DHA for Cognition, Learning, and Behavior in Children

DHA for Cognition, Learning, and Behavior in Children

Introduction

Docosahexaenoic acid (DHA) is a long chain polyunsaturated omega-3 fatty acid (LC-PUFA) that is present in the cellular membranes of the human braincerebral cortex, and retina.1–5 DHA is important for the fetal development and growth.4  It is also the principal omega-3 fatty acid in gray matter and represents about 15% of all fatty acids in the human frontal cortex.6  The DHA is accumulated in the retina by birth but its accumulation in the brain continues throughout the 2 years after birth.4

Relationship of DHA with learning and cognition

Several diet components have been known to influence cognition and learning. However, DHA in particular is recognized pivotal for normal brain functioning. Several studies have demonstrated the link between DHA blood concentration in infant and neurocognitive status.7 As the period of childhood marks the growth and maturation of brain, DHA has been recognized as the major lipid for normal functioning of brain. Within the central nervous system, DHA is implicated in neurogenesis, neurotransmission, and cell survival. DHA supports normal IQ and preserves visuo-spatial learning and memory. Thus pointing out that its adequate composition is vital for optimal functioning of both brain and retina.5,6

Important cognitive processes include attention, processing speed (acquisition of information), memory (the retention of information), and language development (acquisition of vocabulary) while higher-order cognitions or executive functions is attributed to the development of frontal lobes. Executive functions include problem solving, inhibitory control, behavioral regulation, and planning/strategic behavior. DHA is present in high concentration at the synapses that improves synaptic efficiency and neuronal transmission speed. It also plays an important role of laying down of a memory trace. The frontal lobe of brain, during development concentrates significant amount of DHA that manifests its role in the development of executive function.3 DHA-rich frontal lobes are essential for executive and higher-order cognitive activities like planning, problem solving, and focused attention. High-level cognitive function also determines child’s social, emotional, and behavioral development.6

DHA affects neurotransmitter pathways, synaptic transmission, and signal transduction. Adequate levels of DHA in neural membranes are essential for cortical astrocyte maturation and vascular coupling, and for cortical glucose uptake, and metabolism. Also, certain DHA metabolites are bioactive molecules that protect tissues from oxidative stress and injury. Low levels of omega-3 LC-PUFA along with high n-6 to n-3 ratio are associated with certain developmental and behavioral disorders in children like attention deficit hyperactivity disorder (ADHD), dyslexia, or dyspraxia.6

The process of neurite overgrowth in hippocampal neurons which requires the accumulation of lipids in new membranes is enhanced by DHA, which may in turn promote learning. Also, DHA enhances protein kinase B signaling and mTOR (mechanistic target of rapamycin) complex for neuronal growth. DHA improves learning and memory by promoting the formation of pre-and postsynaptic proteins that facilitates synaptic transmission and long-term potentiation (LTP). Under the circumstances of oxidative stress, DHA enables the repair and growth of neurons by activating peroxisome proliferator activates receptor gamma (PPAR) and through its activating effect on syntaxin-3 (STX-3).5

The primary growth phase for the human brain begins from birth to 2 years of age. However by the age of 2, certain areas of brain are not yet fully developed, and thus growth and development continues throughout childhood and adolescence, e.g., myelination of frontal lobes of brain starts as early as 6 months of age and proceeds till adolescence so for this development, tissue content of DHA is important.6

Metabolism of DHA:

After oral ingestion of DHA, the enzyme, lipases in the gut delivers unesterified free fatty acid (DHA-FFA) to the small intestine. DHA-FFA are processed by the small intestine and liver resulting in circulating DHA (DHA-triacylglycerides, DHA-PC, and DHA-FFA) bound to low density lipoprotein and albumin. These circulating forms are dissociated at the blood-brain barrier (BBB) through active and passive processes and brain obtains most of its DHA from unesterified FFA pool in blood.5

Clinical findings:

Observational studies showcase that consuming food rich in DHA, like 16 tablespoons per week of seafood by pregnant mothers during gestation and breastfeeding is linked with better infant health.4  Several studies have proved the importance of consumption of DHA during pregnancy for proper cell membrane function and development of fetal brain and retina.1  A study by Judge et al. showcases the positive result that children whose mothers had consumed DHA supplementation during pregnancy have better problem solving skills at the age of 9 months as compared to the control group wherein mothers did not take DHA supplementation during pregnancy.8

The studies have also proved that children aged 7–9 years, who were given long chain poly unsaturated fatty acids rich diet for 6 months showed higher plasma and red blood cell levels of DHA which correlated with higher verbal learning and reading abilities. Also, brain region for executive function, i.e. prefrontal cortex was enhanced in boys aged 8–10 years, who were given supplements of 1.2 g of DHA for 8 weeks as compared to placebo.5 DHA Oxford learning and Behavior study (DOLAB) performed randomized control trial on 362 healthy school children between ages 7 and 9 years who were initially underperforming in reading ability. For 16 weeks every day the children were given either 600 mg of algal DHA or a corn or soybean oil as placebo. The result showed subtle reading improvements across the sample and significant improvement in reading was seen in the poorest reading subgroup. Also parent-rated behavior problems were significantly reduced with DHA supplementation.5

A large cohort study done on U.S. children, aged 6–16 years for National Health and Nutrition Examination Survey (NHANES III), showed greater benefits of DHA consumption in both boys and girls, but the effect was twice prominent in girls. The study speculated the sex difference was seen as there is a greater need for DHA in girls as they need it for their own growth and development and to keep it as store for neurodevelopment of their offspring.5

Dietary intake of DHA

DHA is found predominantly in fish and fish-oil supplements. Some foods like certain brands of eggs, yoghurt, juices, milk, and soy beverages are also fortified with DHA. Mother’s dietary consumption, maternal stores of DHA and mother’s milk are important determinants of DHA during infancy. As a result the dietary requirements of DHA are increased during pregnancy and lactation when a minimal amount of 200 mg of DHA is recommended for pregnant and nursing mothers. Mother’s milk can have DHA as high as 1.4% of total fatty acids depending on mother’s diet.4,5,7
The accumulation of DHA in the brain increases during the middle of gestation, slows down in infancy, and reaches a plateau in early adulthood. Half of the DHA in brain is accumulated during gestation.5 Postnatally breast milk is an important dietary source of DHA in infants offering several brain-related positive health benefits.5  DHA tissue levels in infants are higher in breastfed infants when compared to formula-fed infants. According to the Food and Agricultural Organization of the United Nations the dietary recommendation of DHA is as follows9:

Need for DHA’s supplementation

DHA is essential for humans since it cannot be effectively de novo synthesized in the body, especially when its demand is high during brain growth. Thus it should be consumed from external sources. The DHA synthesis from its precursor like ALA (α-linolenic acid) is insufficient as it does not increase the plasma concentration of DHA in humans. Thus, both ALA and EPA are ineffective dietary source proving the importance of preformed DHA as the most effective source to maintain DHA tissue stores.5

In order to sustain the benefits from DHA across development, adolescents, and adulthood a sufficient DHA pool should be maintained to replenish depleted neural stores. Thus those who are unable to obtain DHA from dietary sources supplemental sources from fish oil or vegetarian (algal oil) are ideal.5  A fish oil supplement about 1000 mg contains about 120 mg DHA while algal oil provides about 100–300 mg DHA. The bioavailability of DHA from algal oil is equivalent of cooked salmon.4

In a study conducted on young children aged 6–36 months from 76 developing countries including India, the dietary intakes of DHA and arachidonoic acid was evaluated. The key findings of the evaluation revealed that in the vast majority of developing countries the estimated daily intake of DHA and arachidonic acid is significantly lower than current recommendations of 100 mg/day for DHA. Thus, this has great public health implications and future policies and recommendations are required on dietary DHA intake.9

Conclusion

DHA is thus a dietary necessity proving important throughout life.1 Brain’s architecture development prenatally and during infancy provides the template on which the adult brain structure is based. Thus the early dietary modification of levels of long chain polyunsaturated fatty acids, DHA will result in long-term structural and functional consequences.7   DHA supplementation during pregnancy has also shown decreased immune responses in infants with decrease incidence of infant allergies.1

Summing up DHA tends to influence many signaling pathways, receptor systems, enzyme activities, and dynamics of membrane structure that improves overall development, maintenance, and aging of the CNS providing optimal cognition throughout the life.5

References

  1. Swanson D, Block R, Mousa SA. Omega-3 fatty acids EPA and DHA: Health benefits throughout life. Adv Nutr. 2012;3:1-7. doi:10.3945/ an.111.000893.
  2. Lauritzen L, Brambilla P, Mazzocchi A, Harsløf LBS, Ciappolino V, Agoston C. DHA effects in brain development and function. Nutrients. 2016;8(1):E6. doi:10.3390/nu8010006.
  3. Carlson SE, Cheatham CL, Colombo J. Long-chain polyunsaturated fatty acids in the developing central nervous system. In: Polin RA, Abman SH, Rowitch DH, Benitz WE, Fox WW, editors. Fetal and neonatal physiology. 5th ed., Chapter 38. Philadelphia, PA: Elsevier, Inc.; 2017. p. 380-89.e4.
  4. National Institutes of Health. Omega-3 fatty acids—Health professional fact sheet. 2017 [cited November 6, 2017] Available from https://ods.od.nih.gov/factsheets/Omega3FattyAcids-HealthProfessional/.
  5. Weiser MJ, Butt CM, Mohajeri MH. Docosahexaenoic acid and cognition throughout the lifespan. Nutrients. 2016; 8(2):99. doi:10.3390/nu8020099.
  6. Kuratko CN, Barrett EC, Nelson EB, Norman, Jr. S. The relationship of docosahexaenoic acid (DHA) with learning and behavior in healthy children: A review. Nutrients. 2013;5(7):2777-810.
  7. Heaton AE, Meldrum SJ, Foster JK, Prescott SL, Simmer K. Does docosahexaenoic acid supplementation in term infants enhance neurocognitive functioning in infancy? Front Hum Neurosci. 2013;7:774. doi:10.3389/fnhum.2013.00774.
  8. Judge MP, Harel O, Lammi-Keefe CJ. Maternal consumption of a docosahexaenoic acid–containing functional food during pregnancy: Benefit for infant performance on problem-solving but not on recognition memory tasks at age 9 mo. Am J Clin Nutr. 2007;85(6):1572-77.
  9. Forsyth S, Gautier S, Salem, Jr. N.  Estimated dietary intakes of arachidonic acid and docosahexaenoic acid in infants and young children living in developing countries. Ann Nutr Metab. 2016;69:64-74.

 

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