Dietary Advanced Glycation End Products Research Articles

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

BackgroundDietary 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.MethodsThis 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.ResultsThe 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).ConclusionThe present findings suggest that a diet with high AGEs is associated with a higher likelihood of BC in adult women.

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

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). 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. 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). 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.

Dietary Approach of Patients with Hormone-Related Cancer Based on the Glycemic Index and Glycemic Load Estimates.

Hormone-related cancers, namely breast, endometrial, cervical, prostate, testicular, and thyroid, constitute a specific group of cancers dependent on hormone levels that play an essential role in cancer growth. In addition to the traditional risk factors, diet seems to be an important environmental factor that partially explains the steadily increased prevalence of this group of cancer. The composition of food, the dietary patterns, the endocrine-disrupting chemicals, and the way of food processing and preparation related to dietary advanced glycation end-product formation are all related to cancer. However, it remains unclear which specific dietary components mediate this relationship. Carbohydrates seem to be a risk factor for cancer in general and hormone-related cancers, in particular, with a difference between simple and complex carbohydrates. Glycemic index and glycemic load estimates reflect the effect of dietary carbohydrates on postprandial glucose concentrations. Several studies have investigated the relationship between the dietary glycemic index and glycemic load estimates with the natural course of cancer and, more specifically, hormone-related cancers. High glycemic index and glycemic load diets are associated with cancer development and worse prognosis, partially explained by the adverse effects on insulin metabolism, causing hyperinsulinemia and insulin resistance, and also by inflammation and oxidative stress induction. Herein, we review the existing data on the effect of diets focusing on the glycemic index and glycemic load estimates on hormone-related cancers.

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

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. 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. 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. 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.

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.

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

Background & aimsTo 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 results52 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). ConclusionsThese results show knowledge on culinary techniques is relevant to derive the association between dAGEs intake and cardiometabolic risk factors.

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

BackgroundDietary 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.MethodsA 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.ResultsMean ± 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).ConclusionOur results showed that greater adherence to dietary pattern with high dietary AGEs intake was significantly related to increased odds of NAFLD.

Impact of Dietary Advanced Glycation End-Product Restriction on Insulin Resistance and Anthropometric Indices in Coronary Artery Patients Treated with Percutaneous Coronary Intervention: A Randomized Controlled Trial.

Insulin resistance (IR), even in its subclinical state, is a significant risk factor for the onset and progression of coronary artery disease (CAD). IR is a multifactorial condition, and dietary composition is a factor associated with its development. Elevated advanced glycation end products (AGEs) in the body, secondary to highly processed food consumption, can impair glucose metabolism. The present study investigated whether a restricted AGE diet could affect insulin sensitivity and anthropometric indices reflecting visceral adipose tissue in nondiabetic CAD patients. This trial randomly allocated 42 angioplasty-treated patients to follow either low-AGE or control diets based on the AHA/NCEP guidelines for 12 weeks. Serum levels of total AGEs, insulin, HbA1c, and fasting blood sugar, as well as anthropometric measurements, were evaluated before and after the intervention. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and anthropometric indices were calculated according to the proposed formula. The patients' health status was assessed using the Seattle Angina Questionnaire (SAQ) at baseline and after the intervention. Our study showed a significant reduction in anthropometric indices in the low-AGE group after 12 weeks. Insulin levels and IR decreased during the low-AGE diet. No significant changes were observed in the other serum biochemical markers. All SAQ domains significantly decreased in both groups, except for Treatment Satisfaction. A low-AGE diet for 12 weeks had beneficial effects on HOMA-IR and insulin levels in patients with CAD. Regarding the fundamental role of AGE in IR development and body fat distribution, AGE restriction may positively affect these patients.

Dragon Fruit Peel Waste (Hylocereus undatus) as a Potential Ingredient for Reducing Lipid Peroxidation, Dietary Advanced Glycation End Products, and Starch Digestibility in Cookies.

Excessive consumption of cookies has been linked to harmful health outcomes owing to the presence of refined carbohydrates and heat-induced toxicants including end products of lipid peroxidation and dietary advanced glycation end products (dAGEs). To address this issue, this study explores the addition of dragon fruit peel powder (DFP), which is rich in phytochemicals and dietary fibers, to cookies as a potential solution to mitigate their adverse effects. The results indicate that adding DFP at 1%, 2%, and 5% w/w of raw cookie dough significantly improves the total phenolic and betacyanin contents and antioxidant activity, as evidenced by increased ferric-reducing antioxidant power. DFP incorporation also led to reductions in malondialdehyde and dAGEs (p < 0.05). Furthermore, the starch digestibility, hydrolysis index, and predicted glycemic index were all reduced in the presence of DFP, with the latter estimate being due to the higher content of undigested starch. Incorporating DFP in cookies resulted in significant changes in their physical properties, including texture and color. However, sensory evaluation indicates that the overall acceptability of the cookies was not negatively impacted by the addition of up to 2% DFP, suggesting that it is a viable option for enhancing the nutritional value of cookies without compromising their palatability. These findings suggest that DFP is a sustainable and healthier ingredient that can improve the antioxidant capacity of cookies while also mitigating the harmful effects of heat-induced toxins.

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.

Dietary advanced glycation end-products and postmenopausal hot flashes: A post-hoc analysis of a 12-week randomized clinical trial

ObjectivePostmenopausal hot flashes are associated with an increased risk of cardiovascular disease and diabetes. Because dietary advanced glycation end-products (AGEs) may act as endocrine disruptors, this study examined the potential association of modifications to the intake of dietary AGEs with the frequency and severity of postmenopausal hot flashes. MethodsPostmenopausal women (n = 84) reporting ≥2 moderate-to-severe hot flashes daily were randomly assigned to either the intervention group or the control group. The former were asked to follow a low-fat, vegan diet, including cooked soybeans (1/2 cup [86 g]/day) for 12 weeks, and the latter continued their usual diets for 12 weeks. Frequency and severity of hot flashes were recorded with a mobile application. Three-day diet records were analyzed using the Nutrition Data System for Research software and dietary AGEs were estimated, using a database. Seventy-one participants completed the whole study and 63 provided complete hot flash and dietary data for the AGEs analysis (n = 31 in the intervention and n = 24 in the control group). Pearson correlations were used to assess the association between changes in hot flashes and dietary AGEs. ResultsDietary AGEs decreased in the intervention group by 73 %, that is by 5509 ku/day on average (95 % −7009 to −4009; p < 0.001), compared with the control group (+458; 95 % CI −835 to +1751; p = 0.47; treatment effect −5968 ku/day [95 % CI −7945 to −3991]; Gxt, p < 0.001). Severe hot flashes decreased by 92 % (p < 0.001) and moderate-to-severe hot flashes decreased by 88 % in the intervention group (p < 0.001). Changes in dietary AGEs correlated with changes in severe (r = +0.39; p = 0.002) and moderate hot flashes (r = +0.34; p = 0.009) and remained significant after adjustment for changes in energy intake (r = +0.45; p < 0.001; and r = +0.37; p = 0.004, respectively) and changes in body mass index (r = +0.37; p = 0.004; and r = +0.27; p = 0.04, respectively). The reduction in dietary AGEs required to achieve a predicted reduction in hot flashes by 1/day was 6933 ku/day for severe and 4366 ku/day for moderate-to-severe hot flashes. ConclusionsThe reduction in dietary AGEs with a low-fat plant-based diet was associated with a significant reduction in the frequency of severe and moderate-to-severe postmenopausal hot flashes, independent of changes in energy intake and weight loss. Plant-based diets could be used not only to alleviate vasomotor symptoms in postmenopausal women, but also to reduce other health risks associated with AGEs. Trial registrationClinicalTrials.gov, NCT04587154.

Dietary advanced glycation end products (dAGEs): An insight between modern diet and health

Advanced glycation end products (AGEs) are formed by a series of chemical reactions of amino acids, peptides, proteins, and ketones at normal temperature or heated non-enzymatic conditions. A large amount of AGEs derived from Maillard Reaction (MR) during the process of food heat-processing. After oral intake, dietary AGEs are converted into biological AGEs through digestion and absorption, and accumulated in almost all organs. The safety and health risk of dietary AGEs have attracted wide attention. Increasing evidence have shown that uptake of dietary AGEs is closely related to the occurrence of many chronic diseases, such as diabetes, chronic kidney disease, osteoporosis, and Alzheimer’s disease. This review summarized the most updated information of production, bio-transport in vivo, detection technologies, and physiological toxicity of dietary AGEs, and also discussed approaches to inhibit dietary AGEs generation. Impressively, the future opportunities and challenges on the detection, toxicity, and inhibition of dietary AGEs are raised.

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.

Effects of Allergen-Specific and Non-Specific AGEs on the Allergenicity of Ovalbumin in a Mouse Model of Food Allergy.

Epidemiologic studies suggest a link between the incidence of food allergy and the consumption of dietary advanced glycation end-products (AGEs). However, the pathogenic role of dietary AGEs in food allergy is largely unknown. This study aims to investigate the effect of allergen-specific and non-specific AGEs on the allergenic manifestation of ovalbumin (OVA), a typical food allergen in vivo. OVA is glycated by methylglyoxal to prepare allergen-specific AGEs (i.e., OVA-AGE), and a standard AIN-93G diet is heated to obtain allergen-non-specific AGEs. A BALB/c mouse model orally sensitizes to OVA with different forms of AGEs is established and the outcomes are measured as clinical signs, specific antibodies, type-2/type-2 cytokines, immune cell subpopulations, intestinal barrier function, and gut microbiota (GM) composition. The OVA-AGE which has a lower immunoglobulin E (IgE)-binding level in vitro does not reduce the allergenicity of OVA but promotes a stronger T helper 2 cells (Th2)-response than native OVA in vivo. Both forms of AGEs up-regulate the expression of splenic RAGE and aggravate the destruction of gut barrier and GM dysbiosis, especially when exposes to non-relevant AGEs. This study highlights the role of dietary AGEs in food allergy and helps to understand the biological consequences of immune-toxic compounds in modern diet.

Advanced Glycation End-Products and Their Effects on Gut Health.

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.

Occurrence of dietary advanced glycation end-products in commercial cow, goat and soy protein based infant formulas

Thermal treatment is a key step during infant formula (IF) processing which causes protein glycation and formation of dietary advanced glycation end-products (dAGEs). This study aimed to evaluate the glycation degree in IF in relation to the ingredients of the formula. dAGEs concentrations have been determined by UPLC-MS/MS in a range of commercial cow-based, goat-based, and soy-based IF. Results indicated that the protein source, protein composition, and amount and type of carbohydrates determines the level of protein glycation in IFs. The investigated soy-based formula had significant higher concentrations of arginine and arginine-derived dAGEs than cow-based and goat-based formulas. IF containing hydrolyzed proteins had higher dAGEs concentrations than those containing intact proteins. Lactose-containing formula was more prone to glycation than those containing sucrose and maltodextrin. Data showed glycation degree in IF cannot be estimated by a single compound, but the complete picture of the dAGEs should be considered.

Circulating and dietary advanced glycation end products and obesity in an adult population: A paradox of their detrimental effects in obesity.

The detrimental role of advanced glycation end products (AGEs) against cardio-metabolic health has been revealed in several previous reports. However, the results of studies regarding the association between AGEs and obesity measurements are inconsistent. In the current meta-analysis, we aimed to quantitatively summarize the results of studies that evaluated the association between circulating and dietary AGEs with obesity measurements among the adult population. A systematic search from PubMed, Embase, and Scopus electronic databases until 30 October 2022 retrieved a total of 21,429 observational studies. After duplicate removal, title/abstract screening, and full-text reading by two independent researchers, a final number of 18 manuscripts remained to be included in the meta-analysis. Those in the highest category of circulating AGEs had ~1.5 kg/m2 reduced BMI compared with those in the lowest AGEs category [weighted mean difference (WMD): -1.485; CI: -2.459, -0.511; p = 0.003], while a nonsignificant increase in BMI was observed in the highest versus lowest category of dietary AGEs (WMD: 0.864, CI: -0.365, 2.094; p = 0.186). Also, lower amounts of circulating AGEs in individuals with obesity versus individuals without obesity were observed (WMD: -57.220, CI: -84.290, -30.149; p < 0.001). AGE type can be considered as a possible source of heterogeneity. In the current meta-analysis, we observed an inverse association between circulating AGEs and body mass index among adults. Due to low study numbers, further studies are warranted to better elucidate these results.

Dietary advanced glycation end-products (dAGEs) intake and its relation to sarcopenia and frailty - The Rotterdam Study.

Studies on mice have shown a relationship between dietary intake of advanced glycation end-products (dAGEs) and deterioration of musculoskeletal health, but human studies are absent. We investigated the relationship between dietary intake of carboxymethyllysine (dCML) - an AGE prototype - and risk of sarcopenia at baseline and after 5years of follow-up and a single evaluation of physical frailty in participants from the population-based Rotterdam Study. Appendicular lean mass (ALM) was obtained using insight dual-energy X-ray absorptiometry and hand grip strength (HGS) using a hydraulic hand dynamometer. Subjects with both low ALM and weak HGS were classified as having sarcopenia. Frailty (yes/no) was defined by presence of ≥3 and pre-frailty by presence of 1 or 2 components namely, exhaustion, weakness, slowness, weight loss or low physical activity. dCML was calculated using a food frequency questionnaire and dAGE databases. Logistic regression analysis was used to evaluate the odds of physical frailty and prevalent sarcopenia at baseline and follow-up and incident sarcopenia. 2782 participants with an age 66.4±9.9years and dCML intake 3.3±1.3mg/day, had data on sarcopenia at both time points. Of whom 84 had sarcopenia at baseline and 73 developed sarcopenia at follow-up. We observed an association of one SD increase in dCML intake with prevalent sarcopenia at baseline [odds ratio, OR=1.27 (1.01-1.59)] and no association of dCML with incident sarcopenia at 5-year follow-up [OR=1.12 (0.86-1.44)]. For frailty we analyzed 3577 participants, of whom 1972 were pre-frail and 158 were frail. We observed no association of dCML with either pre-frailty [OR=0.99 (0.91-1.07)] or frailty [OR=1.01 (0.83-1.22)] when non-frail subjects were used as reference. Our results show an association of dAGEs with sarcopenia cross-sectionally but not longitudinally where inconclusive findings are observed possibly due to a very low incidence of sarcopenia. There was no association with frailty cross-sectionally.