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Influence Of DHA And AA On Neurological And Visual Development Of Infants
By - Danone Nutricia India
For healthcare professionals only

Influence Of DHA And AA On Neurological And Visual Development Of Infants

DHA (docosahexaenoic acid) and AA (arachidonic acid) are components of lipids in the brain and retina and are incorporated into neural tissues during the brain growth spurt, during the prenatal and postnatal periods up to at least 2 years of age. Endogenous synthesis decreases with postnatal age from birth to 7 months of age. This means that the tissue LCPUFA status remains diet dependent in infants and young children, particularly after weaning, when human milk supplies are reduced and weaning foods are low and/or devoid in LCPUFA, especially DHA. The aim of this article is to discuss the role of DHA and AA on the neurological and visual development of an infant.

The brain is a lipid-rich organ that consumes 20% of the total body energy despite comprising only 2% of the body mass. Further, it is enriched in long-chain omega-3 (n-3) polyunsaturated fatty acids (PUFAs). Quantitatively, docosahexaenoic acid (DHA; 22:6(n-3)) and arachidonic acid (AA, 20:4(n-6)) are the most significant LCPUFAs in the brain suggesting their key roles in the optimal development, maturation, and aging of neural structures and networks. Both, AA and DHA, are found in neural structures and DHA particularly is a component of neuron membranes and external segments of photoreceptors in the retina.

Accumulation of AA and DHA in the brain cortex during the last trimester and first two years of age has prompted the interest in the effects of LCPUFAs on neurological development. The liver is the primary site for biosynthesis of LCPUFAs, which then is secreted into circulating bloodstream and subsequently taken up by the brain. Among neural cells, comprising of neurons, astrocytes, microglia, and oligodendrocytes, only astrocytes can synthesize DHA. Among individual phosphoglyceride classes (phosphatidylethanolamine, phosphatidylserine, phosphatidylcholine, and phosphatidylinositol) in the brain, cerebral gray and white matter have unique LCPUFA profiles. AA greatly exceeds DHA in inositol phosphoglycerides – key to the phosphatidylinositol-3-kinase/Akt pathway and phosphatidylinositol 4,5-bisphosphate signaling, whereas DHA exceeds AA in serine phosphoglycerides – important for long-term potentiation (a process critical to memory formation).

LCPUFAs are also the precursors for physiologically important metabolites, including prostaglandins, leukotrienes, oxygenated metabolites including resolvins that reduce inflammation through nuclear factor kappa B signaling. DHA and AA are also precursors of the endocannabinoids N-docosahexaenoyl-ethanolamide and anandamide, respectively, which are modulators of the central and enteric nervous systems. N-docosahexaenoyl-ethanolamide promotes hippocampal development and anandamide modulates spatial memory after stress. In addition, DHA and AA and their metabolites are ligands for the nuclear receptor, peroxisome proliferator-activated receptor gamma (PPARc) influencing physiologic functions of organs and tissues, and all have the potential for long-term effects on brain function and behavior (programming).

The brain’s frontal lobes are particularly responsive to the supply of DHA during development which begins at 6 months of age and continues throughout childhood and adolescence. The frontal lobes are involved in the executive and higher-order cognitive activities including sustained attention, planning and problem-solving. Further, the prefrontal lobe is responsible in particular for social, emotional and behavioral development. All this emphasizes the importance of DHA and AA supplementation in early childhood.

Maintaining optimal lipid composition in these brain regions, and specifically, DHA levels, is not only important during the development and maturation of the brain from gestation through childhood and adolescence, but such maintenance is also critical for the successful aging of the adult brain.

DHA and AA: Visual Development

Cortical visual acuity was the first brain function studied in preterm infants to determine whether DHA would improve its development. It is well known that visual pigments respond to the degree of unsaturation of the membrane lipids. The retina contains a very high level of DHA and a very considerable amount of diDHA (di-docosahexaenoic acid) species along with DHA coupled to other highly unsaturated fatty acids (HUFA) in the rod outer segment (ROS) membranes.

In n-3-deficient animals, a reduced amplitude and delayed response were noted in the leading portion of the a-wave of electroretinograms which is associated with the visual transduction pathway. Further, a meta-analysis of the trials involving visual acuity concluded that there was a 0.32-octave difference in visual acuity when supplemented and unsupplemented formula groups were compared, with the DHA-fed groups having the higher acuity. The most recent study of visual acuity in DHA supplemented infants was from a large dose-response study, the DIAMOND trial (0.32%, 0.64%, or 0.96% total fatty acids as DHA and 0.64% as AA compared with a formula without DHA and AA). The DIAMOND trial began in 2003 and was conducted at 2 sites in the United States and showed that DHA and AA supplementation significantly enhanced visual acuity at 12 months of age, supporting earlier studies. The study demonstrated that irrespective of DHA dose (while maintaining the minimal dosage of 0.32% DHA of total fatty acids), the visual acuity at 12 months of age was significantly better when using the formula with or without LCPUFA.

DHA and AA Accretion: A Non-recoverable Opportunity

It has long been known that when an adult mammal consumes a diet low in DHA and its n-3 precursors, the nervous system content of DHA is much less altered than are other organs, i.e., DHA is said to be tenaciously retained once neural development has occurred, however, studies have shown that when n-3 fat sources are inadequate during early neural development, then the levels of brain and retinal DHA decline. Once depleted, the brain recovers its DHA rather slowly.

The accretion of DHA in the brain takes place during the brain growth spurt, which typically initiates during the intrauterine period and extends up to 2 years of age. The significant levels of DHA in the brain are maintained throughout life. Due to the absence of de novo LCPUFA synthesis, the rate of membrane DHA incorporation in early life depends on maternal transfer. Human milk contains AA and DHA to support its requirements for the growing and developing brain as well as other organs and tissues after birth. The amount of AA typically exceeds that of DHA with less variability in content, displaying the minimal link to the maternal intake.

Because worldwide DHA intake is variable, breast milk DHA content is also variable across cultures. Reports of breast milk DHA concentration range from 0.05% of total fatty acids in vegan vegetarians to 2.8% in the marine region where a diet high in seafood is consumed; the median value of DHA in human milk worldwide is ~0.32%. DHA makes up 10%–20% of the total lipids of the gray matter and over 90% of the total n-3 PUFAs in the brain.

Generally, it is difficult to deplete DHA from the neural membranes of adult mammals even with a diet low in DHA, presumably because of preferential uptake of DHA into the brain to support the basal turnover. Thus, it can be concluded that restoring the inadequate levels of dietary DHA may restore the neuronal and retinal functions. However, other functions may not be reversible due to missed opportunities in sequential development or changes in structural features of the brain.

Human brain DHA content is exceedingly low at the beginning of the third trimester of pregnancy and accumulates rapidly during the third trimester till the birth, limited only by its availability. Further, the human milk content of DHA is low. This inadequate supply declines the levels in brain and retina during the early infancy, which marks the period of neural development, emphasizing the need of sufficient dietary supply.


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