Dietary Sugars and Endogenous Formation of Advanced Glycation Endproducts: Emerging Mechanisms of Disease

Abstract

The rapid increase in metabolic diseases, which occurred in the last three decades in both industrialized and developing countries, has been related to the rise in sugar-added foods and sweetened beverages consumption. An emerging topic in the pathogenesis of metabolic diseases related to modern nutrition is the role of Advanced Glycation Endproducts (AGEs). AGEs can be ingested with high temperature processed foods, but also endogenously formed as a consequence of a high dietary sugar intake. Animal models of high sugar consumption, in particular fructose, have reported AGE accumulation in different tissues in association with peripheral insulin resistance and lipid metabolism alterations. The in vitro observation that fructose is one of the most rapid and effective glycating agents when compared to other sugars has prompted the investigation of the in vivo fructose-induced glycation. In particular, the widespread employment of fructose as sweetener has been ascribed by many experimental and observational studies for the enhancement of lipogenesis and intracellular lipid deposition. Indeed, diet-derived AGEs have been demonstrated to interfere with many cell functions such as lipid synthesis, inflammation, antioxidant defences, and mitochondrial metabolism. Moreover, emerging evidence also in humans suggest that this impact of dietary AGEs on different signalling pathways can contribute to the onset of organ damage in liver, skeletal and cardiac muscle, and the brain, affecting not only metabolic control, but global health. Indeed, the most recent reports on the effects of high sugar consumption and diet-derived AGEs on human health reviewed here suggest the need to limit the dietary sources of AGEs, including added sugars, to prevent the development of metabolic diseases and related comorbidities.

Products of Early and Advanced Glycation in the Soy Milk Proteome

“…Both AGEs accounted for 70% of all identified AGE modifications, whereas the other Arg-(10 CMA, 7 THP, 6 Glarg, and 3 Argpyr) and Lys-derived AGEs (7 CML, 6 pyrraline, 5 GLAP, and 3 CEL) represent the minority of identified modifications (Figure 2A). Similar numbers of AGE-modified peptides were identified in USM (32-35), SSMSu (27), and SIF products (32-35), but more often in soy milk products sweetened with hexoses (SSM1-3, 89-106) ( Figure 2B). The number of corresponding modification sites followed the same trend ( Figure S7, Supporting Information).…”

“…Thus, higher contents of hexoses, especially fructose, present in the SSMs might trigger this AGE pattern. The lower number of AGE modifications identified in SIFs than in sweetened soy milk products, which is in contrast to the harsher processing conditions, might be related to the absence of fructose, which is a potent glycation agent . CML, CEA, CMA, and Glarg were detected in SIFs at lower counts than in USM and SSMSu, which might be linked to the addition of pyridoxamine (vitamin B6) in SIF, which is known to inhibit the formation of some of these AGEs …”

“…The high numbers of identified AGE‐modification sites in fructose‐sweetened milk raises concerns about potentially harmful effects upon intake. Several studies have associated the intake of fructose‐containing sweeteners with weight gain and onset of dyslipidemia, insulin resistance, and related metabolic diseases in humans and the development of obesity and inflammation in animal models . The mechanisms of these deleterious effects have not been revealed, but it cannot be ruled out that the fructose‐derived dietary AGEs or endogenously formed fructose‐derived AGEs may contribute to these effects.…”

Astrofood, Priorities and Pandemics: Reflections of an Ultra-Processed Breakfast Program and Contemporary Dysbiotic Drift

“…For example, a biscotti, with its oven-baked combination of protein and sugar, is extraordinarily high in AGEs-over 35 times higher than a poached egg [90]. This is of relevance because foods high in pre-formed AGEs have been linked to inflammation, oxidative stress and enhanced allergenicity of foods [91][92][93]; on the other hand, dietary interventions to lower exogenous AGE intake can significantly reduce systemic inflammation and oxidative stress [94].…”

More pieces of the fructose puzzle

“…In just the last twelve months, there have been at least eight reviews published on the subject. Four of these reviews detailed mechanisms by which dietary fructose may have direct deleterious effects on human health . The other four concluded that dietary fructose has no detrimental effects on health except those related to an increased chance of excessive energy intake and weight gain .…”