Evolutionary History of Dairy

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

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

TOPICS FOR THIS PRESENTATION

Evolutionary History of Milk and Dairy

Lactose Intolerance and ALP

HISTORY OF MILK & DAIRY

Homo sapiens

H. neanderthalensis

H. antecessor

H. heidelbergensis

H. erectus

H. ergaster

Au. rudolfensis

Au.bahrelghazali

Au. anamensis

H. habilis

Au. garhi

Au. africanus

Au. afarensis

P. robustus

Paranthropus boisei

Ardipithecus ramidus

Orrorintugenensis

Sahelanthropustchadensis

Kenyanthropus platyops

P. aethiopicus

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ORIGINS OF MAN

Adapted from Wood B. Nature 2002:418:133-35 & from Cordain L, 2009

All humans in

Europe, Asia, Oceania and America have an

AFRICAN ORIGIN

LESS GENETIC DIVERSITY OUTSIDE 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

Etiópia

Liu H, et al., 2006


WHAT WAS OUR ECOLOGICAL NICHE???

HUNTER-GATHERER’S DIETS

Plants

Roots & Tubers

Berries

Fruits

Nuts

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

VEGETABLE SOURCES

Wild Animals

Insects

Seafood

Eggs

ANIMAL SOURCES


WHAT THEY DIDN’T EAT?

CEREALSREFINED SUGARS

SALT

DAIRY

REFINED VEGETABLE OILS

ALCOHOL FEEDLOT MEAT

LEGUMES

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

MILK? WHY NOT?


meses meses meses

Sellen DW. J Nutr. 2001 Oct;131(10):2707-15

BREASTFEEDING PATTERNS

Sellen DW. J Nutr. 2001 Oct;131(10):2707-15

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.

~11,000 YA

Neolithic Revolution in the Middle East

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EVIDENCE FOR THE USE OF DAIRY IN THE MIDDLE EAST

66100133167200233267300333

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First evidence of dairying in the Middle East (Turkey) 4

Domestication of sheeps, goats and cattle (Middle East) 1-3

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.

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.

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EVIDENCE FOR THE USE OF DAIRY IN THE MIDDLE EAST & EUROPE

66100133167200233267300333

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First evidence of dairying in the Middle East (Turkey) 4

First evidence of dairying in Europe (Romania) 5

Domestication of sheeps, goats and cattle (Middle East) 1-3

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

First evidence of dairying in North. Eur (UK) 6

UVB

Jablonski NG, Chaplin G. Proc Natl Acad Sci U S A. 2010 May 11;107 Suppl 2:8962-8

UVA


Miller AL, Kelley GS. Altern Med Rev. 1996;1(4):220-235

FOLATE

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


Chaplin G. Am J Phys Anthropol. 2004 Nov;125(3):292-302

PIGMENTATION AND LATITUDE


Holick MF. J Clin Invest. 2006 Aug;116(8):2062-72

Jablonski NG, Chaplin G. J Hum Evol. 2000 Jul;39(1):57-106

Vitamin D all year

Vitamin D deficiency 1 + months per year




Holick M. Am J Clin Nutr 2004;80(suppl):1678S– 88S.

Pele muito pigmentada


Low Pigmentation

54 mJ/cm2

320 mJ/cm2



High Pigmentation

Low Pigmentation

54 mJ/cm2

320 mJ/cm2


High Pigmentation

High Pigmentation

Low Pigmentation

54 mJ/cm2

320 mJ/cm2

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


Pelvic flattening, permanently narrowing the birth canal

Jablonski NG et al. J Hum Evol. 2000;39(1):57-106

INCREASED MATERNAL MORTALITY DURING CHILDBIRTH


VDR IN MULTIPLE CELLS

Zasloff M. Nat Med. 2006 Apr;12(4):388-90

Darker

DEPIGMENTATION

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.

UVA IS HIGHER IN THE POLES & SNOW REFLECTS UVA


TF – Traditional Foods1 mcg Vit D = 40 IU

Kuhnlein HV, Receveur O. J Nutr. 2007 Apr;137(4):1110-4

HIGH LATITUDE, CLOUDY CLIMATE, REDUCED SUNLIGHT

DECREASED UV EXPOSURE &LESS VITAMIN D SYNTHESIS

Loomis WF. Science. 1967 Aug 4;157(788):501-6.Jablonski NG et al. J Hum Evol. 2000;39(1):57-106

N 65

N 55

N 45

RICKETS

GEOGRAPHIC EXPANSION OF THE FIRST NEOLITHIC CULTURES


Jericho10,000 YA

9000 YA

8000 YA

6000 YA

5000 YA

WHEAT & BARLEY

THE SPREAD OF AGRICULTURE FROM THE MIDDLE EAST TO N. EUROPE BROUGHT NOT ONLY DAIRYING BUT ALSO

Cordain, L., Hickey, M. S. & Kim, K. In press.

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.

The circum North/Baltic Seas land mass is warmed because of 1) Gulf Stream

2) Maritime nearness

Mar doNorte

MarBáltico

55 N

Average Temperature in Winter in

London is 4°C vs - 9 °C in N.

America & Eurásia, at 51º N

Cordain L. World Rev Nutr Diet. 1999;84:19-73

1Mellanby 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

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 5-7

HOW WHOLE GRAINS MAY PROMOTE RICKETS?

1Batchelor AJ et al. Brit J Nutr 1983;49:213-162Cordain L. World Rev Nutr Diet. 1999; 84:19–733Mellanby E. J Physiol 1949;109:488-5334Guinex C. et al. Int J Biochem Cell Biol 2005;37:765-745Findlay DR et al. J Cell Biol 1987;104:189-200

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

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

GEOGRAPHIC DISTRIBUTION FOR SKIN PIGMENTATION



Extreme Dermal Depigmentation originated in Northern Europeans

~ 5,300 – 6,000 years

GEOGRAPHIC DISTRIBUTION FOR HAIR & EYE PIGMENTATION IN EUROPE

Blond Hair / Blue Eyes originated in Europe

~ 6,000 – 10,000 YA

Eiberg 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 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.

INCREASED CALCIUM INTAKE

Pettifor JM. Am J Clin Nutr. 2004 Dec;80(6 Suppl):1725S-9S

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.

Adapted from Cordain L, 2009(with permission)

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



BETA-CELLULIN

Bastian SE, et al. Measurement of betacellulin levels in bovine serum, colostrum and milk. J Endocrinol. 2001 Jan;168(1):203-12.



EGF in saliva: 0.0512 ng/ ml

Total Saliva: 691 ml/24 hours

EGF in 24h Saliva: 35.3 ng

BTC per liter of Bovine Milk:

1930 ng


WGA Lumen

WGA

WGA

BTC

To Lymph

To Circulation

EG

F R

eceptor

EG

F R

eceptor

EGF Receptor

Hormi K et al. Cell Tissue Res 1994;278:439-50

Rebbaa A et al. J Neurochem 1996;67:2265-2272

Lochner N, et al. Pharm Res. 2003 May;20(5):833-9.

or

WGA can bind luminally expressed EGF-R


LACTOSE SOURCES

Park YW, Haenlein GFW. Handbook of Milk of Non-Bovine Mammals. Blackwell Publishing, 2006.

Food Serving (g) Lactose (g)

Cow’s Milk 100 4.6

Buffalo Milk 100 5.1

Goat’s Milk 100 4.1

Sheep’s Milk 100 5.4

Lomer MC, Parkes GC, Sanderson JD. Aliment Pharmacol Ther. 2008 Jan15;27(2):93-103

LACTOSE HYDROLYSIS

LACTOSE SOURCES

Park YW, Haenlein GFW. Handbook of Milk of Non-Bovine Mammals. Blackwell Publishing, 2006.

Food Serving (g) Lactose (g)

Human Milk 100 6.9

Cow’s Milk 100 4.6

Buffalo Milk 100 5.1

Goat’s Milk 100 4.1

Sheep’s Milk 100 5.4

LACTASE EXPRESSION IS COMMON IN MOST YOUNG MAMMALS

After the weaning period is over, lactase

production usually declines , although the

mechanisms and evolutionary reasons for this

downregulation are not fully understood


HIPOLACTASIA IS THE NORMAL PHENOTYPE

IN HUNTER-GATHERERS

AFTER AGE 3-5

Burger J, et al. Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):3736-41

INTOLERÂNCIA À LACTOSE

DIARRHEA DIARRHEA

HIGH OSMOTIC LOAD

HIGH OSMOTIC LOAD


LACTOSE INTOLERANCE

ALP IN EUROPE


Predicted Old World LP phenotype frequencies based on -13,910 C>T allele frequency data only

Estimated Dates of Origin: 2188 - 20650 BP 7450 - 12300 BP(s = 0.014 - 0.150)

N. Sea

Baltic

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)



(s = 0.090 - 0.190)

The combination of 1) high latitude, 2) cloudy weather, 3) whole grain cereals as staples likely represented the unique combination of selective pressures responsible for the evolution of:

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

(5,000 – 12,000 YA) (6,000 – 10,000 YA) (5,300 – 6,000 YA)

ALP Blond Hair/Blue Iris Extreme Dermal Depigmentation



Domestication of the Arabian camel: 6000 BP

Origin of G-13915 allele in the Arabian Pensinsula: 4000 BP

Enattah NS, et al. Am J Hum Genet. 2008 Jan;82(1):57-72

Tishkoff SA, et al. Nat Genet. 2007 Jan;39(1):31-40

Spread of Pastoralism south of the Sahara: 4,500 BP

Spread of Pastoralism into Northern Tanzania: 3,300 BP

000

Various SNPs (G/C-14010, T/G-13915 and C/G-13907) associated

with LP in Sub-Saharan Africans arose

3000-7000 BP

Tishkoff SA, et al. Nat Genet. 2007 Jan;39(1):31-40

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?

Equator

20 N

20 S

Pfitzner MA et al. J Pediatrics 1998;133:740-4. In Cordain, L., Hickey, M. S. & Kim, K. In press.

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.

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



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 2,3

1Kretschmar W et al. Tropenmed Parasit 1973;24:51-59

2Nowell F. Parasitology 1970;61:425-33.

3Kicska GA et al. Infect Dis 2003;188:1776-81


Pentose phosphate cycle Glycolysis

D-Erythrose 4-P Phosphoenolpyruvate

7-Phospho-2-dehydro-3-deoxy-D-arabinoheptulosonate3-Dehydroquinate synthase

3-Dehydroquinate3-Dehydroquinate dehydratase

3-DehydroshikimateShikimate 5-Dehydrogenase

ShikimateShikimate kinase

Shikimate 3-Phosphate3-phosphoskikimate-1-carboxyvinyltransferase (EPSP synthase)

3-Phospho-5-enoylpyruvylshikimate

Chorismate

PABA synthase activity in Plasmodia is low & poorly supports growth1

Dietary deficiencies of PABA & folate may suppress malarial symptoms by impairing folate metabolism1

Dietary PABA and folate reduce efficacy of sulfa drugs in rodent models2

Ubiquinone Aromatic Amino AcidsPABA synthase

PABA

Folate

Sulfonamides(inhibit plasmodial growth)

(additional PABA antagonizes sulfonamides)

MILK DOES NOT CONTAIN PABA & IS A POOR SOURCE OF

FOLATE

(6-9 mg/100g vs. DRI 400 mg)3

1Kicska GA et al. Infect Dis 2003;188:1776-812Jacobs RL. Exp Parasitol 1964;15:213-253Johnston KE et al. J Food Sci 2002;67:817-20

PABA, FOLATE & MALARIAAdapted from Cordain L, 2009

(with permission)

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



Risk (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

HIGH MILK INTAKE ASSOCIATED WITH HIGHER FOLATE RECEPTOR

AUTOANTIBODIES

LACTOSE INTOLERANCE

PREVALENCE OF ALP IN VARIOUS ETHNIC GROUPS

Whit

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Whit

e USA

Hispan

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dia

Blacks

Afro-C

aribb

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Amer

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20

40

60

80 76 75

27 25 2010

3

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ge

Swallow DM. Ann Rev Genet 2003;37:197-219.

Swedis

h

Danes

Irish

Britis

h

Finla

nd Swed

es

NW G

erm

ans

Czech

s

Swiss

Finla

nd

Austria

ns

SW G

erm

ans

N Fre

nch

Spanis

h

Hungaria

ns

Polish

Lapps

S Fre

nch

N Ital

ians

Greek

s

Russia

ns

S Ital

ians

Turks

0

20

40

60

80

10090

83 80 7873 70

6560 58 55 52 52 50

40 40 38 35

26 26 25

1510

Pe

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nta

ge

NORTH WEST SOUTH EASTGRADIENT

PREVALENCE OF ALP IN VARIOUS EUROPEAN POPULATIONS

Swallow DM. Ann Rev Genet 2003;37:197-219.

HIPOLACTASIA

http://nutrigenomics.ucdavis.edu/nutrigenomics/index.cfm?objectid=968814F6-65B3-C1E7-0C7007B71CC9959A

http://nutrigenomics.ucdavis.edu/nutrigenomics/index.cfm?objectid=968814F6-65B3-C1E7-0C7007B71CC9959A

HIPOLACTASIA

Occurs in

~ 65% of adults


LACTOSE INTOLERANCE

Constipation


Abdominal Bloating (Small Bowell)

Flatulence (Colon)

DIARRHEA DIARRHEA

HIGH OSMOTIC LOAD

HIGH OSMOTIC LOAD

Mataix J. Nutrición y Alimentación Humana – Tomo I: Nutrientes y Alimentos. Ergon, 2002.

Lactose

Milk

Yogurt

DIAGNOSIS

LACTOSE FOOD SOURCES

Food Serving Lactose (g)

Cow’s Milk 1 glass 11

Ice-Cream 150 g 9-10

Cottage Cheese ~60 g 7-8

Parmesan ~60 g 1-2

Gouda ~60 g 1-2

Camembert ~60 g 0-1

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.

GOOD TOLERANCE UP TO 12 GRAMS

MILK FERMENTATION

20-30% LESS LACTOSE

Adolfsson O, Meydani SN, Russell RM. Yogurt and gut function. Am J Clin Nutr. 2004 Aug;80(2):245-56.

LACTOBACILLUS BULGARICUS & STREPTOCOCCUS THERMOPHILUS 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.

BEER WILL CURE YOUR HYPOLACTASIA!!!

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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, [email protected], 503-251-5734, and

http://www.uws.edu/Academic_Programs/MS_Nutrition_and_Functional_Medicine.aspx

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Health & Medicine

Evolutionary History of Dairy