Associations between artificial sweeteners and cardiovascular disease, stroke, and diabetes: A Mendelian randomization study.

Background: Erythritol is a widely used artificial sweetener, yet its long-term impact on cardiometabolic health remains debated. This study aimed to investigate the genetic associations of erythritol with cardiovascular disease (CVD), stroke, and diabetes using a two-sample Mendelian randomization (TSMR) approach. Methods: We utilized single-nucleotide polymorphisms (SNPs) associated with erythritol levels from genome-wide association studies (GWAS) as instrumental variables (IVs). The primary analysis employed the inverse-variance weighted (IVW) method. Robustness was assessed using multiple sensitivity analyses (including MR-Egger, weighted median, weighted multitude, and simple mode). Heterogeneity test, pleiotropy test, and sensitivity analysis were also conducted to further ensure the accuracy and stability of the research results. Results: Erythritol showed positive associations with coronary heart disease (CHD) (OR = 1.0020, 95% CI: 1.0007-1.0034, P = 0.0034), myocardial infarction (MI) (OR = 1.0015, 95% CI: 1.0004-1.0026, P = 0.0090), and stroke (OR = 1.0463, 95% CI: 1.0010-1.0937, P = 0.0449) according to the IVW method. There was suggestive evidence of a positive association between erythritol and CHD, MI, and stroke. No significant causal association was observed between erythritol with heart failure (HF) and diabetes. Conclusions: This TSMR study provides genetic evidence suggesting erythritol is associated with an increased risk of CHD, MI, and stroke, but not with HF or diabetes. Our findings could further clarify the effect of erythritol on CVD, stroke and diabetes, and thus be more beneficial in reducing the risk of disease. Clinical trial number: not applicable.