Association Between Artificial Sweetener Consumption and Bladder Cancer Risk: A Systematic Review and Meta-Analysis

Abstract

Background:The potential association between artificial sweetener consumption and bladder cancer risk remains controversial.Therefore, we conducted a comprehensive metaanalysis synthesizing evidence from observational studies to elucidate this relationship.Methods: A systematic literature search was performed across four databases (PubMed, Embase, CENTRAL, and Web of Science), identifying 1,312 records published until June 2025.After removing duplicates (n = 374) and screening titles, abstracts, and full texts, 17 studies were included in the quantitative synthesis.A random-effects Restricted Maximum Likelihood model was used to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs).Subgroup analyses based on sex and publication bias assessment using Egger's test were also performed.Results: The included studies involved 22,438 participants (7,079 patients and 15,359 controls).Overall, artificial sweetener usage was associated with an increased risk of bladder cancer (OR, 1.24; 95% CI, 1.00-1.53),with high heterogeneity (I 2 = 91.43%).Subgroup analysis based on sex showed a non-significant increase in the risk of bladder cancer among women (OR, 1.06; 95% CI, 0.85-1.34)and men (OR, 1.12; 95% CI, 0.82-1.54).Funnel plots and Egger's test revealed potential publication bias overall (P = 0.003) and in men (P = 0.040), but not in women (P = 0.702).Conclusion: Artificial sweetener consumption may be associated with an increased risk of bladder cancer.However, the observed association should be interpreted with caution due to sex-based differences and potential small-study effects.Therefore, further prospective studies are warranted.