Dietary consumption of the essential fatty acids linoleic acid (LA; ω-6) and α-linolenic acid (ALA; ω-3) is necessary for human growth and development. In the past 150 years, the average Western diet has changed dramatically such that humans today consume a much higher proportion of ω-6 fatty acids relative to ω-3 fatty acids than ever before. The importance of ω-3 fatty acids in human development has been well established in fetal and neonatal development, with brain and retinal tissues highly dependent on ω-3 fatty acids, specifically docosahexaenoic acid (DHA) for membrane fluidity and signal transduction. In childhood, ω-3s have been shown to contribute to ongoing cognitive development and may be involved in metabolic programming of bone turnover and adipogenesis. ω-3s may also play important roles in adult neurophysiology and disease prevention.
InnisSM. Essential fatty acids in growth and development. Progress Lipid Res. 1991;30(1):39-103.
2.
InnisSM. Perinatal biochemistry and physiology of long-chain polyunsaturated fatty acids. J Pediatr. 2003;143(4)(suppl):S1-S8.
3.
HaeggstromJZFunkCD. Lipoxygenase and leukotriene pathways: biochemistry, biology, and roles in disease. Chem Rev. 2011;111(10):5866-5898.
4.
HariziHCorcuffJBGualdeN. Arachidonic-acid-derived eicosanoids: roles in biology and immunopathology. Trends Mol Med. 2008;14(10):461-469.
5.
FunkCD. Prostaglandins and leukotrienes: advances in eicosanoid biology. Science. 2001;294(5548):1871-1875.
6.
SerhanCN. Lipoxins and aspirin-triggered 15-epi-lipoxins are the first lipid mediators of endogenous anti-inflammation and resolution. Prostaglandins Leukot Essent Fatty Acids. 2005;73(3-4):141-162.
7.
AritaMYoshidaMHongS. Resolvin E1, an endogenous lipid mediator derived from omega-3 eicosapentaenoic acid, protects against 2,4,6-trinitrobenzene sulfonic acid–induced colitis. Proc Natl Acad Sci U S A. 2005;102(21):7671-7676.
KeyesKTYeYLinY. Resolvin E1 protects the rat heart against reperfusion injury. Am J Physiol Heart Circ Physiol. 2010;299(1):H153-H164.
10.
SimopoulosAP. Importance of the ratio of omega-6/omega-3 essential fatty acids: evolutionary aspects. World Rev Nutr Diet. 2003;92:1-22.
11.
GermanJB. Dietary lipids from an evolutionary perspective: sources, structures and functions. Maternal Child Nutr. 2011;7(suppl 2):2-16.
12.
SimopoulosAP. Evolutionary aspects of diet, the omega-6/omega-3 ratio and genetic variation: nutritional implications for chronic diseases. Biomed Pharmacother. 2006;60(9):502-507.
13.
KangZBGeYChenZ. Adenoviral gene transfer of Caenorhabditis elegans n-3 fatty acid desaturase optimizes fatty acid composition in mammalian cells. Proc Natl Acad Sci U S A. 2001;98(7):4050-4054.
14.
GeYWangXChenZLandmanNLoEHKangJX. Gene transfer of the Caenorhabditis elegans n-3 fatty acid desaturase inhibits neuronal apoptosis. J Neurochem. 2002;82(6):1360-1366.
15.
DobbingJSandsJ. Quantitative growth and development of human brain. Arch Dis Child. 1973;48(10):757-767.
16.
ClandininMTChappellJELeongSHeimTSwyerPRChanceGW. Extrauterine fatty acid accretion in infant brain: implications for fatty acid requirements. Early Hum Dev. 1980;4(2):131-138.
17.
MartinezM. Tissue levels of polyunsaturated fatty acids during early human development. J Pediatr. 1992;120(4, pt 2):S129-S138.
18.
SinghM. Essential fatty acids, DHA and human brain. Indian J Pediatr. 2005;72(3):239-242.
19.
InnisSMde La Presa OwensS. Dietary fatty acid composition in pregnancy alters neurite membrane fatty acids and dopamine in newborn rat brain. J Nutr. 2001;131(1):118-122.
20.
AuestadNHalterRHallRT. Growth and development in term infants fed long-chain polyunsaturated fatty acids: a double-masked, randomized, parallel, prospective, multivariate study. Pediatrics. 2001;108(2):372-381.
21.
ZimmerLVancasselSCantagrelS. The dopamine mesocorticolimbic pathway is affected by deficiency in n-3 polyunsaturated fatty acids. Am J Clin Nutr. 2002;75(4):662-667.
22.
ZickerSCJewellDEYamkaRMMilgramNW. Evaluation of cognitive learning, memory, psychomotor, immunologic, and retinal functions in healthy puppies fed foods fortified with docosahexaenoic acid-rich fish oil from 8 to 52 weeks of age. J Am Vet Med Assoc. 2012;241(5):583-594.
23.
YavinEHimovichiEEilamR. Delayed cell migration in the developing rat brain following maternal omega 3 alpha linolenic acid dietary deficiency. Neuroscience. 2009;162(4):1011-1022.
24.
HellandIBSaugstadODSmithL. Similar effects on infants of n-3 and n-6 fatty acids supplementation to pregnant and lactating women. Pediatrics. 2001;108(5):E82.
25.
InnisSM. Essential fatty acid transfer and fetal development. Placenta. 2005;26(suppl A):S70-S75.
26.
CampbellFMBushPGVeerkampJHDutta-RoyAK. Detection and cellular localization of plasma membrane–associated and cytoplasmic fatty acid–binding proteins in human placenta. Placenta. 1998;19(5-6): 409-415.
27.
CampbellFMGordonMJDutta-RoyAK. Preferential uptake of long chain polyunsaturated fatty acids by isolated human placental membranes. Mol Cell Biochem. 1996;155(1):77-83.
28.
Dutta-RoyAK. Transport mechanisms for long-chain polyunsaturated fatty acids in the human placenta. Am J Clin Nutr. 2000;71(1)(suppl):315S-322S.
29.
CrawfordMAHassamAGWilliamsG. Essential fatty acids and fetal brain growth. Lancet. 1976;1(7957):452-453.
30.
ShandJHNobleRC. The metabolism of 18:0 and 18:2(n-6) by the ovine placenta at 120 and 150 days of gestation. Lipids. 1981;16(1):68-71.
31.
ChambazJRavelDManierMCPepinDMulliezNBereziatG. Essential fatty acids interconversion in the human fetal liver. Biol Neonate. 1985;47(3):136-140.
32.
LarqueEDemmelmairHBergerBHasbargenUKoletzkoB. In vivo investigation of the placental transfer of (13)C-labeled fatty acids in humans. J Lipid Res. 2003;44(1):49-55.
33.
HaggartyPPageKAbramovichDRAshtonJBrownD. Long-chain polyunsaturated fatty acid transport across the perfused human placenta. Placenta. 1997;18(8):635-642.
34.
CarnielliVPWattimenaDJLuijendijkIHBoerlageADegenhartHJSauerPJ. The very low birth weight premature infant is capable of synthesizing arachidonic and docosahexaenoic acids from linoleic and linolenic acids. Pediatr Res. 1996;40(1):169-174.
35.
PawloskyRJHibbelnJRNovotnyJASalemNPhysiological compartmental analysis of alpha-linolenic acid metabolism in adult humans. J Lipid Res. 2001;42(8):1257-1265.
36.
UauyRMenaPWegherBNietoSSalemNLong chain polyunsaturated fatty acid formation in neonates: effect of gestational age and intrauterine growth. Pediatr Res. 2000;47(1):127-135.
37.
SuHMHuangMCSaadNMNathanielszPWBrennaJT. Fetal baboons convert 18:3n-3 to 22:6n-3 in vivo: a stable isotope tracer study. J Lipid Res. 2001;42(4):581-586.
38.
KuipersRSLuxwoldaMFOffringaPJ. Gestational age dependent content, composition and intrauterine accretion rates of fatty acids in fetal white adipose tissue. Prostaglandins Leukot Essent Fatty Acids. 2012;86(1-2):39-49.
39.
LevittP. Structural and functional maturation of the developing primate brain. J Pediatr. 2003;143(4)(suppl):S35-S45.
40.
BrennaJTVaraminiBJensenRGDiersen-SchadeDABoettcherJAArterburnLM. Docosahexaenoic and arachidonic acid concentrations in human breast milk worldwide. Am J Clin Nutr. 2007;85(6):1457-1464.
41.
O’ConnorDLHallRAdamkinD. Growth and development in preterm infants fed long-chain polyunsaturated fatty acids: a prospective, randomized controlled trial. Pediatrics. 2001;108(2):359-371.
42.
SanGiovanniJPParra-CabreraSColditzGABerkeyCSDwyerJT. 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. 2000;105(6):1292-1298.
43.
BirchEECarlsonSEHoffmanDR. The DIAMOND (DHA Intake And Measurement Of Neural Development) Study: a double-masked, randomized controlled clinical trial of the maturation of infant visual acuity as a function of the dietary level of docosahexaenoic acid. Am J Clin Nutr. 2010;91(4):848-859.
44.
JensenCLVoigtRGLlorenteAM. Effects of early maternal docosahexaenoic acid intake on neuropsychological status and visual acuity at five years of age of breast-fed term infants. J Pediatr. 2010;157(6):900-905.
45.
HibbelnJRDavisJMSteerC. Maternal seafood consumption in pregnancy and neurodevelopmental outcomes in childhood (ALSPAC study): an observational cohort study. Lancet. 2007;369(9561):578-585.
46.
BakkerECHornstraGBlancoCEVlesJS. Relationship between long-chain polyunsaturated fatty acids at birth and motor function at 7 years of age. Eur J Clin Nutr. 2009;63(4):499-504.
47.
AbergMAAbergNBrismanJSundbergRWinkvistATorenK. Fish intake of Swedish male adolescents is a predictor of cognitive performance. Acta Paediatr. 2009;98(3):555-560.
48.
JacquesCLevyEMuckleG. Long-term effects of prenatal omega-3 fatty acid intake on visual function in school-age children. J Pediatr. 2011;158(1):83-90, 90.e1.
49.
BoucherOBurdenMJMuckleG. Neurophysiologic and neurobehavioral evidence of beneficial effects of prenatal omega-3 fatty acid intake on memory function at school age. Am J Clin Nutr. 2011;93(5):1025-1037.
50.
MinnsLMKerlingEHNeelyMR. 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 Leukot Essent Fatty Acids. 2010;82(4-6):287-293.
51.
CampoyCEscolano-MargaritMVAnjosTSzajewskaHUauyR. Omega 3 fatty acids on child growth, visual acuity and neurodevelopment. Br J Nutr. 2012;107(suppl 2):S85-S106.
52.
GhysABakkerEHornstraGvan den HoutM. Red blood cell and plasma phospholipid arachidonic and docosahexaenoic acid levels at birth and cognitive development at 4 years of age. Early Hum Dev. 2002;69(1-2):83-90.
53.
RyanASAstwoodJDGautierSKuratkoCNNelsonEBSalemN. Effects of long-chain polyunsaturated fatty acid supplementation on neurodevelopment in childhood: a review of human studies. Prostaglandins Leukot Essent Fatty Acids. 2010;82(4-6):305-314.
54.
DonahueSMRifas-ShimanSLGoldDRJouniZEGillmanMWOkenE. Prenatal fatty acid status and child adiposity at age 3 y: results from a US pregnancy cohort. Am J Clin Nutr. 2011;93(4):780-788.
55.
InnisSM. Metabolic programming of long-term outcomes due to fatty acid nutrition in early life. Maternal Child Nutr. 2011;7(suppl 2):112-123.
56.
AilhaudGGuesnetPCunnaneSC. An emerging risk factor for obesity: does disequilibrium of polyunsaturated fatty acid metabolism contribute to excessive adipose tissue development?Br J Nutr. 2008;100(3):461-470.
57.
BouretSG. Role of early hormonal and nutritional experiences in shaping feeding behavior and hypothalamic development. J Nutr. 2010;140(3):653-657.
58.
HarveyNDhanwalDRobinsonS. Does maternal long chain polyunsaturated fatty acid status in pregnancy influence the bone health of children? The Southampton Women’s Survey. Osteoporos Int. 2012;23(9):2359-2367.
59.
MilteCMParlettaNBuckleyJDCoatesAMYoungRMHowePR. Eicosapentaenoic and docosahexaenoic acids, cognition, and behavior in children with attention-deficit/hyperactivity disorder: a randomized controlled trial. Nutrition. 2012;28(6):670-677.
60.
BirchEEKhouryJCBersethCL. The impact of early nutrition on incidence of allergic manifestations and common respiratory illnesses in children. J Pediatr. 2010;156(6):902-906, 906.e1.
61.
AgrawalRGomez-PinillaF. ‘Metabolic syndrome’ in the brain: deficiency in omega-3 fatty acid exacerbates dysfunctions in insulin receptor signalling and cognition. J Physiol. 2012;590(pt 10):2485-2499.
62.
MuldoonMFRyanCMSheuLYaoJKConklinSMManuckSB. Serum phospholipid docosahexaenonic acid is associated with cognitive functioning during middle adulthood. J Nutr. 2010;140(4):848-853.
63.
KalmijnSvan BoxtelMPOckeMVerschurenWMKromhoutDLaunerLJ. Dietary intake of fatty acids and fish in relation to cognitive performance at middle age. Neurology. 2004;62(2):275-280.
64.
EskelinenMHNganduTHelkalaEL. Fat intake at midlife and cognitive impairment later in life: a population-based CAIDE study. Int J Geriatr Psychiatry. 2008;23(7):741-747.
65.
BeydounMAKaufmanJSSatiaJARosamondWFolsomAR. Plasma n-3 fatty acids and the risk of cognitive decline in older adults: the Atherosclerosis Risk in Communities Study. Am J Clin Nutr. 2007;85(4):1103-1111.
66.
HeudeBDucimetierePBerrC. Cognitive decline and fatty acid composition of erythrocyte membranes: the EVA Study. Am J Clin Nutr. 2003;77(4):803-808.
67.
DullemeijerCDurgaJBrouwerIA. n 3 fatty acid proportions in plasma and cognitive performance in older adults. Am J Clin Nutr. 2007;86(5):1479-1485.
68.
LeesonCPMannAKattenhornMDeanfieldJELucasAMullerDP. Relationship between circulating n-3 fatty acid concentrations and endothelial function in early adulthood. Eur Heart J. 2002;23(3):216-222.
69.
DeanMRaatsMMGrunertKGLumbersM. Factors influencing eating a varied diet in old age. Public Health Nutr. 2009;12(12):2421-2427.
70.
UbedaNAchonMVarela-MoreirasG. Omega 3 fatty acids in the elderly. Br J Nutr. 2012;107(suppl 2):S137-S151.
71.
BarkerDJMartynCN. The maternal and fetal origins of cardiovascular disease. J Epidemiol Commun Health. 1992;46(1):8-11.
72.
MeydaniSNEndresSWoodsMM. Oral (n-3) fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: comparison between young and older women. J Nutr. 1991;121(4):547-555.
73.
PaeMMeydaniSNWuD. The role of nutrition in enhancing immunity in aging. Aging Dis. 2012;3(1):91-129.
74.
RojasCVMartinezJIFloresIHoffmanDRUauyR. Gene expression analysis in human fetal retinal explants treated with docosahexaenoic acid. Invest Ophthalmol Vis Sci. 2003;44(7):3170-3177.
75.
LukiwWJBazanNG. Docosahexaenoic acid and the aging brain. J Nutr. 2008;138(12):2510-2514.
76.
WoodJTWilliamsJSPandarinathanLJaneroDRLammi-KeefeCJMakriyannisA. Dietary docosahexaenoic acid supplementation alters select physiological endocannabinoid-system metabolites in brain and plasma. J Lipid Res. 2010;51(6):1416-1423.
77.
MusiekESBrooksJDJooM. Electrophilic cyclopentenone neuroprostanes are anti-inflammatory mediators formed from the peroxidation of the omega-3 polyunsaturated fatty acid docosahexaenoic acid. J Biol Chem. 2008;283(29):19927-19935.
78.
SongWLLawsonJAReillyD. Neurofurans, novel indices of oxidant stress derived from docosahexaenoic acid. J Biol Chem. 2008;283(1):6-16.
79.
TanZSHarrisWSBeiserAS. Red blood cell omega-3 fatty acid levels and markers of accelerated brain aging. Neurology. 2012;78(9):658-664.
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