Talking Nutrition Editors
Breastmilk is universally recognized as the optimal choice for infant feeding, which has led to extensive investigations into its unique and complex composition. Recently, Salem and Van Dael published a comprehensive review on ARA in breastmilk. ARA, an n-6 fatty acid, is the most predominant long-chain polyunsaturated fatty acid (LC-PUFA) in breastmilk, which contains around 1,000 different fatty acids. Human milk always contains ARA and DHA, another LC-PUFA, though levels vary widely in different parts of the world.
ARA is found in breastmilk, primarily in triglyceride form, though also as milk fat globule membrane phospholipids. While lipids comprise only 2-5% of breastmilk by weight, their composition varies more than any other macronutrient.1 Lipid composition is influenced by a number of factors, including the stage of lactation, duration of feeding, gestational age at birth, maternal diet and nutritional status, and health of the mother.2 The variability of these factors makes it difficult to quantitate the specific amount of various lipids in breastmilk, confirmed by the wide ranges reported across various studies. Salem and Van Dael note reported ARA content ranges from 0.05% to 1.12% of total fatty acids and DHA content ranges from barely
DHA and ARA levels vary across countries and cultures, most likely due to differences in dietary intake of these essential fatty acids. Both DHA and ARA levels tend to be considerably lower in malnourished women, with decreasing levels associated with increased severity of malnourishment.3 Dietary interventions studies show that maternal dietary intake of both DHA and ARA can increase and support adequate levels in breastmilk.4-6 In fact, supplemental DHA in the diet of breastfeeding women results in a linear correlation to the rise of these fatty acids in breastmilk.4
Compared with breastfed infants, infants fed formula without ARA experience declining ARA status.7,8 An infants’ ability to synthesize ARA from linoleic acid (LA) is greatly affected by a genetic variant present in about 30% of Europeans, in over 50% of Asians and in up to 97% of Native Americans.9 It has been suggested that this gene-diet interaction may result in too low DHA and ARA status, and as a consequence, may increase the risk of eczema, asthma and cognitive impairment.10 Further, this highlights the need to provide preformed dietary ARA and DHA to support adequate ARA and DHA status.
ARA is equally as important as DHA for nervous system development and functioning.11,12 During early development, ARA accumulates quickly and reaches high concentrations similar to DHA.13,14 Numerous studies report beneficial effects on brain development and function from infant formulas supplemented with DHA and ARA, compared to unsupplemented formulas. While these benefits were previously ascribed to DHA, the outcomes are more likely the result of both DHA and ARA, which are always found together in breastmilk.
ARA acts as a precursor to bioactive compounds, including eicosanoids and endocannabinoids. Eicosanoids are highly active in various physiological systems and pathological processes, including the inflammatory process. Endocannabinoid receptors are present as early as 14 weeks gestation and appear to serve a variety of roles in human development.
Breastfeeding is linked to optimal cognitive development, which has been associated with its unique lipid composition – particularly the presence of ARA and DHA. Supplementing infant formula with DHA and ARA, with ARA levels typically higher than DHA, can lead to improvements in visual, cognitive, and psychomotor assessments.
Studies generally report that ARA and DHA work best to improve functional outcomes when provided together, most often in a 2:1 ratio.15 The ratio appears particularly important to ensure a balance of these fatty acids in the brain. When DHA is supplemented at levels higher than ARA in infant formula, cognitive performance and brain tissue storage were found to deviate from reference outcomes.16-18
Research into the role of DHA in infant’s growth and development is more widely discussed, which is partially due to the lack of an animal model for ARA research. Rodents fed an n-6-deficient diet experienced severe growth and brain impairment, so that the results could not be directly related to ARA. Correcting ARA deficiency in other rodent models to yield functional benefits resulted in improvements, sometimes with ARA supplementation alone, but always when DHA and ARA were given together.19
Recently, the European Academy of Paediatrics and the Child Health Foundation published a position paper emphasizing the importance of providing both DHA and ARA in infant formula.20 These international experts in infant nutrition concluded that the level of DHA should be at least 0.3% of fatty acids, equivalent to the average global level in breastmilk, but preferably reach 0.5%. The group strongly recommended ARA be provided along with DHA. When DHA is provided in infant formula up to ∼0.64% of fatty acids, ARA should be provided in at least equal amounts.
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 Koletzko B. Human Milk Lipids. Ann Nutr Metab. 2016;69 Suppl 2:28-40.
 Jensen RG. Lipids in human milk. Lipids. 1999;34(12):1243-1271.
 Glew RH, Omene JA, Vignetti S, D'Amico M, Evans RW. Fatty acid composition of breast milk lipids of Nigerian women. Nutrition Research. 1995;15(4):477-489.
 Weseler AR, Dirix CE, Bruins MJ, Hornstra G. Dietary arachidonic acid dose-dependently increases the arachidonic acid concentration in human milk. J Nutr. 2008;138(11):2190-2197.
 Amaral YN, Marano D, Silva LM, Guimaraes AC, Moreira ME. Are There Changes in the Fatty Acid Profile of Breast Milk with Supplementation of Omega-3 Sources? A Systematic Review. Rev Bras Ginecol Obstet. 2017;39(3):128-141.
 Smit EN, Koopmann M, Boersma ER, Muskiet FA. Effect of supplementation of arachidonic acid (AA) or a combination of AA plus docosahexaenoic acid on breastmilk fatty acid composition. Prostaglandins Leukot Essent Fatty Acids. 2000;62(6):335-340.
 Miklavcic JJ, Larsen BM, Mazurak VC, et al. Reduction of Arachidonate Is Associated With Increase in B-Cell Activation Marker in Infants: A Randomized Trial. J Pediatr Gastroenterol Nutr. 2017;64(3):446-453.
 Putnam JC, Carlson SE, DeVoe PW, Barness LA. The effect of variations in dietary fatty acids on the fatty acid composition of erythrocyte phosphatidylcholine and phosphatidylethanolamine in human infants. Am J Clin Nutr. 1982;36(1):106-114.
 Ameur A, Enroth S, Johansson Å, et al. Genetic Adaptation of Fatty-Acid Metabolism: A Human-Specific Haplotype Increasing the Biosynthesis of Long-Chain Omega-3 and Omega-6 Fatty Acids. The American Journal of Human Genetics. 2012;90(5):809-820.
 Koletzko B, Reischl E, Tanjung C, et al. FADS1 and FADS2 Polymorphisms Modulate Fatty Acid Metabolism and Dietary Impact on Health. Annu Rev Nutr. 2019;39:21-44.
 Crawford MA, Wang Y, Forsyth S, Brenna JT. New European Food Safety Authority recommendation for infant formulae contradicts the physiology of human milk and infant development. Nutr Health. 2013;22(2):81-87.
 Hadley KB, Ryan AS, Forsyth S, Gautier S, Salem N, Jr. The Essentiality of Arachidonic Acid in Infant Development. Nutrients. 2016;8(4):216.
 Clandinin MT, Chappell JE, Leong S, Heim T, Swyer PR, Chance GW. Extrauterine fatty acid accretion in infant brain: implications for fatty acid requirements. Early Hum Dev. 1980;4(2):131-138.
 Martinez M. Tissue levels of polyunsaturated fatty acids during early human development. J Pediatr. 1992;120(4 Pt 2):S129-138.
 Carlson SE, Colombo J. Docosahexaenoic Acid and Arachidonic Acid Nutrition in Early Development. Adv Pediatr. 2016;63(1):453-471.
 Alshweki A, Munuzuri AP, Bana AM, et al. Effects of different arachidonic acid supplementation on psychomotor development in very preterm infants; a randomized controlled trial. Nutr J. 2015;14:101.
 Hsieh AT, Anthony JC, Diersen-Schade DA, et al. The influence of moderate and high dietary long chain polyunsaturated fatty acids (LCPUFA) on baboon neonate tissue fatty acids. Pediatr Res. 2007;61(5 Pt 1):537-545.
 Colombo J, Carlson SE, Cheatham CL, et al. Long-term effects of LCPUFA supplementation on childhood cognitive outcomes. Am J Clin Nutr. 2013;98(2):403-412.
 Salem N, Jr., Van Dael P. Arachidonic Acid in Human Milk. Nutrients. 2020;12(3).
 Koletzko B, Bergmann K, Brenna JT, et al. Should formula for infants provide arachidonic acid along with DHA? A position paper of the European Academy of Paediatrics and the Child Health Foundation. Am J Clin Nutr. 2020;111(1):10-16.ublic Health Nutrition, 19(15): 2675-2687.