Studies on the Reaction of Dietary Methylglyoxal and Creatine during Simulated Gastrointestinal Digestion and in Human Volunteers

Abstract

The reactive 1,2-dicarbonyl compound methylglyoxal (MGO) is consumed with food and its concentrations decrease during digestion. In the present paper, the reaction of MGO with creatine, arginine, and lysine during simulated digestion, and its reaction with creatine during the digestion in human volunteers, was studied. Therefore, simulated digestion experiments with a gastric and an intestinal phase were performed. Additionally, an intervention study with 12 subjects consuming MGO-containing Manuka honey and creatine simultaneously or separately was conducted. Derivatization with o-phenylenediamine and HPLC–UV was used to measure MGO, while creatine and glycated amino compounds were analyzed via HPLC–MS/MS. We show that MGO quickly reacts with creatine and arginine, but not lysine, during simulated digestion. Creatine reacts with 56% of MGO to form the hydroimidazolone MG-HCr, and arginine reacted with 4% of MGO to form the hydroimidazolone MG-H1. In the intervention study, urinary MG-HCr excretion is higher in subjects who consumed MGO and creatine simultaneously compared to subjects who ingested the substances separately. This demonstrates that the 1,2-dicarbonyl compound MGO reacts with amino compounds during human digestion, and glycated adducts are formed. These contribute to dietary glycation products consumed, and should be considered in studies investigating their physiological consequences.

Glycation reactions of methylglyoxal during digestion in a dynamic, in vitro model of the upper gastrointestinal tract (TIM‐1)

“…Samples for creatine, creatinine, and MG-HCr analysis were prepared and subjected to high-pressure liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS), as described previously (Treibmann et al, 2019(Treibmann et al, , 2020(Treibmann et al, , 2022. For the analysis of proteinbound MG-H1, CML, and CEL, published protocols for acidic hydrolysis were adjusted (Hegele et al, 2008;Scheijen et al, 2016), and samples were applied to HPLC-MS/MS.…”

“…Some studies have an additional oral stage for 2 min at 37°C (Hamzalıoğlu & Gökmen, 2016 ; Jiang et al., 2019 ). Typically, 10%–50% of MGO are left after 3–8 h simulated digestion, which might explain its poor bioavailability (Amoroso et al., 2013 ; Daglia, Ferrari, et al., 2013 ; Degen et al., 2013 ; Hamzalıoğlu & Gökmen, 2016 ; Jiang et al., 2019 ; Treibmann et al., 2022 ). Simultaneous digestion with amino acids like lysine and cysteine or protein decreased MGO concentrations after digestion, while simulated digestion experiments without enzymes and bile showed only little MGO loss (Hamzalıoğlu & Gökmen, 2016 ; Jiang et al., 2019 ; Treibmann et al., 2022 ).…”

“…Typically, 10%-50% of MGO are left after 3-8 h simulated digestion, which might explain its poor bioavailability (Amoroso et al, 2013;Daglia, Ferrari, et al, 2013;Degen et al, 2013;Hamzalıoğlu & Gökmen, 2016;Jiang et al, 2019;Treibmann et al, 2022).…”

Methylglyoxal, a highly reactive dicarbonyl compound, as a threat for blood brain barrier integrity

“…Additionally, several types of bacteria in the gastro-intestinal tract express MGO synthase and have been shown to produce MGO [31][32][33]. The exact contribution of MGO produced by the gut microbiome, to circulating MGO levels, is difficult to estimate as the accumulation of MGO produced by bacteria is known to be low [32] and because MGO is likely to react with the high amount of protein present in the intestinal tract [34][35][36]. MGO can be cleared through detoxification or elimination [22].…”

Dietary Advanced Glycation End Products: Their Role in the Insulin Resistance of Aging

“…Most food AGEs escape digestion and absorption and end up in the colon, where they affect local microbiota metabolism and gut integrity [ 17 ]. The local colonic action of unabsorbed food AGEs may be as important in the overall proinflammatory actions in the body as those compounds directly absorbed into the systemic circulation [ 18 , 19 , 20 , 21 , 22 ]. The recent demonstration of endocytosis of dietary AGEs by enterocytes [ 23 ] suggests the existence of unmet needs in research evaluating the mechanisms linking dietary AGEs and pathogenic effects.…”