></ul></ul></ul><ul><ul><ul><li> I nsulin secretion and resistance </li></ul></ul></ul><ul><ul><li>Hoppe C et al. High intakes of milk, but not meat increase s-insulin and insulin resistance in 8-year-old boys . </li></ul></ul><ul><ul><li>Eur J Clin Nutr. 2005 Mar;59(3):393-8 </li></ul></ul>Hostettler-Allen RL et al. Insulin resistance, hyperglycemia, and glucosuria in intensively milk-fed calves. J Anim Sci . 1994 Jan;72(1):160-73.
    61. 61. 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
    62. 62. 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
    63. 63. Higher Fructose Intake
    64. 64. Fructose & Insulin Resistance <ul><li>Most ~ (50-60%) of fructose ingested is rapidly taken up by the liver </li></ul><ul><li>Fructose by-passes the major regulatory step (PFK) of glycolysis in liver allowing it: </li></ul><ul><li>1. To serve as an unregulated source of acetyl-CoA, and glycerol 3-P, necessary components of VLDL synthesis </li></ul><ul><li>Fructose increases hepatic de-novo lipogenesis whereas eucaloric glucose ingestion does not </li></ul>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
    65. 65. Fructose & elevation of Serum Uric Acid Concentrations <ul><li>The enzymes of hepatic adenine degradation are normally inhibited by high concentrations of ATP and P(i) </li></ul><ul><li>The removal of this inhibition by lowered ATP & P(i) concentrations leads to increased generation of uric acid </li></ul>Mayes PA. Am J Clin Nutr 1993;58:754S-65S. From Cordain L, with permission
    66. 66. <ul><li>Because fructose by-passes the major regulatory step (PFK) of glycolysis in liver , it elevates: </li></ul><ul><li>Lactate concentrations 1 </li></ul><ul><li>Lactate is a potent inhibitor of uric acid excretion by liver 2 </li></ul><ul><li>Consequently, fructose ingestion both enhances uric acid production and slows its excretion </li></ul>Fructose & elevation of Serum Uric Acid Concentrations <ul><li>Mayes PA. Am J Clin Nutr 1993;58:754S-65S. </li></ul><ul><li>2. Yamamoto T et al. Nephron 1993;65:73-6 </li></ul>From Cordain L, with permission
    67. 67. Higher Net Endogenous Acid Production
    68. 68. 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
    69. 69. <ul><li>The displacement of fruits and vegetables by cereal grains, cheese & salt shifted hominin diets to net acid yielding </li></ul><ul><li>Diseases promoted by a net metabolic acidosis: </li></ul><ul><ul><li>Osteoporosis </li></ul></ul><ul><ul><li>Hypertension </li></ul></ul><ul><ul><li>Kidney stones </li></ul></ul><ul><ul><li>Stroke </li></ul></ul><ul><ul><li>Sarcopenia </li></ul></ul>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.
    70. 70. Disruption of Dietary Fatty Acids Balance
    71. 71. 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 <ul><li>Inflammation, Endothelial activation, smooth muscle cell proliferation, thrombogenesis & plaque rupture ; </li></ul><ul><li>Arrythmogenesis; </li></ul><ul><li>Glucose and insulin metabolism; </li></ul><ul><li>Oxidative stress; </li></ul><ul><li>Adipogenesis </li></ul>
    72. 72. Increase in w6/w3 Ratio
    73. 73. W6/w3 Ratio in various populations Simopoulos, A. World Rev Nutr Diet . Basel, Karger, 2003, vol 92, pp 1–22.
    74. 74. Ω 3 Index <ul><li>Von Schacky e Harris created & proposed a new risk factor for CVD </li></ul><ul><li>Ω 3 Index , which is calculated through the percentage of EPA & DHA in RBC membrane . </li></ul><ul><li> Ω 3 Index ≥ 8%  Risk of death by CVD 90% lower that an Ω 3 Index ≤ 4% . </li></ul>von Schacky C, Harris WS. Cardiovascular benefits of omega-3 fatty acids . Cardiovasc Res. 2007 Jan 15;73(2):310-5.
    75. 75. Ω 6/ Ω 3 Ratio & CVD Okuyama H, Ichikawa Y, Sun Y, Hamazaki T, Lands WE. World Rev Nutr Diet. 2007;96:83-103.
    76. 76. High Ω 6/ Ω 3 Ratio may increase risk for Osteoporosis <ul><li>Weiss LA, Barrett-Connor E, von Muhlen D. Am J Clin Nutr. 2005 Apr;81(4):934-8 </li></ul><ul><ul><li>Watkins BA, Li Y, Seifert MF. J Nutr Biochem . 2006 Apr;17(4):282-9 </li></ul></ul><ul><ul><li>Bhattacharya A, et al. J Am Coll Nutr . 2005 Jun;24(3):200-9. </li></ul></ul><ul><ul><li>Hasturk H et al. FASEB J . 2006 Feb;20(2):401 </li></ul></ul><ul><ul><li>Shen CL, et al. Br J Nutr . 2006 Mar;95(3):462-8 </li></ul></ul><ul><ul><li>. </li></ul></ul>
    77. 77. <ul><li>Epidemiologic & experimental studies sugest that: </li></ul><ul><ul><li>High Ω 6/ Ω 3 Ratio may increase the risk for various types of cancer (prostate, breast, colon, pancreas & lung ) </li></ul></ul>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.
    78. 78. Decrease in Micronutrient intake
    79. 79. Cordain L et al. Am J Clin Nutr . 2005 Feb;81(2):341-54.
    80. 80. 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.
    81. 81. 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
    82. 82. Lifestyle Consequences
    83. 83. Decrease in Vitamin D status Ho lick MF, Chen TC. Am J Clin Nutr . 2008 Apr;87(4):1080S-6S
    84. 84. Sedentarism
    85. 85. Booth FW, Chakravarthy MV, Spangenburg EE. J Physiol . 2002 Sep 1;543(Pt 2):399-411.
    86. 86. <ul><li>CHD </li></ul><ul><li>Angina </li></ul><ul><li>Myocardial Infarction </li></ul><ul><li>Heart Failure </li></ul><ul><li>Hypertension </li></ul><ul><li>Stroke </li></ul><ul><li>T2D & Metabolic Syndrome </li></ul><ul><li>Obesity </li></ul>Diseases of sedentarism <ul><li>Sarcopenia </li></ul><ul><li>Dyslipidemia </li></ul><ul><li>Gallblader disease </li></ul><ul><li>Epithelial cell cancers </li></ul><ul><li>Immune dysfunction </li></ul><ul><li>Osteoporosis </li></ul><ul><li>Cognitive impairment </li></ul>Booth FW, et al. J Appl Physiol. 2002 Jul;93(1):3-30
    87. 87. Disrupted sleep patterns
    88. 88. <ul><li>Impairs spatial learning & affects membrane excitability and mitochondrial protein in the hippocampus </li></ul><ul><li>Disrupts emotional brain reactivity </li></ul>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
    89. 89. <ul><li>Obese individuals sleep less than normal BMI individuals ( NHANES III data ) </li></ul><ul><li>Sleep deprivation: </li></ul><ul><ul><li>Ghrelin </li></ul></ul><ul><ul><li>Craving for high GL foods </li></ul></ul><ul><ul><li>Cortisol </li></ul></ul><ul><ul><li>Growth Hormone </li></ul></ul>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
    90. 90. <ul><li>Associated with increased mortality from cardiovascular disease, noncardiovascular disease/noncancer, and all causes for both sexes </li></ul>Insufficient Sleep Ikehara S, et al. Sleep 2009 Mar 1;32(3):295-301
    91. 91. Shift- and night-time work <ul><li>Disruption of normal circadian rhythm may increase the risk of developing cance rs, especially breast cancer </li></ul>Davis S, Mirick DK. Cancer Causes Control . 2006 May;17(4):539-45 Hansen J. Cancer Causes Control. 2006 May;17(4):531-7.
    92. 92. Are Primitive populations healthy ?????
    93. 93. 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.
    94. 94. 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
    95. 95. 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
    96. 96. 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
    97. 97. 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
    98. 98. 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
    99. 99. 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
    100. 100. Higher Vo2 max in primitive populations versus Average Americans Eaton SB, Konner M, Shostak M. Am J Med . 1988 Apr; 84(4): 739-49.
    101. 101. <ul><li>Absence of Obesity and chronic degenerative diseases among primitive populations </li></ul>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
    102. 102. 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
    103. 103. Pedro Bastos [email_address] www.nutriscience.pt

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