Glycation refers to the irreversible reaction of proteins and lipids with carbohydrates (v.a. The sugars fructose, galactose, and glucose). Glycated reaction products are called "Advanced Glycation Endproducts" (AGEs).
Foods that raise blood sugar the most also exhibit the highest AGE formation. For example, fructose is a stronger AGE-forming agent than glucose. Grains are another example. v.a. Wheat is known to be a strong AGE former.
Furthermore, AGE formation is promoted by oxidative stress and chronic inflammation.
AGEs can not only be produced endogenously in the body, but can also be ingested through food. The AGE content of foods varies considerably. Meat, sausage, ham, and cheese contain high levels of AGEs. Grilling, roasting, frying, and prolonged cooking can increase the AGE content many times over. Generally, foods containing a lot of saturated fatty acids are higher in AGEs.
Why are AGEs harmful?
AGEs are involved in the development of various chronic inflammatory diseases, e.g.Type II diabetes mellitus, vascular and cardiovascular diseases, osteoporosis and arthritis.
The underlying cause is thought to be that glycation disrupts the functionality of important regulatory enzymes and membrane systems, while AGEs themselves also influence important metabolic processes:
- By binding to the AGE receptor (RAGE) on inflammatory cells, they induce NFkB and thus systemic inflammation and oxidative stress.
- This stimulates the release of interleukin-1, interleukin-6, TNF-α and insulin-like growth factor-1 (IGF-1) in monocytes and macrophages.
- Endothelial cells express adhesion molecules such as VCAM-1 and ICAM-1, leading to endothelial inflammation.
- AGEs can also activate inducible NO synthase (iNOS) and thereby promote nitrosative stress.
- All of the aforementioned mediators enhance u.a. Insulin resistance.
- Furthermore, the activation of NFkB increases the cell expression of RAGE, which further enhances the pro-inflammatory effect of AGEs.
Sources:
[1] Sakai M, Experimental studies on the role of fructose in the development of diabetic complications. Kobe J Med Sci. 2002; 48:125-36.
[2] Schiekofer S. et al.: Acute hyperglycemia causes intracellular formation of CML and activation of ras, p42/44 MAPK, and nuclear factor kappaB in PBMCs. Diabetes 52, 2003, pp. 621–633
[3] Koschinsky T, et. al. An environmental risk factor in diabetic nephropathy. PNAS 94, 1997, pp. 6474-6479
[4] Sanguineti R. et al.: Advanced Glycation End Products Play Adverse Proinflammatory Activities in Osteoporosis. Mediators of inflammation 2014, 2014, p. 975872
[5] Vlassara H et al. Recent progress in advanced glycation and diabetic vascular disease: role of advanced glycation end product receptors. Diabetes 1996; 45:65-66
[6] Chuah et al.: Receptor for Advanced Glycation End Products and Its Involvement in Inflammatory Diseases. Int J Inflammation 2013, 2013, p. 403460
[7] Ott C. et al. Role of advanced glycation end products in cellular signaling. Redox biology 2, 2014, pp. 411–429
[8] Wewer RM Arteriosclerosis and the two faces of endothelial nitric oxide synthetase Circulation 1998; 97: 108-112
[9] Singh VP et al.: Advanced Glycation End Products and Diabetic Complications. Korean Journal of Physiology & Pharmacology 18, 2014, pp. 1–14
[10] Angeloni C. Role of Methylglyoxal in Alzheimer's Disease. BioMed Res Int 2014 p. 238485
[11] Uribarri J et al. Single oral challenge by advanced glycation end products acutely impairs endothelial function in diabetic and nondiabetic subjects. Diabetes care.2007;30:2579-82
