ePIDEMic

The physiological impact of dietary methylglyoxal

Bioactive compounds produced during food processing can have strong pro-inflammatory properties with potential health implications. Modulation of chronic inflammation may be the mechanism linking diet to risk of chronic diseases such as diabetes and CVD. Advanced glycation endproducts (AGEs) are a heterogeneous group of pro-inflammatory bioactive compounds produced via Maillard reactions during cooking and processing. It is now well established that AGEs are mainly formed from several dicarbonyl compounds, including methylglyoxal (MGO), glyoxal (GO) and 3-deoxyglucosone (3-DG). The glycation activity of these biologically reactive dicarbonyl compounds is much higher as compared to that of sugars, with MGO as the most reactive precursor in the formation of AGEs. We have recently found high levels of MGO in many different foods. There is increasing evidence that elevated levels of MGO are involved in weight gain and the development of diabetes and other chronic inflammatory diseases including cardiovascular disease. However, bioavailability and physiological consequences of dietary MGO are largely unknown. Our aim is to explore the consequences of dietary MGO on the intestinal microbiota and on the development of metabolic diseases.

We will determine the effect of dietary MGO on the gastrointestinal tract and microbiota (WP1) and on the onset of diabetes, vascular diseases and cognitive function in mice (WP2). We will develop a detailed database of dietary MGO exposures and assess the association of dietary MGO with overweight, weight gain, obesity and risk of associated metabolic diseases (type 2 diabetes, CVD), as well as cognitive function using existing data from 3 large and deep-phenotyping prospective cohort studies (WP3). For WP3, the main objectives are to develop a food composition database of dietary dicarbonyl consumption in major European foods and to utilize that information to investigate associations between these compounds and the risk of development of diabetes, cardiovascular diseases, cognitive function, and obesity in major European prospective cohort studies.

This comprehensive project will elucidate the role of food-derived MGO as a possible risk factor for overweight and overweight-related metabolic diseases.

Consortium

Partner Organization Partner Country
Maastricht University Netherlands
Institute of Food Chemistry, TU Dresden Germany
Section of Nutrition and Metabolism, IARC, Lyon France

 

Highlights

  • For WP1 the main part of dietary methylglyoxal is scavenged during simulated digestion. As shown in a study with human volunteers, the Maillard reaction takes most likely place during digestion to form the glycation compound MG-HCr if Manuka honey with Methylglyoxal and creatine was ingested simultaneously. The concentrations of methylglyoxal that reach the gut seem to be not harmful to gut bacteria.
  • For WP2 on the dietary MGO and physiological consequences in mice. In both healthy and diabetic mice subjected to 1 mM MGO via drinking water, we found improved insulin sensitivity in both healthy and diabetic mice compared to the control. Interestingly, after 13 weeks, both systolic and diastolic blood pressure were significantly increased in diabetic mice compared to the control, which was prevented by MGO. In addition, in both control and diabetic mice, MGO improved NO-mediated vasorelaxation in small and large arteries, NO sensitivity, and arterial nerve functioning. Thus, results indicate that supplementation of 1 mM MGO favors vascular relaxation in both small and large arteries and vascular nerve-ending functioning. In healthy mice, 1 mM MGO supplementation resulted in lower intracellular MGO levels in organs including the heart, kidney, brain, and muscle, except for the liver compared to the control group with no effect on the glyoxalase MGO detoxification system, except for a decreased in muscles compared to the control. Similar analyses of organs of diabetic mice supplemented with 1 mM MGO are currently ongoing. Interestingly, with respect to the microbiome, findings on the first mice study showed that mice fed with a high concentration of methylglyoxal (50 mM) have less Ligilactobacillus and Lactobacillus in their gut microbiota. Measures of 1 mM MGO supplementation in healthy and diabetic mice will follow soon. Also, a large panel of biomarkers, reflecting endothelial dysfunction and low-grade inflammation were analyzed in the plasma of all groups. In diabetic mice supplemented with MGO, increased levels of the pro-inflammatory marker CRP were prevented as well as the endothelial function markers ICAM-1 and E-Selectin, indicative of the protective potential of MGO against inflammation and vascular dysfunction in diabetes.
  • For WP3 on the impact of dietary MGO and its consequences in humans using existing data and resources from large-scale international prospective cohort studies.  We established the (a) first highly detailed and complete database of dietary dicarbonyl content of major European foods and food products, (b) descriptive analysis of the consumption levels of dicarbonyls in Europe, and (c) detailed epidemiological analyses of the association of dietary dicarbonyl consumption levels with risk of diabetes, cardiovascular diseases and obesity in the EPIC and Maastricht prospective cohort studies. The analyses showed surprising inverse associations between the consumption of MGO and 3-DG with the risk of diabetes, as well as with the risk of fatal and non-fatal CVD. Findings on associations of these compounds with cognitive function, overweight/obesity and description of European consumption levels are pending.

Products

Title: Corrigendum to “Quantification of dicarbonyl compounds in commonly consumed foods and drinks; presentation of a food composition database for dicarbonyls” [Food Chemistry, 339 (2020) 128063]
Author: Maasen K, Scheijen JLJM*, Opperhuizen A, Stehouwer CDA, Van Greevenbroek MM, Schalkwijk CG*
Link: https://doi.org/10.1016/j.foodchem.2020.128578
Title: Scavenger”-Potential von Aminokomponenten während der simulierten Verdauung von Dicarbonylverbindungen
Author: F. Manig, S. Treibmann, C. Fromm, T. Henle
Link: https://doi.org/10.1002/lemi.202158106
Title: Higher habitual intake of dietary dicarbonyls is associated with higher corresponding plasma dicarbonyl concentrations and skin autofluorescence: the Maastricht Study.
Author: Maasen K, Eussen SJPM, Scheijen JLJM, van der Kallen CJH, Dagnelie PC, Opperhuizen A, Stehouwer CDA, van Greevenbroek MMJ, Schalkwijk CG.
Link: https://doi.org/10.1093/ajcn/nqab329
Title: Studies on the Reaction of Dietary Methylglyoxal and Creatine during Simulated Gastrointestinal Digestion and in Human Volunteers
Author: Stephanie Treibmann, Julia Groß, Susann Pätzold, Thomas Henle
Link: https://doi.org/10.3390/nu14173598
Title: Reactions of dicarbonyl compounds during simulated digestion of proteins
Author: Friederike Manig, Stephanie Treibmann, Celina Fromm, Thomas Henle

Communication & Dissemination Activities

Target groupAuthorsMeans of communication
Scientists, medical professional audienceF. Manig, S. Treibmann, C. Fromm, S. Pätzold, T. Henle: Reaktionen von Dicarbonylverbindungen während der simulierten Verdauung; Kongress der Deutschen Diabetes Gesellschaft, online event, 12-5-21 – 15-5-21Flash talk poster presentation
ScientistsF. Manig, S. Treibmann, C. Fromm, T. Henle: Reactions of dicarbonyl compounds during simulated digestion of proteins, 14th Symposium on the Maillard Reaction of the International Maillard Reaction Society, Doha/Quatar and online event, 20-9-21 – 24-9-21Poster + audio poster
ScientistsP.Vangrieken, Methylglyoxal impairs endothelial barrier function and vascular reactivity, 14th Symposium on the Maillard Reaction of the International Maillard Reaction Society, Doha/Quatar and online event, 20-9-21 – 24-9-21Poster + audio poster
ScientistsC.Schalkwijk, Methylglyoxal stress in obesity and type 2 diabetes, 14th Symposium on the Maillard Reaction of the International Maillard Reaction Society, Doha/Quatar and online event, 20-9-21 – 24-9-21Talk
ScientistsK. Maasen, S.J.P.M. Eussen, J.L.J.M. Scheijen, C.J.H. van der Kallen, P.C. Dagnelie, A. Opperhuizen, C.D.A. Stehouwer, M.M.J. van Greevenbroek, C.G. Schalkwijk. Presented at the International Maillard Reaction Society conference (iMARS) 2021 (virtual).Talk
Scientists & general publicCatharina Joswig, Friederike Manig, Thomas Henle: Einfluss von alimentärem Methylglyoxal und intestinalen Folgeprodukten auf Vertreter der humanen Darmmikrobiota; Technische Universität Dresden, 2022Presentation

Features

Project number:
ePIDEMic
Duration: 100%
Duration: 100 %
2020
2024
Related funding round:
Project lead and secretary:
Casper Schalkwijk
Responsible organisation:
Maastricht University, The Netherlands