perinatologyРоссийский вестник перинатологии и педиатрииRossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics)1027-40652500-2228Ltd. “The National Academy of Pediatric Science and Innovation”10.21508/1027-4065-2018-63-4-30-42perinatology-693Research ArticleОБЗОР ЛИТЕРАТУРЫREVIEWSРЕАКЦИЯ МАЙАРА – ВАЖНЫЙ ФАКТОР БЕЗОПАСНОСТИ И КАЧЕСТВА ДЕТСКОЙ АДАПТИРОВАННОЙ СМЕСИMAILLARD REACTIONS – AN IMPORTANT FACTOR OF THE SAFETY AND QUALITY OF INFANT FORMULAСкиданИ. Н.SkidanI. N.

к.м.н., руководитель научного отдела,

Мытищи, Московская область

Mytishchi, Moscow Region

ПроссерК.ProsserC.

рофессор, руководитель научного отдела,

18 Gallagher Drive, PO Box 1398 Hamilton 3240 New Zealand

Hamilton

ЗахароваИ. Н.ZakharovaI. N.

д.м.н., проф., зав. кафедрой педиатрии имени академика Г.Н. Сперанского,

125373 г. Москва, ул. Геpоев Панфиловцев, 28

Moscow

Компания «Бибиколь РУС»РоссияBibicall-RUS CompanyRussian FederationКомпания «Дэйри Гоат Кооператив Лтд»Новая ЗеландияDairy Goat Co-operative (N.Z.) LtdNew ZealandФГБОУ ДПО «Российская медицинская академия последипломного образования» РосздраваРоссияFederal State Budgetary Educational Institution of Additional Professional Education Russian Medical Academy of Continuous Post-Graduate Education of the Ministry of Health of RussiaRussian Federation2018100920186343042Copyright © Ltd. “The National Academy of Pediatric Science and Innovation”, 20182018Ltd. “The National Academy of Pediatric Science and Innovation”Ltd. “The National Academy of Pediatric Science and Innovation”https://www.ped-perinatology.ru/jour/about/submissions#copyrightNoticehttps://www.ped-perinatology.ru/jour/article/view/693

Физико-химические свойства детских адаптированных молочных смесей, влияющие на  их переносимость и  эффективность, зависят от состава и качества исходных ингредиентов, процесса производства, условий хранения и контроля качества готовой продукции. Технология изготовления детской сухой молочной смеси для искусственного вскармливания включает разнообразные приемы переработки компонентов, входящих в ее состав, в том числе молока-сырья. Это сопровождается заметным изменением ряда физических, химических и биологических свойств отдельных компонентов молока, их потерей, образованием принципиально новых химических соединений. К  наиболее частым реакциям, наблюдаемым при  тепловой обработке молока, относят образование связей между кетогруппами сахара с аминогруппами аминокислот с последующим возникновением большого количества низко- и высокомолекулярных (полимерных) соединений, так называемых продуктов реакции Майара (ПРМ). Вопрос изучения ПРМ в последние годы все больше привлекает внимание практикующих врачей из-за обнаружения этих соединений в составе детских смесей и их потенциальной опасности для здоровья детей. В настоящем обзоре приводятся доказательства того, что произведенные по оригинальной технологии детские сухие адаптированные смеси на основе цельного козьего молока с нативным соотношением основных групп молочных белков (20% – сывороточные белки и 80% – казеины) имеют минимальный потенциал нежелательных эффектов, связанных с ПРМ.

The physicochemical properties of infant adapted milk formulae that affect their tolerability and effectiveness depend on the composition and quality of the raw ingredients, the production process, the storage conditions and the quality control of the finished products. The technology of manufacturing a powdered infant formula includes a variety of methodsfor processing componentsthat make up its composition, including raw milk. This processing is accompanied by a noticeable change in a number of physical, chemical and biological properties of the individual components of milk, their loss, the formation of fundamentally new chemical compounds. The most frequent reactions observed during the heat treatment of milk include the formation of bonds between reactive carbonyl groups of the sugar and the amino groups of amino acids, followed by the appearance of a large number of low- and high-molecular compounds, the so-called Maillard Reaction Products(MRP). The study of MRP in recent years hasincreasingly attracted the attention of medical practitioners because of the discovery of these compounds in infant formula and their potential danger to children’s health. This review provides evidence that powdered infant adapted formulae produced with an original technology based on whole goat milk with a native ratio of the main groups of milk proteins(whey – 20% and casein – 80%) have a minimum potential for unwanted effects associated with MRP.

реакция Майаракарбоксиметил-лизиндетские сухие адаптированные смеси для искусственного питанияMaillard reactioncarboxymethyl-lysineinfant formulaReferencesJohn Mallett. Malt: A practical Guide from field to brewhouse. Brewers Publications, 2014; 300.John Mallett. Malt: A practical Guide from field to brewhouse. Brewers Publications, 2014; 300.Maillard L.C. Action des acides aminés sur les sucres: formation des mélanoïdines par voie méthodique. C R Hebd. Séances Acad. Sci. 1912; 154, 66–68.Maillard L.C. Action des acides aminés sur les sucres: formation des mélanoïdines par voie méthodique. C R Hebd. Séances Acad. Sci. 1912; 154, 66–68.Rahbar S., Blumenfeld O., Ranney H.M. Studies of an unusual hemoglobin in patients with diabetes mellitus. Biochem Biophys Res Commun 1969; 36:838–843.Rahbar S., Blumenfeld O., Ranney H.M. Studies of an unusual hemoglobin in patients with diabetes mellitus. Biochem Biophys Res Commun 1969; 36:838–843.Vistoli G., De Maddis D., Cipak A. et al. Advanced glycoxidation and lipoxidation end products (AGEs and ALEs): An overview of their mechanisms of formation. Free Radic Res 2013; 47:3–27. DOI: 10.3109/10715762.2013.815348.Vistoli G., De Maddis D., Cipak A. et al. Advanced glycoxidation and lipoxidation end products (AGEs and ALEs): An overview of their mechanisms of formation. Free Radic Res 2013; 47:3–27. DOI: 10.3109/10715762.2013.815348.Delgado-Andrade C., Fogliano V. Dietary advanced glycosylation end-products (dAGEs) and melanoidins formed through Maillard reaction: Physiological consequences of their intake. Annual Review of Food Science and Technology 2018; 9:271–91. DOI: 10.1146/annurev-food-030117-012441.Delgado-Andrade C., Fogliano V. Dietary advanced glycosylation end-products (dAGEs) and melanoidins formed through Maillard reaction: Physiological consequences of their intake. Annual Review of Food Science and Technology 2018; 9:271–91. DOI: 10.1146/annurev-food-030117-012441.Zhao M., Wang P., Li D. et al. Protection against neoformed contaminants (NFCs)-induced toxicity by phytochemicals. Food Chem Toxicol 2017; 108(Pt B):392–406. DOI: 10.1016/j.fct.2017.01.023.Zhao M., Wang P., Li D. et al. Protection against neoformed contaminants (NFCs)-induced toxicity by phytochemicals. Food Chem Toxicol 2017; 108(Pt B):392–406. DOI: 10.1016/j.fct.2017.01.023.Nguyen H.T., van der Fels-Klerx H.J., van Boekel M.A. N-ϵ- (carboxymethyl)lysine: A Review on analytical methods, formation, and occurrence in processed food, and health impact. Food Reviews International 2013; 30(1):36–52. DOI: 10.1080/87559129.2013.853774.Nguyen H.T., van der Fels-Klerx H.J., van Boekel M.A. N-ϵ- (carboxymethyl)lysine: A Review on analytical methods, formation, and occurrence in processed food, and health impact. Food Reviews International 2013; 30(1):36–52. DOI: 10.1080/87559129.2013.853774.Pischetsrieder M., Henle T. Glycation products in infant formulas: chemical, analytical and physiological aspects. Amino Acids 2012; 42:1111–118. DOI: 10.1007/s00726-010-0775-0.Pischetsrieder M., Henle T. Glycation products in infant formulas: chemical, analytical and physiological aspects. Amino Acids 2012; 42:1111–118. DOI: 10.1007/s00726-010-0775-0.Birlouez-Aragon I., Pischetsrieder M., Leclère J. et al. Assessment of protein glycation markers in infant formulas. Food Chem 2004; 87:253–259. DOI: 10.1016/j.foodchem.2003.11.019.Birlouez-Aragon I., Pischetsrieder M., Leclère J. et al. Assessment of protein glycation markers in infant formulas. Food Chem 2004; 87:253–259. DOI: 10.1016/j.foodchem.2003.11.019.Gonzales A.S., Naranjo G.B., Malec L.S. et al. Available lysine, protein digestibility and lactulose in commercial infant formulas. Int. Dairy J 2003; 13:95–99. DOI: 10.1016/S0958-6946(02)00173-5.Gonzales A.S., Naranjo G.B., Malec L.S. et al. Available lysine, protein digestibility and lactulose in commercial infant formulas. Int. Dairy J 2003; 13:95–99. DOI: 10.1016/S0958-6946(02)00173-5.Cardoso H.B., Wierenga P.A., Gruppen H. et al. Maillard induced glycation behaviour of individual milk proteins. Food Chem 2018; 252:311–317. DOI:10.1016/j.foodchem.2018.01.106.Cardoso H.B., Wierenga P.A., Gruppen H. et al. Maillard induced glycation behaviour of individual milk proteins. Food Chem 2018; 252:311–317. DOI:10.1016/j.foodchem.2018.01.106.Czerwenka C., Maier I., Pittner F., et al. Investigation of the lactosylation of whey proteins by liquid chromatographymass spectrometry. Journal of Agricultural and Food Chemistry 2006; 54(23):8874–882. DOI:10.1021/jf061646z.Czerwenka C., Maier I., Pittner F., et al. Investigation of the lactosylation of whey proteins by liquid chromatographymass spectrometry. Journal of Agricultural and Food Chemistry 2006; 54(23):8874–882. DOI:10.1021/jf061646z.Nacka F., Chobert J.M., Burova T., et al. Induction of new physicochemical and functional properties by the glycosylation of whey proteins. Journal of Protein Chemistry 1998; 17(5):495–503;Nacka F., Chobert J.M., Burova T., et al. Induction of new physicochemical and functional properties by the glycosylation of whey proteins. Journal of Protein Chemistry 1998; 17(5):495–503;Kwak E.J., Lim S.I. The effect of sugar, amino acid, metal ion, and NaCl on model Maillard reaction under pH control. Amino Acids 2004; 27:85–90. DOI:10.1007/s00726-004-0067-7.Kwak E.J., Lim S.I. The effect of sugar, amino acid, metal ion, and NaCl on model Maillard reaction under pH control. Amino Acids 2004; 27:85–90. DOI:10.1007/s00726-004-0067-7.Finot P.A., Deutsch R., Bujard E. The extent of the Maillard reaction during the processing of milk. Prog Food Nutr Sci 1981; 5:345–55.Finot P.A., Deutsch R., Bujard E. The extent of the Maillard reaction during the processing of milk. Prog Food Nutr Sci 1981; 5:345–55.Henle T., Walter H., Klostermeyer H. Evaluation of the extent of the early Maillard-reaction in milk products by direct measurement of the Amadori-product lactulosyllysine. Z Lebensm Unters Forsch 1991; 193:119–122.Henle T., Walter H., Klostermeyer H. Evaluation of the extent of the early Maillard-reaction in milk products by direct measurement of the Amadori-product lactulosyllysine. Z Lebensm Unters Forsch 1991; 193:119–122.Lund M.N., Ray C.A. Control of Maillard reactions in foods: Strategies and chemical mechanisms. J. Agric. Food Chem 2017; 65:4537–552. DOI: 10.1021/acs.jafc.7b00882.Lund M.N., Ray C.A. Control of Maillard reactions in foods: Strategies and chemical mechanisms. J. Agric. Food Chem 2017; 65:4537–552. DOI: 10.1021/acs.jafc.7b00882.Uribarri J. Dietary AGEs and their role in health and disease. CRC Press, 2017; 384.Uribarri J. Dietary AGEs and their role in health and disease. CRC Press, 2017; 384.Mericq V., Piccardo C., Cai W. et al. Maternally transmitted and food-derived glycotoxins: a factor preconditioning the young to diabetes? Diabetes Care 2010; 33:2232–237. DOI: 10.2337/dc10-1058.Mericq V., Piccardo C., Cai W. et al. Maternally transmitted and food-derived glycotoxins: a factor preconditioning the young to diabetes? Diabetes Care 2010; 33:2232–237. DOI: 10.2337/dc10-1058.Birlouez-Aragon I., Saavedra G., Tessier F.J. et al. A diet based on high-heat-treated foods promotes risk factors for diabetes mellitus and cardiovascular diseases. Am J Clin Nutr 2010; 91:1220–226. DOI: 10.3945/ajcn.2009.28737.Birlouez-Aragon I., Saavedra G., Tessier F.J. et al. A diet based on high-heat-treated foods promotes risk factors for diabetes mellitus and cardiovascular diseases. Am J Clin Nutr 2010; 91:1220–226. DOI: 10.3945/ajcn.2009.28737.Goh S.Y., Cooper M.E. Clinical review: The role of advanced glycation end- products in progression and complications of diabetes. J Clin Endocrinol Metab 2008; 93:1143–152. DOI: 10.1210/jc.2007-1817.Goh S.Y., Cooper M.E. Clinical review: The role of advanced glycation end- products in progression and complications of diabetes. J Clin Endocrinol Metab 2008; 93:1143–152. DOI: 10.1210/jc.2007-1817.Sandu O., Song K., Cai W. et al. Insulin resistance and type 2 diabetes in high-fat-fed mice are linked to high glycotoxin intake. Diabetes 2005; 54:2314–319.Sandu O., Song K., Cai W. et al. Insulin resistance and type 2 diabetes in high-fat-fed mice are linked to high glycotoxin intake. Diabetes 2005; 54:2314–319.Uribarri J., Cai W., Ramdas M. et al. Restriction of advanced glycation end products improves insulin resistance in human type 2 diabetes: potential role of AGER1 and SIRT1. Daibetes Care 2011; 34:1610–616. DOI: 10.2337/dc11-0091.Uribarri J., Cai W., Ramdas M. et al. Restriction of advanced glycation end products improves insulin resistance in human type 2 diabetes: potential role of AGER1 and SIRT1. Daibetes Care 2011; 34:1610–616. DOI: 10.2337/dc11-0091.Sun H., Yuan Y., Sun Z. Update on mechanisms of renal tubule injury caused by advanced glycation end-products. Biomed Res Int 2016; 5475120. DOI: 10.1155/2016/5475120.Sun H., Yuan Y., Sun Z. Update on mechanisms of renal tubule injury caused by advanced glycation end-products. Biomed Res Int 2016; 5475120. DOI: 10.1155/2016/5475120.Jensen L.J., Ostergaard J., Flyvbjerg A. AGE-RAGE and AGE cross-link interaction: important players in the pathogenesis of diabetic kidney disease. Horm Metab Res 2005; 37:26–34. DOI: 10.1055/s-2005-861360Jensen L.J., Ostergaard J., Flyvbjerg A. AGE-RAGE and AGE cross-link interaction: important players in the pathogenesis of diabetic kidney disease. Horm Metab Res 2005; 37:26–34. DOI: 10.1055/s-2005-861360Rai D.S., Choudhury D., Welbourne T.C. et al. Advanced glycation end- products: a nephrologist’s perspective. Am J Kidney Dis. 2000; 35:365–80. DOI: 10.1016/S0272-6386(00)70189-2.Rai D.S., Choudhury D., Welbourne T.C. et al. Advanced glycation end- products: a nephrologist’s perspective. Am J Kidney Dis. 2000; 35:365–80. DOI: 10.1016/S0272-6386(00)70189-2.Santos J.C., Valentim I.B., de Araújo O.R. et al. Development of nonalcoholic hepatopathy: contributions of oxidative stress and advanced glycation end products. Int J Mol Sci 2013; 14:19846–66. DOI: 10.3390/ijms141019846.Santos J.C., Valentim I.B., de Araújo O.R. et al. Development of nonalcoholic hepatopathy: contributions of oxidative stress and advanced glycation end products. Int J Mol Sci 2013; 14:19846–66. DOI: 10.3390/ijms141019846.Hyogo H., Yamagishi S., Iwamoto K. et al. Elevated levels of serum advanced glycation end products in patients with non-alcoholic steatohepatitis. J Gastroenterol Hepatol 2007; 22:1112–119. DOI: 10.1111/j.1440-1746.2007.04943.x.Hyogo H., Yamagishi S., Iwamoto K. et al. Elevated levels of serum advanced glycation end products in patients with non-alcoholic steatohepatitis. J Gastroenterol Hepatol 2007; 22:1112–119. DOI: 10.1111/j.1440-1746.2007.04943.x.Yağmur E., Tacke F., Weiss C. et al. Elevation of N-epsilon- (carboxymethyl)lysine-modified advanced glycation end products in chronic liver diseases an indicator of liver cirrhosis. Clin Biochem 2006; 39:39–45. DOI: 10.1016/j.clinbiochem.2005.07.016.Yağmur E., Tacke F., Weiss C. et al. Elevation of N-epsilon- (carboxymethyl)lysine-modified advanced glycation end products in chronic liver diseases an indicator of liver cirrhosis. Clin Biochem 2006; 39:39–45. DOI: 10.1016/j.clinbiochem.2005.07.016.Diamanti-Kandarakis E., Piperi C., Kalofoutis A. et al. Increased levels of serum advanced glycation end-products in women with polycystic ovary syndrome. Clin Endocrinol 2005; 62:37–43. DOI: 10.1016/j.clinbiochem.2005.07.016.Diamanti-Kandarakis E., Piperi C., Kalofoutis A. et al. Increased levels of serum advanced glycation end-products in women with polycystic ovary syndrome. Clin Endocrinol 2005; 62:37–43. DOI: 10.1016/j.clinbiochem.2005.07.016.Diamanti-Kandarakis E., Piperi C., Patsouris E. et al. Immunohistochemical localization of advanced glycation end-products (AGEs) and their receptor (RAGE) in polycystic and normal ovaries. Histochem Cell Biol 2007; 127:581–9. DOI: 10.1007/s00418-006-0265-3.Diamanti-Kandarakis E., Piperi C., Patsouris E. et al. Immunohistochemical localization of advanced glycation end-products (AGEs) and their receptor (RAGE) in polycystic and normal ovaries. Histochem Cell Biol 2007; 127:581–9. DOI: 10.1007/s00418-006-0265-3.Kandarakis S.A., Piperi C., Topouzis F. et al. Emerging role of advanced glycation-end products (AGEs) in the pathobiology of eye diseases. Prog Ret Eye Res 2014; 42:85–102. DOI: 10.1016/j.preteyeres.2014.05.002.Kandarakis S.A., Piperi C., Topouzis F. et al. Emerging role of advanced glycation-end products (AGEs) in the pathobiology of eye diseases. Prog Ret Eye Res 2014; 42:85–102. DOI: 10.1016/j.preteyeres.2014.05.002.Kandarakis S.A., Piperi C., Moschonas DP et al. Dietary glycotoxins induce RAGE and VEGF up-regulation in the retina of normal rats. Exp Eye Res. 2015; 137:1–10. DOI: 10.1016/j.exer.2015.05.017.Kandarakis S.A., Piperi C., Moschonas DP et al. Dietary glycotoxins induce RAGE and VEGF up-regulation in the retina of normal rats. Exp Eye Res. 2015; 137:1–10. DOI: 10.1016/j.exer.2015.05.017.Sharaf H., Matou-Nasri S., Wang Q. et al. Advanced glycation end-products increase proliferation, migration and invasion of the breast cancer cell line MDA-MB-231. Biochim Biophys. Acta 2015; 1852:429–41. DOI: 10.1016/j.bbadis.2014.12.009.Sharaf H., Matou-Nasri S., Wang Q. et al. Advanced glycation end-products increase proliferation, migration and invasion of the breast cancer cell line MDA-MB-231. Biochim Biophys. Acta 2015; 1852:429–41. DOI: 10.1016/j.bbadis.2014.12.009.Van Heijst J.W., Niessen H.W., Hoekmann K. et al. Advanced glycation end- products in human cancer tissues: detection of Nepsilon-(carboxymethyl) lysine and argpyrimidine. Ann N Y Acad Sci. 2005, 1043:725–-33; DOI: 10.1196/annals.1333.084Van Heijst J.W., Niessen H.W., Hoekmann K. et al. Advanced glycation end- products in human cancer tissues: detection of Nepsilon-(carboxymethyl) lysine and argpyrimidine. Ann N Y Acad Sci. 2005, 1043:725–-33; DOI: 10.1196/annals.1333.084Jiao L., Weinstein S.J., Albanes D. et al. Evidence that serum levels of the soluble receptor for advanced glycation end-products are inversely associated with pancreatic cancer risk: a prospective study. Cancer Res 2011; 71:3582–589. DOI: 10.1158/0008-5472.CAN-10-2573.Jiao L., Weinstein S.J., Albanes D. et al. Evidence that serum levels of the soluble receptor for advanced glycation end-products are inversely associated with pancreatic cancer risk: a prospective study. Cancer Res 2011; 71:3582–589. DOI: 10.1158/0008-5472.CAN-10-2573.Luevano-Contreras C., Chapman-Novakofski K. Dietary advanced glycation end-products and aging. Nutrients 2010; 2:1247–265. DOI: 10.3390/nu2121247.Luevano-Contreras C., Chapman-Novakofski K. Dietary advanced glycation end-products and aging. Nutrients 2010; 2:1247–265. DOI: 10.3390/nu2121247.Firmin S., Elmhiri G., Crepin D., et al. Formula derived Maillard reaction products in post-weaning intrauterine growthrestricted piglets induce developmental programming of hepatic oxidative stress independently of microRNA-21 and microRNA-155. J Dev Orig Health Dis 2018; 9:1–7. DOI: 10.1017/S2040174417001015.Firmin S., Elmhiri G., Crepin D., et al. Formula derived Maillard reaction products in post-weaning intrauterine growthrestricted piglets induce developmental programming of hepatic oxidative stress independently of microRNA-21 and microRNA-155. J Dev Orig Health Dis 2018; 9:1–7. DOI: 10.1017/S2040174417001015.Holik A.K., Lieder B., Kretschy N., et al. N(ϵ)–Carboxymethyl-lysine increases the expression of miR-103/143 and enhances lipid accumulation in 3T3-L1 Cells. J Cell Biochem 2016; 117(10):2413–22. DOI: 10.1002/jcb.25576.Holik A.K., Lieder B., Kretschy N., et al. N(ϵ)–Carboxymethyl-lysine increases the expression of miR-103/143 and enhances lipid accumulation in 3T3-L1 Cells. J Cell Biochem 2016; 117(10):2413–22. DOI: 10.1002/jcb.25576.Ramasamy R., Vannucci S.J., Yan S.S.D. et al. Advanced glycation end-products and RAGE: a common thread in aging, diabetes, neurodegeneration, and inflammation. Glycobiology 2005; 15:16–28. DOI: 10.1093/glycob/cwi053.Ramasamy R., Vannucci S.J., Yan S.S.D. et al. Advanced glycation end-products and RAGE: a common thread in aging, diabetes, neurodegeneration, and inflammation. Glycobiology 2005; 15:16–28. DOI: 10.1093/glycob/cwi053.Hilmenyuk T., Bellinghausen I., Heydenreich B., et al. Effects of glycation of the model food allergen ovalbumin on antigen uptake and presentation by human dendritic cells. Immunology 2010; 129(3):437–45. DOI: 10.1111/j.1365-2567.2009.03199.x.Hilmenyuk T., Bellinghausen I., Heydenreich B., et al. Effects of glycation of the model food allergen ovalbumin on antigen uptake and presentation by human dendritic cells. Immunology 2010; 129(3):437–45. DOI: 10.1111/j.1365-2567.2009.03199.x.Ilchmann A., Burgdorf S., Scheurer S., et al. Glycation of a food allergen by the Maillard reaction enhances its T-cell immunogenicity: Role of macrophage scavenger receptor class A type I and II. J Allergy Clin Immunol 2010; 125(1):175– 83. DOI: 10.1016/j.jaci.2009.08.013.Ilchmann A., Burgdorf S., Scheurer S., et al. Glycation of a food allergen by the Maillard reaction enhances its T-cell immunogenicity: Role of macrophage scavenger receptor class A type I and II. J Allergy Clin Immunol 2010; 125(1):175– 83. DOI: 10.1016/j.jaci.2009.08.013.Baskara I., Niquet-Leridon C., Anton P.M. et al. Neoformed compounds from the Maillard reaction in infant formulas: a new risk factor for allergy? EMJ Allergy Immunol 2017; 2(1):87-93.Baskara I., Niquet-Leridon C., Anton P.M. et al. Neoformed compounds from the Maillard reaction in infant formulas: a new risk factor for allergy? EMJ Allergy Immunol 2017; 2(1):87-93.Ullah M.A., Loh Z., Gan W.J. et al. Receptor for advanced glycation end- products and its ligand high-mobility group box-1 mediate allergic airway sensitization and airway in flammation. J Allergy Clin Immunol 2014; 134: 440–50. DOI: 10.1016/j.jaci.2013.12.1035.Ullah M.A., Loh Z., Gan W.J. et al. Receptor for advanced glycation end- products and its ligand high-mobility group box-1 mediate allergic airway sensitization and airway in flammation. J Allergy Clin Immunol 2014; 134: 440–50. DOI: 10.1016/j.jaci.2013.12.1035.Milutinovic P.S., Alcorn J.F., Englert J.M. et al. The receptor for advanced glycation end-products is a central mediator of asthma pathogenesis. Am J Pathol 2012; 181:1215–225. DOI: 10.1016/j.ajpath.2012.06.031.Milutinovic P.S., Alcorn J.F., Englert J.M. et al. The receptor for advanced glycation end-products is a central mediator of asthma pathogenesis. Am J Pathol 2012; 181:1215–225. DOI: 10.1016/j.ajpath.2012.06.031.Oczypok E.A., Milutinovic P.S., Alcorn J.F. et al. Pulmonary receptor for advanced glycation end-products promotes asthma pathogenesis through IL-33 and accumulation of group 2 innate lymphoid cells. J Allergy Clin Immunol 2015; 136:747–564. DOI: 10.1016/j.jaci.2015.03.011.Oczypok E.A., Milutinovic P.S., Alcorn J.F. et al. Pulmonary receptor for advanced glycation end-products promotes asthma pathogenesis through IL-33 and accumulation of group 2 innate lymphoid cells. J Allergy Clin Immunol 2015; 136:747–564. DOI: 10.1016/j.jaci.2015.03.011.Kierdorf K., Fritz G. RAGE regulation and signaling in inflammation and beyond. J Leukoc Biol 2013; 94(1):55–68. DOI: 10.1189/jlb.1012519.Kierdorf K., Fritz G. RAGE regulation and signaling in inflammation and beyond. J Leukoc Biol 2013; 94(1):55–68. DOI: 10.1189/jlb.1012519.Skovgaard D., Svensson R.B., Scheijen J., et al. An advanced glycation endproduct (AGE)-rich diet promotes accumulation of AGEs in Achilles tendon. Physiol Rep 2017; 5(6):e13215. DOI: 10.14814/phy2.13215.Skovgaard D., Svensson R.B., Scheijen J., et al. An advanced glycation endproduct (AGE)-rich diet promotes accumulation of AGEs in Achilles tendon. Physiol Rep 2017; 5(6):e13215. DOI: 10.14814/phy2.13215.Egawa T., Tsuda S., Goto A., et al. Potential involvement of dietary advanced glycation end products in impairment of skeletal muscle growth and muscle contractile function in mice. Br J Nutr 2017; 117(1):21–29. DOI: 10.1017/S0007114516004591.Egawa T., Tsuda S., Goto A., et al. Potential involvement of dietary advanced glycation end products in impairment of skeletal muscle growth and muscle contractile function in mice. Br J Nutr 2017; 117(1):21–29. DOI: 10.1017/S0007114516004591.Kutlu T. Dietary glycotoxins and infant formulas. Turk Pediatri Ars 2016; 51: 179–85. DOI: 10.5152/TurkPediatriArs.2016.2543.Kutlu T. Dietary glycotoxins and infant formulas. Turk Pediatri Ars 2016; 51: 179–85. DOI: 10.5152/TurkPediatriArs.2016.2543.Moscovici A.M., Joubran Y., Briard-Bion V., et al. The impact of the Maillard reaction on the in vitro proteolytic breakdown of bovine lactoferrin in adults and infants. Food Funct 2014; 5(8):1898–908. DOI: 10.1039/c4fo00248b.Moscovici A.M., Joubran Y., Briard-Bion V., et al. The impact of the Maillard reaction on the in vitro proteolytic breakdown of bovine lactoferrin in adults and infants. Food Funct 2014; 5(8):1898–908. DOI: 10.1039/c4fo00248b.O’Brien J., Morrissey P.A. Nutritional and toxicological aspects of the Maillard browning reaction in foods. Crit. Rev. Food Sci. Nutr 1989; 28:211–48. DOI: 10.1080/10408398909527499.O’Brien J., Morrissey P.A. Nutritional and toxicological aspects of the Maillard browning reaction in foods. Crit. Rev. Food Sci. Nutr 1989; 28:211–48. DOI: 10.1080/10408398909527499.Lee K.-G., Shibamoto T. Toxicology and antioxidant activities of non-enzymatic browning reaction products: review. Food Rev. Int 2002; 18:151–75. DOI: 10.1081/FRI-120014356Lee K.-G., Shibamoto T. Toxicology and antioxidant activities of non-enzymatic browning reaction products: review. Food Rev. Int 2002; 18:151–75. DOI: 10.1081/FRI-120014356Liu X., Zheng L., Zhang R., et al. Toxicological evaluation of advanced glycation end product Nε-(carboxymethyl)lysine: Acute and subacute oral toxicity studies. Regul Toxicol Pharmacol 2016; 77:65–74. DOI: 10.1016/j.yrtph.2016.02.013.Liu X., Zheng L., Zhang R., et al. Toxicological evaluation of advanced glycation end product Nε-(carboxymethyl)lysine: Acute and subacute oral toxicity studies. Regul Toxicol Pharmacol 2016; 77:65–74. DOI: 10.1016/j.yrtph.2016.02.013.Koschinsky T., He C.J., Mitsuhashi T. et al. Orally absorbed reactive glycation products (glycotoxins): an environmental risk factor in diabetic nephropathy. Proc Natl Acad Sci USA 1997; 94:6474–479.Koschinsky T., He C.J., Mitsuhashi T. et al. Orally absorbed reactive glycation products (glycotoxins): an environmental risk factor in diabetic nephropathy. Proc Natl Acad Sci USA 1997; 94:6474–479.Foerster A., Kuhne Y., Henle T. Studies on absorption and elimination of dietary Maillard reaction products. Ann N Y Acad Sci 2005; 1043:474–481. DOI:10.1196/annals.1333.054.Foerster A., Kuhne Y., Henle T. Studies on absorption and elimination of dietary Maillard reaction products. Ann N Y Acad Sci 2005; 1043:474–481. DOI:10.1196/annals.1333.054.Cerami C., Founds H., Nicholl I. et al. Tobacco smoke is a source of toxic reactive glycation products. Proc. Natl. Acad. Sci. USA 1997; 94:13915–13920.Cerami C., Founds H., Nicholl I. et al. Tobacco smoke is a source of toxic reactive glycation products. Proc. Natl. Acad. Sci. USA 1997; 94:13915–13920.Korbet S.M., Makita Z., Firanek C.A. et al. Advanced glycosylation end- products in continuous ambulatory peritoneal dialysis patients. Am J Kidney Dis 1993; 22(4):588–91.Korbet S.M., Makita Z., Firanek C.A. et al. Advanced glycosylation end- products in continuous ambulatory peritoneal dialysis patients. Am J Kidney Dis 1993; 22(4):588–91.Makita Z., Radoff S., Rayfield E.J. et al. Advanced glycosylation end- products in patients with diabetic nephropathy. N Engl J Med 1991; 325(12):836–42. DOI: 10.1056/NEJM199109193251202.Makita Z., Radoff S., Rayfield E.J. et al. Advanced glycosylation end- products in patients with diabetic nephropathy. N Engl J Med 1991; 325(12):836–42. DOI: 10.1056/NEJM199109193251202.Makita Z., Bucala R., Rayfield E.J. et al. Reactive glycosylation end-products in diabetic uraemia and treatment of renal failure. Lancet 1994; 343(8912):1519–522. DOI: 10.1016/S0140-6736(94)92935-1.Makita Z., Bucala R., Rayfield E.J. et al. Reactive glycosylation end-products in diabetic uraemia and treatment of renal failure. Lancet 1994; 343(8912):1519–522. DOI: 10.1016/S0140-6736(94)92935-1.Qu W., Yuan X., Zhao J., et al. Dietary advanced glycation end-products modify gut microbial composition and partially increase colon permeability in rats. Mol Nutr Food Res 2017; 61(10). DOI: 10.1002/mnfr.201700118.Qu W., Yuan X., Zhao J., et al. Dietary advanced glycation end-products modify gut microbial composition and partially increase colon permeability in rats. Mol Nutr Food Res 2017; 61(10). DOI: 10.1002/mnfr.201700118.Seiquer I., Rubio L.A., Peinado M.J., et al. Maillard reaction products modulate gut microbiota composition in adolescents. Mol Nutr Food Res 2014; 58(7):1552–560. DOI: 10.1002/mnfr.201300847.Seiquer I., Rubio L.A., Peinado M.J., et al. Maillard reaction products modulate gut microbiota composition in adolescents. Mol Nutr Food Res 2014; 58(7):1552–560. DOI: 10.1002/mnfr.201300847.Tuohy K.M., Hinton D.J., Davies S.J., et al. Metabolism of Maillard reaction products by the human gut microbiota-implications for health. Mol Nutr Food Res 2006; 50(9):847–57. DOI: 10.1002/mnfr.200500126.Tuohy K.M., Hinton D.J., Davies S.J., et al. Metabolism of Maillard reaction products by the human gut microbiota-implications for health. Mol Nutr Food Res 2006; 50(9):847–57. DOI: 10.1002/mnfr.200500126.Wiame E., Delpierre G., Collard F. et al. Identification of a pathway for the utilization of the Amadori product fructoselysine in Escherichia coli. J Biol Chem 2002; 277(45):42523–9. DOI: 10.1074/jbc.M200863200.Wiame E., Delpierre G., Collard F. et al. Identification of a pathway for the utilization of the Amadori product fructoselysine in Escherichia coli. J Biol Chem 2002; 277(45):42523–9. DOI: 10.1074/jbc.M200863200.Borrelli R.C., Fogliano V. Bread crust melanoidins as potential prebiotic ingredients. Mol Nutr Food Res 2005; 49(7):673–8. DOI:10.1002/mnfr.200500011Borrelli R.C., Fogliano V. Bread crust melanoidins as potential prebiotic ingredients. Mol Nutr Food Res 2005; 49(7):673–8. DOI:10.1002/mnfr.200500011Alamir I., Niquet-Leridon C., Jacolot P. et al. Digestibility of extruded proteins and metabolic transit of Ne-carboxymethyllysine in rats. Amino Acids 2013; 44 (6):1441–449. DOI: 10.1007/s00726-012-1427-3.Alamir I., Niquet-Leridon C., Jacolot P. et al. Digestibility of extruded proteins and metabolic transit of Ne-carboxymethyllysine in rats. Amino Acids 2013; 44 (6):1441–449. DOI: 10.1007/s00726-012-1427-3.Hellwig M., Bunzel, D., Huch M. et al. Stability of individual Maillard reaction products in the presence of the human colonic microbiota. J. Agric. Food Chem 2015; 63:6723–730. DOI: 10.1021/acs.jafc.5b01391.Hellwig M., Bunzel, D., Huch M. et al. Stability of individual Maillard reaction products in the presence of the human colonic microbiota. J. Agric. Food Chem 2015; 63:6723–730. DOI: 10.1021/acs.jafc.5b01391.Dittrich R., Hoffmann I., Stahl P. et al. Concentrations of Nepsilon-carboxymethyllysine in human breast milk, infant formulas, and urine of infants. J Agric Food Chem 2006; 54(18):6924–928. DOI:10.1021/jf060905h.Dittrich R., Hoffmann I., Stahl P. et al. Concentrations of Nepsilon-carboxymethyllysine in human breast milk, infant formulas, and urine of infants. J Agric Food Chem 2006; 54(18):6924–928. DOI:10.1021/jf060905h.Tareke E., Forslund A., Lindh C.H. et al. Isotope dilution ESI-LC-MS/MS for quantification of free and total Nε-(1-Carboxymethyl)-l-Lysine and free Nε-(1- Carboxyethyl)-l-Lysine: Comparison of total Nε-(1- Carboxymethyl)-l-Lysine levels measured with new method to ELISA assay in gruel samples. Food Chemistry 2013; 141(4):4253–259. DOI: 10.1016/j.foodchem.2013.07.003.Tareke E., Forslund A., Lindh C.H. et al. Isotope dilution ESI-LC-MS/MS for quantification of free and total Nε-(1-Carboxymethyl)-l-Lysine and free Nε-(1- Carboxyethyl)-l-Lysine: Comparison of total Nε-(1- Carboxymethyl)-l-Lysine levels measured with new method to ELISA assay in gruel samples. Food Chemistry 2013; 141(4):4253–259. DOI: 10.1016/j.foodchem.2013.07.003.Chávez-Servín J.L., de la Torre Carbot K., García-Gasca T., et al. Content and evolution of potential furfural compounds in commercial milk-based infant formula powder after opening the packet. Food Chem 2015; 166:486–91. DOI: 10.1016/j.foodchem.2014.06.050.Chávez-Servín J.L., de la Torre Carbot K., García-Gasca T., et al. Content and evolution of potential furfural compounds in commercial milk-based infant formula powder after opening the packet. Food Chem 2015; 166:486–91. DOI: 10.1016/j.foodchem.2014.06.050.Šebeková K., Saavedra G., Zumpe C. et al. Plasma Concentration and Urinary Excretion of Nɛ‐(Carboxymethyl) lysine in Breast Milk–and Formula‐fed Infants. Annals of the New York Academy of Sciences 2008; 1126(1):177–180. DOI: 10.1196/annals.1433.049.Šebeková K., Saavedra G., Zumpe C. et al. Plasma Concentration and Urinary Excretion of Nɛ‐(Carboxymethyl) lysine in Breast Milk–and Formula‐fed Infants. Annals of the New York Academy of Sciences 2008; 1126(1):177–180. DOI: 10.1196/annals.1433.049.Delatour T., Hegele J., Parisod V. et al. Analysis of advanced glycation endproducts in dairy products by isotope dilution liquid chromatography–electrospray tandem mass spectrometry. The particular case of carboxymethyllysine. Journal of Chromatography A 2009; 1216(12):2371–381. DOI: 10.1016/j.chroma.2009.01.011.Delatour T., Hegele J., Parisod V. et al. Analysis of advanced glycation endproducts in dairy products by isotope dilution liquid chromatography–electrospray tandem mass spectrometry. The particular case of carboxymethyllysine. Journal of Chromatography A 2009; 1216(12):2371–381. DOI: 10.1016/j.chroma.2009.01.011.Birlouez-Aragon I., De Saint Louvent E., Stahl P. et al. Protein hydrolysis of infant formulas strongly activates the Maillard reaction. J. Pediatr. Gastr. Nutr 2004; 39:141–45.Birlouez-Aragon I., De Saint Louvent E., Stahl P. et al. Protein hydrolysis of infant formulas strongly activates the Maillard reaction. J. Pediatr. Gastr. Nutr 2004; 39:141–45.Leclère J., Birlouez-Aragon I., Meli M. Fortification of milk with iron-ascorbate promotes lysine glycation and tryptophan oxidation. Food Chem 2002; 76:491–99. DOI: 10.1016/S0308-8146(01)00369-7.90Leclère J., Birlouez-Aragon I., Meli M. Fortification of milk with iron-ascorbate promotes lysine glycation and tryptophan oxidation. Food Chem 2002; 76:491–99. DOI: 10.1016/S0308-8146(01)00369-7.90Roux S., Courel M., Ait-Ameur L. et al. Kinetics of Maillard reactions in model infant formula during UHT treatment using a static batch ohmic heater. Dairy science & technology 2009; 89(3-4):349–362. DOI: 10.1051/dst/2009015.Roux S., Courel M., Ait-Ameur L. et al. Kinetics of Maillard reactions in model infant formula during UHT treatment using a static batch ohmic heater. Dairy science & technology 2009; 89(3-4):349–362. DOI: 10.1051/dst/2009015.Contreras-Calderon J., Guerra-Hernandez E., Garcia-Villanova B. Indicators of non-enzymatic browning in the evaluation of heat damage of ingredient proteins used in manufactured infant formulas. Eur Food Res Technol 2008; 227:117–24. DOI: 10.1007/s00217-007.Contreras-Calderon J., Guerra-Hernandez E., Garcia-Villanova B. Indicators of non-enzymatic browning in the evaluation of heat damage of ingredient proteins used in manufactured infant formulas. Eur Food Res Technol 2008; 227:117–24. DOI: 10.1007/s00217-007.Rutherfurd S., Darragh A.J., Hendriks W.H. et al. True Ileal Amino Acid Digestibility of Goat and Cow Milk Infant Formulas. Journal of Dairy Science 2006; 89(7):2408-413. DOI: 10.3168/jds.S0022-0302(06)72313-X.Rutherfurd S., Darragh A.J., Hendriks W.H. et al. True Ileal Amino Acid Digestibility of Goat and Cow Milk Infant Formulas. Journal of Dairy Science 2006; 89(7):2408-413. DOI: 10.3168/jds.S0022-0302(06)72313-X.Martysiak-Żurowska D., Stołyhwo A. Content of furosine in infant formulae and follow-on formulae. Pol. J. Food Nutr. Sci 2007; 57(2):185–90.Martysiak-Żurowska D., Stołyhwo A. Content of furosine in infant formulae and follow-on formulae. Pol. J. Food Nutr. Sci 2007; 57(2):185–90.Скидан И.Н., Пырьева Е.А., Конь И.Я. Белки грудного молока как целевой ориентир для совершенствования рецептур детских адаптированных молочных смесей. Вопросы Питания 2017; 86 (4):130–142. [Skidan I.N., Pyr’eva E.A., Kon’ I.Ya. Breast milk proteins as a focus for the improvement of recipes for infant adapted milk formulae. Voprosy pitaniia. 2017; 86 (4): 130–42. (in Russ)].Скидан И.Н., Пырьева Е.А., Конь И.Я. Белки грудного молока как целевой ориентир для совершенствования рецептур детских адаптированных молочных смесей. Вопросы Питания 2017; 86 (4):130–142. [Skidan I.N., Pyr’eva E.A., Kon’ I.Ya. Breast milk proteins as a focus for the improvement of recipes for infant adapted milk formulae. Voprosy pitaniia. 2017; 86 (4): 130–42. (in Russ)].Скидан И.Н., Пырьева Е.А., Конь И.Я. Развитие индустрии смесей заменителей грудного молока. Вопросы Питания 2017; 86(5):91–98. [Skidan I.N., Pyr’eva E.A., Kon’ I.Ya. Development of the infant formula industry. Voprosy pitaniia. 2017; 86 (5):91–-98. (in Russ)].Скидан И.Н., Пырьева Е.А., Конь И.Я. Развитие индустрии смесей заменителей грудного молока. Вопросы Питания 2017; 86(5):91–98. [Skidan I.N., Pyr’eva E.A., Kon’ I.Ya. Development of the infant formula industry. Voprosy pitaniia. 2017; 86 (5):91–-98. (in Russ)].Zhou S.J., Sullivan T., Gibson R.A. et al. Nutritional adequacy of goat milk infant formulas for term infants: a double-blind randomised controlled trial. Br. J. Nutr 2014; 111:1641–651. DOI: 10.1017/S0007114513004212.Zhou S.J., Sullivan T., Gibson R.A. et al. Nutritional adequacy of goat milk infant formulas for term infants: a double-blind randomised controlled trial. Br. J. Nutr 2014; 111:1641–651. DOI: 10.1017/S0007114513004212.Prosser C., Carpenter E., Hodgkinson A. Advanced Glycation End-products in formula. JPGN 2017; 64(1):836.Prosser C., Carpenter E., Hodgkinson A. Advanced Glycation End-products in formula. JPGN 2017; 64(1):836.Joubran Y., Moscovici A., Portmann R. et al. Implications of the Maillard reaction on bovine alpha-lactalbumin and its proteolysis during in vitro infant digestion. Food & Function 2017; 8(6):2295-2308. DOI: 10.1039/c7fo00588a.Joubran Y., Moscovici A., Portmann R. et al. Implications of the Maillard reaction on bovine alpha-lactalbumin and its proteolysis during in vitro infant digestion. Food & Function 2017; 8(6):2295-2308. DOI: 10.1039/c7fo00588a.Zhao D., Li L., Le T.T. et al. Digestibility of Glyoxal-Glycated β-Casein and β-Lactoglobulin and Distribution of PeptideBound Advanced Glycation End Products in Gastrointestinal Digests. Journal of Agricultural and Food Chemistry 2017; 65(28):5778-5788. DOI: 10.1021/acs.jafc.7b01951.Zhao D., Li L., Le T.T. et al. Digestibility of Glyoxal-Glycated β-Casein and β-Lactoglobulin and Distribution of PeptideBound Advanced Glycation End Products in Gastrointestinal Digests. Journal of Agricultural and Food Chemistry 2017; 65(28):5778-5788. DOI: 10.1021/acs.jafc.7b01951.Qu W., Yuan X., Zhao J., et al. Dietary advanced glycation end products modify gut microbial composition and partially increase colon permeability in rats. Mol Nutr 2017; 61(10). DOI: 10.1002/mnfr.201700118.Qu W., Yuan X., Zhao J., et al. Dietary advanced glycation end products modify gut microbial composition and partially increase colon permeability in rats. Mol Nutr 2017; 61(10). DOI: 10.1002/mnfr.201700118.Seiquer I., Rubio L.A., Peinado M.J. et al. Maillard reaction products modulate gut microbiota composition in adolescents. Molecular Nutrition & Food Research 2014; 58(7):1552-1560. DOI: 10.1002/mnfr.201300847.Seiquer I., Rubio L.A., Peinado M.J. et al. Maillard reaction products modulate gut microbiota composition in adolescents. Molecular Nutrition & Food Research 2014; 58(7):1552-1560. DOI: 10.1002/mnfr.201300847.Klenovics K.S., Boor P., Somoza V. et al. Advanced glycation end-products in infant formulas do not contribute to insulin resistance associated with their consumption. PLoS ONE 2013; 8(1): e53056. DOI: 10.1371/journal.pone.0053056.Klenovics K.S., Boor P., Somoza V. et al. Advanced glycation end-products in infant formulas do not contribute to insulin resistance associated with their consumption. PLoS ONE 2013; 8(1): e53056. DOI: 10.1371/journal.pone.0053056.Teodorowicz M., Van Neerven J., Savelkoul H. Food processing: The influence of the Maillard Reaction on immunogenicity and allergenicity of food proteins. Nutrients; 2017; 9(8):835. DOI: 10.3390/nu9080835.Teodorowicz M., Van Neerven J., Savelkoul H. Food processing: The influence of the Maillard Reaction on immunogenicity and allergenicity of food proteins. Nutrients; 2017; 9(8):835. DOI: 10.3390/nu9080835.Smith P.K., Masilamani M., Li X.-M., Sampson H.A. The false alarm hypothesis: Food allergy is associated with high dietary advanced glycation end-products and proglycating dietary sugars that mimic alarmins. Journal of Allergy and Clinical Immunologyю 2017; 139(2):429-37. DOI: 10.1016/j.jaci.2016.05.040.Smith P.K., Masilamani M., Li X.-M., Sampson H.A. The false alarm hypothesis: Food allergy is associated with high dietary advanced glycation end-products and proglycating dietary sugars that mimic alarmins. Journal of Allergy and Clinical Immunologyю 2017; 139(2):429-37. DOI: 10.1016/j.jaci.2016.05.040.Contreras-Calderón J., Guerra-Hernández E., García-Villanova B. et al. Effect of ingredients on non-enzymatic browning, nutritional value and furanic compounds in Spanish infant formulas. Journal of Food and Nutrition Research 2017; 5(4):243–252. DOI:10.12691/jfnr-5-4-6.Contreras-Calderón J., Guerra-Hernández E., García-Villanova B. et al. Effect of ingredients on non-enzymatic browning, nutritional value and furanic compounds in Spanish infant formulas. Journal of Food and Nutrition Research 2017; 5(4):243–252. DOI:10.12691/jfnr-5-4-6.

The authors declare that there are no conflicts of interest present.