Long-Chain Polyunsaturated Fatty Acids - Assignment Example

Long-chain polyunsaturated fatty acids: The case for and against the supplementation of infant formula Breast milk is the optimal source of nutrition for the infant but sometimes mothers or health care workers have no choice but to resort to baby formulae. Mothers of preterm infants requiring prolonged hospitalization can rarely produce sufficient milk. Also when mothers are on cytotoxic or potentially toxic drugs, or are unwilling or unable to breastfeed, formula feeding becomes inevitable (1). According to WHO report, there are about 10-11% preterm births worldwide, with about 6.4% in Australia and New Zealand (2). The American Academy of Pediatrics (AAP) recommends that iron-fortified cow’s milk-based infant formula is the most appropriate milk feeding from birth to 12 months for infants who are not breastfed (3). Iron enriched formulae may be appropriate, but are they enough for the optimal development of the infant? LCP in Vision and Brain Docosahexaenoic acid (DHA) (22:6 n-3) is present in a very high concentration in the retinal photoreceptor membranes. 80-90% of the total lipids in these membranes are phospholipids and DHA accounts to about 60% of fatty acids in these phospholipids. Studies on artificial membranes have shown that this high DHA content is very important for maximum photochemical activity of rhodopsin, the rod visual pigment. Hence DHA rich rhodopsin is more likely to be activated by light and initiate the series of biochemical events that ultimately leads to vision (4). DHA deposition causes relative brain weight to be greatest during fetal development and early infancy, it is generally considered that this reflects a critical time during which deficiency of DHA may have long term consequences for later brain function. Several hypotheses have been put forward for the function of long chain polyunsaturated fatty acids (LCPs) in brain development. These include formation of hydrophobic core which confers high degree of flexibility and direct interaction with membrane proteins, which in turn speeds up the signal transduction and neurotransmission. Recent studies suggest that DHA is important in neurogenesis and helps in phospholipid synthesis and turnover in brain (5). DHA and arachidonic acid (AA) (20:4 n-6) are also ligands for retinoid X receptors; along with retinoic acid receptor these LCPs help in development, including neurogenesis during embryogenesis, morphological differentiation of catecholaminergic neurons, and activity-dependent plasticity (6). LCP and Infant Vision and Brain Development LCPs aid in the development of visual and cognitive functions of the infants as indicated by a double-masked follow up study of 39 months. The study clearly indicates that supplementation of baby formulae with DHA and AA supports normal growth in full-term infants and that it supported visual and cognitive developments too (7). Motor development and vocabulary comprehension also increased in pre-term infants upon feeding formulae supplemented with LCPs in a randomized controlled trial (RCT) (8). Other important fact that comes from this study is that supplementation of LCPs do not add to the gain in other body parameters like weight, length, head circumference or other anthropometric measurements but as shown by Groh-Wargo et al. in a RCT, instead increased lean body mass and reduced fat mass in preterm infants at 1 year of age (9). LCPs supplemented formulae not only produces serum lipid profiles similar to mother’s milk fed infants, but also leads to better visual function at 1 year of age than that showed by infants fed non-supplemented formulae in a randomized clinical trial (10). However a Cochrane library database analysis shows no neurodevelopmental improvements in term infants, and inconsistent beneficial effects on visual acuity; hence they do not recommend supplementation of routine baby formulae with LCPs (11). Their study had however excluded 10 out of 25 studies, and reviewed 15 only. A study on infant monkeys showed that 1:1 supplementation of DHA:AA neither harms nor provides substantial benefit to the development of visual acuity or retinal function in the first four postnatal months (12). This may be the transient nature of the effects of LCPs and a study of longer duration may have resulted differently. LCPs and Immunity AA is metabolized to leucotrines of series 4 (LTB4) and prostaglandins of series 2 (PGE2). LTB4s are mediators of allergic inflammation. Their actions include vascular permeability, leucocyte chemotaxis, respiratory burst, and production of inflammatory cytokines, ultimately causing inflammation. PG2 on the other side exert its effect to balance T helper cells Th1 and Th2. They decrease the Th1 type cytokines namely Gamma-INF and IL-2 and increase the Th2 cytokines IL-4 and IL-5. These two actions influence the activity of antigen presenting cells like dendritic cells, and differentiation of T cells. PG2 also promotes IgE synthesis by B cells. In short, AA is pro-inflammatory (13). DHA, when in excess of AA, incorporates in higher amount in immune cells at the expense of AA. This action leads to decreased synthesis of PGE2 and LTB4 by human monocytes and neutrophils. So by replacing AA and by producing its own eicosanoids, DHA acts as anti-inflammatory and inflammation resolving (13). AA is pro-inflammatory and DHA is anti-inflammatory, hence a proper ratio of the two is required for the fine execution of the immune system. LCPs and Infant Immune System A neonate is born with what is called physiological immunodeficiency, where the immune system is naïve and immature due to lack of interleukin (IL)-10 (14) and IL-2 (15). Both the innate and humoral immunity are practically nonexistent. Neonatal immunity begins during and soon after birth when factors in mother’s milk lay the foundations of independent immunity in the infant. LCPs such as DHA and AA are important immune-regulatory and -modulating factors present in mother’s milk but are absent in the general infant formulae (15). DHA and AA, in an appropriate ratio, have been shown to influence an infant’s immune system in a positive manner. When these LCPs form part of the lipid bilayer of cells of the immune system like monocytes, natural killer cells, macrophages and neutrophils, they not only alter their membrane fluidity, but also assist these lymphocytes in their proliferation and activation as concluded by Ganapathy S in his review article (16). He suggests that LCPs should be provided in the baby formulae. His study is also supported by a randomized-controlled study which demonstrates that formulae supplemented with LCPs influenced the presence of specific cell types and function of infant blood immune cells (17). A biochemical study noticed actual biochemical changes in lymphocytes of formula supplemented with LCPs in pre-term infants (18) where deficiency of LCPs was correlated to decreased IL-10 production. The above reference studies indicate that there is no harm in supplementation of baby formulae with LCPs like DHA and AA. In fact they are beneficial to the infant. Foundations of solid immune system are laid faster in supplemented fed formulae; these infants have immune system at par with infants fed on mother’s milk. Brain development is also better in LCPs supplemented baby food as shown by improved cognitive and motor developments. Last but not least, visual acuity also benefits from LCPs supplemented baby foods. There is concern about oxidative stress and lipid peroxidation due LCPs in the diet, but recent studies have shown that DHA has important free radical scavenging properties and protects against peroxidative damage of lipids and proteins in developing brain (19). Hence in view of the above literature supplementation of baby formulae with LCPs is strongly recommended which has been approved by FDA also (20). Reference List 1. Lakshman R, Ogilvie D, Ong KK. Mothers’ experiences of bottle-feeding:a systematic review of qualitative and quantitative studies. Arch Dis Child 2009;94:596–601. 2. Beck S, Wojdyla D, Say L, Betran AP, Merialdi M, Requejo JH, Rubens C, Menon R, Van Look PF. The worldwide incidence of preterm birth: a systematic review of maternal mortality and morbidity. Bull World Health Organ. 2010 Jan;88(1):31-8. 3. Committee on Nutrition, American Academy of Pediatrics. Iron fortification of Infant Formulas. Pediatrics 1999;104(1):119-123. 4. Weidmann TS, Pates RD, Beach JM, Salmon A, Brown MF. Lipidprotein interactions mediate the photochemical function of rhodopsin. Biochemistry 1988;27:6469–74. 5. Salem N, Jr., Litman B, Kim HY, Gawrisch K. Mechanisms of action of docosahexaenoic aicd in the nervous system. Lipids. 2001;36:945–59. 6. Lengqvist J, Mata De Urquiza A, Bergman AC, Willson TM, Sjovall J, Perlmann T, Griffiths WJ. Polyunsaturated fatty acids including docosahexaenoic and arachidonic acid bind to the retinoid X receptor alpha ligand-binding domain. Mol Cell Proteomics. 2004;3:692–703. 7. Auestad N, Scott DT, Janowsky JS, Jacobsen C, Carroll RE, Montalto MB, Halter R, Qiu W, Jacobs JR, Connor WE, Connor SL, Taylor JA, Neuringer M, Fitzgerald KM,Hall RT. Visual, cognitive, and language assessments at 39 months: a follow-up study of children fed formulas containing long-chain polyunsaturated fatty acids to 1 year of age. Pediatrics. 2003 Sep;112(3 Pt 1):e177-83 8. OConnor DL, Hall R, Adamkin D, Auestad N, Castillo M, Connor WE, Connor SL,Fitzgerald K, Groh-Wargo S, Hartmann EE, Jacobs J, Janowsky J, Lucas A, Margeson D, Mena P, Neuringer M, Nesin M, Singer L, Stephenson T, Szabo J, Zemon V; Ross Preterm Lipid Study. Growth and development in preterm infants fed long-chain polyunsaturated fatty acids: a prospective, randomized controlled trial. Pediatrics. 2001 Aug;108(2):359-71. 9. Groh-Wargo S, Jacobs J, Auestad N, OConnor DL, Moore JJ, Lerner E. Body composition in preterm infants who are fed long-chain polyunsaturated fatty acids: a prospective, randomized, controlled trial. Pediatr Res. 2005 May;57(5 Pt 1):712-8. 10. Hoffman DR, Birch EE, Birch DG, Uauy R, Castañeda YS, Lapus MG, Wheaton DH. Impact of early dietary intake and blood lipid composition of long-chain polyunsaturated fatty acids on later development. J Pediatr Gastroenterol Nutr. 2000 Nov;31(5):540-53. 11. Simmer K, Patole SK, Rao SC. Longchain polyunsaturated fatty acid supplementation in infants born at term. Cochrane Database Syst Rev. 2011 Dec 7; 12:CD000376. 12. Jeffrey BG, Mitchell DC, Hibbeln JR, Gibson RA, Chedester AL, Salem N Jr. Visual acuity and retinal function in infant monkeys fed long-chain PUFA. Lipids. 2002 Sep;37(9):839-48. 13. Calder PC. Polyunsaturated fatty acids, inflammation, and immunity. Lipids. 2001 Sep;36(9):1007-24. 14. Field CJ, Thomson CA, Van Aerde JE, Parrott A, Euler A, Lien E, Clandinin MT. Lower proportion of CD45R0+ cells and deficient interleukin-10 production by formula-fed infants, compared with human-fed, is corrected with supplementation of long-chain polyunsaturated fatty acids. J Pediatr Gastroenterol Nutr. 2000 Sep;31(3):291-9 15. Hassan J, Reen DJ. Reduced primary antigen-specific T-cell precursor frequencies in neonates is associated with deficient interleukin-2 production.Immunology. 1996 Apr;87(4):604-8 16. Ganapathy S. Long chain polyunsaturated fatty acids and immunity in infants.Indian Pediatr. 2009 Sep;46(9):785-90 17. Field CJ, Van Aerde JE, Robinson LE, Clandinin MT. Effect of providing a formula supplemented with long-chain polyunsaturated fatty acids on immunity in full-term neonates. Br J Nutr. 2008 Jan;99(1):91-9. 18. Chheda S, Palkowetz KH, Garofalo R, Rassin DK, Goldman AS. Decreased interleukin-10 production by neonatal monocytes and T cells: relationship to decreased production and expression of tumor necrosis factor-alpha and its receptors. Pediatr Res. 1996 Sep;40(3):475-83 19. Green P, Glozman S, Weiner L, Yavin E. Enhanced free radical scavenging and decreased lipid peroxidation in the rat fetal brain after treatment with ethyl docosahexaenoate. Biochim Biophys Acta. 2001; 1532:203–12. 20. New infant formula additives approved by FDA. AAP News. May 2002; 20: 209-10. Read More