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Indian Journal of Pediatrics, Volume 72—March, 2005 239

Special Article
Correspondence and Reprint requests : Dr.Meharban Singh,
Consultant Pediatrician, Child Care and Dental Health Center, 625,
Sector 37, Arun Vihar, Noida (UP). Fax: 011-23746276
Essential fatty acids (EFAs) are required for maintenance
of optimal health but they cannot be synthesized in the
body and must be obtained from dietary sources. They
are also called polyunsaturated fatty acids (PUFAs). They
remain in a liquid form even in cold weather unlike
saturated oils which solidify. There are two classes of
PUFAs, omega-6 and omega-3. The parent omega-6 fatty
acid is linoleic acid (LA) and the parent omega-3 fatty acid
is alpha-linolenic acid (ALA)
1,2
. Till recently, deficiency of
essential fatty acids was believed to cause crazy-
pavement scaly dermatitis, alopecia, thrombocytopenia
and failure to thrive.
3
But there is increasing evidence to
suggest the critical role of EFAs and their active metabolic
products for the maintenance of structural and functional
integrity of central nervous system and retina.
DIETARY SOURCES
The main dietary sources of omega-6 fatty acids are
vegetable oils like sunflower oil, safflower oil, sesame oil,
palmolein oil and corn oil. About 10-15% of omega-6 fatty
acids are obtained as an integral part of cereals, pulses,
tubers, legumes and vegetables as ‘invisible fat’. The rich
dietary sources of omega-3 fatty acids are vegetable oils
like flaxseed or linseed oil, rapeseed or canola oil, peanut
oil, olive oil, soya oil, walnut oil, green leafy vegetables,
Essential Fatty Acids, DHA and Human Brain
Meharban Singh
Child Care and Dental Health Center, Noida, UP, I ndia
Abstract. Essential fatty acids cannot be synthesized in the body but they are required for maintenance of optimal health.
There are two classes of polyunsaturated fatty acids (PUFAs)– omega-6 and omega-3. The parent omega-6 fatty acid, linoleic
acid (LA) is desaturated in the body to form arachidonic acid while parent omega-3 fatty acid alpha- linolenic acid (ALA) is
desaturated by microsomal enzyme system through a series of metabolic steps to form eicosapentaenoic acid (EPA) and
decosahexaenoic acid (DHA). But there is a limited metabolic capability during early life to metabolize PUFAs to more active
long-chain fatty acids. There is a critical role of EFAs and their metabolic products for maintenance of structural and functional
integrity of central nervous system and retina. Most of the brain growth is completed by 5-6 years of age. At birth brain weight
is 70% of an adult, 15% brain growth occurs during infancy and remaining brain growth is completed during preschool years.
DHA is the predominant structural fatty acid in the central nervous system and retina and its availability is crucial for brain
development. It is recommended that the pregnant and nursing woman should take at least 2.6g of omega-3 fatty acids and
100-300 mg of DHA daily to look after the needs of her fetus and suckling infant. The follow-up studies have shown that infants
of mothers supplemented with EFAs and DHA had higher mental processing scores, psychomotor development, eye-hand
coordination and stereo acuity at 4 years of age. Intake of EFAs and DHA during preschool years may also have a beneficial
role in the prevention of attention deficit hyperactivity disorder (ADHD) and enhancing learning capability and academic
performance. [Indian J Pediatr 2005; 72 (3) : 239-242] E-mail: meharbans.singh@gsk.com
Key words : Essential fatty acids; Omega-3 fatty acids; DHA; Brain growth; ADHD
fenugreek seeds, kidney beans, dry fruits, oily cold-water
fish (mackerel, sardine, hilsa and salmon etc.) and fish oil.
4
Vegetarians specially vegans, who do not take even eggs
and milk products, are likely to consume lower quantities
of alpha linolenic acid (ALA) compared to linoleic acid
(LA).
5
Due to their greater availability and low cost, there is
excessive consumption of omega-6 fatty acids in
developing countries. Junk food is also loaded with n-6
fatty acids and transfatty acids. Most Indians consume
omega-6 and omega-3 fatty acids in a ratio of 30-70:1 but
the ideal ratio is 5-10:1 for optimal health benefits.
6
The
Japanese are probably the only nation that consume EFAs
in an ideal ratio of 2-4:1 by taking plenty of sea food.
METABOLISM OF EFAs
In humans, both EFAs (n-3 and n-6 are 18 carbon atoms
fatty acids) are metabolized to long-chain fatty acids by
desaturation and adding extra double bonds to the
carboxyl group end of the molecule. Linoleic acid (LA) is
metabolized to arachidonic acid (AA) while alpha-
linolenic acid (ALA) is metabolized to eicosapentaenoic
acid (EPA) and decosahexaenoic acid (DHA) as active
metabolic end products (Table 1).
7,8
During early life there is limited metabolic capability to
convert ALA to DHA. Therefore, during fetal life, infancy
and early childhood DHA should be consumed de novo.
Meharban Singh
240 Indian Journal of Pediatrics, Volume 72—March, 2005
SOURCES OF DHA
During pregnancy, the fetus depends completely on
maternal sources of DHA from lipid stores, maternal diet
and nutritional supplements. During fetal life, placenta
selectively and substantially transports AA and DHA
from the mother to the fetus. During third trimester of
pregnancy, there is an avid accretion of DHA in the liver,
brain and retina of the fetus at a rate of 4.13g of EFA per
week i.e. 0.59 g/day.
9
Pregnancy leads to a progressive
depletion of maternal plasma DHA, presumably due to
the increased supply of this critical nutrient to the
developing fetal nervous system.
10
After delivery
maternal stores are replaced slowly or incompletely over
a period of 5-6 months (Fig. 1).
11
There is evidence to
suggest that depletion of maternal DHA reserves during
pregnancy is an important correlate of postpartum
depression.
TABLE 1. Metabolic Conversion of EFAs to Their Active Metabolites in Human Adults.
The omega-6 polyunsaturates The omega-3 polyunsaturates
Linoleic acid (C18:2, n-6) Alpha-linolenic acid (C18:3, n-3)
↓ ∆
6
desaturase ↓ ∆
6
desaturase
Gamma-linolenic acid (GLA) (C18:3, n-6) Eicosapentaenoic acid (EPA) (C20:5, n-3)
↓ ∆
5
desaturase ↓ ∆
5
desaturase
Arachidonic acid (AA) (C20:4, n-6) Decosapentaenoic acid (DPA) (C22:5, n-3)
↓ ∆
4
desaturase
Decosahexaenoic acid (DHA) (C22:6, n-3)
animals and chicken. Eggs of chicken fed with flax or
microalgae have been shown to be loaded with DHA
(100-150 mg DHA/egg).
BRAIN GROWTH
Most of the brain growth occurs during fetal life. When a
baby is born, the body weight is only 5% of an adult but
the brain size is 70% of the adult brain.
1
After birth 15% of
brain growth occurs during first year of life and the
remaining 10% of brain growth occurs during pre-school
years (Fig 2). Most of the brain growth is completed by 5-
6 years of age.
9
36 wk
post-partum
*DHASI : DHA sufficiency index based on plasma phospholipid
levels.
Fig 1. Plasma DHA levels decrease as pregnancy advances. The
recovery after delivery is slow and may take 5-6 months.
D
H
A
S
I
*
Gestational age (weeks)
During infancy DHA needs of the baby are met through
breast milk. DHA content of the human milk is atleast 30
times of the milk of other mammals and can be further
improved by giving adequate dietary supplements to the
nursing mother.
12
During preschool years, the DHA
requirement are met by consumption of diet rich in n-3
fatty acids and DHA. Fish oil, sea food, marine algae and
sea weed are eminently rich sources of EPA and DHA.
Sea food is highly brain-friendly because apart from
DHA, it is rich in iodine, taurine and zinc. The DHA
content of the animal milk, meat, poultry and eggs can be
increased by giving omega-3 fatty acid rich diet to the
Fig 2. Brain growth during fetal life and preschool years
Source : Clandinin MT et al. Early Human Dev 1980; 4 : 121-129.
F
0
20
40
60
80
100
25 wk 30 wk 35 wk 40 wk 1 yr 5yr
Brain weight ( grams )
Time period
%

o
f

B
r
a
i
n

d
e
v
e
l
o
p
m
e
n
t
STRUCTURE OF THE BRAIN
“From high fat to low fat with age, first to increase
intelligence and then to increase life span”
- Kurt Widhalm
Brain is the fattiest organ of the body. Almost two-
third of the weight of the human brain is accounted by
phospholipids. DHA is the predominant structural fatty
acid in the brain which is mostly distributed in the
cerebral cortex, membranes of synaptic communication
centers, mitochondria and photoreceptors of the retina.
13
It comprises approximately 40% of the PUFAs in the brain
and 60% of PUFAs in the retina. Almost 50% weight of
the neuronal membranes is accounted by DHA.
13
12
11
10
9
8
7
6
Essential Fatty Acids, DHA and Human Brain
Indian Journal of Pediatrics, Volume 72—March, 2005 241
Arachidonic acid, EPA and DHA along with other smart
micronutrients like vitamin B complex, vitamin C,
vitamin E, iodine, iron, zinc, copper, taurine and choline
etc. are crucial for brain development and its integrity and
functionality.
12
PHYSIOLOGICAL EFFECTS OF EFAs
PUFAs are important source of energy in our diet. When
omega-6 and omega-3 fatty acids are consumed in the
recommended ratio of 5-10:1, they are essential for
maintaining structural and functional integrity of central
nervous system. Omega-6 fatty acids are pro-
inflammatory and promote platelet aggregation while
omega-3 fatty acids are anti-inflammatory and inhibit
platelet aggregation. The metabolism of omega-6 fatty
acids is associated with production of a number of
eicosanoids like thromboxanes, leukotrienes and
prostaglandins which are known to trigger inflammation
in the blood vessels causing atherosclerosis.
14
Archidonic
acid which is the metabolic end product of linoleic acid (n-
6 PUFA) is the most potent inflammatory agent. It also
stimulates the production of glutamate, a
neurotransmitter which potentiates the destruction of
neurons by over production of oxygen free radicals.
“The food that is good for the heart is likely to be good for
the brain.”
- Hippocrates
On the other hand, omega-3 fatty acids and DHA are
credited to reduce cellular and vascular inflammation in
the brain, and ensure integrity of brain cell membranes to
keep them soft and pliable. Fish oil and DHA are credited
to reduce the level of thromboxane (TXA
2
) and increase
prostacyclin (PGI
2
) level leading to enhanced tissue
perfusion and oxygen delivery due to vasodilatation and
decreased blood viscosity. Apart from its role in
fabrication of synaptic communication centers, DHA is
credited to increase the level of “feel good”
neurotransmitter serotonin and “memory boosting”
chemical acetylcholine. DHA is also credited to neutralize
oxygen-free radicals.
HEALTH BENEFITS OF SUPPLEMENTS WITH EFAs
AND DHA
The EFA status of the fetus depends upon the EFA
content of the maternal diet. Pregnant women must take
adequate amount of DHA in their diet or through
nutritional supplements in order to optimize not only
their own health but also the health and mental
development of their offsprings. According to WHO and
FAO the pregnant woman should take atleast 2.6g of
omega-3 fatty acids and 100-300 mg of DHA daily to look
after the needs of her fetus.
15
The clinical studies have
shown that the duration of gestation and birth weight are
significantly increased when omega-3 rich food or DHA
supplements are taken during last trimester of
pregnancy.
11,16,17
Olsen et al
18
showed that risk of preterm
delivery was 4 times less in mothers who received omega-
3 food supplements during pregnancy. DHA is credited
to reduce the levels of thromboxane (TXA
2
) and increase
prostacyclin (PGI
2
) level leading to enhanced utero-
placental perfusion and oxygen delivery, vasodilatation
and thinning of blood. There is reduced risk of
development of toxemia of pregnancy in mothers who
received supplements of DHA. The follow-up studies
have shown that infants born to mothers whose diet was
supplemented with DHA, had higher mental processing
scores and high degree of stereopsis and stereo acuity at
4 years of age .
19,20
The nutritional quality of breast milk depends upon
the nutritional status and dietary supplements taken by
the nursing mother. There is a linear correlation between
the dietary intake of DHA by the nursing mother and the
DHA content of her breast milk.
21,22
It is recommended
that nursing mother should take atleast 2.6g of omega-3
fatty acids and 100-300 mg of DHA daily to look after the
needs of her suckling infant. It has been shown that
supplementation with 200 mg DHA/day is associated
with increase in the concentration of her breast milk DHA
content by 0.20-0.34 wt% i.e. 2-fold increase as compared
to controls. There is a direct correlation between breast
milk DHA levels with DHA content of baby’s RBCs and
neurodevelopment outcome at one year of age. Breast fed
babies have been shown to have more DHA content in
their brains with 8 points higher IQ compared to formula
fed babies. The studies have shown that breast fed infants
of mothers who were supplemented with DHA during
lactation, had significantly better psychomotor
development, eye-hand coordination and visual acuity at
2.5 years compared to breast fed infants of mothers who
received a placebo.
23
Till recently, baby formulae available
in the developed countries were not supplemented with
DHA. But now many formulae available in the west are
fortified with DHA to harness its benefits during the
crucial phase of brain development during infancy.
The weaning foods and diets of preschool children
should contain DHA because metabolic conversion of
alpha-linolenic acid to DHA is limited to less than 0.2% in
children. There is evidence to suggest that 40% of children
with attention hyperactivity disorder (ADHD) have
significantly low levels of plasma DHA.
24
It is believed
that DHA may also have beneficial effects on the learning
capabilities and academic performance of children. It is
recommended that weaning foods should be rich in DHA
(fish oil, sea food and dry fruits) or supplemented with
nutritional supplements containing DHA.
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242 Indian Journal of Pediatrics, Volume 72—March, 2005
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