Comparison of Free and Bound Advanced Glycation End Products in Food: A Review on the Possible Influence on Human Health

Abstract

Debate on the hazards of advanced glycation end products (AGEs) in food has continued for many years as a result of their uncertain bioavailability and ability to bind to their receptors (RAGEs) in vivo. There are increasing evidence that free and bound AGEs have many differences in gastrointestinal digestion, intestinal absorption, binding with RAGEs, in vivo circulation, and renal clearance. Therefore, this paper compares these aspects between free and bound AGEs by summarizing the available knowledge. On the basis of the current knowledge, we conclude that it is time to differentiate free AGEs from bound AGEs in food in future studies, because they vary in many aspects that are closely related to their influence on human health. Several perspectives were proposed at the end of this review for further exploring the difference between free and bound AGEs in food.

Dietary advanced glycation end‐products: Perspectives linking food processing with health implications

“…There is increasing literature suggesting that free‐ and bound‐state dAGEs behave differently in many aspects such as GI digestion, intestinal absorption, interaction with AGE receptors, in vivo circulation, detoxification, and renal clearance, etc. (Zhao et al., 2019). The free dAGEs, including those originally in the foods and those released from peptide‐bound AGEs upon digestion, were presumed to be stable in the GI tract but with a limited bioavailability across the intestinal barrier; whereas, the protein‐bound AGEs were hydrolyzed into smaller fractions (mainly peptide‐bound AGEs) by digestive enzymes, followed by transepithelial transport into the circulation by peptide carriers (i.e., PEPT1) (Ahmed & Thornalley, 2007; Delgado‐Andrade & Fogliano, 2018; Liang et al., 2019; Zhao et al., 2019).…”

“…(Zhao et al., 2019). The free dAGEs, including those originally in the foods and those released from peptide‐bound AGEs upon digestion, were presumed to be stable in the GI tract but with a limited bioavailability across the intestinal barrier; whereas, the protein‐bound AGEs were hydrolyzed into smaller fractions (mainly peptide‐bound AGEs) by digestive enzymes, followed by transepithelial transport into the circulation by peptide carriers (i.e., PEPT1) (Ahmed & Thornalley, 2007; Delgado‐Andrade & Fogliano, 2018; Liang et al., 2019; Zhao et al., 2019). After GI digestion, no free CML, CEL, G, and MG were detected in the digests of β‐casein, β‐lactoglobulin, and BSA, clearly suggesting that protein‐bound AGEs were predominantly degraded into peptide‐bound products in the GI tract (Zhao, Le, et al., 2017; Zhao, Li, et al., 2017).…”

“…By contrast, the unprocessed diet with a high content of free CML did not induce a comparable inflammatory severity, implying that free AGEs were not that efficient to activate RAGE‐mediated signaling cascades (Rajan et al., 2018). In this regard, it was found that only bound CML/CEL with a peptidic structure can interact with RAGEs, thereby inducing a downstream inflammatory milieu (Xie et al., 2008; Zhao et al., 2019). However, as for the other AGE receptors, that is, AGE‐R1 and SRs, whether and how they can participate in the detoxification of dAGEs with different MWs are yet to be elucidated.…”

“…However, due to the complexity and diversity of dAGEs, the relationship between food‐derived AGEs and biological AGEs remains inconclusive. The current debates surrounding dAGEs are mainly their bioavailability, capacity to interact with AGE receptors, mechanisms to bind with functional proteins, and renal clearance (Ames, 2007; Poulsen et al., 2013; Uribarri, 2017; Zhao et al., 2019).…”

Toxicological consequences of the Maillard reaction

“…Additionally, although the databases published give good indications on the levels of specific dAGEs in food products, they do not make a distinction between free and protein-bound dAGEs. Protein-bound dAGEs are in general much more abundant in food products than free dAGEs, as was recently reviewed by Zhao et al (2019) [36]. The ratios in which dAGEs are present in either free or protein-bound form seems to depend on the type of food product, as was shown in the study by Hegele et al (2008) who compared levels of free and proteinbound dAGEs in raw and processed milk products [37].…”