{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:17:35Z","timestamp":1777447055304,"version":"3.51.4"},"reference-count":89,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Committee for Umami"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>Toxicological risk assessment of food ingredients has traditionally relied on identifying a no-observed-adverse-effect level (NOAEL) or benchmark dose (BMD), followed by the application of default uncertainty factors (UFs) to derive health-based guidance values (HBGVs) such as the acceptable daily intake (ADI). While effective for conventional food additives, this approach may be inappropriate for nutrients and intrinsic food components with established physiological functions. This paper critically explores these limitations using free glutamate as a central example, alongside additional cases relevant to infant nutrition, including vitamin C, iodine, and human milk oligosaccharides (HMOs). Data on free glutamate in human milk show that breastfed infants habitually ingest amounts far exceeding additive-based ADIs without adverse effects, underscoring the limitations of applying default uncertainty factors and classical toxicological paradigms to endogenous nutrients. Comparable considerations apply to protein hydrolysates and amino acid-based infant formulas evaluated by EFSA, where growth, tolerance, and compositional suitability are integral to safety assessment. Overall, nutrient safety evaluation requires an integrative, physiology-informed framework that incorporates realistic exposure, developmental stage, and metabolic competence. Breast milk provides a biologically relevant reference, supporting a proportionate and science-based application of toxicological principles in infant nutrition.<\/jats:p>","DOI":"10.3390\/foods15091530","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:33:37Z","timestamp":1777376017000},"page":"1530","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Glutamate: Safe and Adequate Intake Levels for Infants\u2014Should Breast Milk Be Taken Off the Market?"],"prefix":"10.3390","volume":"15","author":[{"given":"Anita","family":"Hartog","sequence":"first","affiliation":[{"name":"Food for Health Consultancy, 6986BK Angerlo, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7952-3530","authenticated-orcid":false,"given":"Hans","family":"Verhagen","sequence":"additional","affiliation":[{"name":"Food Safety & Nutrition Consultancy, 3703EE Zeist, The Netherlands"},{"name":"School of Biomedical Sciences, Faculty of Life and Health Sciences, Ulster University, Coleraine BT52 1SA, UK"},{"name":"National Food Institute, Technical University of Denmark, Kemitorvet 201, 2800 Kgs. Lyngby, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1617S","DOI":"10.1093\/jn\/134.6.1617S","article-title":"Establishing the upper end of the range of adequate and safe intakes for amino acids: A toxicologist\u2019s viewpoint","volume":"134","author":"Renwick","year":"2004","journal-title":"J. Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1017\/S0029665115004310","article-title":"The potential application of a biomarker approach for the investigation of low-calorie sweetener exposure","volume":"75","author":"Logue","year":"2016","journal-title":"Proc. Nutr. Soc."},{"key":"ref_3","first-page":"e06479","article-title":"Statement on the derivation of Health-Based Guidance Values (HBGVs) for regulated products that are also nutrients","volume":"19","author":"More","year":"2021","journal-title":"EFSA J."},{"key":"ref_4","first-page":"e04658","article-title":"Update: Use of the benchmark dose approach in risk assessment","volume":"15","author":"Hardy","year":"2017","journal-title":"EFSA J."},{"key":"ref_5","first-page":"e07584","article-title":"Guidance on the use of the benchmark dose approach in risk assessment","volume":"20","author":"More","year":"2022","journal-title":"EFSA J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1006\/rtph.1999.1319","article-title":"Report of workshop on the significance of excursions of intake above the ADI","volume":"30","author":"Larsen","year":"1999","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.physbeh.2016.02.039","article-title":"The safety and regulatory process for low calorie sweeteners in the United States","volume":"164","author":"Roberts","year":"2016","journal-title":"Physiol. Behav."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2635S","DOI":"10.3945\/jn.116.234591","article-title":"The Safety and Regulatory Process for Amino Acids in Europe and the United States","volume":"146","author":"Roberts","year":"2016","journal-title":"J. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1159\/000494783","article-title":"Risk Assessment Paradigm for Glutamate","volume":"73","author":"Roberts","year":"2018","journal-title":"Ann. Nutr. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"104","DOI":"10.9734\/EJNFS\/2015\/14815","article-title":"Perspectives on Low Calorie Intense Sweeteners with a Focus on Aspartame and Stevia","volume":"5","author":"Logue","year":"2015","journal-title":"Eur. J. Nutr. Food Saf."},{"key":"ref_11","first-page":"e9052","article-title":"Guidance for establishing and applying tolerable upper intake levels for vitamins and essential minerals","volume":"22","author":"Turck","year":"2024","journal-title":"EFSA J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1016\/j.fct.2004.07.013","article-title":"Risk-benefit analysis of micronutrients","volume":"42","author":"Renwick","year":"2004","journal-title":"Food Chem. Toxicol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7479","DOI":"10.1080\/10408398.2021.1915240","article-title":"Human health risk\u2013benefit assessment of fish and other seafood: A scoping review","volume":"62","author":"Thomsen","year":"2022","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"110073","DOI":"10.1016\/j.foodres.2020.110073","article-title":"Risk-benefit in food safety and nutrition\u2014Outcome of the 2019 Parma Summer School","volume":"141","author":"Verhagen","year":"2021","journal-title":"Food Res. Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.fct.2011.06.007","article-title":"State of the art in benefit-risk analysis: Introduction","volume":"50","author":"Verhagen","year":"2012","journal-title":"Food Chem. Toxicol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.fct.2011.06.010","article-title":"State of the art in benefit-risk analysis: Food and nutrition","volume":"50","author":"Tijhuis","year":"2012","journal-title":"Food Chem. Toxicol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.fct.2011.11.044","article-title":"Looking beyond borders: Integrating best practices in benefit-risk analysis into the field of food and nutrition","volume":"50","author":"Tijhuis","year":"2012","journal-title":"Food Chem. Toxicol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.fct.2012.10.028","article-title":"Critical appraisal of the assessment of benefits and risks for foods, \u2018BRAFO Consensus Working Group\u2019","volume":"55","author":"Boobis","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"S684","DOI":"10.1016\/j.fct.2010.05.049","article-title":"BRAFO tiered approach for Benefit-Risk Assessment of Foods","volume":"50","author":"Hoekstra","year":"2012","journal-title":"Food Chem. Toxicol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1016\/j.fct.2007.10.015","article-title":"Integrated risk-benefit analyses: Method development with folic acid as example","volume":"46","author":"Hoekstra","year":"2008","journal-title":"Food Chem. Toxicol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"EFSA Scientific Committee, More, S.J., Benford, D., Bennekou, S.H., Bampidis, V., Bragard, C., Halldorsson, T.I., Hern\u00e1ndez-Jerez, A.F., Koutsoumanis, K., and Lambr\u00e9, C. (2024). Guidance on risk-benefit assessment of foods. EFSA J., 22, e8875.","DOI":"10.2903\/j.efsa.2024.8875"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Dosed\u011bl, M., Jirkovsk\u00fd, E., Mac\u00e1kov\u00e1, K., Kr\u010dmov\u00e1, L.K., Javorsk\u00e1, L., Pourov\u00e1, J., Mercolini, L., Remi\u00e3o, F., Nov\u00e1kov\u00e1, L., and Mlad\u011bnka, P. (2021). Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination. Nutrients, 13.","DOI":"10.3390\/nu13020615"},{"key":"ref_23","unstructured":"Scientific Committee on Food (2006). Tolerable Upper Intake Levels for Vitamins and Minerals, European Food Safety Authority (EFSA). Available online: https:\/\/www.efsa.europa.eu\/sites\/default\/files\/efsa_rep\/blobserver_assets\/ndatolerableuil.pdf."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) (2004). Opinion of the Scientific Panel on Dietetic Products, Nutrition and Allergies (NDA) a request from the Commission related to the Tolerable Upper Intake Level of Vitamin C (L-Ascorbic acid, its calcium, potassium and sodium salts and L-ascorbyl-6-palmitate). EFSA J., 2, 59.","DOI":"10.2903\/j.efsa.2004.59"},{"key":"ref_25","unstructured":"(2015). EFSA Panel on Food Additives and Nutrient Sources Added to Food (ANS). Scientific Opinion on the re-evaluation of ascorbic acid (E 300), sodium ascorbate (E 301) and calcium ascorbate (E 302) as food additives. EFSA J., 13, 4087."},{"key":"ref_26","unstructured":"Institute of Medicine (2000). Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids, The National Academies Press."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1017\/S0029665100000094","article-title":"The role of iodine in brain development","volume":"59","author":"Delange","year":"2000","journal-title":"Proc. Nutr. Soc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1089\/thy.2007.0108","article-title":"The adverse effects of mild-to-moderate iodine deficiency during pregnancy and childhood: A review","volume":"17","author":"Zimmermann","year":"2007","journal-title":"Thyroid"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1210\/endrev\/bnae019","article-title":"Risks of Iodine Excess","volume":"45","author":"Sohn","year":"2024","journal-title":"Endocr. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1111\/nyas.14041","article-title":"Excess iodine intake: Sources, assessment, and effects on thyroid function","volume":"1446","author":"Farebrother","year":"2019","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"EFSA Panel on Dietetic Products, Nutrition and Allergies (2014). Scientific Opinion on Dietary Reference Values for iodine. EFSA J., 12, 3660.","DOI":"10.2903\/j.efsa.2014.3660"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"921S","DOI":"10.1093\/jn\/130.4.921S","article-title":"Umami and Food Palatability","volume":"130","author":"Yamaguchi","year":"2000","journal-title":"J. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1159\/000494778","article-title":"Review of Glutamate Intake from Both Food Additive and Non-Additive Sources in the European Union","volume":"73","author":"Tennant","year":"2018","journal-title":"Ann. Nutr. Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1159\/000522482","article-title":"Glutamate: A Safe Nutrient, Not Just a Simple Additive","volume":"78","author":"Cynober","year":"2022","journal-title":"Ann. Nutr. Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1159\/000494776","article-title":"Metabolism of Dietary Glutamate in Adults","volume":"73","author":"Cynober","year":"2018","journal-title":"Ann. Nutr. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Hawkins, R.A., and Vi\u00f1a, J.R. (2016). How Glutamate Is Managed by the Blood-Brain Barrier. Biology, 5.","DOI":"10.20944\/preprints201609.0077.v1"},{"key":"ref_37","first-page":"e04910","article-title":"Re-evaluation of glutamic acid (E 620), sodium glutamate (E 621), potassium glutamate (E 622), calcium glutamate (E 623), ammonium glutamate (E 624) and magnesium glutamate (E 625) as food additives","volume":"15","author":"Mortensen","year":"2017","journal-title":"EFSA J."},{"key":"ref_38","unstructured":"Scientific Committee for Food (1991). Report of the Scientific Committee for Food on a First Series of Food Additives of Various Technological Functions (Opinion Expressed 18 May 1990), Commission of the European Communities. Available online: https:\/\/food.ec.europa.eu\/system\/files\/2020-12\/sci-com_scf_reports_25.pdf."},{"key":"ref_39","unstructured":"Joint FAO\/WHO Expert Committee on Food Additives (JECFA) (1988). L-glutamic acid and its ammonium, calcium, magnesium, monosodium and potassium salts (evaluation and specifications). Safety Evaluation of Certain Food Additives, WHO. Available online: https:\/\/www.inchem.org\/documents\/jecfa\/jecmono\/v22je12.htm."},{"key":"ref_40","unstructured":"Joint FAO\/WHO Expert Committee on Food Additives (2004). Amino acids and related substances (flavouring agents). Evaluation of Certain Food Additives: Sixty-Third Report of the Joint FAO\/WHO Expert Committee on Food Additives, Proceedings of the 63rd Joint FAO\/WHO Expert Committee on Food Additives (JECFA) Meeting\u2014Food Contaminants. Summary and Conclusions, Geneva, Switzerland 8\u201317 June 2004, World Health Organization."},{"key":"ref_41","unstructured":"Norwegian Scientific Committee for Food Safety (VKM) (2016). Risk Assessment Of \u201cOther Substances\u201d\u2014L-Glutamine and L-Glutamic Acid, VKM. Available online: https:\/\/vkm.no\/download\/18.645b840415d03a2fe8f26029\/1502799994850\/Risk%20assessment%20of%20%22other%20substances%22%20%E2%80%93%20L-glutamine%20and%20L-glutamic%20acid.pdf."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4800","DOI":"10.3390\/nu5124800","article-title":"Amino acid profiles in term and preterm human milk through lactation: A systematic review","volume":"5","author":"Zhang","year":"2013","journal-title":"Nutrients"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Van Sadelhoff, J.H.J., Van de Heijning, B.J.M., Stahl, B., Amodio, S., Rings, E.H.H.M., Mearin, M.L., Garssen, J., and Hartog, A. (2018). Longitudinal Variation of Amino Acid Levels in Human Milk and Their Associations with Infant Gender. Nutrients, 10.","DOI":"10.3390\/nu10091233"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"100432","DOI":"10.1016\/j.advnut.2025.100432","article-title":"Protein and Free Amino Acid Composition of Preterm Human Milk: A Systematic Review and Meta-analysis","volume":"16","author":"Miketinas","year":"2025","journal-title":"Adv. Nutr."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1007\/s00726-013-1573-2","article-title":"Oral administration of MSG increases expression of glutamate receptors and transporters in the gastrointestinal tract of young piglets","volume":"45","author":"Zhang","year":"2013","journal-title":"Amino Acids"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"van Sadelhoff, J.H.J., Wiertsema, S.P., Garssen, J., and Hogenkamp, A. (2020). Free Amino Acids in Human Milk: A Potential Role for Glutamine and Glutamate in the Protection Against Neonatal Allergies and Infections. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01007"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s40104-016-0078-8","article-title":"Amino acids and mammary gland development: Nutritional implications for milk production and neonatal growth","volume":"7","author":"Rezaei","year":"2016","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Poulsen, K.O., Meng, F., Lanfranchi, E., Young, J.F., Stanton, C., Ryan, C.A., Kelly, A.L., and Sundekilde, U.K. (2022). Dynamic Changes in the Human Milk Metabolome Over 25 Weeks of Lactation. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.917659"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1159\/000494780","article-title":"Glutamate Supply and Metabolism in Infants","volume":"73","author":"Koletzko","year":"2018","journal-title":"Ann. Nutr. Metab."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1203\/PDR.0b013e318123f719","article-title":"Dietary glutamate is almost entirely removed in its first pass through the splanchnic bed in premature infants","volume":"62","author":"Ordonez","year":"2007","journal-title":"Pediatr. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5701","DOI":"10.1007\/s00431-023-05215-6","article-title":"Glutamic acid intake by formula-fed infants: Are acceptable daily intakes appropriate?","volume":"182","author":"Mennella","year":"2023","journal-title":"Eur. J. Pediatr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1006\/jfca.1999.0818","article-title":"Amino Acid Contents of Infant Formulas","volume":"12","author":"Lagarda","year":"1999","journal-title":"J. Food Compos. Anal."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/s10295-015-1665-y","article-title":"The many roles of glutamate in metabolism","volume":"43","author":"Walker","year":"2016","journal-title":"J. Ind. Microbiol. Biotechnol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Baj, A., Moro, E., Bistoletti, M., Orlandi, V., Crema, F., and Giaroni, C. (2019). Glutamatergic Signaling Along the Microbiota-Gut-Brain Axis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20061482"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1700231","DOI":"10.1002\/mnfr.201700231","article-title":"Protein Digestion of Baby Foods: Study Approaches and Implications for Infant Health","volume":"62","author":"Gan","year":"2018","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"112","DOI":"10.4172\/2161-0509.1000112","article-title":"Digestion of Protein in Premature and Term Infants","volume":"2","author":"Dallas","year":"2012","journal-title":"J. Nutr. Disord. Ther."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1017\/S0007114512005041","article-title":"Ontogeny of dipeptide uptake and peptide transporter 1 (PepT1) expression along the gastrointestinal tract in the neonatal Yucatan miniature pig","volume":"110","author":"Nosworthy","year":"2013","journal-title":"Br. J. Nutr."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1203\/00006450-200106000-00013","article-title":"Developmental Expression of PEPT1 and PEPT2 in Rat Small Intestine, Colon, and Kidney","volume":"49","author":"Shen","year":"2001","journal-title":"Pediatr. Res."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Barton, J.R., Londregan, A.K., Alexander, T.D., Entezari, A.A., Covarrubias, M., and Waldman, S.A. (2023). Enteroendocrine cell regulation of the gut-brain axis. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1272955"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"832s","DOI":"10.3945\/ajcn.2009.27462V","article-title":"Activation of the gut-brain axis by dietary glutamate and physiologic significance in energy homeostasis","volume":"90","author":"Kondoh","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"978S","DOI":"10.1093\/jn\/130.4.978S","article-title":"Intestinal Glutamate Metabolism","volume":"130","author":"Reeds","year":"2000","journal-title":"J. Nutr."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.aninu.2016.03.007","article-title":"Amino acid sensing in the gut and its mediation in gut-brain signal transduction","volume":"2","author":"Liu","year":"2016","journal-title":"Anim. Nutr."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"875","DOI":"10.3945\/ajcn.111.024919","article-title":"Infant regulation of intake: The effect of free glutamate content in infant formulas","volume":"95","author":"Ventura","year":"2012","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1542\/peds.2010-1675","article-title":"Differential growth patterns among healthy infants fed protein hydrolysate or cow-milk formulas","volume":"127","author":"Mennella","year":"2011","journal-title":"Pediatrics"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1093\/ajcn\/nqy188","article-title":"Type of infant formula increases early weight gain and impacts energy balance: A randomized controlled trial","volume":"108","author":"Mennella","year":"2018","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.3945\/ajcn.2008.27373","article-title":"Short- and long-term effects of feeding hydrolyzed protein infant formulas on growth at \u22646 y of age: Results from the German Infant Nutritional Intervention Study","volume":"89","author":"Rzehak","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"van Sadelhoff, J.H.J., Siziba, L.P., Buchenauer, L., Mank, M., Wiertsema, S.P., Hogenkamp, A., Stahl, B., Garssen, J., Rothenbacher, D., and Genuneit, J. (2021). Free and Total Amino Acids in Human Milk in Relation to Maternal and Infant Characteristics and Infant Health Outcomes: The Ulm SPATZ Health Study. Nutrients, 13.","DOI":"10.3390\/nu13062009"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Balde\u00f3n, M.E., Zertuche, F., Flores, N., and Fornasini, M. (2019). Free Amino Acid Content in Human Milk is Associated with Infant Gender and Weight Gain during the First Four Months of Lactation. Nutrients, 11.","DOI":"10.3390\/nu11092239"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2211917","DOI":"10.1080\/19490976.2023.2211917","article-title":"The infant gut microbiota: In pursuit of non-protein nitrogen","volume":"15","author":"Schimmel","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1203\/PDR.0b013e31813cbeba","article-title":"Splanchnic Oxidation Is the Major Metabolic Fate of Dietary Glutamate in Enterally Fed Preterm Infants","volume":"62","author":"Riedijk","year":"2007","journal-title":"Pediatr. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1203\/01.pdr.0000185130.90205.1f","article-title":"Amino Acids, Glutamine, and Protein Metabolism in Very Low Birth Weight Infants","volume":"58","author":"Parimi","year":"2005","journal-title":"Pediatr. Res."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Hou, Y., Michiels, J., Kerschaver, C.V., Vandaele, M., Majdeddin, M., Vossen, E., and Degroote, J. (2023). The kinetics of glutathione in the gastrointestinal tract of weaned piglets supplemented with different doses of dietary reduced glutathione. Front. Vet. Sci., 10.","DOI":"10.3389\/fvets.2023.1220213"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1093\/nutrit\/nux044","article-title":"Systematic review of the concentrations of oligosaccharides in human milk","volume":"75","author":"Thurl","year":"2017","journal-title":"Nutr. Rev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"11767","DOI":"10.1038\/s41598-019-48337-4","article-title":"Impact of maternal characteristics on human milk oligosaccharide composition over the first 4 months of lactation in a cohort of healthy European mothers","volume":"9","author":"Samuel","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1111\/jhn.12990","article-title":"Biology of human milk oligosaccharides: From basic science to clinical evidence","volume":"35","author":"Sprenger","year":"2022","journal-title":"J. Hum. Nutr. Diet."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2501192","DOI":"10.1080\/19490976.2025.2501192","article-title":"Human milk oligosaccharide metabolism and antibiotic resistance in early gut colonizers: Insights from bifidobacteria and lactobacilli in the maternal-infant microbiome","volume":"17","author":"Samarra","year":"2025","journal-title":"Gut Microbes"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Wici\u0144ski, M., Sawicka, E., G\u0119balski, J., Kubiak, K., and Malinowski, B. (2020). Human Milk Oligosaccharides: Health Benefits, Potential Applications in Infant Formulas, and Pharmacology. Nutrients, 12.","DOI":"10.3390\/nu12010266"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Carr, L.E., Virmani, M.D., Rosa, F., Munblit, D., Matazel, K.S., Elolimy, A.A., and Yeruva, L. (2021). Role of Human Milk Bioactives on Infants\u2019 Gut and Immune Health. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.604080"},{"key":"#cr-split#-ref_79.1","unstructured":"EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA), Turck, D., Castenmiller, J., De Henauw, S., Hirsch-Ernst, K.I., Kearney, J., Maciuk, A., Mangelsdorf, I., McArdle, H.J., and Naska, A. (2020). Safety of lacto-N-neotetraose (LNnT) produced by derivative strains of E. coli BL21 as a novel food pursuant to Regulation"},{"key":"#cr-split#-ref_79.2","unstructured":"(EU) 2015\/2283. EFSA J., 18, e06305."},{"key":"ref_80","first-page":"e08334","article-title":"Safety of the extension of use of 2\u2019-fucosyllactose (2\u2019-FL) as a novel food pursuant to Regulation (EU) 2015\/2283","volume":"21","author":"Turck","year":"2023","journal-title":"EFSA J."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1093\/nutrit\/nuac032","article-title":"A systematic review of iodine intake in children, adults, and pregnant women in Europe-comparison against dietary recommendations and evaluation of dietary iodine sources","volume":"80","author":"Bath","year":"2022","journal-title":"Nutr. Rev."},{"key":"ref_82","first-page":"133","article-title":"Admissible daily intake for glutamate","volume":"23","year":"2020","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_83","first-page":"8955E","article-title":"Preparatory work for the safety evaluation by EFSA of Human-identical Milk Oligosaccharides as Novel Foods","volume":"21","author":"Malih","year":"2024","journal-title":"EFSA Support. Publ."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"EFSA NDA Panel (2014). Scientific Opinion on the essential composition of infant and follow-on formulae. EFSA J., 12, 3760.","DOI":"10.2903\/j.efsa.2014.3760"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"EFSA NDA Panel, Turck, D., Bresson, J., Burlingame, B., Dean, T., Fairweather-Tait, S., Heinonen, M., Hirsch-Ernst, K.I., Mangelsdorf, I., and McArdle, H.J. (2017). Scientific and technical guidance for the preparation and presentation of an application for authorisation of an infant and\/or follow-on formula manufactured from protein hydrolysates. EFSA J., 15, 4779.","DOI":"10.2903\/j.efsa.2017.4779"},{"key":"ref_86","unstructured":"(2016). Commission Delegated Regulation (EU) 2016\/127 of 25 September 2015 Supplementing Regulation (EU) No 609\/2013 as Regards the Specific Compositional and Information Requirements for Infant Formula and Follow-On Formula. Off. J. Eur. Union, L25, 1\u201329. Available online: https:\/\/www.legislation.gov.uk\/eur\/2016\/127."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"EFSA Scientific Committee (2017). Guidance on the risk assessment of substances present in food intended for infants below 16 weeks of age. EFSA J., 15, e04849.","DOI":"10.2903\/j.efsa.2017.4849"},{"key":"ref_88","first-page":"8994E","article-title":"Scientific and technical assistance report on the evaluation of human-identical milk oligosaccharides (HiMOs) as novel foods","volume":"21","author":"Turck","year":"2024","journal-title":"EFSA Support. 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