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Advanced Glycation End Products (AGEs)

Advanced glycation end products (AGEs) are glycosylated proteins, lipids, and nucleic acids because of exposure to sugars. It is a biomarker involved in aging, as well as the onset or worsening of many degenerative diseases, such as diabetes, atherosclerosis, chronic kidney disease, and Alzheimer's disease.

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Glycation is the irreversible reaction of proteins, lipids, and nucleic acids with carbohydrates. The products of glycation are called advanced glycation end products (AGEs). Carbohydrates can be fructose, galactose, and glucose, which react uncontrollably with various body molecules. Biochemically, this type of glycation is a multi-stage process of the Maillard reaction, with an intermediate stage in forming Schiff bases. Enzymes are not involved in this glycation process at all.

When do elevated levels of AGEs appear in the blood?

A distinction should be made between endogenously formed AGEs and exogenously absorbed AGEs. AGEs are formed endogenously through the glycation of proteins, lipids, and nucleic acids but can also be ingested through food.

Endogenous formation results in higher serum concentrations of AGEs, mainly due to increased blood sugar supply. Foods that raise blood sugar the most also show the most significant formation of AGEs (transient hyperglycemia). Fructose has a more substantial AGEs-forming effect than glucose. Cereals, especially wheat, are also an influential factor in creating AGEs. Amylopectin A from wheat is "digested" faster by amylase, rapidly increasing blood glucose. Regardless of the supply of sugar molecules, oxidative stress, and chronic inflammation significantly promote the endogenous formation of AGEs.

Not only can AGEs arise endogenously in the body, but they can also be absorbed through food. The AGEs content of foods varies greatly. Meat, sausages, ham, and cheese contain high amounts of AGEs. In particular, grilling, frying, and cooking over a long period can increase the content of AGEs by many times. Generally, the most decadent foods in AGEs contain many saturated fatty acids.

What differentiates AGEs from glycosylated hemoglobin (HbA1c)?

HbA1c is one of the endogenously formed glycation products. It provides indirect information on blood sugar levels in diabetic patients in recent weeks. However, AGEs are more suitable for evaluating the overall glycation process, as only AGEs record exogenously absorbed glycation products and protein and nucleic acid glycation, information that cannot be obtained directly from glycosylated hemoglobin. In addition, the AGEs test detects glucose-modified molecules and fructose- and galactose-modified molecules.

Why are AGEs harmful?

AGEs are involved in the development of various chronic inflammatory diseases such as type II diabetes mellitus, vascular and cardiovascular diseases, osteoporosis, and arthritis. It is believed that, on the one hand, glycation disrupts the functionality of critical regulatory enzymes and membranes, and on the other hand, the AGEs themselves affect essential metabolic processes. Binding to the receptor for AGEs (RAGE) in immune cells induces NFkB factor, creating 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, which leads to endothelial inflammation. AGEs can also activate inducible synthase NO (iNOS) and thus promote nitrosative stress. All the mediators mentioned increase, among other things, insulin resistance, which in turn increases blood sugar levels and causes a dangerous vicious cycle. Activation of NFkB also increases cellular expression of RAGE, which further enhances the pro-inflammatory effect of AGEs.

As a result of myelin glycation in neurons, neuropathies are created, such as in diabetes mellitus and Alzheimer's disease. Foods and drinks containing high concentrations of AGEs can directly impair blood vessel function, but their long-term destructive effect is the main consequence. The significant adverse effects on metabolism can be explained primarily by the fact that numerous short-lived molecules such as lipids, amino acids, enzymes, hormones (e.g., insulin), or growth factors are structurally and functionally destroyed by glycation.

The goal of treatment should be low AGEs

The reduction of AGE levels in the blood is possible through all measures that, on the one hand, reduce hyperglycemia and, on the other, reduce oxidative stress and chronic inflammation. In any case, a change in diet is beneficial. In this regard, knowing the level of AGEs also motivates the patient to change his diet. In addition to meat, sausages, ham, cheese, and all foods with a high glycemic index, great importance is also given to wheat and other cereals since the intake of cereal products (including whole grain products) can cause a significant increase in blood sugar levels.

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