Date Published: March 2, 2015
Publisher: Public Library of Science
Author(s): Masayoshi Takeuchi, Jun-ichi Takino, Satomi Furuno, Hikari Shirai, Mihoko Kawakami, Michiru Muramatsu, Yuka Kobayashi, Sho-ichi Yamagishi, Barry I Hudson.
Dietary consumption has recently been identified as a major environmental source of pro-inflammatory advanced glycation end-products (AGEs) in humans. It is disputed whether dietary AGEs represent a risk to human health. Nε-(carboxymethyl)lysine (CML), a representative AGE compound found in food, has been suggested to make a significant contribution to circulating CML levels. However, recent studies have found that the dietary intake of AGEs is not associated with plasma CML concentrations. We have shown that the serum levels of glyceraldehyde-derived AGEs (Glycer-AGEs), but not hemoglobin A1c, glucose-derived AGEs (Glu-AGEs), or CML, could be used as biomarkers for predicting the progression of atherosclerosis and future cardiovascular events. We also detected the production/accumulation of Glycer-AGEs in normal rats administered Glu-AGE-rich beverages. Therefore, we assessed the concentrations of various AGEs in a total of 1,650 beverages and foods that are commonly consumed in Japan. The concentrations of four kinds of AGEs (Glu-AGEs, fructose-derived AGEs (Fru-AGEs), CML, and Glycer-AGEs) were measured with competitive enzyme-linked immunosorbent assays involving immunoaffinity-purified specific antibodies. The results of the latter assays indicated that Glu-AGEs and Fru-AGEs (especially Glu-AGEs), but not CML or Glycer-AGEs, are present at appreciable levels in beverages and foods that are commonly consumed by Japanese. Glu-AGEs, Fru-AGEs, CML, and Glycer-AGEs exhibited concentrations of ≥85%, 2–12%, <3%, and trace amounts in the examined beverages and ≥82%, 5–15%, <3%, and trace amounts in the tested foods, respectively. The results of the present study indicate that some lactic acid bacteria beverages, carbonated drinks, sugar-sweetened fruit drinks, sports drinks, mixed fruit juices, confectionery (snacks), dried fruits, cakes, cereals, and prepared foods contain markedly higher Glu-AGE levels than other classes of beverages and foods. We provide useful data on the concentrations of various AGEs, especially Glu-AGEs, in commonly consumed beverages and foods.
In humans, two major sources of advanced glycation end-products (AGEs) have been identified, exogenous and endogenous AGEs [1–5]. AGEs are formed by the Maillard reaction, a non-enzymatic reaction between the aldehyde or ketone groups of reducing sugars, such as glucose, fructose, and glyceraldehyde, and the terminal α-amino groups or ε-amino groups of protein lysine residues [2–5]. AGEs were originally characterized by their yellow-brown fluorescent color and their ability to form cross-links with and between amino groups; however, the term is now used for a broad range of advanced products of the glycation process, including Nε-(carboxymethyl)lysine (CML), Nε-(carboxyethyl)lysine (CEL), and pyrraline, which are colorless, do not fluoresce, and do not form cross-links with proteins [1–5]. The use of CML as a marker of AGE formation in food has recently led to the development of a database containing the CML concentrations of 549 foodstuffs [6,7]. However, the inconsistencies between the information in this database and data obtained with other methods highlight the considerable challenges associated with analyzing AGEs . Moreover, dietary CML might pose a risk to human health, as it enhances oxidative stress and initiates inflammatory responses, which ultimately lead to atherosclerosis [9,10]. While previous studies have suggested that dietary CML makes a significant contribution to in vivo CML concentrations , two recent studies have reported that this is not true for humans  or rats . Semba et al. suggested that the excessive consumption of foods considered to be high in AGEs might not have a major effect on serum CML concentrations .
A previous study indicated that a significant proportion of pro-inflammatory AGEs are derived from dietary components ; however, it is disputed whether such AGEs are a health risk [8,28–30]. ELISA or liquid chromatography-mass spectrometry (LC-MS) are usually used to assess the levels of AGEs in bodily secretions, foods, and beverages. However, it is not possible to assess the levels of both HMW- and LMW-AGEs using any of the current approaches. Subjecting foods to heating results in the formation of various AGE molecules, with the types of AGEs produced depending on the heat treatment method employed and the food involved. Unfortunately, most previous studies only examined the levels of a small number of AGE molecules because of methodological issues [31,32]. The majority of studies of AGEs have focused on representative molecules, particularly CML. Based on assessments of CML levels obtained with ELISA, a database of food products and their AGE concentrations has been produced [6,7]. Foods containing elevated levels of protein and fat, meat substitutes, and processed meats were found to display markedly increased AGE concentrations. However, discrepancies have been detected between the information in the abovementioned database and the data obtained using other approaches, which indicates that more accurate methods for analyzing AGE levels are required . As AGEs are produced when food is heated, eating processed foods, which are subjected to high temperatures during their production, results in greater exposure to AGEs. The Maillard reaction, in which sugar groups react with proteins (which causes foods to turn brown) and cross-links form between proteins, is responsible for AGE synthesis during the heating of foodstuffs . Conversely, CML is colorless and does not promote protein cross-linking or fluoresce [2–5].