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Epidemiologic studies have suggested an association between the consumption of dietary advanced glycation end products (dAGEs) and the incidence of nonalcoholic fatty liver disease (NAFLD). However, the precise mechanism by which dAGEs induce NAFLD development, particularly the pathogenic role of the gut-liver axis, remains poorly understood. In this study, by establishing a high-AGE diet (HAD)-fed C57BL/6 mouse model, we employed multiomics approaches combined with a series of biological analyses to investigate the effect of HAD on NAFLD in vivo . Our results showed that exposure to HAD led to fat accumulation, oxidative stress, inflammation, and fibrosis in the liver of mice. Transcriptome analysis further revealed that HAD exposure disrupted lipid metabolism and activated inflammation-related signaling pathways in the liver. Additionally, exposure to HAD induced perturbations in gut homeostasis, as evidenced by the compromised gut barrier function, reduced probiotic abundance, and increases in pathogenic bacterial proportions. Dysbiosis of gut homeostasis may further act as a trigger for the initiation and progression of NAFLD via the gut-liver axis. This study sheds light on the underlying mechanisms through which dAGEs contribute to the development of NAFLD and helps to understand the detrimental effects of food ultraprocessing products in modern diets. Future studies are needed to explore the in-depth mechanisms related to the gut-liver axis to consolidate our conclusions.

Evidence suggest that dietary advanced glycation end products (AGEs) might exert harmful effects on female reproductive function. However, population-based studies exploring the associations between dietary AGEs intake and female infertility remain lacking. This studyaimed to determine the relationship between dietary AGEs intake and female infertility based on National Health and Nutrition Examination Survey (NHANES). A cross-sectional analysis of 2863 participants in the NHANES 2013-2018 were included. The dietary AGEs, i.e. Nε-(carboxymethyl)lysine(CML), Nε-(1-carboxyethyl)lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were estimated using the combination of ultra-performance LC-tandem MS dietary AGEs database and two 24-h dietary recall interviews. Multivariate Logistic regression analyses were adopted to explore the relationships between dietary AGEs intake and self-reported infertility risk. Compared to the lowest tertile, total dietary AGEs (P-trend = 0.089) and CML (P-trend = 0.032) in the upper tertile were positively correlated with female infertility, and the corresponding odds radios (ORs) (95% confidence interval (CI)) were 1.44 (1.01, 2.06) and 1.64 (1.10, 2.45) respectively. Subgroups analysis found that in participants with overweight and obese, each 1-SD increment in dietary AGEs, CML and MG-H1 level was associated with 18% (95% CI: 1-38%), 21% (95% CI: 1-46%), and 16% (95% CI: 0-36%) elevated risk of infertility. Elevated dietary AGEs intake was associated with the higher risk of infertility for female subjects, this positive association was more pronounced in women with excess body weight., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Advanced Glycation End Products (AGEs) are formed through non-enzymatic reactions between reducing sugars and proteins, nucleic acids or lipids (for example through hyperoxidation). In diabetes, elevated glucose levels provide more substrate for AGEs formation. AGEs can also be ingested through the diet from foods cooked at high temperatures, or containing much sugar. The present work aimed to review all published randomized controlled trials (RCT) on low-dietary AGE (L-dAGEs) interventions in patients with diabetes. Pubmed, Scopus and Cochrane databases were searched (until 29 February 2024) with appropriate keywords (inclusion criteria: RCT, patients with diabetes, age > 18 years, outcomes related to inflammation, glucose, and lipids; exclusion criteria: non-RCTs, case-series, case reports and Letter to the Editor, or animal studies). The present review was registered to the Open Science Framework (OSF). From 7091 studies, seven were ultimately included. Bias was assessed with the updated Cochrane Risk of Bias tool. A reduction in circulating AGEs was documented in 3/3 studies. No particular differences were documented in glycemic parameters after a L-dAGEs diet. Reductions in glucose levels were observed in one out of six studies (1/6), while HbA1c and HOMA did not change in any study (0/6 and 0/3, correspondingly). Lipid profile also changed in one out of four studies (1/4). More consistent results were observed for oxidative stress (beneficial effects in 3/3 studies) and inflammatory markers (beneficial effects in 4/4 studies). Other athero-protective effects, such as adiponectin increases, were reported. Limitations included the small sample size and the fact that dietary and physical activity habits were not considered in most studies. In conclusion, a L-dAGEs pattern may minimize AGEs accumulation and have beneficial effects on oxidative stress and inflammation indices, while its effects on glycemic and lipemic parameters are inconsistent and modest in patients with diabetes.

Advanced glycation end products (AGEs) are formed by the Maillard reaction, a nonenzymatic process that occurs widely in cooking, food processing, and within the human body. Primarily, AGEs are formed by the glycation of reducing sugars with amino groups, and this process is heat-dependent. With changes in lifestyle, there has been an increase in the diversity of dietary habits, including those patterns associated with Western diets, which include the consumption of processed foods that are rich in AGEs. Excessive intake and exposure to AGEs are known to cause abnormalities in body function such as obesity, diabetes, and fatty liver, and the beneficial effects of AGEs in food processing in improving food flavor and quality. To obtain meaningful data regarding AGEs in a variety of food and human samples, it is necessary to more precisely characterize and analyze the AGEs extracted from samples to obtain accurate results. This review explores the recent analytical research and characterization of AGEs in foods, including casein, β-lactoglobulin, soy protein, and meat protein, and in human samples, such as glycated-albumin, hemoglobin, and plasma. Additionally, it explores the metabolic fate of AGEs in the body and the mechanisms of disease associated with metabolic abnormalities that may be caused by the consumption of foods containing AGEs. This review aims to provide an overview of the perspectives of relevant recent and future research on metabolic abnormalities caused by foods containing AGEs or by AGEs produced in the body., (© 2024 The Author(s). Comprehensive Reviews in Food Science and Food Safety published by Wiley Periodicals LLC on behalf of Institute of Food Technologists.)

Background: AGEs accumulate in the skin as a result of a high-sugar diet and play an important role in the skin aging process., Objectives: The aim of this study was to characterize the mechanism underlying the effect of a high-sugar diet on skin aging damage at a holistic level., Methods: We established a high-sugar diet mouse model to compare and analyze differences in physiological indexes. The effect of a high-sugar diet on skin aging damage was analyzed by means of a transcriptome study and staining of pathological sections. Furthermore, the differences in the protein expression of AGEs and ECM components between the HSD and control groups were further verified by immunohistochemistry., Results: The skin in the HSD group mice tended toward a red, yellow, dark, and deep color. In addition, the epidermis was irregular with anomalous phenomena, the epidermis was thinned, and the dermis lost its normal structure and showed vacuolated changes. Transcriptomics results revealed significant downregulation of the ECM-receptor interaction pathway, significant upregulation of the expression of AGEs and significant downregulation of the expression levels of COLI, FN1, LM5, and TNC, among others ECM proteins and ECM receptors., Conclusions: High-sugar diets cause skin aging damage by inducing the accumulation of AGEs, disrupting the expression of ECM proteins and their receptors, and downregulating the ECM-receptor interaction pathway, which affects cellular behavioral functions such as cell proliferation, migration, and adhesion, as well as normal skin tissue structure., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

As the most serious of the many worse new pathological changes caused by diabetes, there are many risk factors for the occurrence and development of diabetic retinopathy (DR). They mainly include hyperglycemia, hypertension, hyperlipidemia and so on. Among them, hyperglycemia is the most critical cause, and plays a vital role in the pathological changes of DR. High-sucrose diets (HSDs) lead to elevated blood glucose levels in vivo, which, through oxidative stress, inflammation, the production of advanced glycation end products (AGEs) and vascular endothelial growth factor (VEGF), cause plenty of pathological damages to the retina and ultimately bring about loss of vision. The existing therapies for DR primarily target the terminal stage of the disease, when irreversible visual impairment has appeared. Therefore, early prevention is particularly critical. The early prevention of DR-related vision loss requires adjustments to dietary habits, mainly by reducing sugar intake. This article primarily discusses the risk factors, pathophysiological processes and molecular mechanisms associated with the development of DR caused by HSDs. It aims to raise awareness of the crucial role of diet in the occurrence and progression of DR, promote timely changes in dietary habits, prevent vision loss and improve the quality of life. The aim is to make people aware of the importance of diet in the occurrence and progression of DR. According to the dietary modification strategies that we give, patients can change their poor eating habits in a timely manner to avoid theoretically avoidable retinopathy and obtain an excellent prognosis.

Advanced glycation end products (AGEs) are a large number of heterogeneous compounds formed by the glycation of proteins, fats or nucleic acids. Endogenous AGEs have been associated with various health problems such as obesity, type 2 diabetes mellitus and cardiovascular disease. Inflammation is thought to be one of the main mechanisms in the development of these disorders. Although AGEs are produced endogenously in the body, exogenous sources such as smoking and diet also contribute to the body pool. Therefore, when the AGE pool in the body rises above physiological levels, different pathological conditions may occur through various mechanisms, especially inflammation. While the effects of endogenous AGEs on the development of inflammation have been studied relatively extensively, and current evidence indicates that dietary AGEs (dAGEs) contribute to the body's AGE pool, it is not yet known whether dAGEs have the same effect on the development of inflammation as endogenous AGEs. Therefore, this review aimed to evaluate the results of cross-sectional and intervention studies to understand whether dAGEs are associated with inflammation and, if there is an effect on inflammation, through which mechanisms this effect might occur., (© 2023 British Nutrition Foundation.)

Background: Dietary advanced glycation end products (AGEs) can play an important role in increasing inflammatory factors and oxidative stress as risk factors for cancers. In the present study, we aimed to assess the relationship between dietary AGEs and the risk of breast cancer (BC) in Iranian adult women., Methods: This hospital-based case-control study includes 401 participants aged ≥ 30 years old. The cases group consisted of 134 women diagnosed with histologically confirmed BC. The control group included 267 women enrolled randomly from patients admitted to the same hospitals. Dietary intake information was determined using a validated food frequency questionnaire, and dietary AGEs intake was computed for all participants. Logistic regression models, adjusted for potential confounders, were used to determine the odds ratios (OR) and 95% confidence interval (CI) of BC across tertiles of dietary AGEs., Results: The mean ± SD age and body mass index of the study population were 47.92 ± 10.33 years and 29.43 ± 5.51 kg/m 2 , respectively. The median (interquartile) of dietary AGEs in all individuals was 9251(7450, 11,818) kU/day. After adjusting for age, first pregnancy age, and energy intake, participants in the highest tertile of dietary AGEs intakes had higher odds of BC compared to those in the lowest tertile of dietary AGEs (OR:2.29;95%CI:1.19-4.39, P trend :0.012). Additionally, in the multivariable model, after adjusting for age, age at first pregnancy, energy, menopausal status, family history of cancer, anti-inflammatory drug use, Vitamin D supplementation, physical activity, body mass index, number of childbirths, and history of abortion, breastfeeding, and oral contraceptive pills use, the odds of BC were increased across tertiles of dietary AGEs intake (OR: 2.33; 95%CI: 1.18-4.60, P trend : 0.017)., Conclusion: The present findings suggest that a diet with high AGEs is associated with a higher likelihood of BC in adult women., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Excessive accumulation of advanced glycation end products (AGEs) in the body has been associated with many adverse health conditions. The common point of the pathologies associated at this point is oxidative stress and inflammation. Pregnancy is an important period in which many physiological, psychological, and biological changes are experienced. Along with the physiological changes that occur during this period, the mother maintaining an AGE-rich diet may cause an increase in the body's AGE pool and may increase oxidative stress and inflammation, as seen in healthy individuals. Studies have reported the negative effects of maternal AGE levels on maternal and fetal health during pregnancy. Although gestational diabetes, preeclampsia, endothelial dysfunction, and pelvic diseases constitute maternal complications, a number of pathological conditions such as intrauterine growth retardation, premature birth, neural tube defect, neurobehavioral developmental disorders, fetal death, and neonatal asphyxia constitute fetal complications. It is thought that the mechanisms of these complications have not been confirmed yet and more clinical studies are needed on this subject. The possible effects of dietary AGE levels during pregnancy on maternal and fetal health are examined in this review., (© The Author(s) 2022. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Podocyte injury leading to albuminuria is a characteristic feature of diabetic nephropathy (DN). Hyperglycemia and advanced glycation end products (AGEs) are major determinants of DN. However, the underlying mechanisms of podocyte injury remain poorly understood. The cytosolic protein TNFAIP2/M-Sec is required for tunneling nanotubes (TNTs) formation, which are membrane channels that transiently connect cells, allowing organelle transfer. Podocytes express TNFAIP2 and form TNTs, but the potential relevance of the TNFAIP2-TNT system in DN is unknown. We studied TNFAIP2 expression in both human and experimental DN and the renal effect of tnfaip2 deletion in streptozotocin-induced DN. Moreover, we explored the role of the TNFAIP2-TNT system in podocytes exposed to diabetes-related insults. TNFAIP2 was overexpressed by podocytes in both human and experimental DN and exposre of podocytes to high glucose and AGEs induced the TNFAIP2-TNT system. In diabetic mice, tnfaip2 deletion exacerbated albuminuria, renal function loss, podocyte injury, and mesangial expansion. Moreover, blockade of the autophagic flux due to lysosomal dysfunction was observed in diabetes-injured podocytes both in vitro and in vivo and exacerbated by tnfaip2 deletion. TNTs allowed autophagosome and lysosome exchange between podocytes, thereby ameliorating AGE-induced lysosomal dysfunction and apoptosis. This protective effect was abolished by tnfaip2 deletion, TNT inhibition, and donor cell lysosome damage. By contrast, Tnfaip2 overexpression enhanced TNT-mediated transfer and prevented AGE-induced autophagy and lysosome dysfunction and apoptosis. In conclusion, TNFAIP2 plays an important protective role in podocytes in the context of DN by allowing TNT-mediated autophagosome and lysosome exchange and may represent a novel druggable target. Abbreviations: AGEs: advanced glycation end products; AKT1: AKT serine/threonine kinase 1; AO: acridine orange; ALs: autolysosomes; APs: autophagosomes; BM: bone marrow; BSA: bovine serum albumin; CTSD: cathepsin D; DIC: differential interference contrast; DN: diabetic nephropathy; FSGS: focal segmental glomerulosclerosis; HG: high glucose; KO: knockout; LAMP1: lysosomal-associated membrane protein 1; LMP: lysosomal membrane permeabilization; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; PI3K: phosphoinositide 3-kinase; STZ: streptozotocin; TNF: tumor necrosis factor; TNFAIP2: tumor necrosis factor, alpha-induced protein 2; TNTs: tunneling nanotubes; WT: wild type.

Dietary advanced glycation end-products (AGEs) are a heterogeneous group of compounds formed when reducing sugars are heated with proteins, amino acids, or lipids at high temperatures for a prolonged period. The presence and accumulation of AGEs in numerous cell types and tissues are known to be prevalent in the pathology of many diseases. Modern diets, which contain a high proportion of processed foods and therefore a high level of AGE, cause deleterious effects leading to a multitude of unregulated intracellular and extracellular signalling and inflammatory pathways. Currently, many studies focus on investigating the chemical and structural aspects of AGEs and how they affect the metabolism and the cardiovascular and renal systems. Studies have also shown that AGEs affect the digestive system. However, there is no complete picture of the implication of AGEs in this area. The gastrointestinal tract is not only the first and principal site for the digestion and absorption of dietary AGEs but also one of the most susceptible organs to AGEs, which may exert many local and systemic effects. In this review, we summarise the current evidence of the association between a high-AGE diet and poor health outcomes, with a special focus on the relationship between dietary AGEs and alterations in the gastrointestinal structure, modifications in enteric neurons, and microbiota reshaping.

A Western diet comprises high levels of dicarbonyls and advanced glycation endproducts (AGEs), which may contribute to flares and symptoms in inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). We therefore investigated the intake of dietary dicarbonyls and AGEs in IBD and IBS patients as part of the habitual diet, and their association with intestinal inflammation. Food frequency questionnaires from 238 IBD, 261 IBS as well as 195 healthy control (HC) subjects were used to calculate the intake of dicarbonyls methylglyoxal, glyoxal, and 3-deoxyglucosone, and of the AGEs Nε-(carboxymethyl)lysine, Nε-(1-carboxyethyl)lysine and methylglyoxal-derived hydroimidazolone-1. Intestinal inflammation was assessed using faecal calprotectin. The absolute dietary intake of all dicarbonyls and AGEs was higher in IBD and HC as compared to IBS (all p < 0.05). However, after energy-adjustment, only glyoxal was lower in IBD versus IBS and HC (p < 0.05). Faecal calprotectin was not significantly associated with dietary dicarbonyls and AGEs in either of the subgroups. The absolute intake of methylglyoxal was significantly higher in patients with low (<15 μg/g) compared to moderate calprotectin levels (15−<50 μg/g, p = 0.031). The concentrations of dietary dicarbonyls and AGEs generally present in the diet of Dutch patients with IBD or IBS are not associated with intestinal inflammation, although potential harmful effects might be counteracted by anti-inflammatory components in the food matrix.

The development of an individual during fetal life and childhood is characterized by rapid growth as well as gradual maturation of organs and systems. Beyond the nutritional intake in essential nutrients, food contaminants can permanently influence the way organs mature and function. These processes are called "programming" and play an essential role in the occurrence of non-communicable chronic diseases throughout the lifespan. Populations as pregnant women, fetuses and young children are vulnerable and particularly sensitive to food contaminants which can induce epigenetic modifications transmissible to future generations. Among these contaminants, pesticides are found in most food matrices exposing humans to cocktails of molecules through variable concentrations and duration of exposure. The Maillard reaction products (MRPs) represent other food contaminants resulting from heat treatment of food. Modern diet, rich in fats and sugars, is also rich in neoformed pathogenic compounds, Advanced Glycation End products (AGEs), the levels of which depend on the heat treatment of foods and eating habits and whose effects on health are controversial. In this review, we have chosen to present the current knowledge on the impacts of selected pesticides and MRPs, on the risk of developing during life non-communicable chronic diseases such as IBD, metabolic disorders or allergies. A large review of literature was performed via Pubmed, and the most appropriate studies were summarised., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Few large epidemiological studies have evaluated the association between dietary advanced glycation end products (AGEs) and cancer risk. We evaluated the relationship between dietary AGE intake and the incidence of total cancer and site-specific cancers in a population-based prospective study in Japan. Participants were 14,173 men and 16,549 women who were 35 years of age or older in 1992. Dietary intake was assessed via a validated food frequency questionnaire. Intake of the AGE N ε -carboxymethyl-lysine (CML) was estimated using databases of CML content in foods determined using ultraperformance liquid chromatography-tandem mass spectrometry. Cancer incidence was confirmed through regional population-based cancer registries. During a mean follow-up period of 13.3 years, 1954 men and 1477 women developed cancer. We did not observe a significant association between CML intake and the risk of total cancer in men or women. In men, compared with the lowest quartile of CML intake, the hazard ratios of liver cancer for the second, third, and highest quartiles were 1.69 (95% CI: 0.92-3.10), 1.48 (95% CI: 0.77-2.84), and 2.10 (95% CI: 1.10-3.98; trend p = 0.04). Conversely, a decreased relative risk of male stomach cancer was observed for the second and highest quartiles of CML intake versus the lowest quartile, with hazard ratios of 0.73 and 0.67, respectively (trend p = 0.08). Our finding on the potential harmfulness of consuming AGEs on liver cancer risk is intriguing and warrants further study., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Advanced glycation end products (AGEs) are glycated proteins or lipids formed endogenously in the human body or consumed through diet. Ultra-processed foods and some culinary techniques, such as dry cooking methods, represent the main sources and drivers of dietary AGEs. Tissue accumulation of AGEs has been associated with cellular aging and implicated in various age-related diseases, including type-2 diabetes and cardiovascular disease. The current review summarizes the literature examining the associations between AGEs and neurocognitive and mental health disorders. Studies indicate that elevated circulating AGEs are cross-sectionally associated with poorer cognitive function and longitudinally increase the risk of developing dementia. Additionally, preliminary studies show that higher skin AGE accumulation may be associated with mental disorders, particularly depression and schizophrenia. Potential mechanisms underpinning the effects of AGEs include elevated oxidative stress and neuroinflammation, which are both key pathogenetic mechanisms underlying neurodegeneration and mental disorders. Decreasing dietary intake of AGEs may improve neurological and mental disorder outcomes. However, more sophisticated prospective studies and analytical approaches are required to verify directionality and the extent to which AGEs represent a mediator linking unhealthy dietary patterns with cognitive and mental disorders.

Background and Aims: Prior studies suggest a positive association between dietary AGEs and adverse health outcomes but have not well-characterized AGEs intake and its association with mortality in a general adult population in the United States., Methods and Results: We included 5474 adults with diabetes from the 2003 to 2018 National Health and Nutrition Examination Survey, a nationally representative sample of the non-institutionalized civilian population in the United States. Concordance to dietary guidelines (Healthy Eating Index 2015 [HEI-2015]) and intake of the AGE Nϵ-(carboxymethyl)lysine (CML) were estimated using an existing database and two 24-h food recalls. Multivariable Cox regression evaluated the association between AGEs intake and all-cause mortality. A secondary analysis measured CML, Nϵ-(1-carboxyethyl)lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MGH1) from an alternative database. Higher AGEs intake was associated with lower concordance to dietary guidelines (Means and standard errors of HEI-2015 score, by quartiles of AGEs intake: Q1 = 55.2 ± 0.6, Q2 = 54.1 ± 0.5, Q3 = 52.1 ± 0.5, Q4 = 49.0 ± 0.5; p < 0.001). There were 743 deaths among 3884 adults in the mortality analysis (mean follow-up = 3.8 years). AGEs intake was not significantly associated with all-cause mortality (Q2 vs. Q1: Hazard Ratio [HR] = 0.91 [0.69-1.21], Q3 vs. Q1: HR = 0.90 [0.63-1.27], Q4 vs. Q1: HR = 1.16 [0.84-1.60]). Results were similar in secondary analyses., Conclusion: While dietary AGEs intake was associated with concordance to dietary guidelines, it was not significantly associated with all-cause mortality among adults with diabetes. Further research may consider other health outcomes as well as the evaluating specific contribution of dietary AGEs to overall AGEs burden., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Published by Elsevier B.V.)

Background: The aim was to assess the association between levels of advanced glycation endproducts (AGEs) in the gingival crevicular fluid (GCF) and periodontal parameters among cigarette-smokers and waterpipe-users., Methods: Self-reported cigarette-smokers; waterpipe-users and never-smokers were included. Demographic data was recorded using a questionnaire. Periodontal parameters (plaque index [PI], gingival index [GI], clinical attachment loss [AL], probing depth [PD], and marginal bone loss [MBL]) were assessed in all groups. The GCF samples were collected using standard techniques and assessed for AGEs levels using enzyme-linked immunosorbent assay. Sample-size estimation was done and group-comparisons were done. Correlation between levels of GCF AGEs levels and periodontal parameters was assessed using a logistic regression model. Level of significance was set at P < 0.01., Results: Eighty-two individuals (28 cigarette-smokers, 28 waterpipe-users and 26 never-smokers) were included. There was no difference in mean ages of all patients. Cigarette-smokers had a smoking history of 5.1 ± 0.2 pack years and waterpipe-users were using waterpipe for 4.4 ± 0.6 years. There was no statistically significant difference in PI, GI, clinical AL, PD and MBL in all groups. Levels of AGEs were significantly higher among cigarette-smokers (P < 0.001) and waterpipe-users (P < 0.001) than never-smokers. There was no significant correlation between levels of GCF AGEs levels and periodontal parameters in all groups., Conclusion: Clinical periodontal status of individuals with a short history of cigarette-smoking and waterpipe-usage may appear similar to never-smokers. On a molecular level, cigarette-smoking and waterpipe-users express raised levels of AGEs than never-smokers that sirens about the ongoing yet latent periodontal inflammatory process., (© 2022. The Author(s).)

Objective: Dietary-derived advanced glycation end products (AGEs) vary for different food types and the methods employed during their preparation may contribute to diverse chronic health conditions. The goal of this study was to investigate the associations of dietary AGEs (dAGEs) with cognitive decline in older adults., Methods: Non-demented older adults ( n = 684) underwent annual testing with 19 cognitive tests summarized as a global cognitive score based on five cognitive domains. We modified a previously validated food frequency questionnaire designed to assess dAGE. The modified questionnaire assessed portion size and frequency of consumption of six food groups (meat, poultry, fish, cheese, spreads, and processed foods), as well as the method of their preparation (e.g., grilling, boiling). dAGE was the sum of the scores of the six food groups. Linear mixed-effect models were used to examine the association of baseline dAGE with cognitive decline. All models controlled for age, sex, education, race, and body mass index (BMI)., Results: Average follow-up was 3.0 years. Higher baseline dAGEs was associated with a faster rate of global cognitive decline (Estimate = -0.003 (standard error = 0.001, p -value = 0.015). This association was driven by declines in episodic memory (-0.004 (0.002, 0.013)) and perceptual speed (-0.003 (0.001, 0.049)) but not by semantic memory, working memory, and visuospatial domains. These associations were not attenuated by controlling for cardiovascular risk factors and diseases, including diabetes. Levels of dAGE of the specific food groups were not associated with cognitive decline., Conclusions: Higher levels of dietary AGE levels in older adults are associated with faster cognitive decline. These data lend further support for the importance of diet and that its modification may slow or prevent late-life cognitive impairment. Further clinical studies will be needed and the molecular mechanisms underlying these associations will need to be identified.

Carbonyl stress is a condition characterized by an increase in the steady-state levels of reactive carbonyl species (RCS) that leads to accumulation of their irreversible covalent adducts with biological molecules. RCS are generated by the oxidative cleavage and cellular metabolism of lipids and sugars. In addition to causing damage directly, the RCS adducts, advanced glycation end-products (AGEs) and advanced lipoxidation end-products (ALEs), cause additional harm by eliciting chronic inflammation through receptor-mediated mechanisms. Hyperglycemia- and dyslipidemia-induced carbonyl stress plays a role in diabetic cardiovascular complications and diabetes-related cancer risk. Moreover, the increased dietary exposure to AGEs/ALEs could mediate the impact of the modern, highly processed diet on cardiometabolic and cancer risk. Finally, the transient carbonyl stress resulting from supraphysiological postprandial spikes in blood glucose and lipid levels may play a role in acute proinflammatory and proatherogenic changes occurring after a calorie dense meal. These findings underline the potential importance of carbonyl stress as a mediator of the cardiometabolic and cancer risk linked to today's unhealthy diet. In this review, current knowledge in this field is discussed along with future research courses to offer new insights and open new avenues for therapeutic interventions to prevent diet-associated cardiometabolic disorders and cancer.

Objective: To examine, following perinatal exposure to a diet high in advanced glycation end products (AGEs), whether the use of standard AGE-free mouse chow during the postweaning period alters metabolism and reproduction differently than exposure to a diet low in AGEs., Design: Experimental animal study., Setting: University-based research laboratory., Animal(s): Female CD1 mice., Intervention(s): Seven-week-old mice were placed on a diet either low or high in AGEs perinatally, before mating and then during pregnancy and lactation. All offspring were weaned onto an AGE-free normal chow., Main Outcome Measure(s): Growth curve, liver and abdominal fat weight, insulin and glucose tolerance tests, vaginal opening, estrous cyclicity, and serum levels of antimüllerian hormone, leptin, and adiponectin were assessed. Ovarian histologic examination for follicular count and gene expression was also performed., Result(s): Compared with the mice exposed to a diet low in AGEs, the mice exposed to a diet high in AGEs showed lower body weight in pups, lower liver weight, delayed vaginal opening, higher serum antimüllerian hormone levels, lower primordial and secondary follicle pools, and higher ovarian Fshr messenger RNA levels., Conclusion(s): Following weaning, perinatal AGEs can target puberty onset and folliculogenesis differently to standard mouse chow., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

With the development of living standards, harmful substances in diet and food safety have seriously endangered people health and life. Advanced glycation end products (AGEs), which formed by Maillard reactions in processed food, have been shown a significantly associated with many chronic diseases, such as nephropathy, atherosclerosis, Alzheimer's disease, and tumors. In recent years, the research about diet advanced glycation end products (dAGEs) have widespread controversy in academia. The main arguments include the production mechanism of dAGEs, metabolic pathways, and relationships with chronic diseases, especially related to the intestines, gut microbiota, and intestinal disorders. So this review attempts to briefly summarize the dAGE in following aspects, including the influencing factors, metabolism, absorption, and so forth. In addition, the effects of dAGEs on intestinal health and gut microbes were discussed, which can offer a goal for boff in to design low dAGEs products and provided some perspectives for further study with AGEs in the future.

The impact of dietary advanced glycation end products (dAGEs) on human health has been discussed in many studies but, to date, no consensual pathophysiological process has been demonstrated. The intestinal absorption pathways which have so far been described for dAGEs, the passive diffusion of free AGE adducts and transport of glycated di-tripeptides by the peptide transporter 1 (PEPT-1), are not compatible with certain pathophysiological processes described. To get new insight into the intestinal absorption pathways and the pathophysiological mechanisms of dAGEs, we initiated an in vivo study with a so-called simple animal model with a complete digestive tract, Caenorhabditis elegans . Dietary bacteria were chemically modified with glyoxylic acid to mainly produce Nε -carboxymethyllysine (CML) and used to feed the worms. We performed different immunotechniques using an anti-CML antibody for the relative quantification of ingested CML and localization of this AGE in the worms' intestine. The relative expression of genes encoding different biological processes such as response to stresses and intestinal digestion were determined. The physiological development of the worms was verified. All the results were compared with those obtained with the control bacteria. The results revealed a new route for the intestinal absorption of dietary CML (dCML), endocytosis, which could be mediated by scavenger receptors. The exposure of worms to dCML induced a reproductive defect and a transcriptional response reflecting oxidative, carbonyl and protein folding stresses. These data, in particular the demonstration of endocytosis of dCML by enterocytes, open up new perspectives to better characterize the pathophysiological mechanisms of dAGEs.

Background: Advanced glycation end-products (AGE) are formed through nonenzymatic glycation of free amino groups in proteins or lipid. They are associated with inflammation and oxidative stress, and their accumulation in the body is implicated in chronic disease morbidity and mortality. We examined the association between postdiagnosis dietary N ε -carboxymethyl-lysine (CML)-AGE intake and mortality among women diagnosed with breast cancer., Methods: Postmenopausal women aged 50 to 79 years were enrolled in the Women's Health Initiative (WHI) between 1993 and 1998 and followed up until death or censoring through March 2018. We included 2,023 women diagnosed with first primary invasive breast cancer during follow-up who completed a food frequency questionnaire (FFQ) after diagnosis. Cox proportional hazards (PH) regression models estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) of association between tertiles of postdiagnosis CML-AGE intake and mortality risk from all causes, breast cancer, and cardiovascular disease., Results: After a median 15.1 years of follow-up, 630 deaths from all causes were reported (193 were breast cancer-related, and 129 were cardiovascular disease-related). Postdiagnosis CML-AGE intake was associated with all-cause (HR T3vsT1 , 1.37; 95% CI, 1.09-1.74), breast cancer (HR T3vsT1 , 1.49; 95% CI, 0.98-2.24), and cardiovascular disease (HR T3vsT1 , 1.91; 95% CI, 1.09-3.32) mortality., Conclusions: Higher intake of AGEs was associated with higher risk of major causes of mortality among postmenopausal women diagnosed with breast cancer., Impact: Our findings suggest that dietary AGEs may contribute to the risk of mortality after breast cancer diagnosis. Further prospective studies examining dietary AGEs in breast cancer outcomes and intervention studies targeting dietary AGE reduction are needed to confirm our findings., (©2021 American Association for Cancer Research.)

Pentagalloylglucose (PGG), a gallotannin polyphenolic compound, has been found to possess a host of beneficial pharmacologic activities, such as anti-inflammatory and antioxidative activities. We previously demonstrated that PGG is capable of binding to the cell membrane of renal mesangial cells, but the pharmacological effect of PGG on diabetic renal injury and the underlying mechanisms are still not yet clear. In this study, the effects of PGG on Nrf2/HO-1 and JAK2/STAT3 signaling were explored in AGE-stimulated mesangial cells. Furthermore, the Nrf2 transcriptional inhibitor ML385 was used to verify the involvement of Nrf2 in the PGG-mediated inhibition of the JAK2/STAT3 cascade. Our results showed that PGG significantly inhibited AGE-induced ROS generation and activated AGE-inhibited Nrf2/HO-1 signaling. Moreover, AGE-induced inflammatory cytokines (IL-1β and TNF-α) and their signaling through JAK2/STAT3 were blocked by PGG. Furthermore, ML385 suppressed Nrf2/HO-1 signaling, elevated ROS and cytokine production, and activated JAK2/STAT3 cascade were reversed by PGG. These findings indicate that PGG inhibits the JAK2/STAT3 cascade by activating Nrf2/HO-1 signaling., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2021 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Dietary advanced glycation end-products (dAGEs) have been hypothesized to be associated with a higher risk of colorectal cancer (CRC) by promoting inflammation, metabolic dysfunction, and oxidative stress in the colonic epithelium. However, evidence from prospective cohort studies is scarce and inconclusive. We evaluated CRC risk associated with the intake of dAGEs in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Dietary intakes of three major dAGEs: N ε -carboxy-methyllysine (CML), N ε -carboxyethyllysine (CEL), and N δ -(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were estimated in 450,111 participants (median follow-up = 13 years, with 6162 CRC cases) by matching to a detailed published European food composition database. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of dAGEs with CRC were computed using multivariable-adjusted Cox regression models. Inverse CRC risk associations were observed for CML (HR comparing extreme quintiles: HR Q5vs . Q1 = 0.92, 95% CI = 0.85-1.00) and MG-H1 (HR Q5vs . Q1 = 0.92, 95% CI = 0.85-1.00), but not for CEL (HR Q5vs . Q1 = 0.97, 95% CI = 0.89-1.05). The associations did not differ by sex or anatomical location of the tumor. Contrary to the initial hypothesis, our findings suggest an inverse association between dAGEs and CRC risk. More research is required to verify these findings and better differentiate the role of dAGEs from that of endogenously produced AGEs and their precursor compounds in CRC development.

Chronic Low-Grade Inflammation (CLGI) is a non-overt inflammatory state characterized by a continuous activation of inflammation mediators associated with metabolic diseases. It has been linked to the overconsumption of Advanced Glycation End-Products (AGEs), and/or macronutrients which lead to an increase in local and systemic pro-inflammatory biomarkers in humans and animal models. This review provides a summary of research into biomarkers of diet-induced CLGI in murine models, with a focus on AGEs and obesogenic diets, and presents the physiological effects described in the literature. Diet-induced CLGI is associated with metabolic endotoxemia, and/or gut microbiota remodeling in rodents. The mechanisms identified so far are centered on pro-inflammatory axes such as the interaction between AGEs and their main receptor AGEs (RAGE) or increased levels of lipopolysaccharide. The use of murine models has helped to elucidate the local and systemic expression of CLGI mediators. These models have enabled significant advances in identification of diet-induced CLGI biomarkers and resultant physiological effects. Some limitations on the translational (murine → humans) use of biomarkers may arise, but murine models have greatly facilitated the testing of specific dietary components. However, there remains a lack of information at the whole-organism level of organization, as well as a lack of consensus on the best biomarker for use in CLGI studies and recommendations as to future research conclude this review.

During food processing and storage, and in tissues and fluids under physiological conditions, the Maillard reaction occurs. During this reaction, reactive 1,2-dicarbonyl compounds arise as intermediates that undergo further reactions to form advanced glycation end products (AGEs). Diet is the primary source of exogenous AGEs. Endogenously formed AGEs have been proposed as a risk factor in the pathogenesis of diet-related diseases such as diabetes, insulin resistance, cardiovascular diseases, or chronic disease. AGEs may differently contribute to the diet-related exacerbation of oxidative stress, inflammation, and protein modifications. Here, to understand the contribution of each compound, we tested individually, for the first time, the effect of five 1,2-dicarbonyl compounds 3-deoxyglucosone (3-DG), 3-deoxygalactosone (3-DGal), 3,4-dideoxyglucosone-3-ene (3,4-DGE), glyoxal (GO), and methylglyoxal (MGO) and four different glycated amino acids N- ε -(carboxyethyl)lysine (CEL), N- ε -(carboxymethyl)lysine (CML), methylglyoxal-derived hydroimidazolone-1 (MG-H1), and pyrraline (Pyrr) in a cell line of human keratinocytes (HaCaT). We found that most of the glycated amino acids, i.e., CEL, CML, and MG-H1, did not show any cytotoxicity. At the same time, 1,2-dicarbonyl compounds 3-DGal, 3,4-DGE, GO, and MGO increased the production of reactive oxygen species and induced cell death. MGO induced cell death by apoptosis, whereas 3-DGal and 3,4-DGE induced nuclear translocation of the proinflammatory NF- κ B transcription pathway, and the activation of the pyroptosis-related NLRP3 inflammasome cascade. Overall, these results demonstrate the higher toxic impact of 1,2-dicarbonyl compounds on mucosal epithelial cells when compared to glycated amino acids and the selective activation of intracellular signaling pathways involved in the crosstalk mechanisms linking oxidative stress to excessive inflammation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Vanesa Cepas et al.)

Advanced glycation end products (AGEs)-induced inflammation and degradation of aggrecan in human chondrocytes play an important role in the progression and development of osteoarthritis (OA). Azilsartan, an angiotensin II receptor antagonist, has been licensed for the treatment of high blood pressure. However, the effects of Azilsartan in OA and AGEs-induced damages in chondrocytes have not been previously reported. The injured chondrocytes model was established by incubating with 5 μmol/L AGEs. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was used to evaluate the cell viability of treated SW1353 cells. The gene expression levels of interleukin-1α (IL-1α), tumor necrosis factor-β (TNF-β), IL-6, a disintegrin-like and metallopeptidase with thrombospondin type motif-4 (ADAMTS-4), ADAMTS-5, Aggrecan, and Sox-4 were evaluated using quantitative real-time polymerase chain reaction and their protein levels were determined using enzyme-linked immunosorbent assay or Western blot analysis. Mitogen-activated protein kinase p38 pathway was surveyed using phosp-p38 level and its specific inhibitor SB203580 was employed to block the p38 pathway. The overexpression of Sox4 plasmid was transfected into SW1353 cells to assess its regulation on ADAMTS-4 and ADAMTS-5. Azilsartan reduced AGEs-induced production of proinflammatory cytokines, such as IL-1α, TNF-β, and IL-6. Azilsartan prevented AGEs-induced expressions of ADAMTS-4 and ADAMTS-5 as well as the reduction of aggrecan. Mechanistically, AGEs treatment increased the expression of Sox4 in a dose-dependent manner. AGE treatment increased the level of phosphorylated p38. However, treatment with the p38 inhibitor SB203580 inhibited AGEs-induced expression of Sox4, suggesting that AGEs-induced expression of Sox4 is mediated by p38. Furthermore, Azilsartan suppressed AGEs-induced phosphorylation of p38 and expression of Sox4. Finally, the overexpression of Sox4 abolished the inhibitory effects of Azilsartan against the expressions of ADAMTS-4 and ADAMTS-5. Azilsartan treatment prevented AGEs-induced inflammatory response and degradation of aggrecan through inhibition of Sox4., (© 2021 Wiley Periodicals LLC.)

Introduction: Advanced glycation end products (AGEs) and receptor of advanced glycation end products (RAGE) mediate renal function during diabetic and non-diabetic nephropathy development. Methylglyoxal-lysine dimer (MOLD), a typical toxic advanced glycation end product (TAGE), contributes to inflammatory responses during renal diseases. This study determines the effect of MOLD on inflammatory responses in mouse mesangial cells., Methods and Results: The murine mesangial cell line SV40 MES 13 is used to assess nuclear factor-kappa B (NF-κB) expression, reactive oxygen species (ROS) production, and mitochondria labeling. The interaction model between RAGE and MOLD is also determined. MOLD treatment of mesangial cells markedly increases RAGE expression and the linkage with V-type Ig domain of RAGE. MOLD induces ROS production and mitochondrial dysfunction. MOLD activates phosphatidylinositol 3-kinase-protein kinase B (PI3KB) and NF-κB signaling pathways. It is confirmed that these changes are reversed when ROS is suppressed. These effects may be regulated through mitogen-activated protein kinases and pro-inflammatory cytokines in circulatory inflammation responses., Conclusion: MOLD plays a major role in nephropathy via ROS production and mitochondrial dysfunction through direct association with RAGE. Further, the NF-kB and PI3K/AKT signaling pathways triggered by ROS mediate the inflammatory response to exacerbate MOLD-induced damages in inflammation-related diabetic and non-diabetic renal diseases., (© 2021 Wiley-VCH GmbH.)

Advanced glycation end products (AGEs) arising from dietary intake have been associated with numerous chronic diseases including cardiovascular diseases. The interaction between platelets and AGEs has been proposed to play a role in the etiology of cardiovascular diseases. However, the effects of the interaction between platelets and Maillard reaction products generated from glyoxal (Gly) or methylglyoxal (MG) are poorly understood. In this work, the effects of AGEs generated by the reaction between Gly or MG with Lys or bovine serum albumin (BSA) on platelet activation and aggregation were assessed. AGEs were generated incubating Gly or MG with Lys or BSA during 5 hours or 14 days, respectively. AGEs generation were characterized by kinetic studies and by amino acid analysis. Human platelet-rich plasma (PRP) was incubated with different concentrations of AGEs from Lys-MG or Lys-Gly and BSA-MG or BSA-Gly. Platelet activation was determined quantifying the expression of CD62 ( P -selectin) in PRP exposed to different AGEs concentrations. It was found that Lys-MG and Lys-Gly induced an increase in P -selectin expression ( p < .05), being 33.9% higher for Lys-MG when compared to Lys-Gly. Platelets incubated in the presence of BSA-MG and BSA-Gly did not show an increase in the P -selectin expression. Platelet aggregation was significantly higher for the mixture Lys-MG (in all the range of concentrations evaluated), whereas for Lys-Gly it was only significant the highest concentration (Lys 168 µM/Gly 168 µM). It was observed a significant increase in platelet aggregation induced by ADP for samples BSA-Gly. AGEs formed with MG-Lys induce a higher activation and aggregation of platelets when compared to those formed from Gly-Lys.

Advanced glycation end products (AGEs) are formed from amino acids and reducing sugars through nonenzymatic Maillard reaction. AGEs are known to induce oxidative stress, which may cause fibrosis or cancer. In this study, we investigated the protective effect of caffeic acid (CA) on AGE-mediated kidney epithelial to mesenchymal transition (EMT) in human HK-2 cells. Exposure to 100 µg/mL of AGEs by kidney epithelial cells raised the production of reactive oxygen species by 5.2-fold and decreased levels of glutathione. In addition, cardamonin, a β-catenin inhibitor, was used to determine the signaling pathway for β-catenin in which cardamonin inhibited the AGEs-induced translocation of β-catenin into the nucleus, resulting in an inhibition of the EMT process. Similarly, our findings showed that, close to the control level, CA treatment decreased AGE-mediated oxidative stress, loss of E-cadherin expression, and overexpression of α-smooth muscle actin and fibronectin by inactivation of the β-catenin pathway. Furthermore, AGE treatment enhanced the expression of collagen type I (1.99-fold) as well as the activity of metalloproteinases 2 (1.86-fold) and 9 (2.79-fold), but such increase was inhibited by the pretreatment of CA. In conclusion, this study determined the inhibitory effect of CA on AGE-induced β-catenin signaling, which prevented the occurrence of EMT in kidney epithelial cells. This suggests that CA may be a potential target for AGE-induced renal fibrosis. PRACTICAL APPLICATION: Exposure of kidney epithelial cells to advanced glycation end products (AGEs) leads to a rise in reactive oxygen species and a decrease in glutathione, thereby increasing oxidative stress that may cause fibrosis. However, treatment of kidney cells with caffeic acid (CA) prior to their exposure to AGEs lowers oxidative stress and decreases fibrosis. This research reveals the beneficial influence of CA on renal fibrosis in laboratory-cultured kidney cells (in vitro), which makes CA a potential therapeutic target for AGE-induced fibrosis., (© 2021 Institute of Food Technologists®.)

Background: Diet is a modifier of metabolic syndrome which in turn is associated with World Trade Center obstructive airways disease (WTC-OAD). We have designed this study to (1) assess the dietary phenotype (food types, physical activity, and dietary habits) of the Fire Department of New York (FDNY) WTC-Health Program (WTC-HP) cohort and (2) quantify the association of dietary quality and its advanced glycation end product (AGE) content with the development of WTC-OAD., Methods: WTC-OAD, defined as developing WTC-Lung Injury (WTC-LI; FEV 1  < LLN) and/or airway hyperreactivity (AHR; positive methacholine and/or positive bronchodilator response). Rapid Eating and Activity Assessment for Participants-Short Version (REAP-S) deployed on 3/1/2018 in the WTC-HP annual monitoring assessment. Clinical and REAP-S data of consented subjects was extracted (7/17/2019). Diet quality [low-(15-19), moderate-(20-29), and high-(30-39)] and AGE content per REAP-S questionnaire were assessed for association with WTC-OAD. Regression models adjusted for smoking, hyperglycemia, hypertension, age on 9/11, WTC-exposure, BMI, and job description., Results: N = 9508 completed the annual questionnaire, while N = 4015 completed REAP-S and had spirometry. WTC-OAD developed in N = 921, while N = 3094 never developed WTC-OAD. Low- and moderate-dietary quality, eating more (processed meats, fried foods, sugary drinks), fewer (vegetables, whole-grains),and having a diet abundant in AGEs were significantly associated with WTC-OAD. Smoking was not a significant risk factor of WTC-OAD., Conclusions: REAP-S was successfully implemented in the FDNY WTC-HP monitoring questionnaire and produced valuable dietary phenotyping. Our observational study has identified low dietary quality and AGE abundant dietary habits as risk factors for pulmonary disease in the context of WTC-exposure. Dietary phenotyping, not only focuses our metabolomic/biomarker profiling but also further informs future dietary interventions that may positively impact particulate matter associated lung disease.

Dual chamber (DC) peritoneal dialysis (PD) dialysates contain fewer glucose degradation products (GDPs), so potentially reducing advanced glycosylation end products (AGEs), which have been reported to increase inflammation and cardiovascular risk. We wished to determine whether use of DC dialysates resulted in demonstrable patient benefits. Biochemical profiles, body composition, muscle strength, and skin autofluorescence measurements of tissue AGEs (SAF) were compared in patients using DC and standard single chamber dialysates. We studied 263 prevalent PD patients from 2 units, 62.4% male, mean age 61.8 ± 16.1 years, 78 (29.7%) used DC dialysates. DC patients were younger (55.9 ± 16.4 vs. 64.2 ± 15.4 years), and more had lower Davies comorbidity score (median 1 (0-1) vs. 1 (0, 2)), slower peritoneal transport (D/P creatinine 0.67 ± 0.12 vs. 0.73 ± 0.13), greater extracellular water-to-total body water (ECW/TBW) ratio (0.46 ± 0.05 vs. 0.42 ± 0.06), all P < .001, whereas there were no differences in the duration of PD (median (IQR) 19 (8-32) vs. 14 (8-23) months), residual renal function (Kt/V urea 0.71 ± 0.71 vs. 0.87 ± 0.82), urine volume (642 (175-1200) vs. 648 (300-1200) mL/day), hand grip strength (26.9 ± 10.5 vs. 24.9 ± 10.7 kg), C-reactive protein (4(1-10) vs. 4(2-12) mg/L), and SAF (median 3.60 (3.02, 4.40) vs. 3.50 (3.00, 4.23)) AU. In our cross-sectional observational study, we were not able to show a demonstrable advantage for using low GDP dialysates over conventional glucose dialysates, in terms of biochemical profiles, residual renal function, muscle strength, or tissue AGE deposition. More patients using low GDP dialysates were slower peritoneal transporters with higher ECW/TBW ratios., (© 2020 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

Increasing clinical and experimental evidence accumulated during the past few decades supports an important role for dietary advanced glycation endproducts (AGE) in the pathogenesis of many chronic non-infectious diseases, such as type 2 diabetes, CVD and others, that are reaching epidemic proportions in the Western world. Although AGE are compounds widely recognised as generated in excess in the body in diabetic patients, the potential importance of exogenous AGE, mostly of dietary origin, has been largely ignored in the general nutrition audience. In the present review we aim to describe dietary AGE, their mechanisms of formation and absorption into the body as well as their main mechanisms of action. We will present in detail current evidence of their potential role in the development of several chronic non-infectious clinical conditions, some general suggestions on how to restrict them in the diet and evidence regarding the potential benefits of lowering their consumption.

Proliferative diabetic retinopathy (PDR) involves persistent, uncontrolled formation of premature blood vessels with reduced number of pericytes. Our previous work showed that advanced glycation endproducts (AGEs) induced angiogenesis in human umbilical vein endothelial cells, mouse retina, and aortic ring, which was associated with moesin phosphorylation. Here we investigated whether moesin phosphorylation may contribute to pericyte detachment and the development of PDR. Primary retinal microvascular pericytes (RMPs) were isolated, purified from weanling rats, and identified by cellular markers α-SMA, PDGFR-β, NG2, and desmin using immunofluorescence microscopy. Effects of AGE-BSA on proliferation and migration of RMPs were examined using CCK-8, wound healing, and transwell assays. Effects on moesin phosphorylation were examined using western blotting. The RMP response to AGE-BSA was also examined when cells expressed the non-phosphorylatable Thr558Ala mutant or phospho-mimicking Thr558Asp mutant of moesin or were treated with ROCK inhibitor Y27632. Colocalization and interaction between CD44, phospho-moesin, and F-actin were observed. Experiments with cultured primary RMPs showed that AGE-BSA inhibited the proliferation, enhanced the migration, and increased moesin phosphorylation in a dose- and time-dependent manner. AGE-BSA also triggered the rearrangement of F-actin and promoted the interaction of CD44 with phospho-moesin in RMPs. These effects were abrogated in cells expressing the non-phosphorylatable moesin mutant and the application of ROCK inhibitor Y27632 attenuated AGE-induced alteration in cultured RMPs by abolishing the phosphorylation of moesin. However, those AGE-induced pathological process occurred in RMPs expressed the phospho-mimicking moesin without AGE-BSA treatment. It is concluded that AGEs could activate ROCK to mediate moesin phosphorylation at Thr558, and resulting phospho-moesin interacts with CD44 to form CD44 cluster, which might stimulate the migration of RMPs and subsequent RMP detachment in microvessel. This pathway may provide new drug targets against immature neovessel formation in PDR., (Copyright © 2020 Zhang, Hu, Liu, Chen, Chen, Guo and Huang.)

Introduction: High serum concentrations of advanced glycation end-products (AGEs) in older adults and diabetics are associated with an increased risk of cognitive impairment. The aim of this pilot study was to assess the feasibility of long-term adherence to a dietary intervention designed to decrease intake and exposure to circulating AGEs among older adults with type 2 diabetes., Methods: Herein, 75 participants were randomized to either a standard of care (SOC) control arm or to an intervention arm receiving instruction on reducing dietary AGEs intake. The primary outcome was a change in serum AGEs at the end of the intervention. Secondary and exploratory outcomes included adherence to diet and its association with circulating AGEs. Cognitive function and brain imaging were also assessed but were out of the scope of this article (ClinicalTrials.gov Identifier: NCT02739971)., Results: The intervention resulted in a significant change over time in several serum AGEs compared to the SOC guidelines. Very high adherence (above 80%) to the AGE-lowering diet was associated with a greater reduction in serum AGEs levels. There were no significant differences between the two arms in any other metabolic markers., Conclusions: A long-term dietary intervention to reduce circulating AGEs is feasible in older adults with type 2 diabetes, especially in those who are highly adherent to the AGE-lowering diet.

Background: Although endogenous advanced glycation end products (AGEs) have been implicated in the development of various chronic diseases, whether AGEs in foods represent a risk to human health remains unknown., Objectives: We aimed to estimate the intake of Nε-carboxymethyl-lysine (CML), a major AGE product, using a database of CML contents on LC-MS methods, and to examine CML's association with total and cause-specific mortality in Japanese adults., Methods: The analysis included 13,355 men and 15,724 women, aged 35 years and older, from the Takayama study. They responded to a self-administered questionnaire in 1992. Their diet, including the CML intake, was assessed using a food-frequency questionnaire at baseline. Mortality was ascertained during 16 years of follow-up. HRs and 95% CIs for mortality were estimated separately for men and women according to CMI quartiles., Results: We noted 2901 deaths in men and 2438 deaths in women during the follow-up. In men, as compared with the lowest quartile of intake, the highest quartile of CML was inversely associated with the risks of both total and non-cancer, non-cardiovascular disease mortality after controlling for covariates [HR = 0.89 (95% CI, 0.79-1.00; P-trend = 0.047) and HR = 0.74 (95% CI, 0.58-0.94; P-trend = 0.03), respectively]. However, stratified analyses showed both inverse and positive associations between CML intake and cause-specific mortality in women, depending on their characteristics. For example, years of education had a modifying effect on both the CML intake and non-cancer, non-cardiovascular disease mortality in women. In men, the associations of CML intake with mortality depended on food sources., Conclusions: Overall, the present study does not support a positive association between CML intake and mortality in Japanese adults. The potential relevance of the food source of CML to the link between dietary CML and mortality warrants further attention., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Dietary advanced glycation end products (dAGEs) are complex and heterogeneous compounds derived from nonenzymatic glycation reactions during industrial processing and home cooking. There is mounting evidence showing that dAGEs are closely associated with various chronic diseases, where the absorbed dAGEs fuel the biological AGEs pool to exhibit noxious effects on human health. Currently, due to the uncertain bioavailability and rapid renal clearance of dAGEs, the relationship between dAGEs and biological AGEs remains debatable. In this review, we provide the most updated information on dAGEs including their generation in processed foods, analytical and characterization techniques, metabolic fates, interaction with AGE receptors, implications on human health and reducing strategies. Available evidence demonstrating a relevance between dAGEs and food allergy is also included. AGEs are ubiquitous in foods and their contents largely depend on the reactivity of carbonyl and amino groups, along with surrounding condition mainly pH and heating procedures. Once being digested and absorbed into the circulation, two separate pathways can be involved in the deleterious effects of dAGEs: an AGE receptor-dependent way to stimulate cell signals, and an AGE receptor-independent way to dysregulate proteins via forming complexes. Inhibition of AGEs formation during food processing and reduction in the diet are two potent approaches to restrict health-hazardous dAGEs. To elucidate the biological role of dAGEs toward human health, the following significant perspectives are raised: molecular size and complexity of dAGEs; interactions between unabsorbed dAGEs and gut microbiota; and roles played by concomitant compounds in the heat-processed foods., (© 2020 Institute of Food Technologists®.)

Background/aims: High-molecular-weight advanced glycation end-products (HMW-AGEs) are abundantly present in our Western diet. There is growing evidence reporting that HMW-AGEs contribute to the development of cardiovascular dysfunction in vivo, next to the well-known low-molecular-weight AGEs. The goal of our study is to assess the ultrastructure and function of cardiomyocytes after chronic exposure to HMW-AGEs. A better understanding of underlying mechanisms is essential to create new opportunities for further research on the specific role of HMW-AGEs in the development and progression of cardiovascular diseases., Methods: Adult male rats were randomly assigned to daily intraperitoneal injection for six weeks with either HMW-AGEs (20 mg/kg/day) or a control solution. Hemodynamic measurements were performed at sacrifice. Single cardiomyocytes from the left ventricle were obtained by enzymatic dissociation through retrograde perfusion of the aorta. Unloaded cell shortening, time to peak and time to 50% relaxation were measured during field stimulation and normalized to diastolic length. L-type Ca 2+ current density (I CaL ) and steady-state inactivation of I CaL were measured during whole-cell ruptured patch clamp. Myofilament functional properties were measured in membrane-permeabilized cardiomyocytes. Ultrastructural examination of cardiac tissue was performed using electron microscopy., Results: Rats injected with HMW-AGEs displayed in vivo cardiac dysfunction, characterized by significant changes in left ventricular peak rate pressure rise and decline accompanied with an increased heart mass. Single cardiomyocytes isolated from the left ventricle revealed concentric hypertrophy, indicated by the increase in cellular width. Unloaded fractional cell shortening was significantly reduced in cells derived from the HMW-AGEs group and was associated with slower kinetics. Peak L-type Ca 2+ current density was significantly decreased in the HMW-AGEs group.
L-type Ca 2+ channel availability was significantly shifted towards more negative potentials after HMW-AGEs injection. The impact of HMW-AGEs on myofilament function was measured in membrane-permeabilized cardiomyocytes showing a reduction in passive force, maximal Ca 2+ activated force and rate of force development. Ultrastructural examination of cardiac tissue demonstrated adverse structural remodeling in HMW-AGEs group characterized by a disruption of the cyto-architecture, a decreased mitochondrial density and altered mitochondrial function., Conclusion: Our data indicate that HMW-AGEs induce structural and functional cellular remodeling via a different working mechanism as the well-known LMW-AGEs. Results of our research open the door for new strategies targeting HMW-AGEs to improve cardiac outcome., Competing Interests: The authors have no conflicts of interest to declare., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)

Heat-processed diets contain high amounts of advanced glycation end products (AGEs). Here we explore the impact of an AGE-enriched diet on markers of metabolic and inflammatory disorders as well as on gut microbiota composition and plasma proteins glycosylation pattern. C57BL/6 mice were allocated into control diet (CD, n = 15) and AGE-enriched diet (AGE-D, n = 15) for 22 weeks. AGE-D was prepared replacing casein by methylglyoxal hydroimidazolone-modified casein. AGE-D evoked increased insulin and a significant reduction of GIP/GLP-1 incretins and ghrelin plasma levels, altered glucose tolerance, and impaired insulin signaling transduction in the skeletal muscle. Moreover, AGE-D modified the systemic glycosylation profile, as analyzed by lectin microarray, and increased Nε-carboxymethyllysine immunoreactivity and AGEs receptor levels in ileum and submandibular glands. These effects were associated to increased systemic levels of cytokines and impaired gut microbial composition and homeostasis. Significant correlations were recorded between changes in bacterial population and in incretins and inflammatory markers levels. Overall, our data indicates that chronic exposure to dietary AGEs lead to a significant unbalance in incretins axis, markers of metabolic inflammation, and a reshape of both the intestinal microbiota and plasma protein glycosylation profile, suggesting intriguing pathological mechanisms underlying AGEs-induced metabolic derangements.

With aging, the kidney undergoes inexorable and progressive changes in structural and functional performance. These aging-related alterations are more obvious and serious in diabetes mellitus (DM). Renal accelerated aging under DM conditions is associated with multiple stresses such as accumulation of advanced glycation end products (AGEs), hypertension, oxidative stress, and inflammation. The main hallmarks of cellular senescence in diabetic kidneys include cyclin-dependent kinase inhibitors, telomere shortening, and diabetic nephropathy-associated secretory phenotype. Lysosome-dependent autophagy and antiaging proteins Klotho and Sirt1 play a fundamental role in the accelerated aging of kidneys in DM, among which the autophagy-lysosome system is the convergent mechanism of the multiple antiaging pathways involved in renal aging under DM conditions. Metformin and the inhibitor of sodium-glucose cotransporter 2 are recommended due to their antiaging effects independent of antihyperglycemia, besides angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Additionally, diet intervention including low protein and low AGEs with antioxidants are suggested for patients with diabetic nephropathy (DN). However, their long-term benefits still need further study. Exploring the interactive relationships among antiaging protein Klotho, Sirt1, and autophagy-lysosome system may provide insight into better satisfying the urgent medical needs of elderly patients with aging-related DN., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Jing Guo et al.)

Background: Advanced glycation end products (AGEs) accumulate in tissues with age and in conditions such as diabetes mellitus and chronic kidney disease (CKD), and they may be involved in age-related diseases. Skin AGEs measured as skin autofluorescence (SAF) are a noninvasive reflection of long-term AGE accumulation in tissues. Whether AGEs present in the diet (dAGEs) contribute to tissue AGEs is unclear., Objectives: Our aim was to investigate the association between dietary and skin AGEs in the Rotterdam Study, a population-based cohort of mainly European ancestry., Methods: In 2515 participants, intake of 3 dAGEs [carboxymethyl-lysine (CML), N-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MGH1), and carboxyethyl-lysine (CEL)] was estimated using FFQs and the content of AGEs measured in commonly consumed foods. SAF was measured 5 y (median value) later using an AGE Reader. The association of dAGEs with SAF was analyzed in linear regression models and stratified for diabetes and chronic kidney disease (CKD, defined as estimated glomerular filtration rate ≤60 mL/min) status., Results: Mean ± SD intake was 3.40 ±0.89 mg/d for CML, 28.98 ±7.87 mg/d for MGH1, and 3.11 ±0.89 mg/d for CEL. None of them was associated with SAF in the total study population. However, in stratified analyses, CML was positively associated with SAF after excluding both individuals with diabetes and individuals with CKD: 1 SD higher daily CML intake was associated with a 0.03 (95% CI: 0.009, 0.05) arbitrary units higher SAF. MGH1 and CEL intake were not significantly associated with SAF. Nevertheless, the associations were stronger when the time difference between dAGEs and SAF measurements was shorter., Conclusions: Higher dietary CML intake was associated with higher SAF only among participants with neither diabetes nor CKD, which may be explained by high AGE formation in diabetes and decreased excretion in CKD or by dietary modifications in these disease groups. The dAGE-SAF associations were also modified by the time difference between measurements. Our results suggest that dAGEs can influence tissue AGE accumulation and possibly thereby age-related diseases. This trial was registered at the Netherlands National Trial Register as NTR6831 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6831) and at the WHO International Clinical Trials Registry Platform as NTR6831 (http://www.who.int/ictrp/network/primary/en/)., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Nutrition is an important source of exogenous AGEs and thermally processed foods present in western-style diets contain a large amount of these pro-inflammatory AGEs. Additionally, the intake of dietary AGEs could upregulate ovarian gene expression of inflammatory macrophage markers. The objective of this study was to investigate the effect of diet rich in AGEs on estrous cyclicity and ovarian function in a mouse model. Six-week old C57BL/6 J female mice were randomly subjected to either a diet low in AGEs (L-AGE) or a diet high in AGEs (H-AGE) for a total of 13 weeks. Experiments performed included daily vaginal smears to assess estrous cyclicity, ovarian superovulation with gonadotropins to assess the number of oocytes released, whole ovarian tissue mRNA quantification by RT-PCR to quantify genes involved in folliculogenesis, steroidogenesis, and macrophage markers, and ovarian morphology for follicle count. Outcome measures included estrous cyclicity, number of oocytes following superovulation, expression of genes involved in folliculogenesis, steroidogenesis, and macrophage infiltration as well as the number of primordial, primary, secondary, antral follicles and corpora lutea. Compared to mice on L-AGE diet, mice on H-AGE spent significantly longer time in the diestrus phase, had similar number of oocytes released following ovarian superovulation, and showed significant alterations in genes involved in steroidogenesis (increase in Star mRNA expression levels) and folliculogenesis (increase in Gdf-9 and Fshr mRNA expression levels). Mouse macrophage marker F4/80 mRNA expression was upregulated in mice on H-AGE diet compared to mice on L-AGE diet. Finally, mice on H-AGE diet had significantly fewer corpora lutea in their ovaries. These results indicate that the ingestion of high amounts of dietary AGEs could disrupt folliculogenesis and steroidogenesis that might lead to abnormal estrous cyclicity. Intake of dietary AGEs could also upregulate ovarian gene expression of inflammatory macrophage markers., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Advanced glycation end products (AGEs) are reactive metabolites produced as a by-product of sugar metabolism and are consumed through the diet in high-fat and highly processed foods. They are associated with chronic inflammatory diseases, and evidence suggests that they play a role in carcinogenesis. The authors evaluated the association of dietary AGE intake and the risk of postmenopausal invasive breast cancer., Methods: This was a prospective cohort study of 183,548 postmenopausal women in the National Institutes of Health-AARP Diet and Health Study. The main outcome was incident invasive breast cancer. AGE intake was estimated from food-frequency questionnaires. Incident breast cancer cases were identified through state cancer registries. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals for developing breast cancer according to AGE intake quintiles. Multivariable regression models were adjusted for breast cancer risk factors., Results: The mean follow-up was 12.8 years, and 9851 breast cancers (1978 advanced stage) were identified. The median AGE daily intake was 5932 kilo units per 100 kilocalories (KU/1000 kcal). Women with higher intake tended to have lower education levels, higher body mass index, less physical activity, were current smokers, and had higher fat and meat intake. The highest quintile of AGE intake (compared with the lowest) was associated with an increased risk of breast cancer (HR, 1.09; 95% CI, 1.02-1.16; P = .03) after adjusting for breast cancer risk factors and particularly was associated with 37% of advanced-stage tumors (HR, 1.37; 95% CI, 1.09-1.74; P < .02) after adjusting for risk factors and fat and meat intake., Conclusions: Dietary AGEs may play a role in the development of postmenopausal breast cancer., (© 2020 American Cancer Society.)

Background: The success of translational research depends on how well animal models mimic the pathophysiology of the human phenotype, and on the identification of disease mechanisms such as enhanced glycation., Methods: Here, we studied cardiac MRI and metabolic phenotypes in human type 2 diabetes (N = 106; 55 patients+51 controls) and animal models with distinct levels of fat diet and end glycation products, to model the role of these factors in the cardiac phenotype. We included four groups of rats, designed to evaluate the role of lipid load and glucotoxicity in cardiac function and to correlate these with the cardiac phenotype observed in humans. We also aimed to assess into which extent phenotypes were related to specific risk factors., Results: Stroke Volume (SV) and Peak Filling Rate (PFR) measures were similarly discriminative both in humans and animal models, particularly when enhanced glycation was present. Factorial analysis showed that reduction of multidimensionality into common main explanatory factors, in humans and animals, revealed components that equally explained the variance of cardiac phenotypes (87.62% and 83.75%, respectively). One of the components included, both in humans and animals, SV, PFR and peak ejection rate (PER). The other components included in both humans and animals are the following: ESV (end systolic volume), left ventricular mass (LVM) and ejection fraction (EF). These components were useful for between group discrimination., Conclusions: We conclude that animal models of enhanced glycation and human type 2 diabetes share a striking similarity of cardiac phenotypic components and relation with metabolic changes, independently of fact content in the diet, which reinforces the role of glucose dysmetabolism in left ventricular dysfunction and provides a potentially useful approach for translational research in diabetes, in particular when testing new therapies early on during the natural history of this condition., (Copyright © 2020 Elsevier Inc. All rights reserved.)

This study investigated the effect of glucose and fructose, and advanced glycation end-products (AGEs) on genome damage in WIL2-NS cells, measured using the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. The effect of AGEs was investigated using the bovine serum albumin (AGE-BSA) model system induced either with glucose (Glu-BSA) or with fructose (Fru-BSA). Liquid chromatography-mass spectrometry (LC-MS/MS) analysis showed higher Nε-carboxymethyllysine (CML; 26.76 ± 1.09 nmol/mg BSA) levels in the Glu-BSA model. Nε-Carboxyethyllysine (CEL; 7.87 ± 0.19 nmol/mg BSA) and methylglyoxal-derived hydroimidazolone-1 (MG-H1; 69.77 ± 3.74 nmol/mg BSA) levels were higher in the Fru-BSA model. Genotoxic effects were measured using CBMN-Cyt assay biomarkers [binucleated(BN) cells with micronuclei (MNi), BN with nucleoplasmic bridges (NPBs) and BN with nuclear buds (NBuds)] following 9 days of treatment with either glucose, fructose, Glu-BSA or Fru-BSA. Fructose treatment exerted a significant genotoxic dose-response effect including increases of BN with MNi (R2 = 0.7704; P = 0.0031), BN with NPBs (R2 = 0.9311; P < 0.0001) and BN with NBuds (R2 = 0.7118; P = 0.0091) on cells, whereas the DNA damaging effects of glucose were less evident. High concentrations of AGEs (400-600 µg/ml) induced DNA damage; however, there was no effect on cytotoxicity indices (necrosis and apoptosis). In conclusion, this study demonstrates a potential link between physiologically high concentrations of reducing sugars or AGEs with increased chromosomal damage which is an important emerging aspect of the pathology that may be induced by diabetes. Ultimately, loss of genome integrity could accelerate the rate of ageing and increase the risk of age-related diseases over the long term. These findings indicate the need for further research on the effects of glycation on chromosomal instability and to establish whether this effect is replicated in humans in vivo., (© The Author(s) 2020. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society.All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Glucocorticoids are very effective anti-inflammatory drugs and widely used for inflammatory bowel disease (IBD) patients. However, approximately 20% of IBD patients do not respond to glucocorticoids and the reason for this is largely unknown. Dietary advanced glycation endproducts (AGEs) are formed via the Maillard reaction during the thermal processing of food products and can induce a pro-inflammatory reaction in human cells. To investigate whether this pro-inflammatory response could be mitigated by glucocorticoids, human macrophage-like cells were exposed to both LPS and AGEs to induce interleukin-8 (IL8) secretion. This pro-inflammatory response was then modulated by adding pharmacological compounds interfering in different steps of the anti-inflammatory mechanism of glucocorticoids: rapamycin, quercetin, and theophylline. Additionally, intracellular reactive oxygen species (ROS) were measured and the glucocorticoid receptor phosphorylation state was assessed. The results show that AGEs induced glucocorticoid resistance, which could be mitigated by quercetin and rapamycin. No change in the phosphorylation state of the glucocorticoid receptor was observed. Additionally, intracellular ROS formation was induced by AGEs, which was mitigated by quercetin. This suggests that AGE-induced ROS is an underlying mechanism to AGE-induced glucocorticoid resistance. This study shows for the first time the phenomenon of dietary AGE-induced glucocorticoid resistance due to the formation of ROS. Our findings indicate that food products with a high inflammatory potential can induce glucocorticoid resistance; these results may be of great importance to IBD patients suffering from glucocorticoid resistance., Competing Interests: The authors declare no conflict of interest.

Background: Autoclaving rodent diets is common in laboratory animals, but autoclaving increases the formation of dietary advanced glycation end-products (AGE). We studied the effect of autoclaved (AC) diet alone or in combination with a diet high in bioavailable phosphorus on biochemistries of chronic kidney disease-mineral and bone disorder (CKD-MBD), intestinal gene expression, and oxidative stress., Methods: Male CKD rats (Cy/+) and normal littermates were fed 1 of 3 diets: AC 0.7% phosphorus grain-based diet for 28 weeks (AC); AC diet for 17 weeks followed by non-autoclaved (Non-AC) 0.7% phosphorus casein diet until 28 weeks (AC + Casein); or Non-AC diet for 16 weeks followed by a Non-AC purified diet until 30 weeks (Non-AC + Casein)., Results: AC diets contained ~3× higher AGEs and levels varied depending on the location within the autoclave. Rats fed the AC and AC + Casein diets had higher total AGEs and oxidative stress, irrespective of kidney function. Kidney function was more severely compromised in CKD rats fed AC or AC + Casein compared to Non-AC + Casein. There was a disease-by-diet interaction for plasma phosphorus, parathyroid hormone, and c-terminal fibroblast growth factor-23, driven by high values in the CKD rats fed the AC + Casein diet. Compared to Non-AC + Casein, AC and AC + Casein-fed groups had increased expression of receptor of AGEs and intestinal NADPH oxidase dual oxidase-2, independent of kidney function., Conclusions: Autoclaving rodent diets impacts the progression of CKD and CKD-MBD, highlighting the critical importance of standardizing diets in experiments., (© 2020 S. Karger AG, Basel.)

Added sugars are ubiquitous in contemporary Western diets. Although excessive sugar consumption is now robustly associated with an array of adverse health consequences, comparatively little research has thus far addressed its impact on the risk of mental illness. But ample evidence suggests that high-dose sugar intake can perturb numerous metabolic, inflammatory, and neurobiological processes. Many such effects are of particular relevance to the onset and maintenance of depressive illness, among them: systemic inflammation, gut microbiota disruption, perturbed dopaminergic reward signaling, insulin resistance, oxidative stress, and the generation of toxic advanced glycation end-products (AGEs). Accordingly, we hypothesize that added dietary sugars carry the potential to increase vulnerability to major depressive disorder, particularly at high levels of consumption. The present paper: (a) summarizes the existing experimental and epidemiological research regarding sugar consumption and depression vulnerability; (b) examines the impact of sugar ingestion on known depressogenic physiological processes; and (c) outlines the clinical and theoretical implications of the apparent sugar-depression link. We conclude that the extant literature supports the hypothesized depressogenic impact of added dietary sugars, and propose that an improved understanding of the effects of sugar on body and mind may aid in the development of novel therapeutic and preventative measures for depression., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Current reports increasingly associate dietary "advanced glycation end products" ("AGEs") resulting from the Maillard reaction (glycation) between reducing sugars and amino compounds in foods with pathophysiological consequences, such as chronic inflammation, atherosclerosis, and metabolic syndrome. Heated foods are therefore suggested to pose a potential risk for human health. However, studies in this field are very often based on questionable quantitative data and inadequate structural characterization. To improve the situation, the present perspective suggests quality criteria for future studies and the assessment of the currently available literature.