Should Arachidonic acid (ARA) be added to infant formulas when Docosahexaenoic acid (DHA) is added? Experts provide the answer

By: Talking Nutrition Editors

Scientists explain why ARA, together with DHA, plays a vital role in infant development 

  • Regulatory standards issued by the European Commission (EC) establish the nutritional compositional criteria of infant and follow-on formula to be sold in the European Union. These standards designate DHA as a mandatory addition to these formulas at levels between 20-50 mg/100 kcal (0.5-1.0% of fatty acids), yet state that ARA is an optional ingredient.1  
  • Allowing for the addition of DHA while omitting ARA is in conflict with breastmilk composition, the benchmark for infant nutrition. Both DHA and ARA play crucial roles in infant development.
  • Pediatric nutrition experts are concerned about this regulatory standard and are educating the pediatric medical community about the importance of providing DHA in conjunction with ARA. A recent publication by Professor Patrick Tounian and colleagues outlines the scientific rationale for this position. 

DHA and ARA – foundational nutrients in early life nutrition  

The first 1,000 days of life represent a critical window of development, and the nutrition delivered during this time plays a foundational role in building lifelong health.3 Breastmilk remains the gold standard for promoting optimal growth and development and protecting against infections and nutritional deficiencies in infants.4 Lipids are an important source of energy in breastmilk and play a unique role in an infant’s health and development. 

Breastmilk always provides the long-chain polyunsaturated fatty acids (LCPUFAs) ARA and DHA, suggesting the essential role of these lipids in infant nutrition. DHA and ARA are abundant in the tissues of the brain, eyes, heart, muscles, blood vessels, and immune cells. These LCPUFAs have been studied for their functional roles in growth, as well as in brain, vision and immune development and function over the last several decades.5-10 

What is the evidence for adding ARA when DHA is present? Scientists outline 4 key areas:   

European regulations now mandate that all infant and follow-on formulas must contain DHA, while ARA is an optional ingredient.1 Despite this regulation, there are several important reasons why ARA should be added in combination with DHA to these formulas. Pediatric nutrition experts outline four key reasons why in a recent publication, summarized below.

DHA and ARA are both found in breastmilk 

Worldwide, with few exceptions, breastmilk samples consistently show that concentrations of ARA are greater than DHA, with up to twice the amount of ARA. Moreover, ARA concentrations are less variable than those of DHA.11-12

Conversion of linoleic acid to ARA may be limited 

An infant’s ability to synthesize ARA from the precursor fatty acid linoleic acid (LA) is influenced by gender, genetics, and the amount of LA in the diet. Conversion of LA to ARA is insufficient to maintain stable ARA concentrations in plasma and red blood cells. Thus, adding a supplemental source of ARA to infant and follow-on formulas may be necessary to more closely resemble reported concentrations of ARA in the breastfed infant.5,13 This is particularly relevant for infants who carry a genetic variation that negatively impacts the ability to convert LA to ARA. Affecting 30% of the general population in Europe, this results in a lower ARA status compared to infants without the genetic variant. Reduced ARA status may impact cognitive and immune system development, and the risk of developing allergies.12,14

The ratio of ARA to DHA matters 

Most studies on LCPUFAs demonstrate that certain developmental and physiologic outcomes are sensitive to the ratio of ARA to DHA. For example, functional outcomes in term infants were affected by the ratio of ARA:DHA in a large, randomized controlled trial that provided a fixed concentration of ARA (0.64%  ARA of total fatty acids) in combination with varied concentrations of DHA (0.32, 0.64 or 0.96% DHA of total fatty acids) through the first 12 months of life.15 In long-term follow-up studies of this cohort,  positive effects on certain measures of neurological development were observed at three to six years of age when ARA concentrations were at least equal to or greater than DHA (1:1 to 2:1 ARA:DHA ratios).8,9  

DHA and ARA participate in immune system development 

An effective immune response includes both activation and resolution of inflammation. ARA supports an infant’s health through its effects on the immune system and the inflammatory response. Indeed, ARA is a major substrate in the synthesis of eicosanoids, which function to modulate inflammation. Additionally, studies show the balance between ARA and DHA is important. Feeding infants formula supplemented with DHA and ARA at ratios found in breastmilk positively impacts immune system markers.13-14 Conversely, providing high doses of omega-3 LCPUFAs (like DHA) without adding ARA results in an imbalance of the omega 6:omega 3 LCPUFA ratio in the diet, which reduces cell content of ARA. Scientists believe this may lead to an anti-inflammatory and immunosuppressive effect that is undesirable during the early postnatal period when the immune system is rapidly developing and acquiring essential functions.14,16   

Nutrition Experts conclude that both DHA and ARA are critical in early life nutrition  

Based on their review of the evidence from research published over the last several decades, pediatric nutrition experts agree on the need to provide infants with a balanced supply of both DHA and ARA in order to support their LCPUFA status, as well as brain and immune system development and function.

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For more information about how DSM can support you in the development of infant nutrition products for optimal early life nutrition, visit our knowledge hub.

Published on

25 January 2021

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References

  1. European Commission: Commission Delegated Regulation (EU) 2016/127 of 25 September 2015 supplementing Regulation (EU) No 609/2013 of the European Parliament and of the Council as regards the specific compositional and information requirements for infant formula and follow-on formula and as regards requirements on information relating to infant and young child feeding. Official Journal of the European Union, 2016, L25/1-29.

  2. Tounian P, Bellaïche M, Legrand P. ARA or no ARA in infant formulae, that is the question. Archives de Pédiatrie, 

  3. Volume 28, Issue 1, 2021.
  4. Beluska-Turkan K, Korczak R, Hartell B, et al. Nutritional gaps and supplementation in the first 1000 days. Nutrients 2019;11(12):2891-2941. 

  5. Ballard O, Morrow AL. Human milk composition: nutrients and bioactive factors. Pediatr Clin North Am 2013;60:49-74. 

  6. Hadley KB, Ryan AS, Forsyth S, et al. The essentiality of arachidonic acid in infant development. Nutrients 2016;8(4):216-263.  

  7. Salem N, Jr., Van Dael P. Arachidonic Acid in Human Milk. Nutrients. 2020;12(3).

  8. Qawasmi A, Landeros-Weisenberger A, Bloch MH. Meta-analysis of LCPUFA supplementation of infant formula and visual acuity. Pediatrics. 2013;131(1):e262-272. 

  9. Colombo J, Jill Shaddy D, Kerling EH, Gustafson KM, Carlson SE. Docosahexaenoic acid (DHA) and arachidonic acid (ARA) balance in developmental outcomes. Prostaglandins Leukot Essent Fatty Acids. 2017;121:52-56.

  10. 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 

  11. Lapillonne A, Pastor N, Zhuang W, et al. 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 2014;14:168-175. 

  12. Fu Y, Liu X, Zhou B, et al. An updated review of worldwide levels of docosahexaenoic and arachidonic acid in human breast milk by region. Public Health Nutr 2016;19:2675-2687. 

  13. 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

  14. Lien EL, Richard C, Hoffman DR. DHA and ARA addition to infant formula: current status and future research directions. Prostaglandins Leukot Essent Fatty Acids 2018;128:26-40.  

  15. Richard C, Lewis ED, Field CJ. Evidence for the essentiality of arachidonic and docosahesaenoic acid in the postnatal maternal and infant diet for the development of the infant’s immune system early in life. Appl Physiol Nutr Metab 2016;41(5):461-475.

  16. Birch EE, Carlson SE, Hoffman DR, et al. 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; 91:848-859.  

  17. Calder PC, Kremmyda LS, Vlachava M, et al. Is there a role for fatty acids in early life programming of the immune system? Proc Nutr Soc 2010;69:373-380.

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