Advanced Glycation End-products Intake Research Articles

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

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. 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). 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. 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.

Front Cover: Effects of Allergen‐Specific and Non‐Specific AGEs on the Allergenicity of Ovalbumin in a Mouse Model of Food Allergy

Mol. Nutr. Food Res. 2023, 67, 202200221 DOI: 10.1002/mnfr.202200221 Epidemiologic evidence suggests a link between food allergy and the intake of advanced glycation end-products (AGEs). This study investigated the role of allergen-specific and non-specific AGEs in allergenicity of ovalbumin (OVA) in a mouse model of food allergy. The OVA-AGE elicits a stronger Th2-response than native OVA, in comparison to severer disruptions in gut barrier function and gut microbiota in mice exposed to non-relevant AGEs. This is reported by Shuifeng Zhang, Linglin Fu, and co-workers in article number 2200221.

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.

Fortification with Morus indica extract attenuates the formation of AGEs in bread

Intake of advanced glycation endproducts (AGEs) may be increased by consuming high-sugar meals and foods cooked at high temperatures. AGEs-induced inflammation has been linked to diabetes and degenerative diseases. Leaves from mulberry (Morus indica L) (MI) trees have been used in Chinese medicine for over 3000 years and are a functional food because of their phytochemical content. MI extract was used to substitute 0, 0.25, 0.50, 0.75 and 1% of wheat ?our for making MI wheat bread (MI-B). 5% of turmeric powdered bread (TM-B) was also prepared and used as a positive control. The bread’s overall acceptability was determined using a sensory evaluation on hedonic test. Further, the antioxidant capacity was assayed by using DPPH method and antiglycation effects of MI extract against the formation of ?uorescent AGEs in fortified bread samples. The overall acceptability of bread with MI extract at substitution levels of 0.5% had a good liking score. The total polyphenol content in the MI-B and TM-B were 2.01 mg GAE g-1 and 1.54 mg GAE g-1 on a dry weight basis. MI-B showed significantly higher antioxidant activities, followed by TM-B > control bread. When compared to TM-B, AGEs inhibit fluorescent formation by 31%. Overall, the findings support MI extract as a functional food ingredient in the bread system, providing consumers with a higher antioxidant intake by depleting AGEs load. However, the stability and reactivity of polyphenols during thermal processing should be considered before commercialization.

The impact of a modified carbohydrate formula, and its constituents, on glycaemic control and inflammatory markers: A nested mechanistic sub-study.

Hyperglycaemia occurs frequently in the critically ill. Dietary intake of advanced glycation end-products (AGEs), specifically Nε-(carboxymethyl)lysine (CML), may exacerbate hyperglycaemia through perturbation of insulin sensitivity. The present study aimed to determine whether the use of nutritional formulae, with varying AGE loads, affects the amount of insulin administered and inflammation. Exclusively tube fed patients (n = 35) were randomised to receive Nutrison Protein Plus Multifibre®, Diason® or Glucerna Select®. Insulin administration was standardised according to protocol based on blood glucose (<10 mmolL-1 ). Samples were obtained at randomisation and 48 h later. AGEs in nutritional formula, plasma and urine were measured using mass spectrometry. Plasma inflammatory markers were measured using an enzyme-linked immunosorbent assay and multiplex bead-based assays. AGE concentrations of CML in nutritional formulae were greatest with delivery of Nutrison Protein Plus® (mean [SD]; 6335pmolmol-1 [2436]) compared to Diason® (4836pmolmol-1 [1849]) and Glucerna Select® (4493pmolmol-1 [1829pmolmol-1 ]) despite patients receiving similar amounts of energy (median [interquartile range]; 12 MJ [8.2-13.7 MJ], 11.5 MJ [8.3-14.5 MJ], 11.5 MJ [8.3-14.5 MJ]). More insulin was administered with Nutrison Protein Plus® (2.47unitsh-1 [95% confidence interval (CI)=1.57-3.37unitsh-1 ]) compared to Diason® (1.06unitsh-1 [95% CI=0.24-1.89unitsh-1 ]) or Glucerna Select® (1.11unitsh-1 [95% CI=0.25-1.97unitsh-1 ]; p = 0.04). Blood glucose concentrations were similar. There were associations between greater insulin administration and reductions in circulating interleukin-6 (r = -0.46, p < 0.01), tumour necrosis factor-α (r = -0.44, p < 0.05), high sensitivity C-reactive protein (r = -0.42, p < 0.05) and soluble receptor for advanced glycation end-products (r = -0.45, p < 0.01) concentrations. The administration of greater AGE load in nutritional formula potentially increases the amount of insulin required to maintain blood glucose within a normal range during critical illness. There was an inverse relationship between exogenous insulin and plasma inflammatory markers.

Dietary intake of advanced glycation endproducts and risk of hepatobiliary cancers: A multinational cohort study.

Advanced glycation endproducts (AGEs) may contribute to liver carcinogenesis because of their proinflammatory and prooxidative properties. Diet is a major source of AGEs, but there is sparse human evidence on the role of AGEs intake in liver cancer etiology. We examined the association between dietary AGEs and the risk of hepatobiliary cancers in the European Prospective Investigation into Cancer and Nutrition prospective cohort (n = 450 111). Dietary intake of three AGEs, Nε‐[carboxymethyl]lysine (CML), Nε‐[1‐carboxyethyl]lysine (CEL) and Nδ‐[5‐hydro‐5‐methyl‐4‐imidazolon‐2‐yl]‐ornithine (MG‐H1), was estimated using country‐specific dietary questionnaires linked to an AGEs database. Cause‐specific hazard ratios (HR) and their 95% confidence intervals (CI) for associations between dietary AGEs and risk of hepatocellular carcinoma (HCC), gallbladder and biliary tract cancers were estimated using multivariable Cox proportional hazard regression. After a median follow‐up time of 14.9 years, 255 cases of HCC, 100 cases of gallbladder cancer and 173 biliary tract cancers were ascertained. Higher intakes of dietary AGEs were inversely associated with the risk of HCC (per 1 SD increment, HR‐CML = 0.87, 95% CI: 0.76‐0.99, HR‐CEL = 0.84, 95% CI: 0.74‐0.96 and HR‐MH‐G1 = 0.84, 95% CI: 0.74‐0.97). In contrast, positive associations were observed with risk of gallbladder cancer (per 1 SD, HR‐CML = 1.28, 95% CI: 1.05‐1.56, HR‐CEL = 1.17; 95% CI: 0.96‐1.40, HR‐MH‐G1 = 1.27, 95% CI: 1.06‐1.54). No associations were observed for cancers of the intra and extrahepatic bile ducts. Our findings suggest that higher intakes of dietary AGEs are inversely associated with the risk of HCC and positively associated with the risk of gallbladder cancer.

Quercetin is protective against short‐term dietary advanced glycation end products intake induced cognitive dysfunction in aged ICR mice

Dietary advanced glycation end products (dAGEs) might be potential toxins involved in the pathogenesis of Alzheimer's disease (AD). Quercetin is a flavonoid possessing neuroprotective effects. We aimed to explore whether a 21days of dAGEs intake would result in cognitive dysfunction in aged ICR mice, and the protective effects of quercetin, with potential mechanisms explored. Fourteen-month old ICR mice were randomly assigned into four groups, that is, Control, AGEs, quercetin, and AGE diet supplemented with quercetin. Key markers involved in Aβ, tau, and neuroinflammation from hippocampus and cortex were measured via western blot. Gut microbiota and short chain fatty acids profiles from intestinal contents were measured via 16S rRNA gene sequencing and gas chromatography (GC), respectively. Quercetin alleviated cognitive impairment induced by dAGEs in aged mice. This might be associated with that quercetin reduced cathepsin B, tau phosphorylation, and neuroinflammation, and elevated α-diversity index (ACE, Chao1, and Shannon index), and reduced phylum Verrucomicrobia of gut microbiota. PRACTICAL APPLICATIONS: Alzheimer's disease (AD) has been regarded as the commonest cause of progressive dementia for the elderly. This study is the very first to demonstrate that even a short-term dietary advanced glycation end product (dAGEs) intake induced impaired cognitive function in aged ICR mice, and querectin is capable of reversing dAGEs-induced cognitive dysfunction. Reduced tau phosphorylation, neuroinflammation, and altered gut microbiota profiles may be involved in querectin's protective effects against dAGEs-induced cognitive impairment. Our study suggested that quercetin supplementation might be beneficial for improving cognitive function in elderly subjects with high consumption of dAGEs such as grilling, frying, and broiling of food.

Association of Dietary Advanced Glycation End Products with Metabolic Syndrome in Young Mexican Adults.

Background: Consumption of dietary advanced glycation end products is linked to metabolic syndrome. The objective was to describe the association between dietary advanced glycation end products intake and metabolic syndrome in young Mexican adults. Methods: The present was a cross-sectional study in 126 Mexican adults 18–35 years old evaluating metabolic syndrome through the harmonized criteria. Macronutrients and dietary advanced glycation end products intake were estimated through three 24-hour dietary recalls and food composition tables. Association between metabolic syndrome and high advanced glycation end products intake (≥10,000 kU/day) was evaluated through three logistic regression models adjusted by sex, age, family history of cardiometabolic diseases and energy intake. Results: Subjects with a higher advanced glycation end products intake were more likely to have impaired fasting glucose (OR: 4.91, 95% CI 1.29–18.60, p < 0.05) and metabolic syndrome (OR: 2.67, 95% CI 0.96–7.44, p = 0.059) than those participants with low consumption of these products after adjustment of sex, age, family history of cardiovascular disease and energy intake. Conclusions: High intake of dietary advanced glycation end products was significantly associated with impaired fasting glucose and marginally with metabolic syndrome in young Mexican adults regardless of sex, age, family history of cardiovascular disease and energy intake.

Mediterranean Diet: A Strategy to Reduce Dietary Advanced Glycation End Products Intake

Mediterranean Diet: A Strategy to Reduce Dietary Advanced Glycation End Products Intake

Dietary advanced glycated end-products and medicines influence the expression of SIRT1 and DDOST in peripheral mononuclear cells from long-term type 1 diabetes patients.

Quantitative polymerase chain reaction was employed to quantify expression of two genes coding for advanced glycation end-product receptors [RAGE ( AGER) and AGER1 ( DDOST)] and of the gene coding the deacetylase SIRT1 ( SIRT1) in peripheral blood mononuclear cells from type 1 diabetes patients without [Group A, n = 35; 28.5 (24-39) years old; median (interquartile interval)] or with at least one microvascular complication [Group B, n = 117; 34.5 (30-42) years old]; 31 healthy controls were also included. In a subgroup of 48 patients, daily advanced glycation end-products intake before blood collection was assessed. Lower expression of DDOST was found in patients than in controls after adjustment for sex, age, use of statins, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Higher expressions of AGER, DDOST and SIRT1 were observed in Group A. Stratifying by complications, AGER and DDOST expressions were higher in those without retinopathy and without diabetic kidney disease, respectively, compared to patients with these complications. Patients using statins or angiotensin receptor blockers presented higher expression of DDOST. Expression of SIRT1 was higher in patients consuming ≥12,872 KU daily of advanced glycation end-products. Although AGER, DDOST and SIRT1 are differently expressed in peripheral blood mononuclear cells from type 1 diabetes patients with and without microvascular complications, they are also influenced by dietary advanced glycation end-products and by statins and angiotensin receptor blockers.

Dietary intake of advanced glycation endproducts is associated with higher levels of advanced glycation endproducts in plasma and urine: The CODAM study

Advanced glycation endproducts (AGEs) are formed by the reaction between reducing sugars and proteins. AGEs in the body have been associated with several age-related diseases. High-heat treated and most processed foods are rich in AGEs. The aim of our study was to investigate whether dietary AGEs, are associated with plasma and urinary AGE levels. In 450 participants of the Cohort on Diabetes and Atherosclerosis Maastricht study (CODAM study) we measured plasma and urine concentrations of the AGEs Nε-(carboxymethyl)lysine (CML), Nε-(1-carboxyethyl)lysine (CEL) and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) using UPLC-MS/MS. We also estimated dietary intake of CML, CEL and MG-H1 with the use of a dietary AGE database and a food frequency questionnaire (FFQ). We used linear regression to investigate the association between standardized dietary AGE intake and standardized plasma or urinary AGE levels, after adjustment for age, sex, glucose metabolism status, waist circumference, kidney function, energy- and macro-nutrient intake, smoking status, physical activity, alcohol intake, LDL-cholesterol and markers of oxidative stress. We found that higher intake of dietary CML, CEL and MG-H1 was associated with significantly higher levels of free plasma and urinary CML, CEL and MG-H1 (βCML=0.253 (95% CI 0.086; 0.415), βCEL=0.194 (95% CI 0.040; 0.339), βMG-H1=0.223 (95% CI 0.069; 0.373) for plasma and βCML=0.223 (95% CI 0.049; 0.393), βCEL=0.180 (95% CI 0.019; 0.332), βMG-H1=0.196 (95% CI 0.037; 0.349) for urine, respectively). In addition, we observed non-significant associations of dietary AGEs with their corresponding protein bound plasma AGEs. We demonstrate that higher intake of dietary AGEs is associated with higher levels of AGEs in plasma and urine. Our findings may have important implications for those who ingest a diet rich in AGEs.

Reduction of serum advanced glycation end-products with a low calorie Mediterranean diet.

Dietary intake of advanced glycation end-products (AGEs) increases circulating and tissue levels of these substances, contributing to a state of increased oxidative stress and inflammation. A low dietary AGE intervention has been shown to reduce body AGE content. Mediterranean diets (MD) are theoretically considered low in AGEs, but the specific effects of a MD on AGEs serum levels has not been tested. Forty-seven overweight and obese premenopausal women underwent a three-month calorie restriction treatment (20 kcal/kg initial weight) with a Mediterranean-type diet that excluded wine intake. The adherence to the MD was assessed before and at the end of treatment using an on-line questionnaire, which scores from 0 to 14 (minimal to maximal adherence). Body composition, insulin resistance, lipoproteins and carboxymethyl-lisine (CML) serum levels were measured at both time periods. Serum CML was assessed through ELISA (enzyme-linked immunosorbent assay). Compliance to calorie restriction was assessed according to weight loss (< or > 5% initial weight). Mean body weight, body fat, waist circumference, total cholesterol, triglycerides and serum CML fell significantly, together with an increase in the Mediterranean score, although none of the patients reached the highest score. Significant changes in CML and insulin resistance were observed in 17 women classified as compliant to caloric restriction, but not in the 27 participants who were considered adherent to the MD (according to improvement of the Mediterranean Score). CML serum levels can be reduced through calorie restricted-Mediterranean-type diet. We could not reach a high enough MD score, so we cannot conclude whether the MD itself has an additive effect to caloric restriction.

Simultaneous analysis of N(ε) -(carboxymethyl)Lysine and N(ε) -(carboxyethyl)lysine in foods by ultra-performance liquid chromatography-mass spectrometry with derivatization by 9-fluorenylmethyl chloroformate.

Isotope dilution ultra-performance liquid chromatography-electrospray tandem mass spectrometry with derivatization by 9-fluorenylmethyl chloroformate was successfully applied to quantify N(ε) -(carboxymethyl)lysine (CML) and N(ε) -(carboxyethyl)lysine (CEL) in processed foods. We demonstrate that this analytical method is well validated for the determination of CML and CEL contents in processed foods. Relative standard deviations (RSD) indicate repeatability (RSD < 6% for CML and CEL) and reproducibility (RSD < 6% for CML and < 7% for CEL) in this method. Percent recovery is also good. We obtain recoveries of 102% to 112% for CML and 86% to 114% for CEL. CML levels detected in the samples vary from 2.29 to 480 mg/kg food, whereas CEL is detected in significantly lower concentrations ranging from 0.56 to 107 mg/kg food. These data could help consumers make better food choices by monitoring intake of advanced glycation end-products, which may pose a risk to human health.