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Health effects of dietary Maillard reaction products: the results of ICARE and other studies

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Abstract

In food science the Maillard reaction is well known to cause degradation of amino acids and an overall decrease in the nutritional value of foods that have been subjected to heat in processing. There has been evidence more recently of the endogenous formation of some Maillard reaction products (MRPs) in biological systems and their association with pathophysiological conditions including diabetes, renal disease and cardiovascular disease. Several studies have suggested that dietary MRPs increase the in vivo pool of MRPs after intestinal absorption and contribute to the development of diabetes and related complications. This review focuses on the animal and human studies which have assessed the eventual implications of dietary MRPs on human health, highlighting the different diets tested, the experimental designs and the biomarkers selected to estimate the health effects. The results of these studies are compared to those of the recently published ICARE study. In this latter study an accurate determination of the MRP content of the diets was achieved, allowing the calculation of the contribution of individual food groups to daily MRP intakes in a regular western diet.

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References

  • Agalou S, Ahmed N, Babaei-Jadidi R, Dawnay A, Thornalley PJ (2005) Profound mishandling of protein glycation degradation products in uremia and dialysis. J Am Soc Nephrol 16:1471–1485

    Article  PubMed  CAS  Google Scholar 

  • Ahmed MU, Thorpe SR, Baynes JW (1986) Identification of N epsilon-carboxymethyllysine as a degradation product of fructoselysine in glycated protein. J Biol Chem 261:4889–4894

    PubMed  CAS  Google Scholar 

  • Ahmed N, Thornalley PJ, Luthen R, Haussinger D, Sebekova K, Schinzel R, Voelker W, Heidland A (2004) Processing of protein glycation, oxidation and nitrosation adducts in the liver and the effect of cirrhosis. J Hepatol 41:913–919

    Article  PubMed  CAS  Google Scholar 

  • Ahmed N, Mirshekar-Syahkal B, Kennish L, Karachalias N, Babaei-Jadidi R, Thornalley PJ (2005) Assay of advanced glycation endproducts in selected beverages and food by liquid chromatography with tandem mass spectrometric detection. Mol Nutr Food Res 49:691–699

    Article  PubMed  CAS  Google Scholar 

  • Assar SH, Moloney C, Lima M, Magee R, Ames JM (2009) Determination of Nepsilon-(carboxymethyl)lysine in food systems by ultra performance liquid chromatography-mass spectrometry. Amino Acids 36:317–326

    Article  PubMed  CAS  Google Scholar 

  • Bergmann R, Helling R, Heichert C, Scheunemann M, Mäding P, Wittrisch H, Johannsen B, Henle T (2001) Radio fluorination and positron emission tomography (PET) as a new approach to study the in vivo distribution and elimination of the advanced glycation endproducts N epsilon-carboxymethyllysine (CML) and N epsilon-carboxyethyllysine (CEL). Nahrung 45:182–188

    Article  PubMed  CAS  Google Scholar 

  • Birlouez-Aragon I, Morales F, Fogliano V, Pain J-P (2010a) The health and technological implications of a better control of neoformed contaminants by the food industry. Path Biol 58:232–238

    Article  CAS  Google Scholar 

  • Birlouez-Aragon I, Saavedra G, Tessier FJ, Galinier A, Ait-Ameur L, Lacoste F, Niamba CN, Alt N, Somoza V, Lecerf JM (2010) A diet based on high-heat-treated foods promotes risk factors for diabetes mellitus and cardiovascular diseases. Am J Clin Nutr. doi:10.3945/ajcn.2009.28737

  • Bucala R, Makita Z, Vega G, Grundy S, Koschinsky T, Cerami A, Vlassara H (1994) Modification of low density lipoprotein by advanced glycation endproducts contributes to the dyslipidemia of diabetes and renal insufficiency. Proc Natl Acad Sci USA 91:9441–9445

    Article  PubMed  CAS  Google Scholar 

  • Buetler T (2007) Heated diets, AGEs and tissue dysfunction. IMARS Highlight 2:1–2

    Google Scholar 

  • Cai W, He JC, Zhu L, Peppa M, Lu C, Uribarri J, Vlassara H (2004) High levels of dietary advanced glycation end products transform low-density lipoprotein into a potent redox-sensitive mitogen-activated protein kinase stimulant in diabetic patients. Circulation 110:285–291

    Article  PubMed  CAS  Google Scholar 

  • Cai W, He JC, Zhu L, Chen X, Wallenstein S, Striker GE, Vlassara H (2007) Reduced oxidant stress and extended lifespan in mice exposed to a low glycotoxin diet. Association with increased AGER1 expression. Am J Pathol 170:1893–1902

    Article  PubMed  CAS  Google Scholar 

  • Cai W, He JC, Zhu L, Chen X, Zheng F, Striker GE, Vlassara H (2008) Oral glycotoxins determine the effects of calorie restriction on oxidant stress, age-related diseases, and lifespan. Am J Pathol 173:327–336

    Article  PubMed  CAS  Google Scholar 

  • Chuyen NV, Arai H, Nakanishi T, Utsunomiya N (2005) Are food advanced glycation end products toxic in biological systems? Ann NY Acad Sci 1043:467–473

    Article  PubMed  CAS  Google Scholar 

  • Delatour T, Hegele J, Parisod V, Richoz J, Maurer S, Steven M, Buetler T (2009) Analysis of advanced glycation endproducts in dairy products by isotope dilution liquid chromatography-electrospray tandem mass spectrometry. The particular case of carboxymethyllysine. J Chromatogr A 1216:2371–2381

    Article  PubMed  CAS  Google Scholar 

  • Delgado-Andrade C, Rufián-Henares JA, Morales FJ (2005) Fast method to determine furosine in breakfast cereals by capillary zone electrophoresis. Eur Food Res Technol 221:707–711

    Article  CAS  Google Scholar 

  • Dittrich R, Hoffmann I, Stahl P, Müller A, Beckmann MW, Pischetsrieder M (2006) Concentrations of N ε-carboxymethyllysine in human breast milk, infant formulas, and urine of infants. J Agric Food Chem 54:6924–6928

    Article  PubMed  CAS  Google Scholar 

  • Dittrich R, Dragonas C, Kannenkeril D, Hoffmann I, Mueller A, Beckmann MW, Pischetsrieder M (2009) A diet rich in Maillard reaction products protects LDL against copper induced oxidation ex vivo, a human intervention trial. Food Res Int 42:1315–1322

    Article  CAS  Google Scholar 

  • Dybing E, Farmer PB, Andersen M, Fennell TR, Lalljie SP, Müller DJ, Olin S, Petersen BJ, Schlatter J, Scholz G, Scimeca JA, Slimani N, Tornqvist M, Tuijtelaars S, Verger P (2005) Human exposure and internal dose assessments of acrylamide in food. Food Chem Toxicol 43:365–410

    Article  PubMed  CAS  Google Scholar 

  • Erbersdobler HF, Faist V (2001) Metabolic transit of Amadori products. Nahrung 45:177–181

    Article  PubMed  CAS  Google Scholar 

  • Erbersdobler HF, Somoza V (2007) Forty years of furosine—forty years of using Maillard reaction products as indicators of the nutritional quality of foods. Mol Nutr Food Res 51:423–430

    Article  PubMed  CAS  Google Scholar 

  • Fenaille F, Parisod V, Visani P, Populaire S, Tabet JC, Guy PA (2006) Modification of milk constituents during processing: a preliminary benchmarking study. Int Dairy J 16:728–739

    Article  CAS  Google Scholar 

  • Förster A, Kühne Y, Henle T (2005) Studies on absorption and elimination of dietary Maillard reaction products. Ann NY Acad Sci 1043:474–481

    Article  PubMed  Google Scholar 

  • Goldberg T, Cai W, Peppa M, Dardaine V, Baliga BS, Uribarri J, Vlassara H (2004) Advanced glycoxidation end products in commonly consumed foods. J Am Diet Assoc 104:1287–1291

    Article  PubMed  CAS  Google Scholar 

  • Henle T (2003) AGEs in foods: do they play a role in uremia? Kidney Int 84:S145–S147

    Article  CAS  Google Scholar 

  • Henle T, Walter A, Haebner R, Klostermeryer H (1994) Detection and identification of a protein-bound imidazolone resulting from the reaction of arginine residues and methylglyoxal. Z Lebensm Unters Forsch 199:55–58

    Article  CAS  Google Scholar 

  • Hofmann SM, Dong HJ, Li Z, Cai W, Altomonte J, Thung SN, Zeng F, Fisher EA, Vlassara H (2002) Improved insulin sensitivity is associated with restricted intake of dietary glycoxidation products in the db/db mouse. Diabetes 51:2082–2089

    Article  PubMed  CAS  Google Scholar 

  • Karachalias N, Babaei-Jadidi R, Rabbani N, Thornalley P (2010) Increased protein damage in renal glomeruli, retina, nerve, plasma and urine and its prevention by thiamine and benfotiamine therapy in a rat model of diabetes. Diabetologia 53:1506–1516

    Article  PubMed  CAS  Google Scholar 

  • Knecht KJ, Dunn JA, Mcfarland KF, McCance DR, Lyons TJ, Thorpe SR, Baynes JW (1991) Effect of diabetes and aging on carboxymethyllysine levels in human urine. Diabetes 40:190–196

    Article  PubMed  CAS  Google Scholar 

  • Koschinsky T, He CJ, Mitsuhashi T, Bucala R, Liu C, Buenting C, Heitmann K, Vlassara H (1997) Orally absorbed reactive glycation products (glycotoxins): an environmental risk factor in diabetic nephropathy. Proc Natl Acad Sci USA 94:6474–6479

    Article  PubMed  CAS  Google Scholar 

  • Kroes R, Muller D, Lambe J, Lowik MRH, Klaveren J, Kleiner J, Massey R, Mayer S, Urieta I, Verger P, Visconti A (2002) Assessment of intake from the diet. Food Chem Toxicol 40:327–385

    Article  PubMed  CAS  Google Scholar 

  • Liardon L, De Weck-Gaudard D, Philippossian G, Finot P-A (1987) Identification of Nepsilon-carboxymethyllysine: a new Maillard reaction product in rat urine. J Agric Food Chem 35:427–431

    Article  CAS  Google Scholar 

  • Lin RY, Choudhury RP, Cai W, Lu M, Fallon JT, Fisher EA, Vlassara H (2003) Dietary glycotoxins promote diabetic atherosclerosis in apolipoprotein E-deficient mice. Atherosclerosis 168:213–220

    Article  PubMed  CAS  Google Scholar 

  • Marko D, Habermeyer M, Kemeny M, Weyand U, Niederberger E, Frank O, Hofmann T (2003) Maillard reaction products modulating the growth of human tumor cells in vitro. Chem Res Toxicol 16:48–55

    Article  PubMed  CAS  Google Scholar 

  • Meng J, Sakata N, Takebayashi S, Asano T, Futata T, Nagai R, Ikeda K, Horiuchi S, Myint T, Taniguchi N (1998) Glycoxidation in aortic collagen from STZ-induced diabetic rats and its relevance to vascular damage. Atherosclerosis 136:355–365

    Article  PubMed  CAS  Google Scholar 

  • Miyata T, Ueda Y, Horie K, Nangaku M, Tanaka S, de Strihou C, Kurokawa K (1998) Renal catabolism of advanced glycation end products: the fate of pentosidine. Kidney Int 53:416–422

    Article  PubMed  CAS  Google Scholar 

  • Morales FJ (2009) Hydroxymethylfurfural (HMF) and related compounds. In: Stadler RH, Lineback DR (eds) Process-induced food toxicants: occurrence, formation, mitigation, and health risks. Wiley, New York, pp 135–174

    Google Scholar 

  • Mucci LA, Wilson KM (2008) Acrylamide intake through diet and human cancer risk. J Agric Food Chem 56:6013–6019

    Article  PubMed  CAS  Google Scholar 

  • Negrean M, Stirban A, Stratmann B et al (2007) Effects of low- and high-advanced glycation endproduct meals on macro- and microvascular endothelial function and oxidative stress in patients with type 2 diabetes mellitus. Am J Clin Nutr 85:1236–1243

    PubMed  CAS  Google Scholar 

  • Peppa M, Brem H, Ehrlich P, Zhang JG, Cai W, Li Z, Croitoru A, Thung S, Vlassara H (2003) Adverse effects of dietary glycotoxins on wound healing in genetically diabetic mice. Diabetes 52:2805–2813

    Article  PubMed  CAS  Google Scholar 

  • Pouillart P, Mauprivez H, Ait-Ameur L, Cayzeele A, Lecerf JM, Tessier FJ, Birlouez-Aragon I (2008) Strategy for the study of the health impact of dietary Maillard products in clinical studies: the example of the ICARE clinical study on health adults. Ann NY Acad Sci 1126:173–176

    Article  PubMed  CAS  Google Scholar 

  • Rabbani N, Sebekova K, Sebekova K Jr, Heidland A, Thornalley PJ (2007) Protein glycation, oxidation and nitration free adduct accumulation after bilateral nephrectomy and ureteral ligation. Kidney Internat 72:1113–1121

    Article  CAS  Google Scholar 

  • Rérat A, Calmes R, Vaissade P, Finot P-A (2002) Nutritional and metabolic consequences of the early Maillard reaction of heat treated milk in the pig. Significance for man. Eur J Nutr 41:1–11

    PubMed  Google Scholar 

  • Rufian-Henares JA, Morales FJ (2007) Functional properties of melanoidins: in vitro antioxidant, antimicrobial and antihypertensive activities. Food Res Int 40:995–1002

    Article  CAS  Google Scholar 

  • Sandu O, Song K, Cai W, Zheng F, Uribarri J, Vlassara H (2005) Insulin resistance and type 2 diabetes in high-fat-fed mice are linked to high glycotoxin intake. Diabetes 54:2314–2319

    Article  PubMed  CAS  Google Scholar 

  • Sebeková K, Saavedra G, Zumpe C, Somoza V, Klenovicsová K, Birlouez-Aragon I (2008) Plasma concentration and urinary excretion of N ε-(carboxymethyl)lysine in breast milk- and formula-fed infants. Ann NY Acad Sci 1126:177–180

    Article  PubMed  Google Scholar 

  • Seiquer I, Diaz-Alguacil J, Delgado-Andrade C, Lopez-Frias M, Munoz Hoyos A, Galdo G, Navarro MP (2006) Diets rich in Maillard reaction products affect protein digestibility in adolescent males aged 11–14 y. Am J Clin Nutr 83:1082–1088

    PubMed  CAS  Google Scholar 

  • Somoza V, Wenzel E, Weiss C, Clawin-Radecker I, Grubel N, Erbersdobler HF (2006) Dose-dependent utilisation of casein-linked lysinoalanine, N(epsilon)-fructoselysine and N(epsilon)-carboxymethyllysine in rats. Mol Nutr Food Res 50:833–841

    Article  PubMed  CAS  Google Scholar 

  • Svistounov D, Smedsrød B (2004) Hepatic clearance of advanced glycation end products (AGEs)-myth or truth? J Hepatol 41:1038–1040

    Article  PubMed  CAS  Google Scholar 

  • Tareke E, Rydberg P, Karlsson P, Eriksson S, Törnqvist M (2002) Analysis of acrylamide, a carcinogen formed in heated foodstuffs. J Agric Food Chem 50:4998–5006

    Article  PubMed  CAS  Google Scholar 

  • Tessier FJ, Niquet C, Rhazi L, Hedhili K, Navarro P, Seiquer I, Delgado-Andrade C (2010) N ε-Carboxymethyllysine: its origin in selected foods and its urinary and faecal excretions in healthy humans. In: Thomas MC, Forbes J (eds) The Maillard reaction. Interface between aging, nutrition and metabolism. Royal Society of Chemistry, London (in press)

  • Ulbricht RJ, Northup SJ, Thomas JA (1984) A review of 5-hydroxymethylfurfural (HMF) in parenteral solutions. Fundam Appl Toxicol 4:843–853

    Article  PubMed  CAS  Google Scholar 

  • Uribarri J, Peppa M, Cai W, Goldberg T, Lu M, He C, Vlassara H (2003a) Restriction of dietary glycotoxins reduces excessive advanced glycation end products in renal failure patients. J Am Soc Nephrol 14:728–731

    Article  PubMed  CAS  Google Scholar 

  • Uribarri J, Peppa M, Cai W, Goldberg T, Lu M, Baliga S, Vassalotti JA, Vlassara H (2003b) Dietary glycotoxins correlate with circulating advanced glycation end product levels in renal failure patients. Am J Kidney Dis 42:532–538

    Article  PubMed  CAS  Google Scholar 

  • Uribarri J, Cai W, Peppa M, Goodman S, Ferrucci L, Striker G, Vlassara H (2007) Circulating glycotoxins and dietary advanced glycation endproducts: two links to inflammatory response, oxidative stress, and aging. J Gerontol A Biol Sci Med Sci 62:427–433

    Article  PubMed  Google Scholar 

  • Uribarri J, Woodruff S, Goodman S, Cai W, Chen X, Pyzik R, Yong A, Striker GE, Vlassara H (2010) Advanced glycation end products in foods and a practical guide to their reduction in the diet. J Am Diet Assoc 110:911–916

    Article  PubMed  Google Scholar 

  • Utsunomiya N, Chuyen NV, Kato H (1990) Nutritional and physiological effects of casein modified by glucose, diacetyl, or hexanal. J Nutr Sci Vitaminol 36:387–397

    Article  PubMed  Google Scholar 

  • Vlassara H (2005) Advanced glycation in health and disease. Role of the modern environment. Ann NY Acad Sci 1043:452–460

    Article  PubMed  CAS  Google Scholar 

  • Vlassara H, Cai W, Crandall J, Goldberg T, Oberstein R, Dardaine V, Peppa M, Rayfield EJ (2002) Inflammatory mediators are induced by dietary glycotoxins, a major risk factor for diabetic angiopathy. Proc Natl Acad Sci USA 99:15596–15601

    Article  PubMed  CAS  Google Scholar 

  • Wadman SK, De Bree PK, Van Sprang FJ, Kamerling JP, Haverkamp J, Vliegenthart JFG (1975) N ε-(Carboxymethyl)lysine, a constituent of human urine. Clin Chim Acta 59:313–320

    Article  PubMed  CAS  Google Scholar 

  • Zheng F, He C, Cai W, Hattori M, Steffes M, Vlassara H (2002) Prevention of diabetic nephropathy in mice by a diet low in glycoxidation products. Diabetes Metab Res Rev 18:224–237

    Article  PubMed  Google Scholar 

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  1. Institut Polytechnique LaSalle Beauvais, Rue Pierre Waguet, 60026, Beauvais, France

    Frédéric J. Tessier

  2. Spectralys Innovation, Biocitech, 102 Avenue Gaston Roussel, 93230, Romainville, France

    Inès Birlouez-Aragon

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  1. Frédéric J. Tessier
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  2. Inès Birlouez-Aragon
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Correspondence to Frédéric J. Tessier.

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Tessier, F.J., Birlouez-Aragon, I. Health effects of dietary Maillard reaction products: the results of ICARE and other studies. Amino Acids 42, 1119–1131 (2012). https://doi.org/10.1007/s00726-010-0776-z

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