ePIDEMic

WP1: Impact of Dietary Methylglyoxal During Digestion
The main part of dietary methylglyoxal is scavenged during simulated digestion. A study with human volunteers showed that the Maillard reaction most likely occurs during digestion, forming the glycation compound MG-HCr when Manuka honey with methylglyoxal and creatine is ingested simultaneously. The concentrations of methylglyoxal that reach the gut do not appear to be harmful to gut bacteria.

WP2: Dietary MGO and Physiological Consequences in Mice
A 13-week study investigated the effects of 1 mM MGO supplementation in both healthy mice and those with high-fat diet-induced type 2 diabetes mellitus (T2-DM). In diabetic mice, MGO significantly improved fasting plasma glucose levels and insulin sensitivity. Transcriptomic analysis revealed a metabolic shift induced by MGO, downregulating glycolysis and enhancing lipid metabolism. MGO also improved vascular function by enhancing NO-mediated vasorelaxation and endothelial function in both healthy and diabetic mice and enhanced microvascular function in diabetic mice. In healthy mice, MGO supplementation reduced brain MGO and GO levels and downregulated pro-inflammatory responses. Initial findings suggest a reduction in specific gut microbiota with MGO supplementation, with potential anti-inflammatory effects in diabetic mice. However, MGO supplementation altered tissue oxo-aldehyde and AGE levels, highlighting organ-specific responses.

WP3: Impact of Dietary MGO and Its Consequences in Humans
For WP3, existing data and resources from large-scale international prospective cohort studies were utilized to address the objectives. We established the first highly detailed and complete database of dietary dicarbonyl content in major European foods and food products created using the state-of-the-art quantitative chromatographic method established in Prof Schalkwijk’ s lab. Furthermore, we conducted descriptive analyses of dicarbonyl consumption levels in different European populations, and performed detailed epidemiological analyses of the association of dietary dicarbonyl consumption levels with the risk of type 2 diabetes, cardiovascular diseases, and obesity in the EPIC and Maastricht prospective cohort studies. The results of the detailed and robust statistical analyses were in contrast to our hypotheses, showing inverse associations between the consumption of MGO and 3-DG and the risk of type 2 diabetes, as well as with the risk of fatal and non-fatal CVD. Analyses in EPIC on associations of MGO and 3-DG on 5-year weight gain were divergent, with MGO being positively associated while 3-DG was inverse (Debras, Charlotte et al., British Journal of Nutrition (2024)). Findings on the associations of these compounds with cognitive function, and descriptions of European consumption levels are pending.