Should formula for infants provide arachidonic acid along with DHA? A position paper of the European Academy of Paediatrics and the Child Health Foundation
Open accessAbstract
Recently adopted regulatory standards on infant and follow-on formula for the European Union stipulate that from February 2020 onwards, all such products marketed in the European Union must contain 20-50 mg omega-3 DHA (22:6n-3) per 100 kcal, which is equivalent to about 0.5-1% of fatty acids (FAs) and thus higher than typically found in human milk and current infant formula products, without the need to also include ω-6 arachidonic acid (AA; 20:4n-6). This novel concept of infant formula composition has given rise to concern and controversy because there is no accountable evidence on its suitability and safety in healthy infants. Therefore, international experts in the field of infant nutrition were invited to review the state of scientific research on DHA and AA, and to discuss the questions arising from the new European regulatory standards. Based on the available information, we recommend that infant and follow-on formula should provide both DHA and AA. The DHA should equal at least the mean content in human milk globally (0.3% of FAs) but preferably reach 0.5% of FAs. Although optimal AA intake amounts remain to be defined, we strongly recommend that AA should be provided along with DHA. At amounts of DHA in infant formula up to ∼0.64%, AA contents should at least equal the DHA contents. Further well-designed clinical studies should evaluate the optimal intakes of DHA and AA in infants at different ages based on relevant outcomes.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
From February 2020 onwards, all infant and follow-on formula products marketed in the European Union must contain 20-50 mg DHA per 100 kcal, equivalent to about 0.5-1% of fatty acids, without the need to also include ARA.
“Those standards stipulate that from February 2020 onwards, all such products marketed in the European Union must contain 20–50 mg DHA per 100 kcal, which is equivalent to about 0.5–1% of fatty acids (higher than that typically found in human milk and current infant formula products) without the need to also include ARA (20:4n-6) [7].”
From Role of n-3 long-chain polyunsaturated fatty acids in human nutrition and health: Review of recent studies and recommendations (2021) · cites this paper as [7]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Functional Roles of Fatty Acids and Their Effects on Human Health
Calder, P. C. (2015) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607115595980 · Cited by 1,190 · see citing works
Self-citationTissue levels of polyunsaturated fatty acids during early human development
Martínez, M. (1992) · The Journal of Pediatrics · doi:10.1016/s0022-3476(05)81247-8 · Cited by 819 · see citing works
Fatty acid composition of brain, retina, and erythrocytes in breast- and formula-fed infants
Makrides, M., Neumann, M., Byard, R. W., Simmer, K. N., & Gibson, R. A. (1994) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/60.2.189 · Cited by 787 · see citing works
Koletzko, B., Lien, E., Agostoni, C., Böhles, H., Campoy, C., Cetin, I., Decsi, T., Dudenhausen, J. W., Dupont, C., Forsyth, S., et al. (2008) · Journal of Perinatal Medicine · doi:10.1515/jpm.2008.001 · Cited by 707 · see citing works
Self-citationDocosahexaenoic and arachidonic acid concentrations in human breast milk worldwide
Brenna, J. T., Varamini, B., Jensen, R. G., Diersen-Schade, D. A., Boettcher, J. A., & Arterburn, L. M. (2007) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/85.6.1457 · Cited by 662 · see citing works
Self-citationKoletzko, B. V., Baker, S. S., Cleghorn, G. J., Neto, U. F., Gopalan, S., Hernell, O., Hock, Q. S., Jirapinyo, P., Lönnerdal, B., Pencharz, P. B., et al. (2005) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/01.mpg.0000187817.38836.42 · Cited by 662 · see citing works
Self-citationSchaeffer, L., Gohlke, H., Müller, M., Heid, I. M., Palmer, L. J., Kompauer, I., Demmelmair, H., Illig, T., Koletzko, B., & Heinrich, J. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl117 · Cited by 561 · see citing works
Self-citationArachidonic acid status correlates with first year growth in preterm infants.
Carlson, S. E., Werkman, S. H., Peeples, J. M., Cooke, R. J., & Tolley, E. A. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.3.1073 · Cited by 510 · see citing works
Self-citationLong chain polyunsaturated fatty acid supplementation in infants born at term
Jasani, B., Simmer, K. N., Patole, S., & Rao, S. C. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd000376.pub4 · Cited by 410 · see citing works
Scientific Opinion on the essential composition of infant and follow-on formulae
EFSA Panel on Dietetic Products, N. A. A. (. (2014) · EFSA Journal · doi:10.2903/j.efsa.2014.3760 · Cited by 405 · see citing works
EFSA Panel on Dietetic Products, N. A. A. (. (2013) · EFSA Journal · doi:10.2903/j.efsa.2013.3408 · Cited by 363 · see citing works
Koletzko, B. V. (2016) · Annals of Nutrition and Metabolism · doi:10.1159/000452819 · Cited by 313 · see citing works
Self-citationPutnam, J., Putnam, S., DeVoe, P. W., & Barness, L. A. (1982) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/36.1.106 · Cited by 274 · see citing works
Arachidonic Acid and Early Human Growth: Is there a Relation?
Koletzko, B. V., & Braun, M. (1991) · Annals of Nutrition and Metabolism · doi:10.1159/000177636 · Cited by 247 · see citing works
Self-citationBreast milk composition and infant nutrient intakes during the first 12 months of life
Grote, V., Verduci, E., Scaglioni, S., Vecchi, F., Contarini, G., Giovannini, M., Koletzko, B. V., Agostoni, C. V., & for the European Childhood Obesity Project (2015) · European Journal of Clinical Nutrition · doi:10.1038/ejcn.2015.162 · Cited by 231 · see citing works
Self-citationMartin, C. R., DaSilva, D. A., Cluette‐Brown, J. E., DiMonda, C., Hamill, A., Bhutta, A. Q., Coronel, E. S., Wilschanski, M. A., Stephens, A. J., Driscoll, D. F., et al. (2011) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2011.04.039 · Cited by 230 · see citing works
Self-citationLong-term effects of LCPUFA supplementation on childhood cognitive outcomes
Colombo, J. A., Carlson, S. E., Cheatham, C. L., Shaddy, D. J., Kerling, E. H., Thodosoff, J. M., Gustafson, K. M., & Brez, C. C. (2013) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.112.040766 · Cited by 194 · see citing works
Self-citationDocosahexaenoic Acid and Bronchopulmonary Dysplasia in Preterm Infants
Collins, C. T., Makrides, M., McPhee, A. J., Sullivan, T., Davis, P. G., Thió, M., Simmer, K. N., Rajadurai, V. S., Travadi, J., Berry, M. J., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1611942 · Cited by 174 · see citing works
Glaser, C., Lattka, E., Rzehak, P., Steer, C., & Koletzko, B. (2011) · Maternal & Child Nutrition · doi:10.1111/j.1740-8709.2011.00319.x · Cited by 165 · see citing works
Self-citationKoletzko, B. V., Boey, C. C. M., Campoy, C., Carlson, S. E., Chang, N., Guillermo-Tuazon, M. A., Joshi, S., Prell, C., Quak, S. H., Sjarif, D. R., et al. (2014) · Annals of Nutrition and Metabolism · doi:10.1159/000365767 · Cited by 159 · see citing works
Self-citationInnis, S. M., Adamkin, D. H., Hall, R. T., et al. (2002) · The Journal of Pediatrics · doi:10.1067/mpd.2002.123282 · Cited by 149 · see citing works
FADS1 and FADS2 Polymorphisms Modulate Fatty Acid Metabolism and Dietary Impact on Health
Koletzko, B. V., Reischl, E., Tanjung, C., González-Casanova, I., Ramakrishnan, U., Meldrum, S. J., Simmer, K. N., Heinrich, J., & Demmelmair, H. (2019) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-082018-124250 · Cited by 138 · see citing works
Self-citationPlacental regulation of fetal nutrient supply
Larqué, E., Ruíz‐Palacios, M., & Koletzko, B. V. (2013) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e32835e3674 · Cited by 132 · see citing works
Self-citationDHA and ARA addition to infant formula: Current status and future research directions
Lien, E. L., Richard, C., & Hoffman, D. R. (2017) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2017.09.005 · Cited by 130 · see citing works
Qawasmi, A., Landeros‐Weisenberger, A., Leckman, J. F., & Bloch, M. H. (2012) · PEDIATRICS · doi:10.1542/peds.2011-2127 · Cited by 114 · see citing works
Shulkin, M., Pimpin, L., Bellinger, D. C., Kranz, S., Fawzi, W. W., Duggan, C., & Mozaffarian, D. (2018) · Journal of Nutrition · doi:10.1093/jn/nxx031 · Cited by 105 · see citing works
Makrides, M., Gibson, R. A., Udell, T., & Ried, K. (2005) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/81.5.1094 · Cited by 97 · see citing works
Aggett, P. J., Agostini, C., Goulet, O., et al. (2001) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/00005176-200103000-00004 · Cited by 95 · see citing works
Arachidonic acid needed in infant formula when docosahexaenoic acid is present
Brenna, J. T. (2016) · Nutrition Reviews · doi:10.1093/nutrit/nuw007 · Cited by 93 · see citing works
Self-citationDietary reference intakes: energy, proteins, fats and digestible carbohydrates
van den Brandt, P. A. (2001) · Research Publications (Maastricht University) · Cited by 93 · see citing works
Meta-analysis of LCPUFA Supplementation of Infant Formula and Visual Acuity
Qawasmi, A., Landeros‐Weisenberger, A., & Bloch, M. H. (2012) · PEDIATRICS · doi:10.1542/peds.2012-0517 · Cited by 83 · see citing works
Placental Fatty Acid Transfer: A Key Factor in Fetal Growth
Larqué, E., Pagán, A., Prieto‐Sánchez, M. T., Blanco‐Carnero, J. E., Gil-Sánchez, A., Moreno, M. Z., Ruíz‐Palacios, M., Gázquez, A., Demmelmair, H., Parrilla, J. J., et al. (2014) · Annals of Nutrition and Metabolism · doi:10.1159/000365028 · Cited by 82 · see citing works
Self-citationCarlson, S. E. (1996) · Journal of Nutrition · doi:10.1093/jn/126.suppl_4.1092s · Cited by 81 · see citing works
Self-citationFu, Y., Liu, X., Zhou, B., Jiang, A. C., & Chai, L. (2016) · Public Health Nutrition · doi:10.1017/s1368980016000707 · Cited by 79 · see citing works
Association of Retinopathy of Prematurity With Low Levels of Arachidonic Acid
Löfqvist, C., Najm, S., Hellgren, G., Engström, E., Sävman, K., Nilsson, A., Andersson, M. X., Hård, A., Smith, L. E. H., & Hellström, A. (2018) · JAMA Ophthalmology · doi:10.1001/jamaophthalmol.2017.6658 · Cited by 78 · see citing works
Hsieh, A. T., Anthony, J. C., Diersen-Schade, D. A., Rumsey, S. C., Lawrence, P., Li, C., Nathanielsz, P. W., & Brenna, J. T. (2007) · Pediatric Research · doi:10.1203/pdr.0b013e318045bec9 · Cited by 75 · see citing works
Self-citationDocosahexaenoic acid (DHA) and arachidonic acid (ARA) balance in developmental outcomes
Colombo, J. A., Shaddy, D. J., Kerling, E. H., Gustafson, K. M., & Carlson, S. E. (2017) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2017.05.005 · Cited by 72 · see citing works
Self-citationLattka, E., Koletzko, B. V., Kunze, S., Hibbeln, J. R., Klopp, N., Ring, S. M., & Steer, C. D. (2012) · British Journal Of Nutrition · doi:10.1017/s0007114512003108 · Cited by 71 · see citing works
Self-citationSellmayer, A., & Koletzko, B. V. (1999) · Lipids · doi:10.1007/s11745-999-0354-z · Cited by 69 · see citing works
Self-citationShould Infant Formula Provide Both Omega-3 DHA and Omega-6 Arachidonic Acid?
Koletzko, B. V., Carlson, S. E., & van Goudoever, J. B. (2015) · Annals of Nutrition and Metabolism · doi:10.1159/000377643 · Cited by 62 · see citing works
Self-citationThiamine Deficiency in Infancy: Long-Term Follow-Up
Mimouni-Bloch, A., Goldberg‐Stern, H., Straussberg, R., Brezner, A., Heyman, E., Inbar, D., Kivity, S., Zvulunov, A., Sztarkier, I., Fogelman, R., et al. (2014) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2014.05.010 · Cited by 60 · see citing works
n-6 and n-3 PUFA intakes of pre-school children in Flanders, Belgium
Sioen, I., Huybrechts, I., Verbeke, W., et al. (2007) · British Journal Of Nutrition · doi:10.1017/s0007114507756544 · Cited by 58 · see citing works
Polyunsaturated fatty acids and infant growth
Lapillonne, A., & Carlson, S. E. (2001) · Lipids · doi:10.1007/s11745-001-0800-y · Cited by 57 · see citing works
Self-citationLepping, R. J., Honea, R. A., Martin, L. E., Liao, K., Choi, I., Lee, P., Papa, V. B., Brooks, W. M., Shaddy, D. J., Carlson, S. E., et al. (2018) · Developmental Psychobiology · doi:10.1002/dev.21780 · Cited by 53 · see citing works
Self-citationLiao, K., McCandliss, B. D., Carlson, S. E., Colombo, J. A., Shaddy, D. J., Kerling, E. H., Lepping, R. J., Sittiprapaporn, W., Cheatham, C. L., & Gustafson, K. M. (2016) · Developmental Science · doi:10.1111/desc.12455 · Cited by 52 · see citing works
Self-citationCrawford, M. A., Wang, Y., Forsyth, S. J., et al. (2015) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2015.07.005 · Cited by 49 · see citing works
González-Casanova, I., Rzehak, P., Stein, A. D., García‐Feregrino, R., Rivera, J. Á., Barraza‐Villarreal, A., Demmelmair, H., Romieu, I., Villalpando, S., Martorell, R., et al. (2016) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.115.121244 · Cited by 47 · see citing works
Self-citationCharacterisation of Infant Food Modifications in the European Union
Koletzko, B. V., Ashwell, M., Beck, B., et al. (2002) · Annals of Nutrition and Metabolism · doi:10.1159/000066499 · Cited by 38 · see citing works
Self-citationLorenzo, I., Tonato, A. M. C., Puentes, A. D. L. G., Nieto-Ruíz, A., Herrmann, F., Diéguez, E., Castellote, A. I., López‐Sabater, M. C., Rodrı́guez-Palmero, M., & Campoy, C. (2019) · Nutrients · doi:10.3390/nu11030602 · Cited by 34 · see citing works
Self-citationAggett, P. J., Agostoni, C. V., Axelsson, I., et al. (2003) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/00005176-200303000-00007 · Cited by 32 · see citing works
Forsyth, S. J., Gautier, S., & Salem, N. (2017) · Annals of Nutrition and Metabolism · doi:10.1159/000463396 · Cited by 32 · see citing works
Forsyth, S. J., Gautier, S., & Salem, N. (2016) · Annals of Nutrition and Metabolism · doi:10.1159/000448526 · Cited by 28 · see citing works
Reduction of Arachidonate Is Associated With Increase in B‐Cell Activation Marker in Infants
Miklavcic, J. J., Larsen, B. K., Mazurak, V. C., et al. (2016) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0000000000001283 · Cited by 24 · see citing works
Bschir, K. (2016) · Science and Engineering Ethics · doi:10.1007/s11948-016-9773-2 · Cited by 18 · see citing works
Tanjung, C., Rzehak, P., Sudoyo, H., Mansyur, M., Munasir, Z., Immanuel, S., Irawan, R., Reischl, E., Demmelmair, H., Hadinegoro, S. R., et al. (2018) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqy166 · Cited by 12 · see citing works
Self-citationA NEUROBEHAVIORAL SYNDROME AFTER FAILURE TO THRIVE ON CHLORIDE‐DEFICIENT FORMULA
Kaleita, T. A., Kinsbourne, M., & Menkes, J. H. (1991) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.1991.tb14933.x · Cited by 11 · see citing works
Blouin, M., Coulombe, M., & Rhainds, M. (2014) · Canadian Journal of Public Health · doi:10.17269/cjph.105.4369 · Cited by 9 · see citing works
The Follow-up of Infants Exposed to Chloride-Deficient Formulas
Malloy, M. H. (1993) · Advances in Pediatrics · doi:10.1016/s0065-3101(24)00010-0 · Cited by 4 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- [8]8. 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:L 25/1.
- [11]11. European-Commission. COMMISSION DIRECTIVE 2006/141/EC of 22 December 2006 on infant formulae and follow-on formulae and amending Directive 1999/21/EC. Official Journal of the European Union 2006(L 401/1).
- [19]19. European-Food-Safety-Authority. Scientific Opinion of the Panel on Dietetic Products, Nutrition and Allergies. DHA and ARA and visual development. Scientific substantiation of a health claim related to docosahexaenoic acid (DHA) and arachidonic acid (ARA) and visual development pursuant to Article14 of Regulation (EC) No 1924/20061S (Question No EFSAQ-2008-211) . Adopted on 22 January 2009. The EFSA Journal 2009;941:1-14.
Cited by
Sorted by citations
Van Dael, P. (2021) · Nutrition Research and Practice · doi:10.4162/nrp.2021.15.2.137 · Cited by 138 · see citing works
- Authors
- Koletzko, B., Bergmann, K., Brenna, J. T., Calder, P. C., Campoy, C., Clandinin, M. T., Colombo, J., Daly, M., Decsi, T., Demmelmair, H., Domellöf, M., FidlerMis, N., Gonzalez-Casanova, I., van Goudoever, J. B., Hadjipanayis, A., Hernell, O., Lapillonne, A., Mader, S., Martin, C. R., Matthäus, V., Ramakrishan, U., Smuts, C. M., Strain, S. J., Tanjung, C., Tounian, P., & Carlson, S. E.
- Affiliations
- Ludwig-Maximilians-Universität München (DE)
- Cornell University (US)
- National Health Service (GB)
- Universidad de Granada (ES)
- University of Alberta (CA)
- University of Kansas (US)
- Fairfax Neonatal Associates (US)
- Umeå University (SE)
- European University Cyprus (CY)
- Hôpital Necker-Enfants Malades (FR)
- Beth Israel Deaconess Medical Center (US)
- Emory University (US)
- North-West University (ZA)
- Sorbonne Université (FR)
- University of Kansas Medical Center (US)
- Corresponding author
- Koletzko, Berthold
- ORCID
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2020-01
- Volume
- 111
- Issue
- 1
- Pages
- 10-16
- ISSN
- 0002-9165 (ISSN-L)
- PMC
- PMC13639460
- OpenAlex
- W2982371600
- Cited by
- 135
- References
- 58
- Citations by year
- 2026: 17 · 2025: 16 · 2024: 11 · 2023: 26 · 2022: 20 · 2021: 24 · 2020: 21
- FWCI
- 12.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- ePrints Soton (University of Southampton) (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Pure Amsterdam UMC (submittedVersion, cc-by)
- Ulster University Research Portal (Ulster University) (submittedVersion, other-oa)
- Boloka Institutional Repository (North-west University) (submittedVersion)
- Funders
- Charitable Child Health Foundation
- European Commission
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
- Health Sciences › Medicine › Epidemiology › Breastfeeding Practices and Influences
- Keywords
- infant formula, arachidonic acid, docosahexaenoic acid, omega-3 fatty acids, omega-6 fatty acids, follow-on formula, infant nutrition
- MeSH terms
- Child Health, Child Development, Docosahexaenoic Acids, European Union, Fatty Acids, Food Additives, Humans, Infant, Pediatrics, Arachidonic Acid, Infant Formula
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
