The role of DHA in neural health

throughout life: The latest news

René van HoornBioriginal

DHA

The nervous system

Role of DHA in building and

maintaining optimal brain function

Presentation Outline

DHA

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

DHA: main sources

Fish

Tuna 23-25%

Atl. Salm

on 12-15%

18/12 Fish oil 1

0-13%

Cod liver 1

0-13%

Mackerel 10-12%

Menhaden 9-10%

Sardine 9-10%

Anchovy 8-10%

Krill

9-10%

Alg

al

35-4

0%

DHA: fish sources

Bioriginal premium DHA source: Biopure DHA™

Fish source

Selection ExtractionCrude

oil

Refining+ QC

Tuna catching ground

DHA-rich Tuna

Caught in pristineWaters of Indian ocean

Heads only

Avoid contaminant-rich livers

Patented cold extraction

Avoiding oxidation

Dedicated plant

Crude BiopureTuna

Crude “Normal”Tuna

The human nervoussystem

Complex network of neurons

located throughout our body

Two parts:

Central nervous system and

Peripheral nervous system

Both controlled by the brain

Nervous system

Numerous functions described

to the brain:

Control of body functions

Voluntary

(thought>movement)

Involuntary (Heartbeat)

Reason of consciousness,

emotions, memory,

imagination, etc

Nervous system: The brain

Regions (lobes) in the brain have special roles

10 % neurons, 90% glial cells

Nervous system: Brain anatomy

Picture taken from Stanford University website

Many brain disorders / imbalances exist:

Mood

Depression / Anxiety / Hyperactivity

Psychotic

Bipolar / Schizophrenia /delusional disorder

Memory related

Light Dementia Alzheimer's

Brain Injury

Stroke / Epilepsy

Nervous system: conditions

Brain development

EarlyChildhood

Bir

th

LateChildhood /adolescence

Pre-birth

Tri

mest

er

1

Tri

mest

er

2

Tri

mest

er

3

4 y

rs o

ld

18 y

rs o

ld

Young-Mid age

Adult

55 y

rs

0ld

Olderadults

Death

Bra

in

weig

ht

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

Nervous system: Brain structure

Sinclair 1975

Brain health: genetic factors

Noguchi et al, 1993Owada et al, 2006

Veerkamp and Zimmerman, 2001

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

Role of DHA in building and maintaining optimal brain

function

Gamma-Linolenic Acid (GLA)*

Stearidonic Acid

Dihomo-Gamma-Linolenic Acid (DGLA)*

Eicosatetraenoic Acid (20:4n-3)

Arachidonic Acid (AA) Eicosapentaenoic Acid (EPA)

Longer Chain Fatty Acid Metabolites

Docosahexaenoic Acid (DHA)

Alpha-Linolenic Acid (ALA)

Linoleic Acid (LA)

Western diet: High in n-6’s : LA and AA

D6D Enzyme

Elongase

D5D Enzyme

Elongase

Desaturase

Elongase

Gamma-Linolenic Acid (GLA)*

Stearidonic Acid

Dihomo-Gamma-Linolenic Acid (DGLA)*

Eicosatetraenoic Acid (20:4n-3)

Arachidonic Acid (AA) Eicosapentaenoic Acid (EPA)

Longer Chain Fatty Acid Metabolites

Docosahexaenoic Acid (DHA)

Alpha-Linolenic Acid (ALA)Linoleic Acid (LA)

Western diet: n3 mostly ALA from plant sources

D6D Enzyme

Elongase

D5D Enzyme

Elongase

Conversion:slow

Desaturase

Elongase

Possible shortage of DHA in the body

Williams and Burdge, 2006

Split up: Development/Decline vs Problems

LateChildhood /adolescence

Young-Mid age

Adult

EarlyChildhood

Pre-birth Olderadults

Research focusedon development and decline

Research focusedon “problems”

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, 2001Mayes et al, 2006

Brain development: Uptake and incorporation

Interpreted from Hsieh et al, 2007

Diets:Control No added PUFAL 0.42% DHA (+ 39 mg/Kcal ARA)L3 1.13% DHA (+ 39mg/Kcal ARA)

9.8

% DHAIn baboonfrontal lobe after 12 wks

C L L3

12.8 13.9

* *

Effect of dietary intake ARA and DHA uponDHA status in Frontal lobe of the Cerebral cortex

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

Brain development: Effect of maternal DHA intake

Interpreted from Helland et al, 2003

Brain development: Effect of maternal DHA intake

K-A

BC

sco

re

107.8101.7

*

CLOCorn oil

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

Brain development: Effect of DHA intake between 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

Brain development: DHA & the effect on child behavior (0-4yrs)

Interpreted from Hart et al, 2006

Brain development: DHA & the effect on child behavior (0-4yrs)

DHA in Breast milk

Lability of State(Higher score is more stable)

r=0.57P<0.01

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

Brain development: Effect of DHA intake during “adolescence”

Interpreted from Lim and Suzuki, 2000

Brain development: Time to reach Maze exit shortens with prolonged DHA diet

1wk 2 wk 1 mth 3 mths

Time (% control)

bars Con

trol

Con

trol

Con

trol

Con

trol

DH

A

DH

A

DH

A DH

A

*

DHA in BrainLines

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

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 Mo), P=0.001

Brain health Problems & DHA: ADHD

Richardson and Puri, 2002Stevens et al, 2003Stevens et al, 1995

Hamazaki et al, 2004

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

Brain health Problems & DHA: Depression

Sinclair et al, 2007Llorente at al, 2003

Memory related problems increase with aging:

Dementia:

65 and older = 6 %

80 and older = 20%

Forgetfulness > Dementia > Alzheimer

Cognitive decline : A major future problem

Wimo et al, 2003Crook et al, 1993

Babyboomers getting older

Cognitive decline : A major future problem

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

Cognitive decline : DHA might have benefits

Johnson and Schaefer, 2006Soderberg et al, 1991Morris et al, 2003

Brain health & DHA: Lifetime dietary effects

Whalley et al, 2004

Born 1936

IQ-test1947

IQ-test1999-2000

Non -fish oil users

n=60IQ: 100.2

Fish oil users

n=60IQ: 100.7

Non -fish oil users

n=60IQ: 95.2

Fish oil users

n=60IQ: 105.9

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

How much DHA do we need? For optimum brain function

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

Bioriginal neural concepts:

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

Conclusions