A Systematic Review of Nonsugar Sweeteners and Cancer Epidemiology Studies.

Nonsugar sweeteners (NSSs) are added to foods and beverages to provide sweetness in place of sugar while reducing the total caloric content. Reducing sugar intake, and corresponding calories, may decrease the risk of diabetes and other health conditions associated with obesity (e.g., cancer). Numerous observational epidemiology studies have evaluated the effect of NSSs on cancer risk, sometimes focusing on a specific NSS or a specific cancer, other times focusing on all NSSs or all cancers. We conducted a systematic review of epidemiology studies of NSS intake (of all types in aggregate and individually) and the risks of all types of cancer published through Fall 2024 [preregistered with Open Science Framework (https://osf.io/gc8v6)]. We considered how major study quality concerns might have impacted the interpretation of individual study results, as well as the evidence as a whole. We identified 90 studies of acesulfame potassium (ace-K), aspartame, cyclamate, saccharin, sucralose, or nonspecific NSSs in aggregate [e.g., diet sodas, artificially sweetened beverages], and 17 specific types of cancer. We found no consistent associations between any NSS or NSSs in aggregate and any cancer overall, and no evidence for dose-response. NSS intake information was always self-reported, rendering exposure misclassification an ongoing challenge in all studies, and recall bias remains a significant possibility in all case-control studies. Many studies also did not fully account for potential confounders. Experimental animal and mechanistic evidence for NSSs does not support human-relevant carcinogenicity or any biologically plausible mechanisms by which NSSs could cause genotoxicity or cancer in humans. Overall, the epidemiology evidence does not support associations between any NSS and any cancer type.