Based primarily on the work of Professor Loren Cordain (Colorado State University), Professor Nina Jablonski, (Penn State) and Professor Dallas Swallow (University College London)
UWS Master's in Nutrition and Functional Medicine covers Milk, Dairy and Human Health
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
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. aethiopicus
Milhões 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 AFRICA
Relethford JH. Heredity. 2008 Jun;100(6):555-63. Jakobsson M, et al. Nature 2008; 451(7181):998-1003
Manica A, et al. Nature; 2007; 448(7151):346-8 Hellenthal G, Auton A, Falush D. PLoS Genet. 2008 May 23;4(5):e1000078
Liu 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):15942-7
Conrad D, et al. Nat Genet 2006; 38: 1251–1260 Prugnolle F, Manica A, Balloux F. Current Biology 2005; 15:R159–R160
RAY N, et al. Genome Res 2005; 15:1161–1167 Cavalli-Sforza LL, Feldman MW. Nat Genet 2003; 33:266–275
Macaulay V, et al. Science 2005; 308(5724):1034-6 Tishkoff S, Williams S. Nat Rev Genet 2002; 3: 611–621
Currat 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
18. DAIRY
REFINED 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
22. ~11,000 YA
Neolithic
Revolution
in the Middle
East
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.
23. 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
1,000
Generations
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.
24. 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.
25. 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
1,000
Generations
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
29. 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
35. Vitamin D deficiency 6 + months per year
Vitamin D deficiency 1 + months per year
Vitamin D all year
Vitamin D deficiency 1 + months per year
Vitamin D deficiency 6 + months per year
Jablonski NG, Chaplin G. J Hum Evol. 2000 Jul;39(1):57-106
36. Low
Pigmentation
54 mJ/cm2
Pele muito
pigmentada
Pele muito
320 mJ/cm2 pigmentada
Holick M. Am J Clin Nutr 2004;80(suppl):1678S– 88S.
37. Low
Pigmentation
54 mJ/cm2
High
Pigmentation
Pele muito
320 mJ/cm2 pigmentada
Holick M. Am J Clin Nutr 2004;80(suppl):1678S– 88S.
38. Low
Pigmentation
54 mJ/cm2
High
Pigmentation
High
320 mJ/cm2 Pigmentation
Holick M. Am J Clin Nutr 2004;80(suppl):1678S– 88S.
39. FOOD SOURCES OF VITAMIN D
Food Vit. D (IU)
Cod Liver Oil (10 g) 1360
Sardins (105 g) 500
Tuna (105 g) 402
Farmed Salmon (105 g) 360
Egg (1 medium) 20
Liver (105 g) 15
Ozkan B. J Clin Res Pediatr Endocrinol. 2010 Dec;2(4):137-43
44. DEPIGMENTATION
Darker
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.
45. 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
46.
47. TF – Traditional Foods
1 mcg Vit D = 40 IU
Kuhnlein HV, Receveur O. J Nutr. 2007 Apr;137(4):1110-4
48. HIGH LATITUDE, CLOUDY
CLIMATE, REDUCED SUNLIGHT
N 65
DECREASED UV EXPOSURE & N 55
LESS 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
49. 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.
50. THE SPREAD OF AGRICULTURE FROM THE MIDDLE EAST TO
N. 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.
51. 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.
53. 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
1Mellanby E. Lancet 1919;1:407-08.
2Thomas BH et al. Biochem J 1936;30:12-177-88
3Sly MR et al. Calcif Tissue Int 1984;36:370-79
4Grammer JC et al. Poult Sci 1983;62: 103-9
5Gibson RS et al. Brit J Nutr 1987;58:23-29
6Brooke OG et al. Brit J Obstet Gynaecol 1981;88:18-26
7Hunt SP et al. BMJ 1976;2:1351-54.
In Cordain L. World Rev Nutr Diet. 1999;84:19-73
54. 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
55. 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
56. Extreme Dermal Depigmentation
originated in Northern Europeans
~ 5,300 – 6,000 years
GEOGRAPHIC DISTRIBUTION FOR SKIN PIGMENTATION
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.
57. 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.
60. 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.
61. 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.
62. BETA-CELLULIN
Bastian SE, et al. Measurement of betacellulin levels in bovine serum, colostrum and milk. J Endocrinol. 2001 Jan;168(1):203-12.
63. Adapted from Cordain L, 2009
(with permission)
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
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.
64. Adapted from Cordain L, 2009
(with permission)
WGA can bind luminally
BTC
expressed 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.
67. LACTOSE SOURCES
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
Park YW, Haenlein GFW. Handbook of Milk of Non-Bovine Mammals. Blackwell Publishing, 2006.
68. After the weaning period is over, lactase
production usually declines , although the
mechanisms and evolutionary reasons for this
downregulation are not fully understood
69. 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.
70. Burger J, et al. Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):3736-41
71. LACTOSE INTOLERANCE
INTOLERÂNCIA À LACTOSE
HIGH OSMOTIC HIGH OSMOTIC
LOAD LOAD
DIARRHEA DIARRHEA
Lomer MC, Parkes GC, Sanderson JD. Aliment Pharmacol Ther. 2008 Jan15;27(2):93-103
72. 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
73. 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 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.
74. 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 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.
75. 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
76. Spread of Pastoralism south
of the Sahara: 4,500 BP
Spread of Pastoralism
into Northern Tanzania: 3,300 BP
Tishkoff SA, et al. Nat Genet. 2007 Jan;39(1):31-40
77. 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
78. 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.
79. 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.
80. 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.
81. 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 2,3
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
82. Adapted from Cordain L, 2009
(with permission)
PABA, FOLATE & MALARIA
Pentose 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
83.
84. 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.
85. HIGH MILK INTAKE ASSOCIATED WITH HIGHER
FOLATE RECEPTOR AUTOANTIBODIES
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
92. DIAGNOSIS
Lactose
Milk
Yogurt
Mataix J. Nutrición y Alimentación Humana – Tomo I: Nutrientes y Alimentos. Ergon, 2002.
93. 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
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.
94. 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.
95. 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.
98. 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
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