Erythritol as a Potential Causal Contributor to Cardiometabolic Disease: A Mendelian Randomization Study

People with type 2 diabetes frequently use low-calorie sweeteners to manage glycemia and reduce caloric intake. Use of erythritol, a low-calorie sweetener, has increased recently. Higher circulating concentration associates with major cardiac events and metabolic disease in observational data, prompting some concern. As observational data may be prone to confounding and reverse causality, we undertook bidirectional Mendelian randomization (MR) to investigate potential causal associations between erythritol and coronary artery disease (CAD), BMI, waist-hip-ratio (WHR), and glycemic and renal traits in cohorts of European ancestry. Analyses were undertaken using instruments comprising genome-wide significant variants from three cohorts with erythritol measurement. Across instruments, we did not find supportive evidence that increased erythritol increases CAD (b = -0.033 ± 0.02, P = 0.14; b = 0.46 ± 0.37, P = 0.23). MR indicates erythritol may decrease BMI (b = -0.04 ± 0.018, P = 0.03; b = -0.04 ± 0.0085, P = 1.23 × 10-5; b = -0.083 ± 0.092, P = 0.036), with potential evidence from one instrument of increased BMI adjusted for WHR (b = 0.046 ± 0.022, P = 0.035). No evidence of causal association was found with other traits. In conclusion, we did not find supportive evidence from MR that erythritol increases cardiometabolic disease. These findings await confirmation in well-designed prospective studies.