Long chain polyunsaturated fatty acids (LCPUFAs) such as DHA have been shown to serve as important cell membrane components, as well as precursors for an extensive network of biologic mediators with many effects in the body[1].

DHA is used in formula to boost synapse formation and to diminish the negative effects of prematurity on cognitive development.

DHA benefits brain development that clinically shown to support the achievement of intellectual, motor, emotional and communication milestones. It also supports gut health as clinically shown to reduce the incidence of diarrhea in infants compared to standard formula.

Aspects of DHA related to brain

DHA – an important building block for the brain during development[2],[3],[4]

  • ŸDHA is an important structural component of cells in the central nervous system and incorporates into neural tissues from the third trimester of pregnancy up to 18 years of age[2]. This period corresponds with significant changes in brain structures and advances in neurocognitive development[5],[6].

DHA plays a role in brain development and function through several potential mechanisms. From animal and cell models, it appears that DHA:

  • Is enriched in neuronal synaptic and excitable membranes where signal transmission takes place[7],[8]
  • Enhances neurite outgrowth and branching[9],[10],[11]. Neurites are projections from the cell body of immature neurons, which eventually mature into axons and dendrites[12]
  • Plays a role in synaptogenesis[10],[11]. Synaptogenesis is a process which involves the formation of synapses, the structures that permit signaling between nerve cells[13].
  • ŸPlays a role in synaptic transmission in the brain hippocampus and long term potentiation[14],[10],[15]. Long term potentiation is a long-lasting strengthening of a synaptic link, thought to contribute to the synaptic basis of learning and memory[16].

Clinical studies in infants have demonstrated the importance of DHA in neurocognitive development by comparing infant formula with recommended levels of DHA to infant formula lacking DHA, fed up to 4 – 12 months of age. Formulas with 0.32% DHA and 0.64% ARA of total fatty acids have been clinically proven to improve sustained attention, problem solving, visual acuity, mental development index, and long-term improvements in cognitive development, executive function and verbal IQ[17],[18],[19],[20],[21],[22].

Aspects of DHA related to immunity

DHA is believed to play a role in immunity through the inhibition and/or resolution of inflammation[23].

DHA can inhibit pro-inflammatory signaling[24],[25],[26] and metabolites of DHA, including resolvins, protectins and endocannabinoids, have anti-inflammatory and/or inflammation-resolving activity[27],[28].

DHA may play a role in immunity by helping to support protection against common pediatric conditions including respiratory infections and symptoms, diarrhea requiring medical attention, and allergy[29],[30],[31].

  • ŸIncreasing research is highlighting the role of LCPUFA, especially n-3 LCPUFA, as immunomodulatory nutrients with the potential to improve respiratory health early in life. A recent review on the impact of dietary LCPUFA on respiratory illness in infants and children reported the beneficial effects of omega-3 LCPUFA supply on respiratory outcomes, including reductions in asthma and other allergy manifestations[32].

 

[1] Hageman, J. H., P. Hooyenga, D. A. Diersen-Schade, D. M. Scalabrin, H. J. Wichers, and E. E. Birch. 2012. The impact of dietary long-chain polyunsaturated fatty acids on respiratory illness in infants and children. Curr Allergy Asthma Rep 12(6):564-573.
[2] Martinez, M. 1992. Tissue levels of polyunsaturated fatty acids during early human development. J Pediatr 120(4 Pt 2):S129-138.
[3] Carver, J. D., V. J. Benford, B. Han, and A. B. Cantor. 2001. The relationship between age and the fatty acid composition of cerebral cortex and erythrocytes in human subjects. Brain Res Bull 56(2):79-85.
[4] Hoffman, D. R., J. A. Boettcher, and D. A. Diersen-Schade. 2009. Toward optimizing vision and cognition in term infants by dietary docosahexaenoic and arachidonic acid supplementation: a review of randomized controlled trials. Prostaglandins Leukot Essent Fatty Acids 81(2-3):151- 158.
[5] Giedd, J. N., J. Blumenthal, N. O. Jeffries, F. X. Castellanos, H. Liu, A. Zijdenbos, T. Paus, A. C. Evans, and J. L. Rapoport. 1999. Brain development during childhood and adolescence: a longitudinal MRI study. Nat Neurosci 2(10):861-863.
[6] Bunge, S. A., A. P. Mackey, and K. J. Whitaker. 2009. Brain changes underlying the development of cognitive control and reasoning. Pages 73-85 in The Congnitive Neurosciences. 4 ed. M. S. Gazzaniga, ed. Massachusetts Institute of Technology, Cambridge, MA.
[7] Breckenridge, W. C., G. Gombos, and I. G. Morgan. 1972. The lipid composition of adult rat brain synaptosomal plasma membranes. Biochim Biophys Acta 266(3):695-707.
[8] Morgan, I. G., J. P. Zanetta, W. C. Breckenridge, G. Vincendon, and G. Gombos. 1973. The chemical structure of synaptic membranes. Brain Res 62(2):405-411.
[9] Calderon, F. and H. Y. Kim. 2004. Docosahexaenoic acid promotes neurite growth in hippocampal neurons. J Neurochem 90(4):979-988.
[10] Cao, D., K. Kevala, J. Kim, H. S. Moon, S. B. Jun, D. Lovinger, and H. Y. Kim. 2009. Docosahexaenoic acid promotes hippocampal neuronal development and synaptic function. J Neurochem 111(2):510-521.
[11] Kim, H. Y., H. S. Moon, D. Cao, J. Lee, K. Kevala, S. B. Jun, D. M. Lovinger, M. Akbar, and B. X. Huang. 2011. N-Docosahexaenoylethanolamide promotes development of hippocampal neurons. Biochem J 435(2):327-336.
[12] Purves, D., G. J. Augustine, D. Fitzpatrick, W. C. Hall, A.-S. LaMantia, and L. E. White. 2012. Neuroscience, 5th edition. Sinauer Associates, Inc., Sunderland, MA, USA.
[13] Kandel, E. R., J. H. Schwartz, and T. M. Jessell. 2000. Principles of Neuroscience. 4 ed. McGraw-Hill, New York.
[14] Fujita, S., Y. Ikegaya, M. Nishikawa, N. Nishiyama, and N. Matsuki. 2001. Docosahexanoic acid improves long-term potentiation attenuated by phospholipase A2 inhibitor in rat hippocampal slices. Br J Pharmacol 132(7):1417-1422.
[15] Connor, S., G. Tenorio, M. T. Clandinin, and Y. Sauve. 2012. DHA supplementation enhances high-frequency, stimulation-induced synaptic transmission in mouse hippocampus. Appl Physiol Nutr Metab 37(5):880-887.
[16] Baars, B. J. and N. M. Gage. 2010. Cognition, Brain, and Consciousness. 2nd ed. Academic Press, Elsevier Ltd.
[17] Birch, E. E., S. Garfield, D. R. Hoffman, R. Uauy, and D. G. Birch. 2000. A randomized controlled trial of early dietary supply of long-chain polyunsaturated fatty acids and mental development in term infants. Dev Med Child Neurol 42(3):174-181.
[18] Morale, S. E., D. R. Hoffman, Y. S. Castaneda, D. H. Wheaton, R. A. Burns, and E. E. Birch. 2005. Duration of long-chain polyunsaturated fatty acids availability in the diet and visual acuity. Early Hum Dev 81(2):197-203.
[19] Birch, E. E., S. Garfield, Y. Castañeda, D. Hughbanks-Wheaton, R. Uauy, and D. R. Hoffman. 2007. Visual acuity and cognitive outcomes at 4 years of age in a  double-blind, randomized trial Global Messaging Toolkit; Lighthouse. Confidential. For internal use only. Page 74 of long-chain polyunsaturated fatty acid-supplemented infant formula. Early Hum Dev 83(5):279- 284.
[20] Drover, J., D. R. Hoffman, Y. S. Castañeda, S. E. Morale, and E. E. Birch. 2009. Three randomized controlled trials of early long-chain polyunsaturated fatty acid supplementation on means-end problem solving in nine-month olds. Child Dev 80(5):1376-1384.
[21] Colombo, J., S. E. Carlson, C. L. Cheatham, K. M. Fitzgerald-Gustafson, A. Kepler, and T. Doty. 2011. Long-chain polyunsaturated fatty acid supplementation in infancy reduces heart rate and positively affects distribution of attention. Pediatr Res 70(4):406-410.
[22] Colombo, J., S. E. Carlson, C. L. Cheatham, D. J. Shaddy, E. H. Kerling, J. M. Thodosoff, K. M. Gustafson, and C. Brez. 2013. Long-term effects of LCPUFA supplementation on childhood cognitive outcomes. Am J Clin Nutr 98(2):403-412.
[23] Hageman, J. H., P. Hooyenga, D. A. Diersen-Schade, D. M. Scalabrin, H. J. Wichers, and E. E. Birch. 2012. The impact of dietary long-chain polyunsaturated fatty acids on respiratory illness in infants and children. Curr Allergy Asthma Rep 12(6):564-573.
[24] Oh, D. Y., S. Talukdar, E. J. Bae, T. Imamura, H. Morinaga, W. Fan, P. Li, W. J. Lu, S. M. Watkins, and J. M. Olefsky. 2010. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 142(5):687-698.
[25] Draper, E., C. M. Reynolds, M. Canavan, K. H. Mills, C. E. Loscher, and H. M. Roche. 2011. Omega-3 fatty acids attenuate dendritic cell function via NF-kappaB independent of PPARgamma. J Nutr Biochem 22(8):784-790.
[26] van den Elsen, L., J. Garssen, and L. Willemsen. 2012. Long chain N-3 polyunsaturated fatty acids in the prevention of allergic and cardiovascular disease. Curr Pharm Des 18(16):2375- 2392.
[27] Serhan, C. N., N. Chiang, and T. E. Van Dyke. 2008. Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol 8(5):349-361.
[28] Balvers, M. G., K. C. Verhoeckx, P. Plastina, H. M. Wortelboer, J. Meijerink, and R. F. Witkamp. 2010. Docosahexaenoic acid and eicosapentaenoic acid are converted by 3T3-L1 adipocytes to N-acyl ethanolamines with anti-inflammatory properties. Biochim Biophys Acta 1801(10):1107- 1114.
[29] Pastor, N., B. Soler, S. H. Mitmesser, P. Ferguson, and C. Lifschitz. 2006. Infants fed docosahexaenoic acid- and arachidonic acid-supplemented formula have decreased incidence of bronchiolitis/bronchitis the first year of life. Clin Pediatr (Phila) 45(9):850-855.
[30] Birch, E. E., S. Garfield, D. R. Hoffman, R. Uauy, and D. G. Birch. 2000. A randomized controlled trial of early dietary supply of long-chain polyunsaturated fatty acids and mental development in term infants. Dev Med Child Neurol 42(3):174-181.
[31] Lapillonne, A., N. Pastor, W. Zhuang, and D. M. Scalabrin. 2014. Infants fed formula with added long chain polyunsaturated fatty acids have reduced incidence of respiratory illnesses and diarrhea during the first year of life. BMC Pediatr 14:168.
[32] Hageman, J. H., P. Hooyenga, D. A. Diersen-Schade, D. M. Scalabrin, H. J. Wichers, and E. E. Birch. 2012. The impact of dietary long-chain polyunsaturated fatty acids on respiratory illness in infants and children. Curr Allergy Asthma Rep 12(6):564-573.