Dietary Advanced Glycation End Products (D-AGEs): Formation, Detection, and Health Implications

Öz

Advanced glycation end products (AGEs), also known as glycotoxins, are harmful compounds formed through non-enzymatic reactions between reducing sugars such as glucose, ribose, and fructose and amino groups in proteins, lipids, or nucleic acids. While AGEs are naturally produced in the body during normal metabolism (endogenous AGEs), they are also ingested through external sources, primarily via diet and smoking (exogenous AGEs). The formation of dietary AGEs (d-AGEs) is significantly influenced by food composition and processing factors, including heat exposure, cooking duration, humidity, pH, food additives, marination, and cooking methods. Higher temperatures and longer cooking times notably increase AGE levels in foods. These compounds are associated with various physiological toxicities and contribute to aging and the development of chronic diseases. This article explores the mechanisms of d-AGEs formation, their transport and toxic effects in the body, methods for detecting them, and strategies to inhibit their formation or intake. By raising awareness and providing practical inhibition methods, this work aims to reduce the health risks posed by dietary AGEs and support public health efforts.

Anahtar Kelimeler

• Maillard reaction
• Browning reaction
• Amadori products
• Advanced glycation end products

Kaynakça

1. Akın Ö, Özbek YD. 2022. İleri glikasyon son ürünlerinin gebelik üzerine etkisi. Sakarya Üniversitesi Holistik Sağlık Dergisi, 5(1): 39-55.
2. Almeida F. 2013. Effects of the Maillard reactions on chemical composition and amino acid digestibility of feed ingredients and on pig growth performance. University of Illinois at Urbana-Champaign, Doctoral dissertation, Urbana, IL, USA, pp: 154.
3. Almeida FN, Htoo JK, Thomson J, Stein HH. 2014. Effects of balancing crystalline amino acids in diets containing heat-damaged soybean meal or distillers dried grains with solubles fed to weanling pigs. Animal, 8(10): 1594-1602.
4. Andrades ME, Lorenzi R, Nagai R, Moreira JCF, Ritter C, Dal-Pizzol F. 2012. Plasma glycation levels are associated with severity in sepsis. Eur J Clin Invest, 42(10): 1055-1060.
5. Anwar S, Khan S, Almatroudi A, Khan AA, Alsahli MA, Almatroodi SA, Rahmani AH. 2021. A review on mechanism of inhibition of advanced glycation end products formation by plant derived polyphenolic compounds. Mol Biol Rep, 48(1): 787-805.
6. Bronowicka-Szydełko A, Gostomska-Pampuch K, Kuzan A, Pietkiewicz J, Krzystek-Korpacka ML, Gamian A. 2024. Effect of advanced glycation end-products in a wide range of medical problems including COVID-19. Adv Med Sci, 69(1): 36-50.
7. Çatak J, Balcı E. 2022. Paketli keklerde ileri glikasyon son ürünleri öncüllerinin HPLC ile tespiti ve değerlendirilmesi. J Characterization, 2(1): 82-90.
8. Chen JH, Xing YL, Zhao LY, Ma HJ. 2019. The association between Helicobacter pylori infection and glycated hemoglobin A in diabetes: A meta-analysis. J Diabetes Res, 2019: 1-10.

9. Chilelli NC, Burlina S, Lapolla A. 2013. AGEs, rather than hyperglycemia, are responsible for microvascular complications in diabetes: A "glycoxidation-centric" point of view. Nutr Metab Cardiovasc Dis, 23(10): 913-919.
10. Demirel Y, Yıldıran H. 2018. İleri glikasyon son ürünleri ve böbrek hastalıkları. Gümüşhane Üniv Sağlık Bilim Derg, 7(1): 210-217.
11. Demirer B, Yardımcı H. 2022. İleri glikasyon son ürünlerinin diyabet komplikasyonları üzerine etkileri: Bir derleme. Beslenme ve Diyet Dergisi, 50(1): 101-108.
12. Erim B, Ergene E, Hecer C. 2022. Besin hazırlama ve pişirme yöntemlerinin ileri glikasyon son ürünleri üzerine etkisi. Aydın Gastronomy, 6(2): 275-281.
13. Gao QM, Jiang YY, Zhou DY, Li GF, Han YF, Yang JZ, Xu K, Jing YY, Bai L, Geng Z, Zhang H, Zhou GY, Zhu MR, Ji N, Han RN, Zhang YW, Li ZH, Wang CD, Hu Y, Su JC. 2024. Advanced glycation end products mediate biomineralization disorder in diabetic bone disease. Cell Rep Med, 5(9): 100966.
14. Ho SC, Wu SP, Lin SM, Tang YL. 2010. Comparison of anti-glycation capacities of several herbal infusions with that of green tea. Food Chem, 122(3): 768-774.
15. Hu H, Wang Y, Shen M, Huang Y, Li C, Nie S, Xie M. 2022. Effects of baking factors and recipes on the quality of butter cookies and the formation of advanced glycation end products (AGEs) and 5-hydroxymethylfurfural (HMF). Curr Res Food Sci, 5: 940-948.
16. Huang CY, Chen SH, Lin TC, Liao YW, Chang YC, Chen CC, Yu CC, Chen CJ. 2024. Resveratrol attenuates advanced glycation end product-induced senescence and inflammation in human gingival fibroblasts. J Dent Sci, 19(1): 580-586.
17. Karaköse D. 2023. Yüksek yağlı diyetle beslenen fare modellerinin yağ dokularında ileri glikasyon ürünlerinin incelenmesi. İstanbul Sabahattin Zaim Üniversitesi, Fen Bilimleri Enstitüsü, İstanbul, Türkiye, pp: 100.
18. Karakütük I. 2025a. Figure 1. Created in BioRender. https://BioRender.com/b07x896
19. Karakütük I. 2025b. Figure 2. Created in BioRender. https://BioRender.com/e31j367
20. Karakütük I. 2025c. Figure 3. Created in BioRender. https://BioRender.com/i45b405
21. Karakütük I. 2025d. Figure 4. Created in BioRender. https://BioRender.com/x24r992
22. Karakütük I. 2025e. Figure 5. Created in BioRender. https://BioRender.com/l87g434
23. Karakütük I. 2025f. Figure 6. Created in BioRender. https://BioRender.com/m27q949
24. Kellow NJ, Coughlan MT. 2015. Effect of diet-derived advanced glycation end products on inflammation. Nutr Rev, 73(11): 737-759.
25. Khan M, Liu HL, Wang J, Sun BG. 2020. Inhibitory effect of phenolic compounds and plant extracts on the formation of advance glycation end products: A comprehensive review. Food Res Int, 130: 108933.
26. Kosmopoulos M, Drekolias D, Zavras PD, Piperi C, Papavassiliou AG. 2019. Impact of advanced glycation end products (AGEs) signaling in coronary artery disease. BBA-Mol Basis Dis, 1865(3): 611-619.
27. Kuzan A. 2021. Toxicity of advanced glycation end products (Review). Biomed Rep, 14(5): 1-9.
28. Lee HHL, Ha SK, Kim Y, Hur J. 2024. Simultaneous analysis of advanced glycation end products using dansyl derivatization. Food Chem, 432: 137248.
29. Lim JM, Yoo HJ, Lee KW. 2022. High molecular weight fucoidan restores intestinal integrity by regulating inflammation and tight junction loss induced by methylglyoxal-derived hydroimidazolone-1. Mar Drugs, 20(9): 587.
30. Luevano-Contreras C, Chapman-Novakofski K. 2010. Dietary advanced glycation end products and aging. Nutrients, 2(12): 1247-1265.
31. Mendes NP, Cândido FG, Valente FX, Peluzio MDG, Juvanhol LL, Alfenas RCG. 2024. Dietary advanced glycation end products, body composition, and anthropometric measures: A cross-sectional analysis in women with excess body weight. Nutr Metab Cardiovasc Dis, 34(7): 1721-1730.
32. Nowotny K, Jung T, Höhn A, Weber D, Grune T. 2015. Advanced glycation end products and oxidative stress in type 2 diabetes mellitus. Biomolecules, 5(1): 194-222.
33. Ott C, Jacobs K, Haucke E, Santos AN, Grune T, Simm A. 2014. Role of advanced glycation end products in cellular signaling. Redox Biol, 2: 411-429.
34. Öztürk SA, Garipoğlu G. 2022. Determination of glyoxal and methylglyoxal bioaccessibility in pastas and noodles varieties by in vitro digestion method. J Characterization, 5(2): 102-110.
35. Patregnani JT, Fujiogi M, Camargo CA, Brooks BA, Hoptay CE, Mansbach JM, Teach SJ, Freishtat RJ, Hasegawa K. 2021. Serum soluble receptor for advanced glycation end products in infants with bronchiolitis: Associations with acute severity and recurrent wheeze. Clin Infect Dis, 73(9): e2665-e2672.
36. Peppa M, Vlassara H. 2005. Advanced glycation end products and diabetic complications: A general overview. Hormones, 4(1): 28-37.
37. Perrone A, Giovino A, Benny J, Martinelli F. 2020. Advanced glycation end products (AGEs): Biochemistry, signaling, analytical methods, and epigenetic effects. Oxid Med Cell Longev, 2020: 1-15.
38. Peterson LL, Ligibel JL. 2024. Dietary and serum advanced glycation end-products and clinical outcomes in breast cancer. BBA-Rev Cancer, 1879(1): 188786.
39. Peyroux J, Sternberg M. 2006. Advanced glycation endproducts (AGEs): pharmacological inhibition in diabetes. Pathol Biol, 54(7): 405-419.
40. Prasad C, Davis KE, Imrhan V, Juma S, Vijayagopal P. 2019. Advanced glycation end products and risks for chronic diseases: Intervening through lifestyle modification. Am J Lifestyle Med, 13(4): 384-404.
41. Qiang X, Liang SM, Lv YC, Wang XY, Zhang H, Zhan J. 2024. Advanced glycation end products (AGEs) impair the intestinal epithelial barrier via STAT3 activation mediated by macrophages. Food Chem Toxicol, 192: 113869.
42. Qu WT, Yuan XJ, Zhao JS, Zhang YX, Hu J, Wang JW, Li JX. 2017. Dietary advanced glycation end products modify gut microbial composition and partially increase colon permeability in rats. Mol Nutr Food Res, 61(10): 1700176.
43. Ruiz HH, Ramasamy R, Schmidt AM. 2020. Advanced glycation end products: Building on the concept of the "common soil" in metabolic disease. Endocrinology, 161(1).
44. Scheijen JLJM, Clevers E, Engelen L, Dagnelie PC, Brouns F, Stehouwer CDA, Schalkwijk CG. 2016. Analysis of advanced glycation endproducts in selected food items by ultra-performance liquid chromatography tandem mass spectrometry: Presentation of a dietary AGE database. Food Chem, 19: 1145-1150.
45. Schwarzenbolz U, Hofmann T, Sparmann N, Henle T. 2016. Free Maillard reaction products in milk reflect nutritional intake of glycated proteins and can be used to distinguish "organic" and "conventionally" produced milk. J Agric Food Chem, 64(24): 5071-5078.
46. Sharma C, Kaur A, Thind SS, Singh B, Raina S. 2015. Advanced glycation end-products (AGEs): An emerging concern for processed food industries. J Food Sci Technol-Mysore, 52(12): 7561-7576.
47. Shen CY, Lu CH, Wu CH, Li KJ, Kuo YM, Hsieh SC, Yu CL. 2020. The development of Maillard reaction, and advanced glycation end product (AGE)-receptor for AGE (RAGE) signaling inhibitors as novel therapeutic strategies for patients with AGE-related diseases. Molecules, 25(23).
48. Singh VP, Bali A, Singh N, Jaggi AS. 2014. Advanced glycation end products and diabetic complications. Korean J Physiol Pharmacol, 18(1): 1-14.
49. Snelson M, Tan SM, Clarke RE, de Pasquale C, Thallas-Bonke V, Nguyen TV, Penfold SA, Harcourt BE, Sourris KC, Lindblom RS, Ziemann M, Steer D, El-Osta A, Davies MJ, Donnellan L, Deo P, Kellow NJ, Cooper ME, Woodruff TM, Coughlan MT. 2021. Processed foods drive intestinal barrier permeability and microvascular diseases. Sci Adv, 7(14).
50. Sprenger HG, Bierman WF, Martes MI, Graaff R, van der Werf TS, Smit AJ. 2017. Skin advanced glycation end products in HIV infection are increased and predictive of development of cardiovascular events. AIDS, 31(2): 241-246.
51. Srey C, Hull GL, Connolly L, Elliott CT, del Castillo MD, Ames JM. 2010. Effect of inhibitor compounds on Nε-(carboxymethyl)lysine (CML) and Nε-(carboxyethyl)lysine (CEL) formation in model foods. J Agric Food Chem, 58(22): 12036-12041.
52. Takeuchi M, Suzuki H, Takeda K, Sakai-Sakasai A. 2024. Toxic advanced glycation end-products (TAGE) are major structures of cytotoxic AGEs derived from glyceraldehyde. Med Hypotheses, 183.
53. Tessier FJ, Niquet‐Léridon C, Jacolot P, Jouquand C, Genin M, Schmidt AM, Grossin N, Boulanger E. 201
54. Tessier FJ, Niquet‐Léridon C, Jacolot P, Jouquand C, Genin M, Schmidt AM, Grossin N, Boulanger E. 2016. Quantitative assessment of organ distribution of dietary protein‐bound 13C‐labeled Nɛ‐carboxymethyllysine after a chronic oral exposure in mice. Mol Nutr Food Res, 60(11): 2446-2456.
55. Tominaga Y, Sugawa H, Hirabayashi K, Ikeda T, Hoshi Y, Nagai R. 2020. Extract containing multiple phenolic compounds inhibits the formation of advanced glycation end-products. Arch Biochem Biophys, 693.
56. 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(4): 427-433.
57. Uribarri J, Woodruff S, Goodman S, Cai WJ, 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(6): 911-916.
58. van Dongen KCW, Kappetein L, Estruch IM, Belzer C, Beekmann K, Rietjens IMCM. 2022. Differences in kinetics and dynamics of endogenous versus exogenous advanced glycation end products (AGEs) and their precursors. Food Chem Toxicol, 164.
59. Vasilj M, Goni L, Gayoso L, Razquin C, Sesma MT, Etxeberria U, Ruiz-Canela M. 2023. Correlation between serum advanced glycation end products and dietary intake of advanced glycation end products estimated from home cooking and food frequency questionnaires. Nutr Metab Cardiovasc Dis, 33(9): 1768-1777.
60. Vıcıl S, Ulutaş E. 2020. Metilglioksal ve ileri glikasyon son ürünleri. Bozok Vet Sci, 1(1-2): 74-79.
61. Villanueva M. 2017. Glyoxalase 1 attenuates the effects of chronic hyperglycemia on explant-derived cardiac stem cells. Université d'Ottawa/University of Ottawa, Doctoral dissertation, Ottawa, Canada, pp: 134.
62. Wang H, Tu ZC, Liu GX, Liu CM, Huang XQ, Xiao H. 2013. Comparison of glycation in conventionally and microwave-heated ovalbumin by high resolution mass spectrometry. Food Chem, 141(2): 985-991.
63. Wu Q, Chen HY, Lv ZJ, Li SY, Hu B, Guan YF, Xie BJ, Sun ZD. 2013. Oligomeric procyanidins of lotus seedpod inhibits the formation of advanced glycation end-products by scavenging reactive carbonyls. Food Chem, 138(2-3): 1493-1502.
64. Yalçın E, Rakıcıoğlu N. 2022. Besinlerde oluşan ileri glikasyon son ürünlerine polifenollerin etkisi. Beslenme ve Diyet Dergisi, 50(2): 66-75.
65. Yaman M. 2021. İleri glikasyon son ürünlerinin (AGEs) öncüllerinin in vitro biyoerişilebilirliklerinin bazı gıdalarda belirlenmesi. Avrupa Bilim ve Teknoloji Dergisi, (27): 598-604.
66. Yılmaz B, Karabudak E. 2016. Besinlerdeki ileri glikasyon son ürünleri ve azaltma yöntemleri. Beslenme ve Diyet Dergisi, 44(3): 280-288.
67. Zhao WB, Cai PJ, Zhang N, Wu TT, Sun AD, Jia GL. 2022. Inhibitory effects of polyphenols from black chokeberry on advanced glycation end-products (AGEs) formation. Food Chem, 392.
68. Zheng XY, Ai BL, Zheng LL, Liu WY, Yang Y, Xiao D, Sheng ZW. 2024. Modulatory effects of tryptophan on advanced glycation end products formation and flavor enhancement in high-protein intermediate-moisture food during storage. LWT-Food Sci Technol, 197.
69. Zhou Q, Cheng KW, Xiao JB, Wang MF. 2020. The multifunctional roles of flavonoids against the formation of advanced glycation end products (AGEs) and AGEs-induced harmful effects. Trends Food Sci Technol, 103: 333-347.
70. Zolakova B, Zolak V, Hatok J, Matasova K, Nosal S, Zibolen M. 2016. Soluble receptor for advanced glycation end products in late onset neonatal infection. Bratisl Med J, 117(1): 15-18.