Advanced Glycation End Products,Inflammation, and Chronic Metabolic Diseases: Links in a Chain?

Advanced glycation end products (AGEs) are a diverse group of compounds produced when reducing sugars react with proteins or other compounds to form glycosylated molecules. AGEs may form endogenously, and glycation of molecules may negatively affect their function. AGEs may also be consumed in food form with dietary AGEs reported to be particularly high in foods treated with high heat: baked, broiled, grilled, and fried foods. Whether dietary AGEs are absorbed in significant quantities and whether they are harmful if absorbed is a question under current debate. The American Diabetes Association makes no recommendation regarding avoidance of these foods, but many researchers are concerned that they may be pro-inflammatory and way worsen cardiac function, kidney function, diabetes and its complications and may even contribute to obesity.     

Dietary advanced glycation endproducts (AGEs) and their health effects--PRO

Thermal processing of food results in the formation of various novel compounds, among others advanced glycation endproducts (AGEs). AGEs result from nonenzymatic glycation reactions between reducing sugars and free amino groups of proteins, peptides, or amino acids. Due to their potential noxious effects, alimentary AGEs are also called glycotoxins. This review provides a summary of the available evidence on the health effects of exaggerated intake of thermally treated food. Data from experimental studies in rodents and from clinical studies in healthy volunteers and in patients suffering from selected diseases in which AGEs are of pathogenetic importance (diabetes, chronic renal failure) are summarized. It is concluded that, an exaggerated intake of thermally processed foods may exert in vivo diabetogenic and nephrotoxic effects, induce low-grade inflammation, enhance oxidative stress, and promote atherosclerosis.     

食品中晚期糖基化末端产物的研究进展

晚期糖基化末端产物(advanced glycation end products, AGEs)是还原糖与氨基酸发生非酶褐变反应的产物之一。医学研究结果表明,AGEs与人类诸多疾病的发生有密切关系,而膳食摄入是体内AGEs的重要来源。但是由于AGEs种类较多,对于食品中的AGEs含量的检测尚缺乏标准的方法,食品加工工艺对食品中AGEs形成的影响报道较少。因此,本文从食品中AGEs形成、结构、检测方法及AGEs在体内代谢、对人体健康影响和预防措施等方面对AGEs进行了较系统的阐述,为进一步研究AGEs奠定基础。     

Evidence against dietary advanced glycation endproducts being a risk to human health

In vivo, advanced glycation endproducts (AGEs) are linked to various diseases, particularly those associated with diabetes. AGEs are also formed when many foods are thermally processed. The extent to which dietary AGEs are absorbed by the gastrointestinal (GI) tract and their possible role in the onset and promotion of disease are currently of considerable interest. This paper reviews information that supports the argument that dietary AGEs are not a risk to human health.     

The Inhibition of Advanced Glycation End Products by Carnosine and Other Natural Dipeptides to Reduce Diabetic and Age‐Related Complications

As people age they are at a greater risk for many disorders including cardiovascular, renal, and neurodegenerative diseases, and these conditions are exacerbated by diabetes. An important cause of the maladies associated with both age and diabetes is the formation of advanced glycation end products (AGEs). AGE formation is initiated by glycation reactions between reducing sugars and free amine groups. A cascade of other reactions follows, leading to alterations in membrane function and damage to the proteome, such as protein crosslinking. Compounds that prevent these reactions are currently being researched, but peptides hold great potential as they tend to lack toxicity, are absorbed intact, are easily produced, and are cheaper than other options. Of the peptides researched, carnosine is the most promising. Research suggests that carnosine is absorbed into the plasma unaltered and intact. Carnosine has been shown to prevent AGE formations through reduction of blood glucose, prevention of early glycation, and even reversing previously formed AGEs. Other promising peptides and amino acids include β‐alanine, L‐histidine, homocarnosine, anserine, and glutathione. If bioactive peptides and amino acids can minimize the formation of AGEs, foods containing these peptides could be used to improve health.     

N ϵ-(carboxymethyl)lysine: A Review on Analytical Methods,Formation, and Occurrence in Processed Food,and Health Impact

Foods are often heat processed and may contain advanced glycation end products (AGE). One of the most widely studied AGE is N ^?-(carboxymethyl)lysine (CML); nevertheless, knowledge on dietary CML is fragmentary. This study aimed to review current scientific knowledge on analytical methods to determine CML contents in food, chemical pathways of CML formation in food, occurrence of CML in food, and health implications of dietary exposure to CML. Chemical analyses of CML in food products are carried out by immunochemical assays and instrumental methods, but the former method may interfere with the food matrix. CML is formed in food through various chemical pathways, depending on food ingredients and processing conditions. The compound is present in many cooked foods, with relatively high concentrations in carbohydrate-rich foods and dairy products. Dietary CML is very likely to impair human health, but full cause-effect evidence is not available yet. More studies on metabolic effects and impact of food-derived CML on human health should be performed. Food production should be optimized to minimize CML concentrations, while maintaining acceptable microbiological safety and organoleptic properties of the final food product. To this end, more insights into effects of food composition and processing conditions on CML formation are necessary.     

Dietary N-epsilon-carboxymethyllysine as for a major glycotoxin in foods: A review

N-epsilon-carboxymethyllysine (CML), as a potential glycotoxin and general marker for dietary advanced glycation end products (dAGEs), exists in raw food and is formed via various formation routes in food processing such as Maillard reaction between the reducing sugars and amino acids. Although comprehensive cause-effect proof is not available yet, current research suggests a potential risk of chronic diseases such as diabetes is associated with exogenous CML. Thus, CML is causing public health concerns regarding its dietary exposure, but there is a lack of explicit guidance for understanding if it is detrimental to human health. In this review, inconsistent results of dietary CML contributed to chronic disease are discussed, available concentrations of CML in consumed foods are evaluated, measurements for dietary CML and relevant analytic procedures are listed, and the possible mitigation strategies for protecting against CML formation are presented. Finally, the main challenges and future efforts are highlighted. Further studies are needed to extend the dietary CML database in a wide category of foods, apply new identifying methods, elucidate the pathogenic mechanisms, assess its detrimental role in human health, and propose standard guidelines for processed food.     

The Role of Dietary Advanced Glycation End Products in Metabolic Dysfunction

Advanced glycation end products (AGEs) are a heterogeneous group of molecules produced, non‐enzymatically, from the interaction between reducing sugars and the free amino groups of proteins, nucleic acids, and lipids. AGEs are formed as a normal consequence of metabolism but can also be absorbed from the diet. They have been widely implicated in the complications of diabetes affecting cardiovascular health, the nervous system, eyes, and kidneys. Increased levels of AGEs are also detrimental to metabolic health and may contribute to the metabolic abnormalities induced by the Western diet, which is high in processed foods and represents a significant source of AGEs. While increased AGE levels are a consequence of diabetic hyperglycaemia, AGEs themselves activate signaling pathways, which compromise insulin signaling and pancreatic β‐cell function, thus, contributing to the development of type 2 diabetes mellitus (T2DM). Furthermore, AGEs may also contribute to the obesogenic effects of the Western diet by promoting hypothalamic inflammation and disrupting the central control of energy balance. Here, the role of dietary AGEs in metabolic dysfunction is reviewed with a focus on the mechanisms underpinning their detrimental role in insulin resistance, pancreatic β‐cell dysfunction, hypothalamic control of energy balance, and the pathogenesis of T2DM and obesity.     

食品中晚期糖基化终产物的研究进展

晚期糖基化终产物(advanced glycation end products,AGEs)被认为和氧化应激、多种慢性疾病以及人体衰老等具有密切关系,近年来成为医药和健康领域的研究热点,但在食品领域研究相对较少。事实上,食物由于不同的加工处理方法和存放条件,可能会产生AGEs;若长期摄入AGEs可能增加体内的AGEs水平从而对人体造成危害,对食品中AGEs的研究已引起食品领域科学家的关注。文中主要对食品中AGEs的生成机理、主要种类、检测方法、对人体的影响,以及控制方法等几方面进行综述。     

Advanced glycation end-products (AGEs) in foods and their detecting techniques and methods: A review

BackgroundAdvanced glycation end-products (AGEs) are a sort of complex products formed by the Maillard reaction between the carbonyls of reducing sugars and the free amino groups of amino acids. Some of AGEs ingested through foods accumulate in human body, causing a series of chronic diseases. However, due to the complex and varied structures, there is lack of systematic reviews on dietary AGEs.Scope and approachThis paper summarizes the aspects of AGE formation, influencing factors and hazards, as well as their distribution in foods. The detecting methods available for dietary AGEs are also highlighted. Finally, the main challenges and future efforts for studying AGEs in foods and their effects on health are discussed.Key findings and conclusionsThe study of AGEs has great significance in foods and human health. Although great advances in understanding the effects of AGEs in human body are made, more unequivocal guidance for dietary AGEs to people should be provided in future.     

Toxicity of the AGEs generated from the Maillard reaction: on the relationship of food-AGEs and biological-AGEs

Advanced glycation end products (AGEs) are generated in the late stages of Maillard reaction in foods and biological systems. These products are mostly formed by the reactions of reducing sugar or degradation products of carbohydrates, lipids, and ascorbic acid. AGEs exist in high concentration in foods, but in relatively low concentrations in most of the biological systems. Recently, some AGEs have been reported to be toxic, and were proposed to be causative factors for various kinds of diseases, especially diabetes and kidney disorder, through the association with receptor of AGE (RAGE). It has also been reported that food-derived AGEs (food-AGEs) may not be a causative factor for pro-oxidation. However, the relationship of food-AGEs and biological-derived AGEs (biological-AGEs) is not clear. In this review, the following issues are discussed: the formation of AGEs in foods and biological systems; identification of the main AGEs in foods and biological systems; absorption of food-AGEs; the effects of AGEs in vivo; relationship between food-AGEs and biological-AGEs; possible defense mechanism against AGEs in vivo and finally, the problems to be solved concerning the toxicity of AGEs.     

Glycolaldehyde‐modified β‐lactoglobulin AGEs are unable to stimulate inflammatory signaling pathways in RAGE‐expressing human cell lines

Scope: Advanced glycation endproducts (AGEs) are suspected to stimulate inflammatory signaling pathways in target tissues via activation of the receptor for AGEs. Endotoxins are generally recognized as potential contamination of AGE preparations and stimulate biological actions that are very similar as or identical to those induced by AGEs. Methods and results: In our study, we used glycolaldehyde‐modified β‐lactoglobulin preparations as model AGEs and employed two methods to remove endotoxin using either affinity columns or extraction with Triton X‐114 (TX‐114). Affinity column‐purified AGEs retained their ability to stimulate inflammatory signaling as measured by mRNA expression of inflammatory cytokines in the human lung epithelial cell line Beas2b. However, glycolaldehyde‐modified AGEs purified by extraction with TX‐114 did not show any stimulation of mRNA expression of inflammatory cytokines. The presence of a cell stimulating endotoxin‐like activity was demonstrated in the detergent phase after extraction with TX‐114, thus indicating that not AGEs but a lipophilic contamination was responsible for the stimulation of inflammatory signaling. Conclusion: Our results demonstrate that glycolaldehyde‐modified AGEs are unable to induce inflammatory signaling in receptor for AGE‐expressing cells. The observed cell‐activating activity can be ascribed to an endotoxin‐like lipophilic contamination present in AGE preparations and affinity column purification was insufficient to remove this contamination.     

Maillard reaction in food allergy: Pros and cons

Food allergens have a notable potential to induce various health concerns in susceptible individuals. The majority of allergenic foods are usually subjected to thermal processing prior to their consumption. However, during thermal processing and long storage of foods, Maillard reaction (MR) often takes place. The MR is a non-enzymatic glycation reaction between the carbonyl group of reducing sugars and compounds having free amino groups. MR may sometimes be beneficial by damaging epitope of allergens and reducing allergenic potential, while exacerbation in allergic reactions may also occur due to changes in the motifs of epitopes or neoallergen generation. Apart from these modulations, non-enzymatic glycation can also modify the food protein(s) with various type of advance glycation end products (AGEs) such as N?-(carboxymethyl-)lysine (CML), pentosidine, pyrraline, and methylglyoxal-H1 derived from MR. These Maillard products may act as immunogen by inducing the activation and proliferation of various immune cells. Literature is available to understand pathogenesis of glycation in the context of various diseases but there is hardly any review that can provide a thorough insight on the impact of glycation in food allergy. Therefore, present review explores the pathogenesis with special reference to food allergy caused by non-enzymatic glycation as well as AGEs.     

Naturally occurring inhibitors against the formation of advanced glycation end-products

Advanced glycation end-products (AGEs) are the final products of the non-enzymatic reaction between reducing sugars and amino groups in proteins, lipids and nucleic acids. Recently, the accumulation of AGEs in vivo has been implicated as a major pathogenic process in diabetic complications, atherosclerosis, Alzheimer's disease and normal aging. The early recognition of AGEs can ascend to the late 1960s when a non-enzymatic glycation process was found in human body which is similar to the Maillard reaction. To some extent, AGEs can be regarded as products of the Maillard reaction. This review firstly introduces the Maillard reaction, the formation process of AGEs and harmful effects of AGEs to human health. As AGEs can cause undesirable diseases or disorders, it is necessary to investigate AGE inhibitors to offer a potential therapeutic approach for the prevention of diabetic or other pathogenic complications induced by AGEs. Typical effective AGE inhibitors with different inhibition mechanisms are also reviewed in this paper. Both synthetic compounds and natural products have been evaluated as inhibitors against the formation of AGEs. However, considering toxic or side effects of synthetic molecules present in clinical trials, natural products are more promising to be developed as potent AGE inhibitors.     

Arguing for the motion: yes, RAGE is a receptor for advanced glycation endproducts

Advanced glycation endproducts (AGEs) are an heterogenous class of compounds formed by diverse stimuli, including hyperglycemia, oxidative stress, inflammation, renal failure, and innate aging. Recent evidence suggests that dietary sources of AGE may contribute to pathology. AGEs impart diverse effects in cells; evidence strongly suggests that crosslinking of proteins by AGEs may irrevocably alter basement membrane integrity and function. In addition, the ability of AGEs to bind to cells and activate signal transduction, thereby affecting broad properties in the cellular milieu, indicates that AGEs are not innocent bystanders in the diseases of AGEing. Here, we present evidence that receptor for AGE (RAGE) is a receptor for AGEs.     

N-(carboxymethyl)lysine content of foods commonly consumed in a Western style diet

The potential adverse effects on health of diet-derived advanced glycation end-products (AGEs) is of current interest, due to their proposed involvement in the disease progression of diabetic and uraemic conditions. However, accurate information about levels of AGEs in foods is lacking. The objective of this investigation was to determine the level of one particular AGE, N^ε-(carboxymethyl)lysine (CML), a marker of AGE formation, in a wide range of foods commonly consumed in a Western style diet. Individual foods (n = 257) were mixed, lyophilised, ground, reduced, fat-extracted, hydrolysed, and underwent solid-phase extraction. Extracts were analysed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Cereal (2.6 mg/100 g food) and fruit and vegetable (0.13 mg/100 g food) categories had the highest and lowest mean level of CML, respectively, when expressed in mg/100 g food. These data can be used for estimating potential consumer intakes, and provide information that can be used to educated consumers on how to reduce their CML intake.     

Iron sources used in food fortification and their changes due to food processing∗

The effect of food processing on the biological availability of iron in iron‐fortified foods is critically reviewed. Studies on changes in the chemistry of the iron in processed foods are examined. Various iron sources currently used in food fortification in the U.S. are defined with emphasis on their biological availabilities under various conditions. The availability of iron in foods depends upon numerous factors, most of which are not fully understood. A factor which is often overlooked is the interaction of the iron with the food during events such as cooking or processing. Evidence is presented of significant changes in the available iron from food due to common types of food processing. Chemical changes in the iron compounds occur which may correlate with changes in the biological availability.     

食品中甲基乙二醛的来源、毒性及其清除剂研究进展

生物体内存在多种活性羰基化合物（reactive carbonyl species,RCS）,其中甲基乙二醛（methylglyoxal, MG）是人体内最主要的RCS,它是机体内源性代谢产物,也能在食品加工和贮藏过程中产生,尤其在含糖量高的 焙烤食品和加入高果糖玉米糖浆的碳酸饮料中含量较高。除了具有直接的细胞毒性,MG也参与体内蛋白质和核酸 的糖化反应,引起羰基应激,诱发组织病理损伤,加剧慢性退行性疾病的恶性发展。本文概述了食品加工中MG的 产生、健康危害及其清除等方面的国内外研究进展,为清除MG功能食品的研发提供理论依据。     

食源性晚期糖基化终末产物检测技术研究进展

晚期糖基化终末产物（advanced glycation end products,AGEs）是还原糖与蛋白质自由氨基间发生美拉德反应形成的一类异质性共价化合物的总称。研究发现食源性AGEs摄入后会在体内蓄积并对机体健康产生有害影响,因此有必要开展食物中各类AGEs的检测分析研究。食品中的AGEs种类繁多、结构复杂,目前缺少通用的检测分析方法。因此,本文针对食源性AGEs的结构和类型、与人体健康的关系以及相关检测技术进行综述,重点介绍食源性AGEs的免疫分析和仪器分析方法,深入探讨各类技术的特点和优劣势,并对后续研究方向进行展望,以期为食源性AGEs检测技术的发展以及相关研究体系的形成提供参考和借鉴。