Evolutionary History of Dairy

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Based primarily on the work of Professor Loren Cordain (Colorado State University), Professor Nina Jablonski, (Penn State) and Professor Dallas Swallow (University College London)

Based primarily on the work of Professor Loren Cordain (Colorado State University), Professor Nina Jablonski, (Penn State) and Professor Dallas Swallow (University College London)

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  • Furthermore,infantswerebreastfeduntilabout 30 months
  • Becausethe spread of AgriculturetoEuropetook time,
  • Well,Exposure of 5MTHF to UVB results in oxidationto 5methyldihydrofolate,whichdoesn’t re-enter the Folate pool. Moreover, 5MTHF is oxidized by ROS produced by naturally photosensitizers (flavins, porphyrins, bilirubin, etc.) after UVA exposure.5MTHF is first oxidized to 5MDHF, and then the molecule is cleaved into PGA and an unknown pterin.
  • Constantexposureto UVA and UVB radiationwill lead tolessFolateforCelldivision, compromisingReproduction and hencethesurvivalpfthespecies. Ifyoubelieve in Evolution, through natural selection, as I do, youwouldassumethatsuchanenvironmentalpressureisexpectedtoresult in geneticadaptations
  • Indeed, thereis a stronginversecorrelationbetweenskinpigmentation and latitude
  • We know that Hunter-Gatherers living below 30º latitude where in a UVB and UVA rich environment, allowing optimal cutaneous generation of vitamin D-3 from its precursor 7-dehydrocholesterol. But as further North they went, they could get Vitamin D deficiency during many months.Most studies of the effects of UV radiation on human skin have utilized as a standard the minimum-erythemal dose (UVMED), which is the quantity of UV radiation required to produce a barely perceptible reddening of lightly-pigmented skin
  • Vitamin D deficiency significantly decreases Ca absorption, which decreases serum CaThis leads toincreasedParathyroid hormone releasefromtheparathyroidglandsParathyroid hormone increases Ca resorption in ordertomaintainstableserum Ca concentrationsPTH increaseshydrogenphosphateurinarylossThis leads toLesscalciumphosphateThis will lead to a Mineralization defectAnd hence Rickets
  • Sunlight converts 7-dehydrocholesterol (7-DHC) in the skin to vitamin D3, which is converted successively to 25-hydroxy-D3 (25-D3) and then to 1,25-dihydroxy- D3 (1,25-D3) within keratinocytes. Sunlight also induces expression of the vitamin D receptor(VDR). 1,25-D3 and the VDR then together induce the expression of the gene encoding the human antimicrobial peptide LL-37. Vitamin D3 enters the systemic circulation and is converted to 25-D3 by the liver. Circulating monocytes are activated by TLR2/1 agonists present on specific microbes. The genes encoding VDR and CYP 27B1 are induced. CYP27B1 converts 25-D3 from the circulation to 1,25-D3, joins with the VDR and activates the gene encoding LL-37, leading to an increase in cellular LL-37 and enhanced microbicidal activity of the phagocyte.
  • Thesolutiontothisproblemwasskindepigmentation
  • Bu what about the Inuit people? They live at high latitudes, so why they do not have light pigmented skin???
  • Normally at high latitudes extreme temperatures cause the growing season to be too short for plant foods to compete with animal foods as staplesThe circum North/Baltic Seas land mass is warmed because of Gulf Stream 2) Maritime nearnessFor instance, AverageTemperatureinWinterinLondonis4°Cvs- 9 °C in N. America & Eurásia, at51º N
  • Hence, this 1000 km radius of surrounding land was the furthest North that cereals could be grown prior to modern agriculture
  • Whole Wheat Flour contains30-50 mg/kg WGA, so a Neolithic Farmer would be consuming 15-25 mg/dayof WGA
  • A geneticadaptationtoincraesedrickets in NorthernEuropewasExtremeDermal Depigmentation about5,300 – 6,000 years
  • Another adaptation was hair depigmentation and lowconcentrations of melanin in the stroma of the iris, whichgivestheblueeyeappearanceundercertainexternallightingconditions. Againthishappen in Europeabout6,000 – 10,000 YA Quanto+ claraé a corcastanha, maisclaroé o cabelo e olhos
  • Anothersolutiontoavoidricketswould be increasing Ca intake. SinceMilkcontains 300 mg of Ca per 225 ml, itwould be thelogicalchoice.
  • lactase-phlorizin hydrolase in the brush border efficiently hydrolyses lactose into galactose (Gal) and glucose (Glu) and is rapidly absorbed into the bloodstream taking luminal water with it. Hydrolysis typically occurs in the jejunum, which has low concentrations of bacteria 101-4 mL-1; thus, little lactose is fermented.
  • Indeed, thearchaeological dates for the spread of domesticated animals and dairying into Europe fit into the date estimate for the emergence of the SNP in the gene encoding lactase, which is associated with adults lactase persistence in Europeans. The selection coefficient (s) for this allele in Europeans is 0.014 - 0.150
  • The selection coefficient (s) for this allele in Scandinavians is = 0.090 - 0.190Which has been labeled: 1) “among the strongest yet seen for any gene in the genome”“one of the strongest genetic signatures of natural selection yet reported in humans”The frequency of this allele is much higher in Northern Europe than anywhere else. And, just like skin depigmentation, light hair and blue eyes it is centered concentrically within ~ 1000 km radius of the North & Baltic Seas
  • Andcoming back totheMiddle East again, wehavethedomestication oftheArabiancamelabout 6,000 years ago. Thisfitsinto the date estimate (about 4,000 years ago) for the emergence of anotheralleleassociatedwithadult lactase persistence. Thisalleleisfound in highfrequencyamong a fewpastoralistgroupssuch as SaudiArabians and Bedouins of Sinai, amongwhichtheArabiancamel has beenthemaindomesticated animal usedformilk
  • In Africa, the Spread of Pastoralism south of the Sahara occurred about 4,500 years ago and into Northern Tanzania happened about 3,300 years ago.
  • In accordance with this, the date estimate for at least 3 SNPsassociatedwithlactase persistence in Sub-SaharanAfricansis3000-7000 years ago.
  • CompromisedUV exposure would not have been a selective pressure for the evolution of ALPin sub-Saharan Africans, since African children typically maintain normalplasma concentrations of vitamin DNevertheless, the high selection coefficient (s) for putative LCT alleles in sub-Saharan Africans (s = 0.035-0.097), which is suggestive that milk drinking is highly protective of other pre-existing causes of mortality
  • Indeed, in geographic areas where Malaria is Endemic there were genetic changes that resulted in Sickle cell anemia,Glucose-6-phosphate dehydrogenase Deficiency and other Hemoglobinopathies & conditions influencing erythrocyte longevity.Another genetic change believed to be driven by Malaria was ALP in certain parts of Africa. Why it didn’t happen all over sub-Saharan Africa?Because Selection for ALP may have been prevented by animal trypanosomiasiswhich precludes widespread cattle husbandry in much of Africa.Anemia falciforme (ou drepanocitose) é o nome dado a uma doença hereditária que causa a malformação das hemácias, que assumem forma semelhante a foices (de onde vem o nome da doença), com maior ou menor severidade de acordo com o caso, o que causa deficiência do transporte de oxigênio nos indivíduos acometidos pela doença. – resulta de uma mutação no gene da hemoglobinaG6PDH) is a cytosolicnzyme in the pentose phosphate pathway (see image), a metabolic pathway that supplies reducing energy to cells (such as erythrocytes) by maintaining the level of the co-enzyme nicotinamide adenine dinucleotide phosphate (NADPH). The NADPH in turn maintains the level of glutathione in these cells that helps protect the red blood cells against oxidative damage
  • Because PABA, pterin and glutamate moieties are required for the de novo synthesis of folate in bacteria (including Plasmodia sp.)1

Transcript

  • 1. UWS Master of Science in Nutrition and Functional Medicine Course: Supplementation and Whole Food Nutrition Week #: 4 Topic: Milk, Dairy and Human Health Instructor: Pedro Carrera Bastos, MS
  • 2. OBJECTIVES FOR THIS WEEK To understand the evolutionary pressures behind Adult lactase persistence To recognize that Milk is a mammalian signaling system, with various hormonal effects To know the current scientific evidence concerning Dairy, Metabolic Syndrome and Cancer To understand the potential value of Dairy and/or its Proteins in Exercise Performance To know the current evidence regarding Dairy and Body Composition To understand the mechanisms behind Milk and Acne To know the Casein A1/A2 controversy To recognize the main differences between raw milk and pasteurized/homogenized milk To understand the role of Calcium in Osteoporosis and Cardiovascular Disease To recognize Milk Allergy To understand the connection between Milk proteins and auto-immune diseases To learn to prepare lactose/dairy-free, rich-calcium meals, and to know how to ferment milk
  • 3. TOPICS FOR THIS PRESENTATIONEvolutionary History of Milk and DairyLactose Intolerance and ALP
  • 4. HISTORY OF MILK & DAIRY
  • 5. ORIGINS OF MAN Homo sapiens 0 H. heidelbergensis H. erectus Paranthropus H. neanderthalensis boisei 1 H. antecessor H. habilis P. robustus 2 H. ergaster Au. garhi Au. 3 rudolfensis P. aethiopicusMilhões de anos Kenyanthropus Au. africanus platyops Au. bahrelghazali 4 Ardipithecus ramidus Au. afarensis Au. anamensis 5 Orrorin tugenensis 6 7 Sahelanthropus tchadensis 8 Adapted from Wood B. Nature 2002:418:133-35 & from Cordain L, 2009
  • 6. All humans in Europe, Asia, Oceania and America have an AFRICAN ORIGIN Etiópia LESS GENETIC DIVERSITY Liu H, et al., 2006 OUTSIDE AFRICARelethford JH. Heredity. 2008 Jun;100(6):555-63. Jakobsson M, et al. Nature 2008; 451(7181):998-1003Manica A, et al. Nature; 2007; 448(7151):346-8 Hellenthal G, Auton A, Falush D. PLoS Genet. 2008 May 23;4(5):e1000078Liu H, et al. Am J Hum Genet. 2006 Aug;79(2):230-7 Ramachandran S, et al. Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):15942-7Conrad D, et al. Nat Genet 2006; 38: 1251–1260 Prugnolle F, Manica A, Balloux F. Current Biology 2005; 15:R159–R160RAY N, et al. Genome Res 2005; 15:1161–1167 Cavalli-Sforza LL, Feldman MW. Nat Genet 2003; 33:266–275Macaulay V, et al. Science 2005; 308(5724):1034-6 Tishkoff S, Williams S. Nat Rev Genet 2002; 3: 611–621Currat M, Excoffier L. PLoS Biology 2004; 2: 2264–2274 Harpending, H, Rogers, AR. Annu Rev Genomics Hum Genet 2000; 1:361–385
  • 7. Liu H, et al. Am J Hum Genet. 2006 Aug;79(2):230-7
  • 8. WHAT WAS OUR ECOLOGICAL NICHE???
  • 9. HUNTER-GATHERER’S DIETS
  • 10. VEGETABLE SOURCES Plants Roots & Tubers Berries Fruits Nuts Cordain L et al. Am J Clin Nutr. 2005 Feb;81(2):341-54
  • 11. ANIMAL SOURCES  Wild Animals  Insects  Seafood  EggsCordain L et al. Am J Clin Nutr. 2005 Feb;81(2):341-54
  • 12. WHAT THEY DIDN’T EAT?
  • 13. DAIRYREFINED SUGARS SALT LEGUMES CEREALS ALCOHOL FEEDLOT MEAT REFINED 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
  • 14. MILK? WHY NOT?Cordain L et al. Am J Clin Nutr. 2005 Feb;81(2):341-54
  • 15. meses meses mesesSellen DW. J Nutr. 2001 Oct;131(10):2707-15
  • 16. BREASTFEEDING PATTERNS Sellen DW. J Nutr. 2001 Oct;131(10):2707-15
  • 17. ~11,000 YA Neolithic Revolution in the Middle EastCordain 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.
  • 18. EVIDENCE FOR THE USE OF DAIRY IN THE MIDDLE EAST First evidence of dairying in the Middle East (Turkey) 4 Domestication of sheeps, goats and cattle (Middle East) 1-3 Present 10,000 9,000 8,000 7,000 6,000 5,000 4,000 3,000 2,000 1,000Generations Human 333 300 267 233 200 167 133 100 66 33 1 - Hiendleder S, et al. Proc Biol Sci. 2002 May 7;269(1494):893-904 2 - Luikart G, et al. Proc Natl Acad Sci U S A. 2001 May 8;98(10):5927-32 3 - Loftus RT, et al. Mol Ecol. 1999 Dec;8(12):2015-22 4 - Evershed RP et al. Nature. 2008 Sep 25;455(7212):528-31.
  • 19. GEOGRAPHIC EXPANSION OF THE FIRST NEOLITHIC CULTURES Gerbault P, et al. Philos Trans R Soc Lond B Biol Sci. 2011 Mar 27;366(1566):863-77.
  • 20. EVIDENCE FOR THE USE OF DAIRY IN THE MIDDLE EAST & EUROPE First evidence of dairying in North. Eur (UK) 6 First evidence of dairying in Europe (Romania) 5 First evidence of dairying in the Middle East (Turkey) 4 Domestication of sheeps, goats and cattle (Middle East) 1-3 Present 10,000 9,000 8,000 7,000 6,000 5,000 4,000 3,000 2,000 1,000Generations Human 333 300 267 233 200 167 133 100 66 33 1 - Hiendleder S, et al. Proc Biol Sci. 2002 May 7;269(1494):893-904 2 - Luikart G, et al. Proc Natl Acad Sci U S A. 2001 May 8;98(10):5927-32 3 - Loftus RT, et al. Mol Ecol. 1999 Dec;8(12):2015-22 4 - Evershed RP et al. Nature. 2008 Sep 25;455(7212):528-31. 5 - Craig OE, et al. Antiquity 2005; 79:882-894 6 - Copley MS et al. Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1524-9
  • 21. UVBJablonski NG, Chaplin G. Proc Natl Acad Sci U S A. 2010 May 11;107 Suppl 2:8962-8
  • 22. UVAJablonski NG, Chaplin G. Proc Natl Acad Sci U S A. 2010 May 11;107 Suppl 2:8962-8
  • 23. FOLATEMiller AL, Kelley GS. Altern Med Rev. 1996;1(4):220-235
  • 24.  5MTHF absorbs UVB  oxidized to 5MDHF 5MDHF doesn’t re-enter the Folate pool 5MTHF is oxidized by ROS produced by naturally photosensitizers (flavins, porphyrins, bilirubin, etc.) after UVA exposure
  • 25. Jablonski NG, Chaplin G. Proc Natl Acad Sci U S A. 2010 May 11;107 Suppl 2:8962-8
  • 26. PIGMENTATION AND LATITUDE Chaplin G. Am J Phys Anthropol. 2004 Nov;125(3):292-302
  • 27. Liu H, et al. Am J Hum Genet. 2006 Aug;79(2):230-7
  • 28. Holick MF. J Clin Invest. 2006 Aug;116(8):2062-72
  • 29. Vitamin D deficiency 6 + months per yearVitamin D deficiency 1 + months per year Vitamin D all yearVitamin D deficiency 1 + months per yearVitamin D deficiency 6 + months per year Jablonski NG, Chaplin G. J Hum Evol. 2000 Jul;39(1):57-106
  • 30. Low Pigmentation54 mJ/cm2 Pele muito pigmentada Pele muito320 mJ/cm2 pigmentada Holick M. Am J Clin Nutr 2004;80(suppl):1678S– 88S.
  • 31. Low Pigmentation54 mJ/cm2 High Pigmentation Pele muito320 mJ/cm2 pigmentada Holick M. Am J Clin Nutr 2004;80(suppl):1678S– 88S.
  • 32. Low Pigmentation54 mJ/cm2 High Pigmentation High320 mJ/cm2 Pigmentation Holick M. Am J Clin Nutr 2004;80(suppl):1678S– 88S.
  • 33. FOOD SOURCES OF VITAMIN D Food Vit. D (IU)Cod Liver Oil (10 g) 1360Sardins (105 g) 500Tuna (105 g) 402Farmed Salmon (105 g) 360Egg (1 medium) 20Liver (105 g) 15 Ozkan B. J Clin Res Pediatr Endocrinol. 2010 Dec;2(4):137-43
  • 34. Holick MF. J Clin Invest. 2006 Aug;116(8):2062-72
  • 35. Pelvic flattening, permanently narrowing the birth canalINCREASED MATERNAL MORTALITY DURING CHILDBIRTH Jablonski NG et al. J Hum Evol. 2000;39(1):57-106
  • 36. VDR IN MULTIPLE CELLS Holick MF. J Clin Invest. 2006 Aug;116(8):2062-72
  • 37. Zasloff M. Nat Med. 2006 Apr;12(4):388-90
  • 38. DEPIGMENTATION DarkerCordain, L., Hickey, M. S. & Kim, K. In press. Malaria and rickets represent selective forces for the convergent evolution of adultlactase persistence. In Biodiversity in agriculture: domestication, evolution and sustainability (eds P. Gepts, R. Bettinger, S. B. Brush, T. Famula, P. E. McGuire & C. O. Qualset). Cambridge, UK: Cambridge University Press.
  • 39. UVA IS HIGHER IN THE POLES & SNOW REFLECTS UVA Jablonski NG, Chaplin G. Proc Natl Acad Sci U S A. 2010 May 11;107 Suppl 2:8962-8
  • 40. TF – Traditional Foods1 mcg Vit D = 40 IU Kuhnlein HV, Receveur O. J Nutr. 2007 Apr;137(4):1110-4
  • 41. HIGH LATITUDE, CLOUDYCLIMATE, REDUCED SUNLIGHT N 65DECREASED UV EXPOSURE & N 55LESS VITAMIN D SYNTHESIS N 45 RICKETS Loomis WF. Science. 1967 Aug 4;157(788):501-6. Jablonski NG et al. J Hum Evol. 2000;39(1):57-106
  • 42. GEOGRAPHIC EXPANSION OF THE FIRST NEOLITHIC CULTURES Gerbault P, et al. Philos Trans R Soc Lond B Biol Sci. 2011 Mar 27;366(1566):863-77.
  • 43. THE SPREAD OF AGRICULTURE FROM THE MIDDLE EAST TON. EUROPE BROUGHT NOT ONLY DAIRYING BUT ALSO WHEAT & BARLEY 5000 YA 6000 YA 8000 YA Jericho 10,000 YA 9000 YA Cordain, L., Hickey, M. S. & Kim, K. In press.
  • 44. The circum North/Baltic Seas land mass is warmed because of 1) Gulf Stream 2) Maritime nearness Mar do Mar Norte Báltico 55 N Average Temperature in Winter in London is 4 C vs - 9 C in N. America & Eurásia, at 51º N Seager R. The source of Europe’s mild climate. Am Sci 2006;94;334-41 . In Cordain, L., Hickey, M. S. & Kim, K. In press.
  • 45. Cordain L. World Rev Nutr Diet. 1999;84:19-73
  • 46.  High consumption (>50% energy) of whole grains (whole wheat, maize, oats, rye) are routinely used to induce rickets in dogs, rats, chickens and primates1-4  Epidemiological studies of human populations consuming high intakes of unleavened bread show rickets and vitamin D deficiency to be widespread 5-71Mellanby E. Lancet 1919;1:407-08.2Thomas BH et al. Biochem J 1936;30:12-177-883Sly MR et al. Calcif Tissue Int 1984;36:370-794Grammer JC et al. Poult Sci 1983;62: 103-95Gibson RS et al. Brit J Nutr 1987;58:23-296Brooke OG et al. Brit J Obstet Gynaecol 1981;88:18-267Hunt SP et al. BMJ 1976;2:1351-54. In Cordain L. World Rev Nutr Diet. 1999;84:19-73
  • 47. HOW WHOLE GRAINS MAY PROMOTE RICKETS? Increased elimination of vitamin D in bile1 Low Ca/P thereby promoting bone resorption2 Impaired labile calcium absorption via high phytate content3 Lectin (WGA) blockade of the nuclear pore, thereby preventing gene transcription of VDR4,5 1Batchelor AJ et al. Brit J Nutr 1983;49:213-16 2Cordain L. World Rev Nutr Diet. 1999; 84:19–73 3Mellanby E. J Physiol 1949;109:488-533 4Guinex C. et al. Int J Biochem Cell Biol 2005;37:765-74 5Findlay DR et al. J Cell Biol 1987;104:189-200
  • 48. WGA Wheat Germ: 300 – 350 mg/kg WGA (1) Whole Wheat Flour: 30-50 mg/kg WGA (2) Refined Wheat Flour: 4.4 mg/kg WGA (2) 1. Vincenzi S, et al. J Agric Food Chem. 2002 Oct 23;50(22):6266-70. 2. Matucci A et al. Food Control 2004;15: 391-95
  • 49. Extreme Dermal Depigmentation originated in Northern Europeans ~ 5,300 – 6,000 years GEOGRAPHIC DISTRIBUTION FOR SKIN PIGMENTATIONCordain, L., Hickey, M. S. & Kim, K. In press. Malaria and rickets represent selective forces for the convergent evolution of adultlactase persistence. In Biodiversity in agriculture: domestication, evolution and sustainability (eds P. Gepts, R. Bettinger, S. B. Brush, T. Famula, P. E. McGuire & C. O. Qualset). Cambridge, UK: Cambridge University Press.
  • 50. GEOGRAPHIC DISTRIBUTION FOR HAIR & EYE PIGMENTATION IN EUROPE Blond Hair / Blue Eyes originated in Europe ~ 6,000 – 10,000 YAEiberg H et al. Hum Genet 2008;123:177-187.Cordain, L., Hickey, M. S. & Kim, K. In press. Malaria and rickets represent selective forces for the convergent evolution of adultlactase persistence. In Biodiversity in agriculture: domestication, evolution and sustainability (eds P. Gepts, R. Bettinger, S. B.Brush, T. Famula, P. E. McGuire & C. O. Qualset). Cambridge, UK: Cambridge University Press.
  • 51. INCREASED CALCIUM INTAKE Pettifor JM. Am J Clin Nutr. 2004 Dec;80(6 Suppl):1725S-9S
  • 52. Adapted from Cordain L, 2009 (with permission) Cordain L. Dietary implications for the development of acne: a shifting paradigm.In: U.S. Dermatology Review II 2006, (Ed.,Bedlow, J). Touch Briefings Publications, London, 2006.
  • 53. TGF-α: Transforming Growth Factor Alpha HB-EGF: Heparin Binding EGF EPR: Epiregulin AR: Amphiregulin (NRG1, NRG2, NRG3, NRG4): Neuregulins 1, 2, 3 and 4 ErB1 – EGF-R Cordain L. Dietary implications for the development of acne: a shifting paradigm.In: U.S. Dermatology Review II 2006, (Ed.,Bedlow, J). Touch Briefings Publications, London, 2006.
  • 54. BETA-CELLULINBastian SE, et al. Measurement of betacellulin levels in bovine serum, colostrum and milk. J Endocrinol. 2001 Jan;168(1):203-12.
  • 55. Adapted from Cordain L, 2009 (with permission)EGF in saliva: 0.0512 ng/ mlTotal Saliva: 691 ml/24 hoursEGF in 24h Saliva: 35.3 ng BTC per liter of Bovine Milk: 1930 ng Cordain L. Dietary implications for the development of acne: a shifting paradigm. In: U.S. Dermatology Review II 2006, (Ed.,Bedlow, J). Touch Briefings Publications, London, 2006.
  • 56. Adapted from Cordain L, 2009 (with permission)WGA can bind luminally BTCexpressed EGF-R or WGA Lumen EGF Receptor EGF Receptor To Lymph WGA Hormi K et al. Cell Tissue Res 1994;278:439-50 To Rebbaa A et al. J Neurochem 1996;67:2265-2272 Circulation Lochner N, et al. Pharm Res. 2003 May;20(5):833-9.
  • 57. LACTOSE SOURCES Food Serving (g) Lactose (g)Cow’s Milk 100 4.6Buffalo Milk 100 5.1Goat’s Milk 100 4.1Sheep’s Milk 100 5.4 Park YW, Haenlein GFW. Handbook of Milk of Non-Bovine Mammals. Blackwell Publishing, 2006.
  • 58. LACTOSE HYDROLYSISLomer MC, Parkes GC, Sanderson JD. Aliment Pharmacol Ther. 2008 Jan15;27(2):93-103
  • 59. LACTOSE SOURCES Food Serving (g) Lactose (g)Human Milk 100 6.9Cow’s Milk 100 4.6Buffalo Milk 100 5.1Goat’s Milk 100 4.1Sheep’s Milk 100 5.4 LACTASE EXPRESSION IS COMMON IN MOST YOUNG MAMMALS Park YW, Haenlein GFW. Handbook of Milk of Non-Bovine Mammals. Blackwell Publishing, 2006.
  • 60. After the weaning period is over, lactase production usually declines , although themechanisms and evolutionary reasons for thisdownregulation are not fully understood
  • 61. HIPOLACTASIA IS THE NORMAL PHENOTYPE IN HUNTER-GATHERERS AFTER AGE 3-5 Gerbault P, et al. Philos Trans R Soc Lond B Biol Sci. 2011 Mar 27;366(1566):863-77.
  • 62. Burger J, et al. Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):3736-41
  • 63. LACTOSE INTOLERANCE INTOLERÂNCIA À LACTOSEHIGH OSMOTIC HIGH OSMOTIC LOAD LOADDIARRHEA DIARRHEA Lomer MC, Parkes GC, Sanderson JD. Aliment Pharmacol Ther. 2008 Jan15;27(2):93-103
  • 64. ALP IN EUROPE Gerbault P, et al. Philos Trans R Soc Lond B Biol Sci. 2011 Mar 27;366(1566):863-77. Predicted Old World LP phenotype frequencies based on -13,910 C>T allele frequency data only Estimated Dates of Origin: 2188 - 20650 BP(s = 0.014 - 0.150) 7450 - 12300 BP
  • 65. THE HIGHEST FREQUENCY OF THE -13,910 C>T allele IS CENTERED CONCENTRICALLY WITHIN ~ 1000 KM RADIUS OF THE NORTH & BALTIC SEAS(between 53º and 58º N) Baltic N. Sea (s = 0.090 - 0.190)Cordain, L., Hickey, M. S. & Kim, K. In press. Malaria and rickets represent selective forces for the convergent evolution of adultlactase persistence. In Biodiversity in agriculture: domestication, evolution and sustainability (eds P. Gepts, R. Bettinger, S. B. Brush, T. Famula, P. E. McGuire & C. O. Qualset). Cambridge, UK: Cambridge University Press.
  • 66. The combination of 1) high latitude, 2) cloudy weather, 3)whole grain cereals as staples likely represented the uniquecombination of selective pressures responsible for theevolution of: ALP Blond Hair/Blue Iris Extreme Dermal Depigmentation (5,000 – 12,000 YA) (6,000 – 10,000 YA) (5,300 – 6,000 YA)  ALP: Ad libitum consumption of milk with GI distress protects against rickets by milk’s high calcium content1  Blond hair & blue eyes; extreme dermal depigmentation enhances dermal synthesis of vitamin D and further protects against rickets2 Cordain, L., Hickey, M. S. & Kim, K. In press. Malaria and rickets represent selective forces for the convergent evolution of adult lactase persistence. In Biodiversity in agriculture: domestication, evolution and sustainability (eds P. Gepts, R. Bettinger, S. B. Brush, T. Famula, P. E. McGuire & C. O. Qualset). Cambridge, UK: Cambridge University Press.
  • 67. Domestication of the Arabian camel: 6000 BPOrigin of G-13915 allele in the Arabian Pensinsula: 4000 BP Enattah NS, et al. Am J Hum Genet. 2008 Jan;82(1):57-72
  • 68. Spread of Pastoralism southof the Sahara: 4,500 BPSpread of Pastoralisminto Northern Tanzania: 3,300 BP Tishkoff SA, et al. Nat Genet. 2007 Jan;39(1):31-40
  • 69. Various SNPs (G/C-14010, T/G-13915 and C/G-13907) associated with LP in Sub-Saharan Africans arose 000 3000-7000 BP Tishkoff SA, et al. Nat Genet. 2007 Jan;39(1):31-40
  • 70. 20 N Equator 20 S African children typically maintain normal plasma concentrations of vitamin D High selection coefficient (s) for putative LCT alleles in sub-Saharan Africans (s = 0.035-0.097) Is milk drinking protective of other pre-existing causes of mortality? Pfitzner MA et al. J Pediatrics 1998;133:740-4. In Cordain, L., Hickey, M. S. & Kim, K. In press.
  • 71. MALARIA INCIDENCE MALARIA MORBIDITY AND MORTALITY WORLD WIDE ARE HIGHEST IN SUB-SAHARAN AFRICA ~75% of all cases of P. falciparum malaria and >80% of all malaria attributable deaths occur in sub-Saharan Africa Walther B et al. Ann Trop Med Parasitol 2007;101:657-72.
  • 72. GENETIC CHANGES IN GEOGRAPHIC AREAS WHERE MALARIA IS ENDEMIC Hemoglobinopathies and other mutations influencing erythrocyte longevity  Sickle cell anemia  G6PD Deficiency ALP in parts of Africa where animal Trypanosomiasis doesn’t occur Cordain, L., Hickey, M. S. & Kim, K. In press. Malaria and rickets represent selective forces for the convergent evolution of adult lactase persistence. In Biodiversity in agriculture: domestication, evolution and sustainability (eds P. Gepts, R. Bettinger, S. B. Brush, T. Famula, P. E. McGuire & C. O. Qualset). Cambridge, UK: Cambridge University Press.
  • 73. Adapted from Cordain L, 2009 (with permission) MILK & MALARIA ???  All milk diets suppress malarial infections in birds, rodents and primates by restricting para amino benzoic acid (PABA) intake 1,2  The suppression of malarial symptoms is abrogated when supplemental PABA is added to all milk diets or PABA deficient diets of infected animals 2,31Kretschmar W et al. Tropenmed Parasit 1973;24:51-592Nowell F. Parasitology 1970;61:425-33.3Kicska GA et al. Infect Dis 2003;188:1776-81
  • 74. Adapted from Cordain L, 2009 (with permission) PABA, FOLATE & MALARIAPentose phosphate cycle Glycolysis  PABA synthase activity in Plasmodia is D-Erythrose 4-P Phosphoenolpyruvate low & poorly supports growth1  Dietary deficiencies of PABA & folate 7-Phospho-2-dehydro-3-deoxy-D-arabinoheptulosonate may suppress malarial symptoms by 3-Dehydroquinate synthase impairing folate metabolism1 3-Dehydroquinate 3-Dehydroquinate dehydratase  Dietary PABA and folate reduce 3-Dehydroshikimate efficacy of sulfa drugs in rodent Shikimate 5-Dehydrogenase models2 Shikimate Shikimate kinase Shikimate 3-Phosphate MILK DOES NOT CONTAIN PABA & IS 3-phosphoskikimate-1-carboxyvinyl transferase (EPSP synthase) A POOR SOURCE OF FOLATE 3-Phospho-5-enoylpyruvylshikimate (6-9 mg/100g vs. DRI 400 mg)3 Ubiquinone Chorismate Aromatic Amino Acids PABA synthase PABA Sulfonamides (additional PABA antagonizes sulfonamides) 1KicskaGA et al. Infect Dis 2003;188:1776-81(inhibit plasmodial growth) Folate 2JacobsRL. Exp Parasitol 1964;15:213-25 3Johnston KE et al. J Food Sci 2002;67:817-20
  • 75. ALP & MALARIA The pastoralist Fulani (>50 % ALP) exhibit resistance to malaria compared to other non-milk drinking African ethnic groups Unexplained by genetic resistance factors, but rather by enhanced immunity Displacement of PABA & Folate rich foods by milk may attenuate malaria infection while allowing immune exposure, thereby preventing serious symptoms & facilitate establishment of protective immunity Cordain, L., Hickey, M. S. & Kim, K. In press. Malaria and rickets represent selective forces for the convergent evolution of adult lactase persistence. In Biodiversity in agriculture: domestication, evolution and sustainability (eds P. Gepts, R. Bettinger, S. B. Brush, T. Famula, P. E. McGuire & C. O. Qualset). Cambridge, UK: Cambridge University Press.
  • 76. HIGH MILK INTAKE ASSOCIATED WITH HIGHER FOLATE RECEPTOR AUTOANTIBODIESRisk (OR [95% CI]) of FR-autoantibodies for each quintile compared with the lowest quintile of milk intake in men and women J. Nutr. 139: 1037–1041, 2009
  • 77. LACTOSE INTOLERANCE
  • 78. PREVALENCE OF ALP IN VARIOUS ETHNIC GROUPS 80 76 75 70Percentage 60 50 40 30 27 25 20 20 10 10 3 0 Swallow DM. Ann Rev Genet 2003;37:197-219.
  • 79. PREVALENCE OF ALP IN VARIOUS EUROPEAN POPULATIONS 100 90 90 83 80 78 80 73 70Percentage 70 65 60 58 60 55 52 52 50 50 40 40 38 40 35 30 26 26 25 20 15 10 10 0 GRADIENT NORTH WEST SOUTH EAST Swallow DM. Ann Rev Genet 2003;37:197-219.
  • 80. HIPOLACTASIAhttp://nutrigenomics.ucdavis.edu/nutrigenomics/index.cfm?objectid=968814F6-65B3-C1E7-0C7007B71CC9959A
  • 81. HIPOLACTASIA Occurs in~ 65% of adults Gerbault P, et al. Philos Trans R Soc Lond B Biol Sci. 2011 Mar 27;366(1566):863-77.
  • 82. LACTOSE INTOLERANCE Abdominal Bloating (Small Bowell) Flatulence (Colon) Constipation HIGH OSMOTIC HIGH OSMOTIC LOAD LOAD DIARRHEA DIARRHEA Lomer MC, Parkes GC, Sanderson JD. Aliment Pharmacol Ther. 2008 Jan15;27(2):93-103
  • 83. DIAGNOSIS Lactose Milk YogurtMataix J. Nutrición y Alimentación Humana – Tomo I: Nutrientes y Alimentos. Ergon, 2002.
  • 84. LACTOSE FOOD SOURCES Food Serving Lactose (g)Cow’s Milk 1 glass 11Ice-Cream 150 g 9-10Cottage Cheese ~60 g 7-8Parmesan ~60 g 1-2Gouda ~60 g 1-2Camembert ~60 g 0-1 GOOD TOLERANCE UP TO 12 GRAMS Pribila BA, et al. J Am Diet Assoc. 2000 May;100(5):524-8. Shils M.E. et al. Modern Nutrition in Health and Disease. Lippincott Williams & Wilkins, US; 10Rev Ed edition, 2005.
  • 85. MILK FERMENTATION20-30% LESS LACTOSE Adolfsson O, Meydani SN, Russell RM. Yogurt and gut function. Am J Clin Nutr. 2004 Aug;80(2):245-56.
  • 86. LACTOBACILLUS BULGARICUS & STREPTOCOCCUSTHERMOPHILUS EXPRESS FUNCTIONAL LACTASE YOGURT BETTER TOLERATED Adolfsson O, Meydani SN, Russell RM. Yogurt and gut function. Am J Clin Nutr. 2004 Aug;80(2):245-56.
  • 87. BEER WILL CURE YOUR HYPOLACTASIA!!!
  • 88. ADDITIONAL INFORMATION Established in 1904, University of Western States is located at  2900 NE 132nd Avenue, Portland, Oregon, USA, 97230. Comprised of 50 quarter credits (550 hours, 33 semester credits), the UWS Master of Science degree program is accredited by Northwest Commission on Colleges and Universities. Course notes are copyrighted by University of Western States. Additional information is available at www.UWS.edu, Admissions@uws.edu, 503-251-5734, and http://www.uws.edu/Academic_Programs/MS_Nutrition_and_Functional_Medicine.aspx