Ilex paraguariensis and its main component chlorogenic acid inhibit fructose formation of advanced glycation endproducts with amino acids at conditions compatible with those in the digestive system

Advanced Glycation Endproducts form During Ovalbumin Digestion in the Presence of Fructose

“…Fructose ketone carbonyl is known to be 7-10 times more reactive than glucose due to the high concentration of the open ring form in fructose vis-à-vis glucose [11,43] 2) The reaction is inhibited by chlorogenic acid at concentrations compatible with those found in the gut 3) The reaction is inhibited by AG, a specific antiglycation agent. These findings add another layer of support to our previous report that fructose-AGE adducts may be forming in situ (in the intestinal lumen) and contributing to circulating AGE load [27]. This phenomenon, in particular when OVA is involved, may be of pathogenic significance, as US average per capita HFCS consumption levels remain high vs other parts of the world, and the fructose to glucose ratio in US soft drinks (and more significantly in apple juice where the ratio is 2/1) has been found to exceed levels generally recognized as safe.…”

“…Chlorogenic acids are a family of esters formed between certain trans cinnamic acids and (−)-quinic acid and are major phenolics compounds in coffee, strawberries, pineapple, apple, sunflower, blueberries [37][38][39][40] . We and others have shown a potent effect of these compounds as glycation inhibitors in model systems under intracellular conditions [27,[41][42]. The formation of these compounds is readily inhibited by chlorogenic (5-caffeoylquinic acid ) acid with potencies comparable to the standard antiglycating agent aminoguanidine.…”

“…This study was designed to test a biochemical hypothesis which was elucidated and motivated by the results of a rigorous food elimination diet with HFCS [15,20] and tested by us in an earlier proof of principle study [27] where we showed that unlike glucose, fructose forms fluorescent advanced glycation endproducts with basic and neutral aminoacids at conditions and times compatible with those in the digestive system lumen. In this follow-up work we have simulated the gastrointestinal proteolysis of OVA using an in vitro digestion system in two steps, which mimics the successive passage through the stomach and duodenum.…”

“…AG is a specific AGE formation inhibitor, very efficacious and widely used in animal models to study the role of glycation in disease [27,[34][35][36]. We reasoned that better candidates to avoid intraluminal AGE formation by fructose would be known dietary compounds, especially those with poor absorption which get concentrated in the lumen.…”

“…Other food AGEs (preformed in cooking) have been shown to actually be absorbed and be pro-inflammatory in animal and human intervention studies [16]. They may participate in chronic inflammation enhancing insulin resistance in metabolic syndrome and diabetes as well as in renal failure [24][25][26] Given the ubiquity of ovalbumin and excess fructose in our diets, we reasoned that the possibility of an interaction between them during digestion needed exploration, especially in the light of the plausibility of this new hypothesis and our recent proof of principle study [27]. We showed that fluorescent AGE adducts form between fructose and amino acids at times and concentration ranges plausibly found in the intestines, whereas no detectable reaction occurs with glucose [27] .…”