4. DHA: 22:6 n-3
22:6 n-3
In the brain present as phospholipid
Can be synthesized from ALA (also by Glial cells),
but conversion rates are low.
Innis, 2007
5. DHA: main sources
5% %
15
23-2 12
-
3%
na lmon l 10-1
Tu Sa oi
tl. ish 1 3%
A 2 F r 10- 2%
1 8/1 live 0-1
l1 %
d
Co kere n 9- 10
0%
ac ade
-4
Fis 0%
l
M
a
h
35
1
en e 9- 10%
Alg
h
M n 8-
rd i
Sa hovy
Krill A nc
9-10%
9. Nervous system
Complex network of neurons
located throughout our body
Two parts:
Central nervous system and
Peripheral nervous system
Both controlled by the brain
10. Nervous system: The brain
Numerous functions described
to the brain:
Control of body functions
Voluntary (thought>movement)
Involuntary (Heartbeat)
Reason of consciousness,
emotions, memory,
imagination, etc
11. Nervous system: Brain anatomy
Regions (lobes) in the brain have special roles
10 % neurons, 90% glial cells
Picture taken from Stanford University website
13. Brain development
weight
Brain
Late Young-
Pre-birth Early Older
Childhood / Mid age
Childhood adults
adolescence Adult
Trimester 1
Trimester 2
Trimester 3
18 yrs old
55 yrs 0ld
4 yrs old
Death
Birth
14. Nervous system: Brain structure
Lipids main constituent of neuronal cell membrane
Total brain rich in lipids: 50-65 % of dry matter
35 % of lipids are PUFA, mostly DHA
Grey matter, nervous system and retina have highest
concentrations of DHA
A healthy brain is rich in DHA
Sinclair 1975
15. Brain health: genetic factors
Possible genetic variation in Fatty acid binding
proteins (B-FABP)
Dopamine transporter candidate genes for
ADHD
Occurrence of apolipoprotein epsilon-4 allele is
associated with Alzheimer
Noguchi et al, 1993
Owada et al, 2006
Veerkamp and Zimmerman, 2001
16. Role of DHA in building and
maintaining optimal brain
function
17. Western diet: High in n-6’s : LA and AA
Linoleic Acid (LA) Alpha-Linolenic Acid
(ALA)
D6D Enzyme
Gamma-Linolenic Acid Stearidonic Acid
(GLA)*
Elongase
Dihomo-Gamma-Linolenic Eicosatetraenoic Acid
Acid (DGLA)* (20:4n-3)
D5D Enzyme
Arachidonic Acid (AA) Eicosapentaenoic Acid
(EPA)
Elongase
Elongase
Longer Chain Fatty Acid
Metabolites Desaturase
Docosahexaenoic Acid
(DHA)
18. Western diet: n3 mostly ALA from plant sources
Linoleic Acid (LA) Alpha-Linolenic Acid (ALA)
D6D Enzyme
Gamma-Linolenic Acid Stearidonic Acid
(GLA)*
Elongase
Dihomo-Gamma-Linolenic Eicosatetraenoic Acid Conversion:
Acid (DGLA)* (20:4n-3) slow
Possible shortage of DHA in the body
D5D Enzyme
Arachidonic Acid (AA) Eicosapentaenoic Acid
(EPA)
Elongase
Elongase
Longer Chain Fatty Acid
Metabolites Desaturase
Docosahexaenoic Acid
(DHA)
Williams and Burdge, 2006
19. Split up:
Development/Decline vs Problems
Research
Late Young- focused
Pre-birth Early Older
Childhood / Mid age on development
Childhood adults
adolescence Adult
and decline
Research focused
on “problems”
20. Brain development: Uptake and incorporation
Uptake DHA around 60%, usually higher for ALA
10-20 % used for energy (B-oxidation)
Incorporation into brain cells phospholipids
highly dependent on ARA in the diet.
Higher DHA intake leads to Higher DHA status in
the brain.
Moya et al, 2001
Mayes et al, 2006
21. Effect of dietary intake ARA and DHA upon
DHA status in Frontal lobe of the Cerebral cortex
% DHA
In baboon
frontal lobe
after *
*
12 wks
9.8 12.8 13.9
C L L3
Diets:
Control No added PUFA
L 0.42% DHA (+ 39 mg/Kcal ARA)
L3 1.13% DHA (+ 39mg/Kcal ARA) Interpreted from Hsieh et al, 2007
22. Brain development: Effect of maternal DHA intake
Set-up:
Pregnant women on 2 diets (randomised:
Corn oil
Cod liver oil (+/- 1200 mg DHA)
18 wks in Pregnancy -> 3 months breastfeeding
Intelligence test at 4 yrs of age (n=90)
Helland et al, 2003
23. Brain development: Effect of maternal DHA intake
K-ABC score
*
107.8
101.7
Corn oil CLO
Interpreted from Helland et al, 2003
24. Brain development: Effect of DHA intake between
0-4yrs
Breastfed infants from mothers taking DHA
supplements showed:
Higher infant PL DHA
higher Index score on Bailey’s Psychomotor (at 30
months)
Infants (6 wks +) fed High PUFA diets (ALA + DHA) showed
improved visual acuity compared to those fed low PUFA
diets.
Jensen et al, 2005
Birch et al, 2002
25. Brain development: DHA & the effect on child
behavior (0-4yrs)
Set-up:
Infants being breastfed (n=20)
Breast milk analysed on lipids
Infants assessed on neurobehavioral functions
(NBAS, 9 point scales)
Hart et al, 2006
26. Brain development: DHA & the effect on child
behavior (0-4yrs)
r=0.57
P<0.01
Lability of
State
(Higher score
is more stable)
DHA in Breast milk
Interpreted from Hart et al, 2006
27. Brain development: Effect of DHA intake during
“adolescence”
Set-up:
3 Mo old mice
Group fed DHA and palm oil
Group fed just palm oil
Measurement = Maze-learning ability at
1 wk, 2wks, 1 Mth, 3 Mths
Lim and Suzuki, 2000
28. Brain development: Time to reach Maze exit
shortens with prolonged DHA diet
Time DHA in
(% control) Brain
bars Lines
Control
Control
Control
Control
DHA
*
DHA
DHA
DHA
1wk 2 wk 1 mth 3 mths
Interpreted from Lim and Suzuki, 2000
29. Brain health Problems & DHA: ADHD
Attention-Deficit Hyperactivity Disorder
Diagnosis difficult, many factors
3-5 % of those under 19 affected
Now believed to continue into adulthood
Common medicine, Ritalin, has shown serious
potential side effects
30. Brain health Problems & DHA: ADHD
Lower plasma PUFA seen in sufferers
Most studies done with Fish oil (DHA + EPA)
Positive effects with fish oil seen in several studies
DHA alone less effective, but symptom
(aggression) decreases with DHA intake (> 2
Richardson and Puri, 2002
Mo), P=0.001 Stevens et al, 2003
Stevens et al, 1995
Hamazaki et al, 2004
31. Brain health Problems & DHA: Depression
Clinical symptoms of depression (glucose metabolism,
Pro-inflammatory cytokine, neurotransmitter concentration):
Increase when deficiency n-3 PUFA exists
Decrease when n-3 PUFA are supplemented
Unclear if effects are due to DHA+EPA or one
the separate components.
Some studies show no effect Sinclair et al, 2007
Llorente at al, 2003
32. Cognitive decline : A major future problem
Babyboomers getting older increase with aging:
Memory related problems
Dementia:
65 and older = 6 %
80 and older = 20%
Forgetfulness > Dementia > Alzheimer
Wimo et al, 2003
Crook et al, 1993
34. Cognitive decline : DHA might have benefits
Alzheimer patients have 30 % less DHA in brain
tissue
Epidemiological evidence suggest 180 mg
DHA/day is associated with a 50-60 % reduced
chance of getting dementia
Johnson and Schaefer, 2006
Soderberg et al, 1991
Morris et al, 2003
35. Brain health & DHA: Lifetime dietary effects
Born IQ-test IQ-test
1936 1947 1999-2000
Non -fish oil Non -fish oil
users users
n=60 n=60
IQ: 100.2 IQ: 95.2
Fish oil Fish oil
users users
n=60 n=60
IQ: 100.7 IQ: 105.9
Whalley et al, 2004
36. How much DHA do we need? For optimum brain function
No daily recommended intake defined
Most recommendations on Fish oil and heart health
Defined in some countries:
Pregnant and nursing women : 115-300 mg DHA/day
Infants (0-5 Months): 20 mg/kg/day – 500 mg DHA+EPA
Most Heart health recommendation “fit” with studies on
brain development / cognitive health
Some studies use very high concentrations
37. Bioriginal neural concepts:
The optimum amount of DHA for 3 age
groups:
Young children (150 mg)
Teens (200 mg)
Seniors (250 mg)
3 great flavors (oils and capsules)
Additional supportive vitamins fitting for that age group
38. Conclusions
Research on the effects of DHA and Brain health
still in its’ infancy
DHA shown to play an important role in brain
health throughout life
Dietary recommendations for heart health
probably sufficient for optimum brain health
Notes de l'éditeur
Glial cells: support & protection role for Neurons The four main functions of glial cells are to surround neurons and hold them in place, to supply nutrients and oxygen to neurons, to insulate one neuron from another, and to destroy pathogens and remove dead neurons.
High LA + AA, ratio n6:n3 generally hig
High LA + AA, ratio n6:n3 generally hig
The uptake of DHA in brain tissue is established
Kaufman assesment Battery scores for Mental processing composite
Most studies done with fish oil
Most studies done with fish oil
Most studies done with fish oil
Most studies done with fish oil
Most studies done with fish oil
Most studies done with fish oil
Recommendations need closer look by authorities once more evidence is collected.
