Genetically predicted artificial sweeteners and stroke susceptibility: a multivariable Mendelian randomization study

Area of Science:

• Nutritional Epidemiology
• Genetic Epidemiology

Background:

• Artificial sweeteners are widely used as sugar substitutes.
• Understanding their potential health impacts, such as on stroke risk, is crucial.

Purpose of the Study:

• To investigate the causal associations between artificial sweetener consumption and stroke risk using a Mendelian randomization (MR) design.

Main Methods:

• A two-sample MR design was employed using genome-wide association study (GWAS) summary data.
• Analyses included inverse variance weighted (IVW) methods, sensitivity analyses (Cochran's Q-test, MR-Egger, MR-PRESSO, leave-one-out), and multivariate MR (MVMR).

Main Results:

• Artificial sweeteners in tea showed a nominal association with increased small vessel stroke risk.
• Low-calorie drink intake and sucralose metabolite levels were nominally linked to cardioembolic stroke.
• After adjustments in MVMR, associations between tea-based sweeteners and small vessel stroke, and sucralose metabolites and cardioembolic stroke, remained significant, though attenuated by BMI or beverage habits.

Conclusions:

• This MR study suggests potential associations between artificial sweeteners (particularly in tea) and sucralose metabolites with specific stroke types.
• Confounding by adiposity or beverage habits may influence these associations.
• Findings warrant cautious interpretation and further investigation.