Higher intakes of dietary dicarbonyl compounds are associated with lower risk of cardiovascular disease

Aims Dicarbonyl compounds such as methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG) are present in numerous foods. They are pro-inflammatory and pro-oxidative, but their potential role in cardiovascular disease (CVD) development has been scarcely studied. We explored associations between dietary dicarbonyls with fatal and non-fatal CVD.Methods and results We conducted a case-cohort analysis based on 32 873 subjects drawn from 346 055 participants of the multi-national prospective EPIC cohort. Cases (15 863 subjects) were CVD-free at baseline and later developed CVD [coronary heart disease (CHD) and/or stroke] with non-fatal (n CVD = 17 837; n CHD = 12 003; n stroke = 6791; not mutually exclusive) and/or fatal (n CVD = 2894; n CHD = 2284; n stroke = 908) outcomes. Dietary intake of dicarbonyl compounds was estimated using country-specific questionnaires linked to a food composition database of dicarbonyl compounds. Multivariable prentice weighted Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs for incident non-fatal and fatal CVD. The main food sources of dicarbonyl compounds include cereals, sugar and confectionaries, coffee, fruits, and vegetables. Higher dietary dicarbonyl intakes were inversely associated with non-fatal CVD (per 1 SD increase, GO: HR = 0.95, 95% CI 0.92-0.98; 3-DG: HR = 0.95, 95% CI 0.92-0.98), fatal CVD (MGO: HR = 0.92, 95% CI 0.87-0.97; GO: HR = 0.91, 0.86-0.96; 3-DG: HR = 0.93, 0.86-0.99), non-fatal CHD (3-DG: HR = 0.95, 0.92-0.99), non-fatal stroke (MGO: HR = 0.93, 95% CI 0.90-0.96; GO: HR = 0.90, 95% CI 0.86-0.95; 3-DG: HR = 0.92, 95% CI 0.89-0.96), and fatal CHD (MGO: HR = 0.94, 95% CI 0.88-0.99; GO: HR = 0.92, 0.86-0.98; 3-DG: HR = 0.89, 0.82-0.96).Conclusion Higher intakes of dietary MGO, GO, and 3-DG intake are associated with lower risk of non-fatal or fatal CVD. Further research is required to confirm these findings, assess circulating levels of dicarbonyls, and explore potential underlying mechanisms for their observed CVD risk associations.Lay summary Dicarbonyl compounds are known to promote oxidative stress, inflammation, endothelial dysfunction, and vascular complications. They are formed endogenously in the body as a byproduct in glucose metabolism but are also present in some foods during food preparation and processing. We studied the role of three major dicarbonyl compounds coming from foods on cardiovascular diseases using data from the prospective EPIC cohort, which includes over 520 000 participants from 10 European countries.We observed that higher consumption of dietary dicarbonyl compounds resulted in a lower risk of non-fatal or fatal CVD.Our findings highlight the need to better understand the roles of these dietary compounds along with their potential underlying mechanisms of action.