Dietary Advanced Glycation End Products (AGEs) and Urinary Fluorescent AGEs in Children and Adolescents: Findings from the Italian I.Family Project.

Advanced glycation end products (AGEs) have been implicated in chronic diseases in adults, but their role in paediatric populations remains uncertain. This study, conducted on the Italian sample of the I.Family project, aimed to investigate the relationship between dietary and urinary fluorescent AGEs in children and adolescents. The secondary objective was to investigate the sources of dietary AGEs (dAGEs) and their association with dietary composition and anthropometric parameters. Dietary data were collected from 1048 participants via 24 h dietary recall in 2013/2014 to estimate dAGEs intake, while urinary fluorescent AGE levels were measured in 544 individuals. Participants were stratified based on dAGEs intake and compared with respect to urinary fluorescent AGE levels, anthropometric measurements, and dietary intake. The results showed no significant correlation between dietary and urinary fluorescent AGE levels, nor between dAGEs and anthropometric parameters. Notably, higher dAGEs were associated with a diet richer in protein (especially from meat sources) and fat and lower in carbohydrates. In addition, the consumption of ultra-processed foods was lower in participants with a higher DAGE intake. This study highlights the lack of a clear association between dietary and urinary fluorescent AGEs in children, but suggests a distinctive dietary pattern associated with increased dAGEs intake. Further investigation is warranted to elucidate the potential health implications of dAGEs in paediatric populations.

Development, Validity, and Reliability of a Food Frequency Questionnaire Eliciting the Dietary Advanced Glycation End Product Consumption among Obese Adolescents Aged 10-19 Years.

BACKGROUND: Obesity has reached an alarming rate affecting all categories of the population. A tremendous rise in obesity has been observed in children and adolescents. In India, the prevalence of adolescent obesity is more than 30% of the population. Advanced glycation end products (AGEs) are a diverse group of compounds formed by the amalgamation of glucose and a protein moiety. These glycated compounds are found in processed foods subjected to high-temperature cooking techniques contributing to the formation of dietary AGEs (dAGEs). The enormous consumption of dAGE attributes to the development of metabolic diseases. OBJECTIVES: The objective of this study was to develop and validate a food frequency questionnaire (FFQ) among obese adolescents aged 10-19 years to gauge their dAGE consumption. MATERIALS AND METHODS: This questionnaire was developed from previous literature (15 articles), validated using the content validity ratio (CVR) by Lawshe, and estimated for reliability using the test-retest method. A pilot study was done among 50 obese adolescents aged 10-19 years, who completed the questionnaire twice, with a gap of 15 days. RESULTS: A total of 54 items were validated (CVR ≥0.99) from the 60 food items. A reliability score >0.7 was observed, and a significant correlation (P ≥ 0.01) between the test and retest results was determined. CONCLUSION: Hence, this FFQ is reliable and can be used for future research studies to elicit dAGE consumption among obese adolescents.

Dietary advanced glycation end products, body composition, and anthropometric measures: A cross-sectional analysis in women with excess body weight.

BACKGROUND AND AIMS: To assess the association between dietary advanced glycation end products (dAGEs) versus body composition and anthropometric variables. METHODS AND RESULTS: Body composition (dual-energy X-ray absorptiometry), anthropometry, and habitual food intake were cross-sectionally evaluated in women with excess body weight and body fat. Mean dAGEs content was estimated using a database containing the Nԑ-(carboxymethyl)lysine (CML) content of 549 foods, which was adjusted by mean energy intake, and categorized into low, medium, and high dAGEs, by the 10th and 50th percentiles of the sample. Associations were tested by linear regression adjusted for age, education, marital status, and physical activity level. Eighty participants had mean ± standard deviation dAGEs 7.85 ± 2.65 AGEs kU/kcal. Compared with high dAGEs, women with low dAGEs ingested more carbohydrate (62% vs. 50% of calories, p < 0.001) and fiber (≈25 g vs. ≈18 g, p = 0.027) and less protein (13% vs. 17% of calories, p = 0.006) and fat (26% vs. 33% of calories, p = 0.011). Women with low dAGEs had waist/hip ratio 0.05 higher than those with high dAGEs (R2 = 0.256, p = 0.005). Low dAGEs relative to medium (p = 0.009) and high (p = 0.002) dAGEs was associated with a ≈5% gynoid fat reduction (R2 = 0.164). CONCLUSION: Low dAGEs was associated with a higher waist/hip ratio and lower percentage of gynoid fat in women with excess body weight and excess body fat. REGISTRATION NUMBER: RBR-7z358j.

Intake of dietary advanced glycation end products may be associated with depression and sleep quality in young adults.

BACKGROUND: This study examined the relationship between dietary intake of advanced glycation end products (dAGEs) and depression and sleep quality in young adults. METHODS: This study, which included 420 university students (F = 80.2 %; M = 19.8 %), is observational and cross-sectional. Dietary AGEs intakes of individuals were taken with a 24-h food consumption record system. Measuring the depression status of the participants was evaluated with the Beck Depression Inventory (BDI), and the assessment of their sleep quality was evaluated with the Pittsburg Sleep Quality Index (PSQI). Individuals' dAGEs intakes were divided into three equal groups (low, medium, and high). The energy was adjusted in all analyzes of dAGEs intake. Study data were analyzed with the SPSS (27.0 version) and GraphPad program (8.0 version). RESULTS: The BDI and PSQI total score averages of individuals in the high dAGEs intake group were higher than the other groups, and this difference was statistically significant (p < 0.001). There is no significant difference between individuals' dAGEs intakes and energy and macronutrient intakes. Students' dAGEs intake was affected by BDI (ß = 0.722, 95 % Cl = 0.639;0.811) and PSQI (ß = 0.286, 95 % Cl = 0.179;0.431) scores (p < 0.001). This effect persisted even when various confounding factors were included (age, gender, smoking, body mass index, chronic disease) (p < 0.001). LIMITATIONS: These data are cross-sectional, which limits the generalizability of results and establishing cause-effect relationships. CONCLUSION: There may be an association between dAGEs intake and the development of depression and sleep quality in young adults. Clinical intervention studies using objective measurement methods should be conducted on this issue in the future.

Associations of dietary advanced glycation end products with liver steatosis via vibration controlled transient elastography in the United States: a nationwide cross-sectional study.

PURPOSE: Large population-based studies for the associations between dietary advanced glycation end products (dAGEs) intake and liver steatosis remain lacking. It is necessary to clarify the relationship of dAGEsintake with liver steatosis through the National Health and Nutrition Survey (NHANES). METHODS: A total of 5856 participants in the NHANES 2017-2018 were included. The dietary AGEs intake, including ε-(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. Liver steatosis was assessed by controlled attenuation parameter via transient elastography. Logistic regression model was adopted to explore the relationships between dAGEs intake and hepatic steatosis. RESULTS: Compared with individuals of total dAGEs, CML, MG-H1 in the lowest tertile, those in the highest tertile had highest risk of hepatic steatosis, and the corresponding odds radios(ORs) (95% confidence interval(CI)) were 1.37 (1.01, 1.84), 1.36 (1.04,1.78) and 1.40 (1.06, 1.85), respectively. Subgroups analysis found that the positive association between dAGEs, CML, CEL and MG-H1 and hepatic steatosis appeared stronger in subjects with obesity and those with abnormal waist circumference (WC). CONCLUSION: There was a positive correlation between dAGEs, CML, MG-H1, and hepatic steatosis, and this association mainly existed in subjects with obesity and those with abnormal WC. Dietary AGEs restriction might be of high priority for subjects with obesity for the prevention of fatty liver disease. Further longitudinal studies are required to confirm the causal associations and explore the potential mechanisms.

How dietary advanced glycation end products could facilitate the occurrence of food allergy.

BACKGROUND: Food allergy (FA) is one of the most common chronic conditions in children with an increasing prevalence facilitated by the exposure to environmental factors in predisposed individuals. It has been hypothesized that the increased consumption of ultra-processed foods, containing high levels of dietary advanced glycation end products (AGEs), could facilitate the occurrence of FA. OBJECTIVE: We sought to provide preclinical and clinical evidence on the potential role of AGEs in facilitating the occurrence of FA. METHODS: Human enterocytes, human small intestine organ culture, and PBMCs from children at risk for allergy were used to investigate the direct effect of AGEs on gut barrier, inflammation, TH2 cytokine response, and mitochondrial function. Intake of the 3 most common glycation products in Western diet foods, Nε-(carboxymethyl) lysine, Nε-(1-carboxyethyl) lysin, and Nδ-(5-hydro-5- methyl-4-imidazolone-2-yl)-ornithine (MG-H1), and the accumulation of AGEs in the skin were comparatively investigated in children with FA and in age-matched healthy controls. RESULTS: Human enterocytes exposed to AGEs showed alteration in gut barrier, AGE receptor expression, reactive oxygen species production, and autophagy, with increased transepithelial passage of food antigens. Small intestine organ cultures exposed to AGEs showed an increase of CD25+ cells and proliferating crypt enterocytes. PBMCs exposed to AGEs showed alteration in proliferation rate, AGE receptor activation, release of inflammatory and TH2 cytokines, and mitochondrial metabolism. Significant higher dietary AGE intake and skin accumulation were observed children with FA (n = 42) compared with age-matched healthy controls (n = 66). CONCLUSIONS: These data, supporting a potential role for dietary AGEs in facilitating the occurrence of FA, suggest the importance of limiting exposure to AGEs children as a potential preventive strategy against this common condition.

Evaluation of the effects of dietary advanced glycation end products on inflammation.

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.

Dietary advanced glycation end products are associated with an increased risk of breast cancer in Iranian adults.

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/m2, 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, Ptrend: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, Ptrend: 0.017). CONCLUSION: The present findings suggest that a diet with high AGEs is associated with a higher likelihood of BC in adult women.

Pubertal exposure to dietary advanced glycation end products disrupts ductal morphogenesis and induces atypical hyperplasia in the mammary gland.

BACKGROUND: Advanced glycation end products (AGEs) are reactive metabolites intrinsically linked with modern dietary patterns. Processed foods, and those high in sugar, protein and fat, often contain high levels of AGEs. Increased AGE levels are associated with increased breast cancer risk, however their significance has been largely overlooked due to a lack of direct cause-and-effect relationship. METHODS: To address this knowledge gap, FVB/n mice were fed regular, low AGE, and high AGE diets from 3 weeks of age and mammary glands harvested during puberty (7 weeks) or adulthood (12 weeks and 7 months) to determine the effects upon mammary gland development. At endpoint mammary glands were harvested and assessed histologically (n ≥ 4). Immunohistochemistry and immunofluorescence were used to assess cellular proliferation and stromal fibroblast and macrophage recruitment. The Kruskal-Wallis test were used to compare continuous outcomes among groups. Mammary epithelial cell migration and invasion in response to AGE-mediated fibroblast activation was determined in two-compartment co-culture models. In vitro experiments were performed in triplicate. The nonparametric Wilcoxon rank sum test was used to compare differences between groups. RESULTS: Histological analysis revealed the high AGE diet delayed ductal elongation, increased primary branching, as well as increased terminal end bud number and size. The high AGE diet also led to increased recruitment and proliferation of stromal cells to abnormal structures that persisted into adulthood. Atypical hyperplasia was observed in the high AGE fed mice. Ex vivo fibroblasts from mice fed dietary-AGEs retain an activated phenotype and promoted epithelial migration and invasion of non-transformed immortalized and tumor-derived mammary epithelial cells. Mechanistically, we found that the receptor for AGE (RAGE) is required for AGE-mediated increases in epithelial cell migration and invasion. CONCLUSIONS: We observed a disruption in mammary gland development when mice were fed a diet high in AGEs. Further, both epithelial and stromal cell populations were impacted by the high AGE diet in the mammary gland. Educational, interventional, and pharmacological strategies to reduce AGEs associated with diet may be viewed as novel disease preventive and/or therapeutic initiatives during puberty.

Inhibitory mechanism of carboxymethyl chitosan-lotus seedpod oligomeric procyanidin nanoparticles on dietary advanced glycation end products released from glycated casein during digestion.

Lotus seedpod oligomeric procyanidins (LSOPC) are potent inhibitors of advanced glycation end products (AGEs), whose gastrointestinal susceptibility to degradation limits their use in vivo. In this study, carboxymethyl chitosan-lotus seedpod oligomeric procyanidin nanoparticles (CMC-LSOPC NPs) were constructed with a binding ratio of 1:6.51. CMC-LSOPC NPs significantly inhibited the release of AGEs from glycated casein (G-CS) during digestion, increasing the inhibition rate by 25.76% in the gastric phase and by 14.33% in the intestinal phase compared with LSOPC alone. To further investigate the inhibition mechanism, fluorescence microscopy, scanning electron microscopy and FTIR were used to find that CMC-LSOPC NPs could form cohesions to encapsulate G-CS in the gastric phase and hinder G-CS hydrolysis. In the intestinal phase, LSOPC was targeted for release and bound to trypsin through hydrophobic interactions and hydrogen bonding, resulting in protein peptide chain rearrangement, changes in secondary structure and significant reduction in trypsin activity. In addition, CMC-LSOPC NPs increased the antioxidant capacity of digestive fluid and could reduce the oxidative stress in the gastrointestinal tract caused by the release of AGEs. It's the first time that CMC-LSOPC NPs were constructed to enhance the stability of LSOPC during digestion and explain the mechanism by which CMC-LSOPC NPs inhibit the release of AGEs from G-CS in both stomach and intestine. This finding will present a novel approach for reducing AGEs during gastrointestinal digestion.

Higher dietary advanced glycation products intake is associated with increased risk of dementia, independent from genetic predisposition.

BACKGROUND: Dietary advanced glycation end products (AGEs) might exert adverse effects on cognition. The associations between dietary AGEs and long-term risk of dementia are yet to be assessed in large population studies. We aimed to explore whether elevated dietary AGEs intake is associated with increased risk of dementia, and whether this association might be affected by genetic risk. METHODS: A prospective cohort study, which included a total of 93,830 participants (aged≥ 50 years) free from dementia at baseline of the UK Biobank study (2006-2010) and had at least two 24-h dietary assessments and were followed up until 2021. Dietary AGEs, including Nε-(1-Carboxyethyl)-l-lysine (CEL), Nε-(carboxymethyl) lysine (CML), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were estimated via averaged data from the multiple 24-h food assessments according to the ultra-performance LC-tandem MS based dAGEs database. Incidence of all-cause dementia was ascertained through hospital inpatient and mortality records. Multivariable Cox regression models were utilized to estimate hazards ratios (HRs) and 95% confidence interval (CI) of dementia risk associated with dietary AGEs. RESULTS: During a median follow-up of 11.9 years, 728 participants developed dementia. In multivariable adjusted model, when comparing the highest with the lowest tertile of intake level, HRs (95% CI) of dementia were 1.43 (1.16, 1.76) for total AGEs Z score, 1.53 (1.25, 1.89) for CEL, 1.27 (1.03, 1.56) for CML and 1.24 (1.02, 1.52) for MG-H1 (all P trend<0.01). There was no significant interaction between dietary AGEs intake, genetic risk and APOE ε4 carrier status for dementia. CONCLUSIONS: Higher intakes of dietary AGEs including CEL, CML and MG-H1 were associated with a higher risk of dementia, independent from genetic risk, highlighting the significance of dietary AGEs restriction for dementia prevention.

Changes in screen time from 4 to 7 years of age, dietary patterns and obesity: Findings from the Generation XXI birth cohort.

BACKGROUND AND AIMS: Increased screen exposure is associated with unhealthy eating behaviours and obesity. Screen time (ST) changes from pre-school to school age, and associations with dietary patterns (DP) and obesity remain unknown. We, therefore, analysed ST changes from 4 to 7 years of age, associated factors, and the relation with DP and obesity. METHODS AND RESULTS: We included 4531 children evaluated at 4 and 7 years, as part of the Generation XXI birth cohort (Porto, Portugal). ST was assessed for weekdays and weekend, and average daily time was estimated. Associations between covariates and ST changes, and between ST changes and 3 DP previously identified (Energy-dense foods, Snacking, and Healthier) were estimated by odds ratios (OR) and 95% confidence interval (95%CI), using adjusted multinomial regression models. From 4 to 7 years, 31.5% of the children decreased their ST, 21.8% increased, 16.5% maintained low (≤60 min), and 30.2% maintained high (61-120 min or >120 min) ST. After adjustment, lower maternal education (OR = 2.33, 95%CI:1.82-2.99) and lower family income (OR = 1.72, 95%CI:1.35-2.21) were associated with higher odds of increasing ST, while being a girl was associated with 35% decreased odds of increasing ST. Children that increased and those that maintained high ST showed greater odds of presenting a Snacking DP at 7 years (OR = 2.34, 95%CI:1.64-3.35) and (OR = 2.65, 95%CI:1.89-3.72), respectively. No statistically significant differences were found regarding changes in ST and the child's BMI. CONCLUSION: Children increasing screen exposure during this period were more frequently from lower socioeconomic strata and presented unhealthier DP.

Correlation between serum advanced glycation end products and dietary intake of advanced glycation end products estimated from home cooking and food frequency questionnaires.

BACKGROUND & AIMS: To our knowledge the association between dietary advanced glycation end-products (dAGEs) and cardiometabolic disease is limited. Our aim was to examine the association between dAGEs and serum concentration of carboxymethyl-lysine (CML) or soluble receptor advanced glycation end-products (sRAGEs), and to assess the difference on dAGEs and circulating AGEs according to lifestyle and biochemical measures. METHODS AND RESULTS: 52 overweight or obese adults diagnosed with type 2 diabetes were included in this cross-sectional analysis. dAGEs were estimated from a Food Frequency Questionnaire (FFQ) or from a FFQ + Home Cooking Frequency Questionnaire (HCFQ). Serum concentrations of CML and sRAGEs were measured by ELISA. Correlation tests were used to analyze the association between dAGEs derived from the FFQ or FFQ + HCFQ and concentrations of CML or sRAGEs. Demographic characteristics, lifestyle factors and biochemical measures were analyzed according to sRAGEs and dAGEs using student t-test and ANCOVA. A significant inverse association was found between serum sRAGEs and dAGEs estimated using the FFQ + HCFQ (r = -0.36, p = 0.010), whereas no association was found for dAGEs derived from the FFQ alone. No association was observed between CML and dAGEs. dAGEs intake estimated from the FFQ + HCFQ was significantly higher among younger and male participants, and in those with higher BMI, higher Hb1Ac levels, longer time with type 2 diabetes, lower adherence to Mediterranean diet, and higher use of culinary techniques that generate more AGEs (all p values p < 0.05). CONCLUSIONS: These results show knowledge on culinary techniques is relevant to derive the association between dAGEs intake and cardiometabolic risk factors.

Dietary Advanced Glycation End Products: Their Role in the Insulin Resistance of Aging.

Insulin resistance (IR) is commonly observed during aging and is at the root of many of the chronic nontransmissible diseases experienced as people grow older. Many factors may play a role in causing IR, but diet is undoubtedly an important one. Whether it is total caloric intake or specific components of the diet, the factors responsible remain to be confirmed. Of the many dietary influences that may play a role in aging-related decreased insulin sensitivity, advanced glycation end products (AGEs) appear particularly important. Herein, we have reviewed in detail in vitro, animal, and human evidence linking dietary AGEs contributing to the bodily burden of AGEs with the development of IR. We conclude that numerous small clinical trials assessing the effect of dietary AGE intake in combination with strong evidence in many animal studies strongly suggest that reducing dietary AGE intake is associated with improved IR in a variety of disease conditions. Reducing AGE content of common foods by simple changes in culinary techniques is a feasible, safe, and easily applicable intervention in both health and disease. Large-scale clinical trials are still needed to provide broader evidence for the deleterious role of dietary AGEs in chronic disease.

Habitual intake of advanced glycation endproducts is not associated with worse insulin sensitivity, worse beta cell function, or presence of prediabetes or type 2 diabetes: The Maastricht Study.

BACKGROUND & AIMS: A diet high in advanced glycation endproducts (AGEs) is a potential risk factor for insulin resistance, beta cell dysfunction, and ultimately type 2 diabetes. We investigated associations between habitual intake of dietary AGEs and glucose metabolism in a population-based setting. METHODS: In 6275 participants of The Maastricht Study (mean ± SD age: 60 ± 9, 15.1% prediabetes and 23.2% type 2 diabetes), we estimated habitual intake of dietary AGEs Nε-(carboxymethyl)lysine (CML), Nε-(1-carboxyethyl)lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) by combining a validated food frequency questionnaire (FFQ) with our mass-spectrometry dietary AGE database. We determined insulin sensitivity (Matsuda- and HOMA-IR index), beta cell function (C-peptidogenic index, glucose sensitivity, potentiation factor, and rate sensitivity), glucose metabolism status, fasting glucose, HbA1c, post-OGTT glucose, and OGTT glucose incremental area under the curve. Cross-sectional associations between habitual AGE intake and these outcomes were investigated using a combination of multiple linear regression and multinomial logistic regression adjusting for several potential confounders (demographic, cardiovascular, and lifestyle factors). RESULTS: Generally, higher habitual intake of AGEs was not associated with worse indices of glucose metabolism, nor with increased presence of prediabetes or type 2 diabetes. Higher dietary MG-H1 was associated with better beta cell glucose sensitivity. CONCLUSIONS: The present study does not support an association of dietary AGEs with impaired glucose metabolism. Whether higher intake of dietary AGEs translates to increased incidence of prediabetes or type 2 diabetes on the long term should be investigated in large prospective cohort studies.

Dietary Advanced Glycation End products interacting with the intestinal epithelium: What do we really know?

BACKGROUND: Advanced Glycation End products (AGEs) are a heterogeneous group of stable reaction products formed when amino acids, peptides, or proteins are glycated by the non-enzymatic Maillard Reaction. The formation and accumulation of these products in vivo are linked to many inflammation-based pathological outcomes and part of the pathophysiology of non-communicable diseases like eye cataracts and Alzheimer's disease. Since our diet contains high levels of the same compounds, it has been questioned whether their consumption is also detrimental to health. However, this is still under debate. In this context, the intestinal epithelium is an important target tissue since it is chronically exposed to relatively high concentrations of dietary AGEs. SCOPE OF REVIEW: This review summarizes the current evidence on the impact of dietary AGEs on the intestinal epithelium and critically reflects on its methodology. MAJOR CONCLUSIONS: In healthy rodent models, an inflammation-independent impaired intestinal barrier function is claimed; however, dietary AGEs showed anti-inflammatory activity in IBD models. In vitro studies could be a valuable tool to unravel the underlying mechanisms of these effects, however the available studies face some limitations, e.g. lack of the physicochemical characterization of the glycated proteins, the inclusion of the proper controls and the dose-dependency of the effect. In addition, studies using more advanced in vitro models like intestinal organoids and co-cultures with immune cells exposed to gut microbial metabolites derived from the fermentation of AGEs are still needed.

Dietary advanced glycation end products are associated with an increased risk of non-alcoholic fatty liver disease in Iranian adults.

BACKGROUND: Dietary advanced glycation end products(AGEs) may contribute to increased inflammation and oxidative stress as risk factors for chronic diseases such as liver disease. In the current study, we aimed to examine the possible association of dietary AGEs with the odds of non-alcoholic fatty liver disease (NAFLD) in Iranian adults. METHODS: A total of 675 participants (225 newly diagnosed NAFLD cases and 450 controls), aged 20-60 years, were recruited for this case-control study. Nutritional data were measured using a validated food frequency questionnaire, and dietary AGEs were determined for all participants. An ultrasound scan of the liver performed the detection of NAFLD in participants of the case group without alcohol consumption and other causes of hepatic disorders. We used logistic regression models, adjusted for potential confounders, to estimate the odds ratios(ORs) and 95% confidence interval(CI) of NAFLD across tertiles of dietary AGEs. RESULTS: Mean ± SD age and body mass index of the participants were 38.13 ± 8.85 years and 26.85 ± 4.31 kg/m2, respectively. The median(IQR) of dietary AGEs in participants was 3262(2472-4301). In the sex and age-adjusted model, the odds of NAFLD were increased across tertiles of dietary AGEs intake(OR:16.48;95%CI:9.57-28.40, Ptrend<0.001). Also, in the final model, after controlling for confounding effects of BMI, smoking, physical activity, marital status, socio-economic status, and energy intake, the odds of NAFLD were increased across tertiles of dietary AGEs intake(OR:12.16; 95%CI:6.06-24.39, Ptrend<0.001). CONCLUSION: Our results showed that greater adherence to dietary pattern with high dietary AGEs intake was significantly related to increased odds of NAFLD.

Blood and Tissue Advanced Glycation End Products as Determinants of Cardiometabolic Disorders Focusing on Human Studies.

Cardiometabolic disorders are characterised by a cluster of interactive risk determinants such as increases in blood glucose, lipids and body weight, as well as elevated inflammation and oxidative stress and gut microbiome changes. These disorders are associated with onset of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). T2DM is strongly associated with CVD. Dietary advanced glycation end products (dAGEs) attributable from modern diets high in sugar and/or fat, highly processed foods and high heat-treated foods can contribute to metabolic etiologies of cardiometabolic disorders. This mini review aims to determine whether blood dAGEs levels and tissue dAGEs levels are determinants of the prevalence of cardiometabolic disorders through recent human studies. ELISA (enzyme-linked immunosorbent assay), high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) for blood dAGEs measurement and skin auto fluorescence (SAF) for skin AGEs measurement can be used. Recent human studies support that a diet high in AGEs can negatively influence glucose control, body weight, blood lipid levels and vascular health through the elevated oxidative stress, inflammation, blood pressure and endothelial dysfunction compared with a diet low in AGEs. Limited human studies suggested a diet high in AGEs could negatively alter gut microbiota. SAF could be considered as one of the predictors affecting risks for cardiometabolic disorders. More intervention studies are needed to determine how dAGEs are associated with the prevalence of cardiometabolic disorders through gut microbiota changes. Further human studies are conducted to find the association between CVD events, CVD mortality and total mortality through SAF measurement, and a consensus on whether tissue dAGEs act as a predictor of CVD is required.

Characterizing Dietary Advanced Glycation End-Product (dAGE) Exposure and the Relationship to Colorectal Adenoma Recurrence: A Secondary Analysis.

Limited studies have evaluated the association between dietary advanced glycation end-product AGE (dAGEs) intake and cancer risk; however, no studies have addressed adenoma risk or recurrence. The objective of this study was to determine an association between dietary AGEs and adenoma recurrence. A secondary analysis was conducted using an existing dataset from a pooled sample of participants in two adenoma prevention trials. Participants completed a baseline Arizona Food Frequency Questionnaire (AFFQ) to estimate AGE exposure. NƐ- carboxymethyl-lysine (CML)-AGE values were assigned to quantify foods in the AFFQ using a published AGE database, and participants' exposure was evaluated as a CML-AGE (kU/1000 kcal) intake. Regression models were run to determine the relationship between CML-AGE intake and adenoma recurrence. The sample included 1976 adults with a mean age of 67.2 y ± 7.34. The average CML-AGE intake was 5251.1 ± 1633.1 (kU/1000 kcal), ranging between 4960 and 17032.4 (kU/1000 kcal). A higher intake of CML-AGE had no significant association with the odds of adenoma recurrence [OR(95% CI) = 1.02 (0.71,1.48)] compared to participants with a lower intake. In this sample, CML-AGE intake was not associated with adenoma recurrence. Future research is needed and should be expanded to examine the intake of different types of dAGEs with consideration for the direct measurement of AGE.

Dietary Advanced Glycation End Products and Risk of Overall and Cause-Specific Mortality: Results from the Golestan Cohort Study.

Controversy exists regarding the association of dietary advanced glycation end products (dAGEs) with the risk of disease outcomes and mortality. We aimed to examine, prospectively, the association between dAGEs intake and the risk of overall and cause-specific mortality in the Golestan Cohort Study. The cohort was conducted between 2004 and 2008 in Golestan Province (Iran) recruiting 50,045 participants aged 40-75 years. Assessment of dietary intake over the last year was performed at baseline using a 116-item food frequency questionnaire. The dAGEs values for each individual were calculated based on published databases of AGE values of various food items. The main outcome was overall mortality at the time of follow-up (13.5 years). Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall and cause-specific mortality were estimated according to the dAGEs quintiles. During 656, 532 person-years of follow-up, 5406 deaths in men and 4722 deaths in women were reported. Participants at the highest quintile of dAGE had a lower risk of overall mortality (HR: 0.89, 95% CI: 0.84, 0.95), CVD mortality (HR: 0.89, 95% CI: 0.84, 0.95), and death from other causes (HR: 0.89, 95% CI: 0.84, 0.95) compared to those in the first quintile after adjusting for confounders. We found no association of dAGEs with risk of mortality from cancer (all), respiratory and infectious diseases, and injuries. Our findings do not confirm a positive association between dAGEs and the risk of mortality in Iranian adults. There is still no agreement among studies investigating dAGEs and their health-related aspects. So, further high-quality studies are required to clarify this association.