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DHA -a precursor to geniuses?
(Journal Review)
Annaliza Chandrasegar
13 – 06 -12
 There are three major
omega-3 fatty acids:
 Alpha-linolenic acid
(ALA)
 Eicosaentaenoic acid
(EPA)
 Docosahexaenoic acid
(DHA)
 ALA
 parent omega-3
 cannot be produced by
the body.
Docosahexaenoic acid (DHA) and the developing central nervous system
(CNS) – Implications for dietary recommendations, Philippe Guesnett and
Jean-Marc Alessandri
Adults (some
DHA from
Diet)
100mg daily
Adults (little
DHA from
Diet)
Recommended
Dosages
200mg Daily
Pregnant &
Breastfeeding
200mg daily
Children
100mg daily
DHA highly
unsaturated LCP
-Lots of gaps
- Missing Hydrogen
atoms
gaps make DHA very
flexible
Brain cells rich in DHA
communicate quickly
When DHA is in short
supply
- membranes
surrounding each
synapse – Fluid state
nerve cell membranes
become less flexible
and less efficient in
passing on electrical
and chemical messages
Synapses
speed of
communication
between one brain cell
and another is slowed
development of a
baby’s eyes and brain
obtained from the
mother’s richest store her own brain
slight shrinkage (2% 3%) in maternal brain
size
last three months of
pregnancy
If maternal levels of
DHA are low
poor concentration,
forgetfulness and
vagueness
baby’s levels of DHA
are twice as high as his
mother’s
newborn baby is
unable to produce
DHA from essential
fatty acids until he is at
least 4 months old
placenta extracts it
from the mother’s own
blood
Deposition of
DHA in early
development
Respiratory
Health
Why DHA
for Infants?
NeuroDevelopment
Retinal
Health
 DHA, the end-product of the -3 series, is the
predominant fatty acid of membrane phospholipids in
the brain grey matter and in the retina of mammals 1,2
 DHA takes account for about 25% (wt%) of total fatty
acids in the human cerebral cortex.
 for more than 30% in the whole retina, and up to 60%
in the discs of the rod photoreceptor cells.
Docosahexaenoic acid (DHA) and the developing central nervous system (CNS) – Implications for dietary recommendations, Philippe
Guesnett and Jean-Marc Alessandri
[1] L.Lauritzen, H.S.Hansen, M.H.Jørgensen, K.F.Michaelsen, The essentiality of long chain n-3 fatty acids in relation to development and
function of the brain and retina.Prog.LipidRes.40(2001)1-94.
[2] J.M.Alessandri, P.Guesnet, S.Vancassel et al., Polyunsaturated fatty acids in the central nervous system: evolution of concepts and
nutritional implications throughout life.Reprod.Nutr.Dev.44(2004)509-538.
Long-Chain Polyunsaturated Fatty Acids in the Growth and Development of the Brain and Memory, U. N. Das, MD, FAMS, Nutrition
19:62– 65, 2003
 LCPUFA supplemented infants tend to maintain
their plasma and erythrocyte phospholipid DHA
concentrations at birth levels 1 ,and show improved
visual2,3 and developmental outcomes (mental and
psychomotor)4.
L.G. Smithers et al. DINO trial/ Prostaglandins, Leukotrienes and Essential Fatty Acids 79 (2008) 141–146
[1] G. Boehm, M. Borte, H.J. Bohles, H. Muller, G. Kohn, G. Moro, Docosahexaenoic and arachidonic acid content of serum and red blood
cell membrane phospholipids of preterm infants fed breast milk, standard formula or formula supplemented with n-3 and n-6 longchain polyunsaturated fatty acids, Eur. J. Pediatr. 155 (1996) 410–416.
[2] E. Birch, D. Birch, D.R. Hoffman, R. Uauy, Dietary essential fatty acid supply and visual acuity development, Invest. Ophthalmol. Vis.
Sci. 33 (1992) 3242–3253.
[3] D.L. O’Connor, R. Hall, D. Adamkin, et al., Growth and development in preterm infants fed long-chain polyunsaturated fatty acids: a
prospective randomized controlled trial, Pediatrics 108 (2001) 359–371.
[4] M.T. Clandinin, J.E. Van Aerde, K.L. Merkel, et al., Growth and development of preterm infants fed infant formulas containing
docosahexaenoic acid and arachidonic acid, J. Pediatr. 146 (2005) 461–468.
 A large corpus of data is in favor of the
recommendation of regular dietary intakes of
DHA(during at least the first 6 months of life) and
suggest that DHA should be added in formulas at the
level generally found in human milk
(0.2 - 0.3 wt% of total fatty acids)
P.Guesnet, J.M.Alessandri, Docosahexaenoic acid (DHA) and the developing central nervous
system(CNS) Implications for dietary...,Biochimie (2010),doi:10.1016/j.biochi.2010.05.005
 The deposition of DHA in human brain phospholipids
occurs primarily during the foetal period of active
neurogenesis and cell maturation(from the sixth
month of pregnancy/third trimester) and the early
post- natal period of development of intense
synaptogenesis, and continues during at least the first
two years of life.
P.Guesnet, J.M.Alessandri, Docosahexaenoic acid (DHA) and the developing central nervous
system(CNS) Implications for dietary...,Biochimie (2010),doi:10.1016/j.biochi.2010.05.005
 The prenatal period represents a critical window for
brain membrane biogenesis and for
neurodevelopment.
 Dietary -3 PUFA, supplied in adequate proportion
with  -6 PUFA, are thus crucial throughout the preand post-natal periods for the cerebral accretion of
DHA, and are determining for early
neurodevelopment.
P.Guesnet, J.M.Alessandri, Docosahexaenoic acid (DHA) and the developing central nervous
system(CNS) Implications for dietary...,Biochimie (2010),doi:10.1016/j.biochi.2010.05.005
RETINAL FUNCTION

Deficiency of PUFA : Based on a clinical trial, Significant abnormalities In the
development of visual functions were observed in formula-fed(low PUFA)
premature infants comparatively to breast-fed premature infants. The
electro-retinogram thresholds of rod cells was increased after 6 wk of feeding (i.e.36 wk
post conception) and were normalized 20 wk later (57 wk post conception) indicating a
delay in photo-receptor maturation 1,2

More over, lower visual acuities measured by visual-evoked potential(VEP) and by the
preferential-looking methods were detected 3

Similar abnormalities in visual acuities measured at 57 wk post-conception were also
reported in full-term infants fed during 4 months of formula low in n-3 PUFA 3.

Results/ conclusion : In preterm infants, feeding with DHA-enriched
formulas resulted (in most cases) In better early visual development
outcomes than feeding with standard formulas containing only a-LNA 4
Docosahexaenoic acid (DHA) and the developing central nervous system (CNS) – Implications for dietary recommendations, Philippe Guesnett and Jean-Marc
Alessandri
[1] R.D.Uauy, D.G.Birch, E.E.Birch, J.E.Tyson, D.R.Hoffman, Effect of dietary omega-3 fatty acids on retinal function of very-low-birth-weight neonates. Pediatr.
Res.28(1990)485-492.
[2] D.G.Birch, E.E.Birch, D.R.Hoffman, R.D.Uauy, Retinal development in very- low-birth-weight infants fed diets differing in omega-3fattya cids.Invest.
Ophthalmol. Vis.Sci.33(1992)2365-2376.
[3] E.E.Birch, D.G.Birch, D.R.Hoffman, R.Uauy, Dietary essential fatty acid supply and visual acuity development.Invest.Ophthalmol.Vis.Sci.33(1992) 3242-3253.
[4] J.P.SanGiovanni, S.Parra-Cabrera, G.A.Colditz, C.S.Berkey, J.T.Dwyer, Meta- analysis of dietary essential fatty acids and long-chain polyunsaturated fatty acids
as they relate to visual resolution acuity in healthy preterm infants. Pediatrics 105(2000)1292-1298.
RESPIRATORY HEALTH

The objectives of this double-blind, randomized study among US toddlers below age of 3
were to:
(A)Determine usual DHA intakes,
(B)Measure the effect of consuming formulas with DHA on red blood cell(rbc)and plasma DHA and
(C)Record adverse events in US children between 18 and 36months of age.

Children aged 18–36months were provided 237-ml formula with 0, 43, or 130mg DHA per
day for 60days.

Blood was obtained at 0and 60days and24-hour dietary recalls at 0, 30 and 60days.

Usual median daily DHA intake was13.3mg.

RBC DHA increased in a dose-dependent manner with increasing DHA intake(p=0.05).

Toddlers consuming the formula with 130mg DHA per day have fewer adverse events
(p=0.007) and a lower incidence of respiratory illness(p=0.024), compared to the formula
without DHA.
 Modest increases in DHA intake in toddlers might improve development,
including respiratory health.
Laura M. Minns et al, Toddler formula supplemented with docosahexaenoic acid (DHA) improves DHA status and respiratory health in a
randomized, double-blind, controlled trial of US children less than 3 years of age, Prostaglandins, Leukotrienes and Essential Fatty Acids
82 (2010) 287–293 .
NEURODEVELOPMENT
 Some clinical studies have also evidenced lower
performance on mental development(Bayley MDI
score) at 12months of age in preterm infants fed
standard formulas compared to infants fed DHAsupplemented formulas.
Docosahexaenoic acid (DHA) and the developing central nervous system (CNS) – Implications for dietary recommendations, Philippe
Guesnett and Jean-Marc Alessandri:
S.E.Carlson, S.H.Werkman, J.M.Peeples, W.M.Wilson, Long-chain fatty acids and early visual and cognitive development of preterm
infants. Eur.J.Clin. Nutr. 48(1994)S27-S30.
 Some studies suggest that babies of women with
higher DHA consumption during pregnancy may have
better mental, visual, social and motor development
than babies of women with lower DHA consumption (2).
 A Norwegian study
 4-year-old children of women who received DHA supplements
during pregnancy and lactation
 scored higher on tests of intelligence than babies of unsupplemented women (6).
 A study in Great Britain
 women who didn’t eat any fish during pregnancy were 48
percent more likely than women who ate at least 12 ounces of
fish a week to have a child with low verbal IQ scores (7).
 However, it is unclear whether the benefits of eating more than
12 ounces of fish a week (which exceeds the current U.S.
recommendations) outweighs the potential risks of higher
levels of mercury exposure.
 One recent study also found that children of women
who took fish oil supplements during pregnancy were
less likely to have developed asthma by age 16, possibly
due to the effect of omega-3s on the immune
system (8).
12 ounces = 340.194 grams
 Studies show that premature infants (<37 weeks) ->
addition of omega-3s in formula -> improvements
in visual function and mental development (9, 10).
 The American Dietetic Association recommends
 full-term and premature infants who are not
breastfed be fed a formula containing DHA and
other omega-3s for at least the first year of life (10).
 Pregnant and breastfeeding women :200 mg DHA
OD(2).
 2 servings of fish, including fatty fish, per week
(2).
 Fish are good sources of DHA because of what they
eat in the wild.
 Farm-raised fish may not contain DHA unless they are
fed foods rich in DHA.
 Pregnant women should avoid fish that can be high in
mercury,
 shark, swordfish, king mackerel and tilefish (5).
 Women can safely eat up to 12 ounces of fish that have
small amounts of mercury (5).
 Women who do not want to eat fish can look for other
sources of DHA, such as fortified foods.
 Daily supplements of DHA.
 A pregnant woman, however, should always check with her
health care provider before taking any supplements.
 Flaxseed
 Walnuts
 Soybeans
 Canola oil
 Pumpkin seeds
 Dark green leafy vegetables, like spinach and salad greens
 Cold water fish/fatty fish (such as salmon, herring, sardines
and fresh-water trout, tuna, anchovies )
 Organ meats (such as calf’s liver).
 Fortified foods (such as milk, juice, bread and yogurt)
 Supplements containing fish oil or algae oil.
 The "Alternative Medicine Review" journal outlines
the dosage of DHA per 100gm of fish or seafood.






Mackerel contains 2,500mg.
Herring supplies 1,700mg.
Chinook salmon and anchovy provide 1,400mg.
Rainbow trout furnishes 500mg.
Pacific halibut contains 400mg.
Cod, shrimp and catfish supply 300mg.
 Researchers found that intake of olive oil with omega-
3 fatty acids in fish oil increases the amount supplied
to tissues in the body, according to the journal "Poultry
Science.”
 It has been shown that alterations in dopamine
neurotransmission, spatial learning memory
performance and electro-retinograms in the offspring,
which result from n-3 deficiency in mothers, maybe
irreversible even though an n-3 fatty acid diet is given
to deficient animals at weaning, and even though the
DHA content in brain and retina is totally recovered 1,2
P.Guesnet, J.M.Alessandri, Docosahexaenoic acid (DHA) and the developing central nervous system(CNS) Implications for
dietary...,Biochimie (2010),doi:10.1016/j.biochi.2010.05.005
[1] E.Kodas,S.Vancassel,B.Lejeune,D.Guilloteau,S.Chalon,Reversibilityofn-3 fatty acid deficiency-induced changes in dopaminergic
neurotransmission in rats: critical role of developmentalstage.J.LipidRes.43(2002)1209e1219.
[2] W.L.Chung, J.J.Chen,H.M.Su,Fish oil supplementation of control and(n-3) fatty acid-deficient male rats enhances reference and
working memory performance and increases brain regional docosahexaenoic acid levels.J.Nutr. 138 (2008)1165e1171.
 Post-mortem analysis showed that the DHA
concentration regularly increased in the cerebral
cortex of breast-fed infants, but not in formula-fed
infants, its concentration after 48 wk was 30% lower in the
formula- fed infants compared to those who had been
breast-fed.
 Brain of the formula-fed infant consuming adequate intake
of a-LNA(and no DHA)during the first 6 months of life
accumulates DHA at half the rate of the breast-fed
infant’s brain (450mgvs.905mg)
 More over in formula-fed infants, the other organs
(liver, adipose and lean tissues) lost about 1g of DHA,
whereas the same amount of body DHA is gained in
breast-fed infants.
P.Guesnet, J.M.Alessandri, Docosahexaenoic acid (DHA) and the developing central nervous system(CNS) Implications for
dietary...,Biochimie (2010),doi:10.1016/j.biochi.2010.05.005
 The size of a baby’s brain, and its head circumference
are linked to its blood levels of DHA during the first
year of life.
 By the age of nine months after birth, babies fed on
mother’s milk (which contains DHA) or formula
enriched with DHA seem to have significantly better
visual acuity /cognition/respiratory health than baby’s
receiving formula that does not contain DHA.
 So yeah!..maybe 
1.
U.S. Departments of Health and Human Services and Agriculture. The Report of the Dietary Guidelines Advisory
Committee on Dietary Guidelines for Americans, 2005.
2.
Koletzko, B., et al., for the Perinatal Lipid Intake Working Group. Consensus Statement: Dietary Fat Intakes for
Pregnant and Lactating Women. British Journal of Nutrition, volume 98, 2007, pages 873-877.
3.
Office of Dietary Supplements, National Institutes of Health. Omega-3 Fatty Acids and Health. Last updated,
10/28/05, accessed 3/30/09.
4.
American Dietetic Association. DHA: A Good Fat. Nutrition Fact Sheet, accessed 3/30/09.
5.
U.S. Department of Health and Human Services and U.S. Environmental Protection Agency. What You Need to Know
About Mercury in Fish and Shellfish. Accessed 4/2/09.
6.
Helland, I.B., et al. Maternal Supplementation with Very-Long-Chain n-3 Fatty Acids During Pregnancy and
Lactation Augments Children’s IQ at 4 Years of Age. Pediatrics, volume 111, number 1, January 2003, pages e39-e44.
7.
Hibbeln, J.R., et al. Maternal Seafood Consumption in Pregnancy and Neurodevelopmental Outcomes in Childhood
(ALSPAC Study): An Observational Cohort Study. The Lancet, volume 369, February 17, 2007, pages 578-585.
8.
Olsen, S.F. Fish Oil Intake Compared to Olive Oil Intake in Late Pregnancy and Asthma in the Offspring: 16 Years of
Registry-Based Follow-Up from a Randomized Trial. American Journal of Clinical Nutrition, volume 88, 2008, pages
167-175.
9.
Makrides, M. Outcomes for Mothers and Their Babies: Do n-3 Long-Chain Polyunsaturated Fatty Acids and Seafoods
Make a Difference? Journal of the American Dietetic Association, volume 108, number 10, October 2008, pages 16221626.
10.
American Dietetic Association. Position of the American Dietetic Association and Dietitians of Canada: Dietary
Fatty Acids. Journal of the American Dietetic Association, volume 107, number 9, September 2007, pages 1599-1611.
11.
American Heart Association. Fish and Omega-3 Fatty Acids: AHA Recommendations. Accessed 3/30/09.
12.
Olsen, S.F., et al. Duration of Pregnancy in Relation to Seafood Intake During Early and Mid Pregnancy: Prospective
Cohort. European Journal of Epidemiology, volume 21, 2006, pages 749-758.
13.
Oken, E., et al. Associations of Maternal Fish Intake During Pregnancy and Breastfeeding Duration with Attainment
of Developmental Milestones in Early Childhood: A Study from the Danish National Birth Cohort. American Journal
of Clinical Nutrition, volume 88, 2008, pages 789-796.
Annaliza A.C