Advanced Glycation End Products (AGEs) May Be a Striking Link Between Modern Diet and Health

Abstract

The Maillard reaction is a simple but ubiquitous reaction that occurs both in vivo and ex vivo during the cooking or processing of foods under high-temperature conditions, such as baking, frying, or grilling. Glycation of proteins is a post-translational modification that forms temporary adducts, which, on further crosslinking and rearrangement, form permanent residues known as advanced glycation end products (AGEs). Cooking at high temperature results in various food products having high levels of AGEs. This review underlines the basis of AGE formation and their corresponding deleterious effects on the body. Glycated Maillard products have a direct association with the pathophysiology of some metabolic diseases, such as diabetes mellitus type 2 (DM2), acute renal failure (ARF), Alzheimer's disease, dental health, allergies, and polycystic ovary syndrome (PCOS). The most glycated and structurally abundant protein is collagen, which acts as a marker for diabetes and aging, where decreased levels indicate reduced skin elasticity. In diabetes, high levels of AGEs are associated with carotid thickening, ischemic heart disease, uremic cardiomyopathy, and kidney failure. AGEs also mimic hormones or regulate/modify their receptor mechanisms at the DNA level. In women, a high AGE diet directly correlates with high levels of androgens, anti-Müllerian hormone, insulin, and androstenedione, promoting ovarian dysfunction and/or infertility. Vitamin D3 is well-associated with the pathogenesis of PCOS and modulates steroidogenesis. It also exhibits a protective mechanism against the harmful effects of AGEs. This review elucidates and summarizes the processing of infant formula milk and the associated health hazards. Formulated according to the nutritional requirements of the newborn as a substitute for mother's milk, formula milk is a rich source of primary adducts, such as carboxy-methyl lysine, which render an infant prone to inflammation, dementia, food allergies, and other diseases. We therefore recommend that understanding this post-translational modification is the key to unlocking the mechanisms and physiology of various metabolic syndromes.

Keywords: Alzheimer’s disease; Maillard reaction; advanced glycation end products; diabetes; infant formula; polycystic ovarian syndrome.

Figure 1

The Maillard reaction: A simple condensation reaction of protein and glucose. They are generally known as glycated proteins.

Figure 2

Early glycosylation protein adducts, such as glyoxal, methylglyoxal, N-ε(1-deoxy-D-fructose-1-yl)lysine. (Diagrams are drawn using the KingDraw application software).

Figure 3

Pathway of protein glycation forming Maillard reaction products (MRP). Amadori rearrangements are highlighted within the early reversible adducts, such as Schiff’s bases. These glycated adducts are irreversibly modified into advanced glycation end-products [14].

Figure 4

Formulation of infant formula milk powder describing high-temperature ranges during its complete process. Reconstitution of 40% dry material obtained by stirring at T < 60 °C, and high-temperature processing at later stages, i.e., addition of fat at 90–92 °C, sterilization at 90–95 °C, and atomization drying up to 280 °C [27].

Figure 5

(a) An illustration of the role of dietary advanced glycation end products and common lifestyle disorders. Graphic interpretation of the relationship of diseases with serum levels of AGEs and RAGE [15,90]. RAGE: Receptor for Advanced glycation end products; PCOS: polycystic ovarian syndrome; ROS: Reactive oxygen species; BMI: Body mass index; IS: Insulin Sensitivity; GM: Glucose metabolism; AA: amino acid; FA oxidation: fatty acid oxidation. (b) Pictorial representation of the molecular hacking of hormones and their receptor complex by AGEs: Binding of AGEs to a hormone receptor by mimicking it or trapping of hormones by blocking their receptors. AGEs can bind antagonistically to cell surface receptors causing over/no protein expression [15].

Figure 5

(a) An illustration of the role of dietary advanced glycation end products and common lifestyle disorders. Graphic interpretation of the relationship of diseases with serum levels of AGEs and RAGE [15,90]. RAGE: Receptor for Advanced glycation end products; PCOS: polycystic ovarian syndrome; ROS: Reactive oxygen species; BMI: Body mass index; IS: Insulin Sensitivity; GM: Glucose metabolism; AA: amino acid; FA oxidation: fatty acid oxidation. (b) Pictorial representation of the molecular hacking of hormones and their receptor complex by AGEs: Binding of AGEs to a hormone receptor by mimicking it or trapping of hormones by blocking their receptors. AGEs can bind antagonistically to cell surface receptors causing over/no protein expression [15].