Nutrition and Evolution Fiskefett i hjernen

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Nutrition and Evolution Fiskefett i hjernen

• M. A. Crawford, Institute of Brain Chemistry
  Human Nutrition
• London Metropolitan University.
• m.crawford_at_londonmet.ac.uk
• www.londonmet.ac.uk/ibchn

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BRAIN ESSENTIAL FATTY ACID COMPOSITIONETHANOLAMIN
E PHOSPHOGLYCERIDES
Crawford Sinclair (1972) Nutritional
influences in the evolution of the mammalian
brain Ciba Foundation Symposium (1971), Ed K
Elliot J Knight, 267-292
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Grants Gazelle
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Williams, G. and Crawford, M.A. (1987). J. Zool.
Lond. 213 673 - 684.
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Dolphins have the closest brain body weight ratio
to humans, They have a language and see in 3
dimensions with sonar.
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EVIDENCE FOR AN AQUATIC PRE-HISTORY

• FISSION TRACK AGEING OF FOSSILS ON THE ISLAND OF
  FLORES
• Hominids had 'acquired the capacity to make water
  crossings' 0.9 Million years ago suggests that
  the cognitive capabilities of this species may
  be due for re-appraisal
• Morwood et al (1998) Nature vol 393 pp 173-176.

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Klasies Estuary, Southern Cape.

• Incontrovertible evidence of extensive
  exploitation of the marine food chain dated to
  125,000 ya the period of cerebral expansion.

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Early human occupation of the Red Sea coast of
Eritrea during the last interglacial

• The multiregional evolution' hypothesis
• Modern humans evolved semi-independently in
  Europe, Asia and Africa between 100,000 and
  40,000 years ago.
• Out of Africa' hypothesismodern humans evolved
  in Africa 200 to 100 kyr ago.
• Here we report the discovery of early
  Middle Stone Age artefacts in an emerged reef
  terrace on the Red Sea coast of Eritrea, which we
  date to the last interglacial (ca 125 kyr ago).
• Robert C. Walter et al. Nature, 4th May 2000

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Abundant stone tools are found in situ in the
basal cobble zone,the lower part of the lower
shell zone and the beach facies of the emerged
reef terrace on the Red Sea coast of Eritrea

•   Together with similar, tentatively dated
  discoveries from South Africa this is the
  earliest well-dated evidence for human adaptation
  to a coastal marine environment, heralding an
  expansion in the range and complexity of human
  behaviour from one end of Africa to the other.
  This new, wide-spread adaptive strategy may, in
  part, signal the onset of modern human behaviour,
  which supports an African origin for modern
  humans by 125 kyr ago
• Nature 4th May 2000.

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DUAL CONGRESS Sun City 29th June - 3rd July 1998

• H. Sapiens vs Chimp Genome 1 difference.
• Australopithecines brain capacity stagnated at
  450 600 cc like the chimpanzee for 3 Myr.
• Cerebral expansion was rapid mostly over the
  last 260,000 years. Consistent with
  mitochondrial DNA.
• Far East populated along coast line migrations
  and water crossings.
• At 60,000 yrs ago Cro Magnon walks into Europe
  with brain capacity of 1,300 cc
• They wore necklaces of sea shells and painted in
  three dimensions and had a lunar calander.

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Out of Africa Stringer C. (2000)
Palaeoanthropology. Coasting out of Africa.
Nature 2000 May 4405(6782)24-5, 27
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Origin of the five written languages were beside
water.
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Contemporary Health

• Diet andVascular disorder

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Deaths From Diseases of the HeartUnited States
1900-99
Deaths in thousands
Year
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Dramatic rise in colon cancer in JapanColon
cancer incidence per 100,000

• Japan 1950-1960 was an example of a highly
  successful, technically advanced country which
  had avoided the diet induced disease of Western
  land based food economies through dependence on a
  sea food as opposed to a land based food economy.
• By 1990 they had caught up with the UK for colon
  cancer and are rapidly approaching mortalities
  for CHD.
• NCDs are now world wide www.globalforumhealth.org

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Fish Consumption and the Annual Prevalence of
Major Depression
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New Zealand (5.8)
r -0.84 plt 0.005
Canada (5.2)
5
France (4.5)
W. Germany
(5.0)
4

Major Depression, Annual prevalence, (rate /100
persons)
3
United States (3.0)
Puerto Rico (3.0)
Korea
(2.3)
2
1
Taiwan (0.8)
Japan (0.12)
0
20
40
60
80
100
120
140
160
Apparent Fish Consumption (lbs./ person/year)
Hibbeln, The Lancet, 1998
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Postpartum depression and fish consumption After
Dr. Joe Hibbeln
25.0
South Africa
Brazil
22.5
New Zealand
r - 0.76 p lt 0.0001

W. Germany
20.0
Australia
United States
Saudi Arabia
17.5
Italy
15.0
UK
Netherlands
Canada
Postpartum depreessed Edinburgh Postnatal
Depression Scale
12.5
France
Israel
Ireland
Chile
10.0
Switzerland
Sweden
Hong Kong
7.5
5.0
Malaysia
Japan
2.5
Singapore
0
0
20
40
60
80
100
120
140
160
Fish Consumption (lbs/ person/year)
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Geographical distribution of fish intake survey
in males and females for the 65 Chinese rural
counties in 1983, by quartile (g/day, as consumed
basis).

• Fish intake as expected follows the coast,
  Yangste and other waterways.
• Filled circles high intakes
• (200 1,000 g/day
• Blank circles lowest
• lt 1.0 g/day.
• NB a) Fish intake correlates with red cell
  membrane DHA
• b) China is the world leader in
  aquaculture.

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Chronic diseases 65 Counties In China vs Red
cell DHA. (1)

Primary carcinoma of the liver is a surrogate
for humid near water eco-systems which encourage
aspergillus flavus growth and aflatoxin
(2) 1.Chen JS, Campbell TC, Li JY, Peto R. Diet,
Life-style and Mortality in China. Oxford
University Press, Beijing Peoples Medical
Publishing House 1990. 2. Lopez A, Crawford MA.
Aflatoxin content of groundnuts sold for human
consumption in Uganda. Lancet 1967
232(7530)1351-4.
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Rift Valley Lake Turkana people compared to Bantu
Europeans
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Omega 3 foods consistently protective for heart
brainin the three clinical trials

• DART
• Lyons
• GISSI

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Conclusion A New Paradigm for Nutrition and
Health

• The nutritional paradigm of last century was
  protein and body growth.
• The human species is not noted for fat body
  growth but is for fast brain growth.
• A new paradigm is required for nutrition and
  brain growth.
• The brain as a lipid rich organ, requires the new
  paradigm to focus on its lipid requirements.
• This new focus is all the more important because
  the vascular and immune systems share lipid
  requirements in common with the brain.

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Synthesis of Arachidonic (AA)
Docosahexaenoic (DHA) Acids from LINOLEIC a
-LINOLENIC ACIDS
N-6 or OMEGA 6 Family
AA

182
Þ
204
w
6
w
6
183
203
Þ


6
6


w
w
Þ
224
w
6

Þ
225
w
6
Þ

Gamma-linolenic
Arachidonic
Linoleic
ß

prostaglandins
leukotrienes
N-3 or OMEGA 3 Family
EPA
DHA

Þ
183
226
3
w
w
3
225
w
3

184
3
204
3
205
3
w
w
Þ
w
Þ
Þ
Docosahexaenoic
Eicosapentaenoic
ß



Alpha-linolenic
ß
Ý

Peroxisomes
ß Ý



Þ
w3
246
w3
245
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PLACENTAL PERFUSION Fetal Plasma Uptake of
Bolus Dose of
14C Linoleic acid in Maternal Circulation
C14 d p m / ml 1000
600
TG
"
FFA
500
"
"
!
"
"
!
"
400
!
"
"
PL

300


"

!



200


!
"
100

!
!
!
!
!

"
!
0
0
1
2
3
4
5
Minutes
Crawford MA (2000) The placental delivery of
arachidonic and docosahexaenoic acids
implications for the lipid nutrition of the
preterm infant. Am J Clin Nutr. 71275S-284S
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PLACENTAL PERFUSION Fetal Plasma Uptake 14C
Arachidonic Acid
From Bolus Dose in Maternal Circulation.
C14 d p m / ml 1000
800
FFA
PL
!
700







600

!
500

!
400
300
TG
200
!
"
"
"
"
"
"
!
100
"
!
!
!
"
!
"

!
"

"
!
0
0
1
2
3
4
5
Minutes
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Biomagnification Across The Placenta
Crawford, M.A., Hassam, A.G., Williams, G. and
Whitehouse, W.L. (1976) Essential fatty acids and
fetal brain growth. Lancet (i) 452-453. Am J
Clin Nutr. 71275S-284S
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BRAIN ESSENTIAL FATTY ACID COMPOSITIONETHANOLAMIN
E PHOSPHOGLYCERIDES
Crawford Sinclair (1972) Nutritional
influences in the evolution of the mammalian
brain Ciba Foundation Symposium (1971), Ed K
Elliot J Knight, 267-292
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Liver Essential Fatty Acid CompositionEthanolamin
e Phosphoglycerides
Crawford M, Casperd N. Sinclair AJ (1976) The
long chain metabolites of linoleic and linolenic
acids in liver and brain in herbivores and
carnivores. Comp. Biochem. Physiol. 54B 395-401.
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Brain Essential Fatty Acid CompositionEthanolamin
e Phosphoglycerides
Crawford M, Casperd N. Sinclair AJ (1976) The
long chain metabolites of linoleic and linolenic
acids in liver and brain in herbivores and
carnivores. Comp. Biochem. Physiol. 54B 395-401.
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Human Cord Lymphocytes at Term Ethanolamine
Phosphoglycerides
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Human Adult Vascular EndotheliumEthanolamine
Phosphoglycerides
Crawford, M.A., Costeloe K, Ghebremeskel K,
Phylactos A., Skirvin L, Stacey F. (1997) Are
deficits of arachidonic and docosahexaenoic acids
responsible for the neural and vascular
complications of preterm babies? Am J. Clin.
Nutr. 66 1032S-1041S.
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PRETERM INFANT RAPID LOSS OF PLACENTAL AA

• POSTNATALLY AA DROPS TO THIRD OF INTRAUTERINE
  LEVEL DESPITE PRECURSOR LA RISING THREE TO FOUR
  FOLD.
• N 63 - After Leaf AA, Leighfield MJ, Costeloe
  KL Crawford MA. (1992) J. Pediatr.
  Gastroenterol. Nutr. 14 300-308.

In utero AA
In utero LA
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COMPARISON OF TERM MILK FETAL NUTRITION FOR AA
DHA APPROPRIATE FOR PRETERM INFANTSCrawford
et al (1998),The inadequacy of the essential
fatty acid content of present preterm feeds Eur.
J. Pediatr. 157 S1 S23-S27.
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PLACENTA SUPER PUMP IMPLICATIONS FOR PRETERMS

• VASCULAR COMPLICATIONS
• IVH - HEMORRHAGE EVEN BEFORE BIRTH
• PVL - ISCHEMIA
• BPD - LEAKAGE IN PULMONARY BLOOD
  VESSELS FORMS HYALINE LAYER
• ROP - OBLITERATION OF THE RETINAL
  BLOOD VESSELS.
• NEC - VASCULAR/IMMUNE INVOLVEMENT

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ISCHEMIA PEROXYNITRITE IN BRAIN DAMAGE

• (i) Synaptic discharge.
• (ii)Glutamate release opens gate.
• (iii) Ca activates NO synthase -gt
• reperfusion NO O2 -gt ONOO-.
• (Beckman JS J. Dev Physiol 15 53-59, 1991.
• Bolanos JP et al J. Neurochem 68 2227-2240,
  1997).

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Conclusion on Preterm Nutrition.

• Arachidonic acid may have a special vascular
  role.
• Lipid nutrition of preterm babies is-
• false maybe pathogenic
• Remodel based on placenta
• Crawford MA, Costeloe K., Ghebremeskel K. and
  Phylactos A (1998),The inadequacy of the
  essential fatty acid content of present preterm
  feeds. Eur. J. Pediatr. 157 S1 S23-S27.
• .

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MATERNAL MAL-NUTRITION AND RISK OF ADULT DISEASE

• Epidemiological evidence from studies on
  birthweight and heart disease suggests that poor
  maternal/fetal nutrition can alter developmental
  programming and lead to heart disease, stroke and
  diabetes in later life.
• Barker DJ (1997) Fetal nutrition and
  cardiovascular disease in later life. Br Med Bull
  53 96-108.

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Experimental Plan
Sprage Dawley Rats
mating

• Low-Fat Diet
• (4.2 g/)

pregnancy
10 days
birth

• High-Fat Diet
• (33 g/)

16 days
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HIGH FAT DIET/DIABETES FEMORAL ARTERY RELAXATION

• Rat Pups 15 days old.
• Precontraction w. norepinephrine
• relaxation to acetylcholine.
• High fat Diabeticlt High fat lt Diabetic ltControls
  plt0.01
• Dysfunction membrane
• lipid effect persists at
• 60, 90 120 days i.e PROGRAMMED IN UTERO

Ghosh P, Bitsanis D, Ghebremeskel K, Crawford MA,
Poston L. J Physiol 2001533(Pt 3)815-22
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Experimental Plan II
Incubation 40mM FA (AA, EPA, DHA) 30min
Sprague Dawley Rats
Mesenteric arteries
Dose Response Curve
Myograph

• NA
• Ach
• U46619
• Spermine
• NoNoate

250-300mMø
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(n7)
Log Ach (mol/L)
55
n10
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Arachidonic acid and endothelial function

• AA had pronounced vasodilatory effects. The
  vasodilatory response to acetylcholine was
  independent of nitric oxide - relaxation to
  spermine was unaffected.
• Maximum response to NA was increased in arteries
  pre-incubated with AA
• ACh, NA, spermine, thromboxane mimetic U46619
  unaffected by DHA.
• Ascorbic acid did not affect the result.
• Mechanisms increased receptor affinity to Ach,
  PGI2 hyperpolarisation.

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Conclusion

• Arachidonic acid may have a special vascular
  role.
• Docosahexaenoic acid is concentrated in neural
  signalling systems.
• Crawford MA, Costeloe K., Ghebremeskel K. and
  Phylactos A (1998),The inadequacy of the
  essential fatty acid content of present preterm
  feeds. Eur. J. Pediatr. 157 S1 S23-S27.
• Suzuki, H., Manabe, S., Wada O and Crawford, MA.,
  (1997) Rapid incorporation of docosahexaenoic
  acid from dietary sources into brain microsomal,
  synaptosomal and mitochondrial membranes in adult
  mice. Internat. J. Vit. Res., 67 272-278.

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ConclusionII Dietary lipids operate on plasma
membrane lipids, nuclear receptors and gene
expression

• The human and chimpanzee genomes are little
  different.
• To explain DHA and cerebral expansion,we need an
  influence on gene expression.
• DHA induces expression of neuronal cell growth,.
  those controlling synaptic plasticity, dendrite,
  cytoskeleton, ion channel formation, signal
  transduction, energy metabolism and regulatory
  proteins. Kitajka K,, et al. (2002) The role of
  n-3 polyunsaturated fatty acids in brain
  modulation of rat brain gene expression by
  dietary n-3 fatty acids. Proc Natl Acad Sci U S
  A 99(5)2619-24

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LAST CENTURY
)
Average height increased by 0.4 inches/decade
)
Increase in mortality from vascular disease
)
OPTIONS FOR THIS CENTURY
)
Increase in neurological disorders, decline in
IQ,
)
)
Increase in anti-social behaviour.

)
OR
)
Increase in IQ, health and abilities.
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Global Forum For HealthFirst Seven In Order

• BURDEN OF DISEASE --------- 1990 2020
• Lower respiratory infections 8.2 3.1
• Diarrhorheal disease 7.2 2.7
• Perinatal Conditions 6.7 5.7
• Mental ill health 3.7 5.7
• Coronary Heart Disease 3.4 5.9
• Tuberculosis 2.8 3.1
• Cerebrovascular disease 2.8 4.4

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Collaborators

• Myer Bloom - Physics Vancouver
• Leigh Broadhurst MD, USDA, Beltsville.
• Stephen Cunnane - NMR Toronto
• Kate Costeloe Neonatology, Royal London
• Keb Gebremeskel Lipids, ,IBCHN, London
• Laurance Harbige - Immunology Greenwich
• Holm Holmsen Membrane signalling Bergen, Norway
• Ivan Golfetto, Vascular myography, Venezuela.
• Douglas Kuhn, Placental perfusion, Royal Free,
  London.
• Alison Leaf - Pediatrics - Bristol.
• Trish Moodley, immunology, IBCHN, London.
• Lucilla Poston, Vascular myography, St Thomas,
  London.
• John Parkington, Anthropology, Capetown.
• Walt Schmidt, MD, USDA, Beltsville.
• Hiramitsu Suzuki Synaptic uptake of DHA, NFRI,
  Japan
• Ephraim Yavin Ram Reifen Gene expression
  Israel