Search Results (53)

Soy sauce (SS) is one of the most popular condiments in the world. However, Nε-carboxymethyl-lysine (CML) and 5-hydroxymethylfurfural (5-HMF), harmful Maillard reaction products, are present in SS. Worse still, their primary sources in SS production remain unclear, and their contents increase during the consumption of heated SS. In this study, CML and 5-HMF were simultaneously monitored, and thermal treatment and the addition of natural product were used to simultaneously reduce their contents during SS production and consumption. During SS production, CML and 5-HMF primarily originated from the raw materials used in SS production, Maillard reactions during fermentation, and the addition of food additives. Also, CML and 5-HMF were simultaneously found in commercial light soy sauce, dark soy sauce, and infant SS, and thermal treatment could increase their contents. Fortunately, additional thermal treatment of semi-finished SS (especially raw sauce and rude light SS) and appropriate concentrations of (−)-epicatechin (100 μM) and ascorbic acid (5 μM), respectively, added to SS for direct and heated consumption, could simultaneously reduce the CML and 5-HMF contents. This study highlights the presence of CML and 5-HMF in SS and proposes practical methods to simultaneously minimize their contents during production and consumption. Full article

Background: N^ε-(carboxymethyl)-lysine (CML) is formed in the human body by non-enzymatically driven reactions including glycation, oxidation, and lipoxidation. CML is a ubiquitous product of normal physiology, but its levels are increased under disease conditions like chronic kidney disease (CKD) and diabetes mellitus (DM). Free CML is eliminated from the human body mainly through kidney excretion, and its accumulation in the kidney tissue is linked to CKD pathogenesis. Aim: The main goal of this study was to evaluate the relative contribution of CKD and Type 2 DM (T2DM) to the accumulation of CML in patients’ sera. Methods: The study included 22 patients with CKD without DM, 55 with CKD and comorbid T2DM, and 21 with T2DM without CKD. Serum CML levels were measured by ELISA. The Kruskal-Wallis test was used to detect differences among groups. Spearman correlation analysis was performed, and the one-tailed Dunn test was considered to indicate statistical significance at p < 0.05. Results: The median serum CML levels (CKD, 658.4 ± 434.3 ng/mL; CKD + T2DM, 431.3 ± 327.9 ng/mL; T2DM, 273.9 ± 134.2 ng/mL) differed significantly (p < 0.05) among the three patient groups. A positive correlation was observed between serum CML and microalbuminuria (p = 0.004; r = 0.58), proteinuria (p = 0.002; r = 0.6), and age (p = 0.007; r = 0.52) only in the CKD patients. In all T2DM patients, independent of CKD status, serum CML correlated negatively (p < 0.05) with postprandial glucose and duration of diabetes, while its correlation with fasting glucose and HbA1c was negative only in the T2DM cohort without CKD. Conclusions: In patients with CKD, higher levels of CML were observed compared to those with T2DM. Serum CML correlated positively with proteinuria, albuminuria, and patient age in non-diabetic CKD patients, and negatively with blood glucose, HbA1c, and DM duration of T2DM in patients without CKD. Full article

When breastfeeding is not possible, infant formulas may be used instead of human milk. However, harmful advanced glycation end-products (AGEs) may be formed during thermal processing of infant formulas. The exposure to AGEs at such an early age can lead to chronic diseases in the future. Therefore, the aim of this study was to develop a sensitive method to determine the content of AGEs in infant formulas. Twenty commercial infant formulas (initial and follow-on) in liquid and powder form were investigated using liquid chromatography with tandem mass spectrometry (LC-MS/MS) with a multistep sample pretreatment procedure. Five selected glycation products were analyzed: N^ε-carboxyethyllysine (CEL), N^ε-carboxymethyllysine (CML), furosine, glyoxal lysine dimer (GOLD), and methylglyoxal lysine dimer (MOLD). The mean contents of the tested glycation products did not differ significantly between the initial and follow-on formulas. No significant differences were found in the concentrations of the analyzed compounds from different manufacturers. However, the liquid formulas contained significantly more CML. The estimated dietary exposure to the tested compounds was in the range of 42.5–92.6 μg/day, except for furosine (almost 2 mg/day). The developed method enabled the determination of selected AGEs in complex matrices such as infant formulas. Consumption of liquid infant formulas can result in higher exposure to some AGEs. Full article

Background: Diabetics accumulate Advanced Glycation End products (AGEs) such as Nε-(carboxymethyl)lysine (CML) in their skin, which can provoke changes in the skin’s biomechanical properties. The same changes are also observed during aging. Collagen is one of the first targets of glycation, and this leads to the disruption of the dermis, potentially contributing to the skin complications seen in diabetes, like impaired wound healing and the formation of chronic ulcers. We therefore investigated whether it was possible to detect differences in the biomechanical properties of the reticular dermis by comparing C57/BL6 control mice, type 1 and type 2 diabetic mice, and aged mice. Methods: To investigate this, we used an Atomic Force Microscope (a type of local probe microscope used to visualize the surface topography of a sample) to measure the elastic modulus of each skin sample. The elastic modulus is a parameter that describes a tissue’s resistance to elastic deformation when stress is applied. We also determined whether diabetes is associated with the accumulation of AGEs via Western blots. Results: We found that type 2 diabetic mice and aged mice had a stiffer reticular dermis than young control mice. No differences were found in type 1 diabetic mice. The results of the Western blot did not reveal any significant differences in the CML content in different types of mice, although a non-significant increase was found in type 2 diabetic and aged mice. We show that there is a significant positive correlation between the amount of CML in a mouse and the rigidity of its reticular dermis. Conclusions/interpretation: We have demonstrated that increased glycation in mouse skin is correlated with the biomechanical properties of that skin, which explains the wound healing defects diabetic patient’s experience. AFM is therefore a powerful technique that could be used to characterize the mechanical effects of treatments aimed at reducing the level of AGEs in the skin. Full article

Glycation influences skin aging through non-enzymatic reactions between reducing sugars and proteins, forming advanced glycation end-products (AGEs) that accelerate skin deterioration. This study evaluates the curative anti-glycation effects of an injectable formulation combining dual-molecular-weight hyaluronic acid (low and mid/high) with trehalose in methylglyoxal-induced glycation in human skin explants. Thirty-six human skin explants were allocated across five experimental groups in a 12-day study. Glycation was induced using methylglyoxal (500 μM) on days 1 and 4, followed by curative product administration on day 5. CML (Nε-(carboxymethyl)lysine) immunohistochemistry was performed to assess glycation levels in the reticular dermis at days 6, 8, and 12, with quantitative analysis conducted through standardized image analysis. The formulation significantly reduced CML formation by 60% on day 6 compared to untreated controls (p < 0.001). Under methylglyoxal-induced glycation stress the product showed sustained curative effects, with CML reductions of 69% on day 6 (p = 0.008), 68% on day 8 (p = 0.012), and 61% on day 12 (p = 0.033) compared to methylglyoxal treatment alone. Cell viability remained unaffected throughout the study period across all experimental conditions. The tested injectable formulation exhibits significant and sustained curative anti-glycation properties in human skin explants for 12 days, effectively counteracting methylglyoxal-induced glycation damage without affecting cell viability. These findings advance anti-aging skin interventions, offering a novel approach to address glycation-induced skin damage with potential applications in clinical dermatology and aesthetic medicine. Full article

The dietary intake amount of processing contaminants does not reflect their actual exposure risk due to interactions with the food matrix during gastrointestinal processes, which significantly modulate their bioaccessibility. This study systematically investigated the in vitro digestion patterns of advanced glycation end products (AGEs) and α-dicarbonyl compounds (α-DCs) in biscuits and the modulatory effects of ferulic acid and epicatechin. The results demonstrated that more than 80% of AGEs and α-DCs were present in the bioaccessible fraction of the samples after intestinal digestion. Ferulic acid (FA, 0.05%, w/w) significantly increased the AGEs content in the bioaccessible fraction after intestinal digestion compared to control samples. Conversely, FA at 0.2% and 0.5%, as well as epicatechin (EC) at 0.05%, significantly reduced the glyoxal and 3-deoxyglucosone levels during oral digestion and significantly increased these contaminants contents after gastric digestion. The higher the concentration of EC, the lower the level of methylglyoxal during oral and gastric digestion. In addition, we identified the adducts of FA with lysine and the adducts of EC with Nε-Carboxymethyl-lysine using LC-QTOF-MS, demonstrating the reactivity between polyphenols, amino acids and contaminants. This study provides guidance and suggestions for mitigating dietary exposure to AGEs and α-DCs. Full article

Background: Advanced glycation end products (AGEs), a group of food processing byproducts, have been implicated in the development of various diseases. However, the relationship between circulating AGEs and sleep disorders remains uncertain. Methods: This cross-sectional study elucidated the association of plasma AGEs with sleep disorders among 1732 Chinese adults who participated in the initial visit (2019–2020) of the Tongji–Shenzhen Cohort (TJSZC). Sleep behavior was assessed using self-reported questionnaires and precise accelerometers. Plasma levels of AGEs, including Nε-(Carboxymethyl)lysine (CML), Nε-(Carboxyethyl)lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolone-2-yl)-ornithine (MG-H1), were quantified by ultra-high performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Results: In logistic regression, per IQR increment in individual AGEs was associated with an increased odds ratio of short sleep duration (CML: 1.11 [1.00, 1.23]; CEL: 1.16, [1.04, 1.30]), poor sleep quality (CML: 1.33 [1.10, 1.60]; CEL: 1.53, [1.17, 2.00]; MG-H1: 1.61 [1.25, 2.07]), excessive daytime sleepiness (CML: 1.33 [1.11, 1.60]; MG-H1: 1.39 [1.09, 1.77]), and insomnia (CML: 1.29 [1.05, 1.59]). Furthermore, in weighted quantile sum regression and Bayesian kernel machine regression analyses, elevated overall exposure levels of plasma AGEs were associated with an increased risk of sleep disorders, including short sleep duration, poor sleep quality, excessive daytime sleepiness, and insomnia, with CML being identified as the leading contributor. Insufficient vegetable intake and higher dietary fat intake was associated with an increase in plasma CEL. Conclusions: These findings support a significant association between plasma AGEs and sleep disorders, indicating that AGEs may adversely influence sleep health and reducing the intake of AGEs may facilitate preventing and ameliorating sleep disorders. Full article

(1) Background: The non-enzymatic glycation of proteins is a significant contributor to the formation of advanced glycation end products (AGEs) and intermediates that are responsible for diabetic complications. It is imperative to explore effective inhibitors to prevent protein glycation. (2) Methods: This study aimed to investigate the inhibitory potential of various aqueous ethanol extracts of poplar-type propolis on AGEs and oxidative modifications in bovine serum albumin (BSA)-glucose and BSA-methylglyoxal models. (3) Results: The results revealed that these propolis extracts exhibited significant effectiveness in inhibiting the formation of total AGEs, pentosidine, and Nε-carboxymethyllysine (CML). Furthermore, the investigation discovered that these propolis extracts can effectively inhibit oxidative modification, based on measuring the levels of carbonyl and thiol groups and analyzing tryptophan fluorescence quenching. Notably, 75% ethanol extracts of propolis (EEP) exhibited the highest inhibitory activity, surpassing the chemical inhibitor aminoguanidine (AG). (4) Conclusions: The remarkable anti-glycation potency of aqueous ethanol extracts of poplar-type propolis can be attributed to their elevated contents of phenolic compounds, especially abundant flavonoids, which inhibit the formation of AGEs by scavenging free radicals, decreasing the levels of reactive oxygen species (ROS), and capturing reactive carbonyl species (RCS) in the protein glycation process. Our results indicate that poplar-type propolis may be a potential AGE inhibitor and could be used to develop functional foods and nutraceuticals to prevent diabetic complications. Full article

To investigate the impact of extrusion parameters on the formation of N^ε-(carboxymethyl)lysine (CML), N^ε-(carboxyethyl)lysine (CEL) and acrylamide in plant-based meat analogues (PBMAs), the content changes and the correlations of compounds related to their formation were studied. The extrusion promoted CML, CEL and acrylamide formation, with more CEL being formed than CML. Variations in the moisture level and barrel temperature exerted a greater influence on the CML, CEL, acrylamide and α-dicarbonyl compounds than the screw speed and the feed rate. An increase in the moisture content led to a decrease in the CEL content, whereas it enhanced CML formation. The impact of moisture on acrylamide formation varied depending on whether low- or high-moisture extrusion was applied. Elevated temperatures promoted the accumulation of CEL, methylglyoxal and 2,3-butanedione while diminishing the accumulation of CML, acrylamide, glyoxal and 3-deoxyglucosone. CML and CEL were positively correlated with glyoxal and methylglyoxal, respectively. CEL and methylglyoxal were negatively correlated with protein and water content, whereas CML, glyoxal and 3-deoxyglucosone displayed positive correlations. In summary, higher moisture levels and feed rates and lower screw speeds and barrel temperatures are advantageous for producing PBMAs with lower CEL and total advanced glycation end-products contents, while lower or higher moisture contents, a lower feed rate and a higher barrel temperature are beneficial to reducing the acrylamide content. Full article

Non-alcoholic fatty liver disease (NAFLD) is a major issue because it is closely associated with metabolic diseases. Advanced glycation end products (AGEs) are implicated as risk factors for steatosis during NAFLD progression. AGEs influence NAFLD progression through a receptor-independent pathway involving AGE cross-link formation and a receptor-dependent pathway that binds to receptors like receptors for advanced glycation end products (RAGE). The objectives of this study are to examine the effect of Lindera obtusiloba Blume (LO) on NAFLD promoted by Nε-(carboxymethyl)lysine (CML), one of the most common dietary AGEs. The anti-glycation effects of LO were evaluated by inhibiting the AGEs formation and AGEs-collagen cross-links breaking. The efficacy of LO against NAFLD promoted by CML was assessed using both in vitro and in vivo models. NAFLD was induced in mice by feeding a high-fat diet and orally administering CML over a period of 12 weeks, and the effects of LO on lipid metabolism and its regulatory mechanisms were investigated. LO showed the effect of inhibited AGEs formation and breakage, and collagen cross-linking. Fed a high-fat diet with administered CML by gavage, LO administration resulted in a reduction in body weight, fat mass, serum triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels. LO reduced hepatic CML accumulation and RAGE expression in mice fed a high-fat diet and orally administered CML. LO alleviated hepatic steatosis accompanied by lipid accumulation and histological damage by suppressing the expression of sterol regulatory element-binding protein 1c, carbohydrate response element binding protein, fatty acid synthase, stearoyl-CoA desaturase1, tumor necrosis factor-α, and interleukin-1β. LO alleviated the MAPK/NF-κB expression by attenuating CML and RAGE expression. Taken together, our results demonstrate that LO alleviates the progression of NAFLD by lowering the levels of AGEs by downregulating CML/RAGE expression. Full article

The contents of free and protein-bound advanced glycation end-products (AGEs) including N^ε-carboxymethyllysine (CML) and N^ε-carboxyethyllysine (CEL), along with glyoxal (GO), methylglyoxal (MGO), chemical components, and salt in commercially prepared and prefabricated fish products were analyzed. Snack food classified as commercially prepared products exhibited higher levels of GO (25.00 ± 3.34–137.12 ± 25.87 mg/kg of dry matter) and MGO (11.47 ± 1.39–43.23 ± 7.91 mg/kg of dry matter). Variations in the contents of free CML and CEL increased 29.9- and 73.0-fold, respectively. Protein-bound CML and CEL in commercially prepared samples were higher than those in raw prefabricated ones due to the impact of heat treatment. Levels of GO and MGO demonstrated negative correlations with fat (R = −0.720 and −0.751, p < 0.05) in commercially prepared samples, whereas positive correlations were observed (R = 0.526 and 0.521, p < 0.05) in raw prefabricated ones. The heat-induced formation of protein-bound CML and CEL showed a negative correlation with the variations of GO and MGO but was positively related to protein levels in prefabricated products, suggesting that GO and MGO may interact with proteins to generate AGEs during heating. The influence of NaCl on the formation of GO and MGO exhibited variations across different fish products, necessitating further investigation. Full article

The extracellular matrix (ECM) is a dynamic complex protein network that provides structural integrity and plays an active role in shaping fibroblast behavior both in health and disease. Despite its essential functions, the impact of age-associated post-translational modifications on ECM-driven fibroblast activities such as proliferation, survival, fibroblast-to-myofibroblast transformation (FMT), and extracellular matrix production remains largely unknown. Nε-carboxymethyl-lysine (CML) is one of the well-characterized advanced glycation end-products (AGEs) that can occur on lysine residues within ECM proteins through non-enzymatic glycation. In this study, we determined the accumulation and the effects of the CML-modified ECM (CML-ECM) on fibroblast activation. Immunostainings and immunoblot analysis demonstrated significant increases in CML-AGE content in idiopathic pulmonary fibrosis (IPF) compared to age-matched healthy lungs. Gene expression analysis and fibroblast activation assays collectively implicate the ECM as a negative regulator of fibroblast activation. Notably, the CML modification of the ECM resulted in a significant decrease in its anti-fibrotic effects including proliferation, FMT, apoptosis, and ECM production. Together, the results of this study revealed an unexplored pathological role played by the CML-ECM on fibroblast activation, which has wide implications in IPF and other fibrotic diseases. Full article

This study aims to evaluate the relationship between the four processing stages of cooked sausage preparation (raw, drying, baking, and steaming) and the formation of advanced glycation end products (AGEs), 1,2-dicarbonyl compounds, and lipid and protein oxidation in sausages with spices. Baking and steaming significantly promoted lipid and protein oxidation. The Nε-carboxymethyllysine (CML) content increased from 4.32–4.81 µg/g in raw samples to 10.68–16.20 µg/g in the steamed sausages. Nε-carboxyethyllysine (CEL) concentrations increased by approximately 1.7–3.7 times after steaming. The methylglyoxal concentration increased dramatically after baking and then rapidly decreased in the steaming stage. Chili promoted the formation of CML and CEL. The CEL concentration increased in samples containing garlic, but yellow mustard and garlic slightly reduced CML concentrations in the cooked sausages. The spices decreased the lipid and protein stability of the cooked sausages, increasing malondialdehyde and protein carbonyls. Lipid oxidation and 3-deoxyglucosone positively correlated with CML and CEL levels. Black pepper had no impact on CML when the sausages were baked but remarkably increased the content of both CML and CEL in the steaming stage. Thus, the impact of spices on sausages depends on both the specific spices used and the category of AGEs formed. Full article

This study aimed to determine the effects of fat type (sheep tail fat (STF) and beef fat (BF)), fat levels (10, 20, or 30%), and cooking time (0, 2, 4, and 6 min, dry heat cooking at 180 °C) on the carboxymethyl lysine (CML) content in meatballs. pH, thiobarbituric acid reactive substance (TBARS), and volatile compound analyses were also performed on the samples. The use of STF and the fat level had no significant effect on the pH value. The highest TBARS value was observed with the combination of a 30% fat level and STF. CML was not affected by the fat level. The highest CML content was determined in meatballs with STF at a cooking time of 6 min. In the samples cooked for 2 min, no significant difference was observed between STF and BF in terms of the CML content. STF generally increased the abundance of aldehydes. Aldehydes were also affected by the fat level and cooking time. A PCA provided a good distinction between groups containing STF and BF regardless of the fat level or cooking time. Pentanal, octanal, 2,4-decadienal, hexanal, and heptanal were positively correlated with CML. Full article

High temperatures applied in the production of plant-based meat analogs (PBMA) lead to the occurrence of Maillard reactions, in which harmful compounds N^ε-(carboxymethyl)lysine (CML), N^ε-(carboxyethyl)lysine (CEL) and acrylamide are formed. However, little research has focused on these compounds in PBMA. In this study, the contents of CML, CEL and acrylamide in 15 commercial-sold PBMA were determined by an ultra-high performance liquid chromatograph coupled with a triple quadrupole tandem mass spectrometer (UHPLC-QqQ-MS/MS). Nutrients (protein, amino acids, fatty acids and sugars) which are related to the formation of these compounds were also studied. The results showed that CML, CEL and acrylamide contents were in the range of 16.46–47.61 mg/kg, 25.21–86.23 mg/kg and 31.81–186.70 μg/kg, respectively. Proteins account for 24.03–53.18% of PBMA. Except for Met + Cys, which is the limiting amino acid of most PBMA, all other indispensable amino acids met the requirements for adults. Besides, PBMA had more n-6 fatty acids than n-3 fatty acids. A correlation analysis showed that proteins and the profiles of amino acid and fatty acid had little influence on CML but significant influence on CEL and acrylamide. The results of the present study can be used as a reference to produce PBMA with higher amounts of nutrients and lower amounts of CML, CEL and acrylamide. Full article