Lack of Genotoxic and Carcinogenic Potential for Nonsugar Sweeteners: A Review of Animal and Mechanistic Evidence

Globally, nonsugar sweeteners (NSSs) are commonly used in foods and beverages to enhance sweetness without added calories. NSSs have been the subject of numerous in vitro and animal studies to assess their potential carcinogenic risk to humans. As a complement to a larger systematic evaluation of the epidemiology evidence of NSSs and cancer, here we present a comprehensive review of the available experimental evidence from animal and mechanistic studies for the NSSs acesulfame-K (Ace-K), advantame, aspartame, cyclamate, neotame, saccharin, steviol glycosides, and sucralose within the context of ingredient safety. For this evaluation, we focused on genotoxicity, other potential cancer modes of action (MoAs), and carcinogenicity. Overall, high-quality studies have not shown evidence for carcinogenicity in animal models, except for saccharin, which causes bladder tumors in rats via a mechanism not relevant to humans. There is also no consistent or compelling evidence for any biologically plausible MoA by which any of these NSSs could cause cancer in humans. The results of this evaluation are consistent with the results of epidemiology studies, which have shown no consistent associations between NSS intake and cancer risk. Taken together, the body of available evidence supports previous conclusions by authoritative and regulatory bodies that Ace-K, advantame, aspartame, cyclamate, neotame, saccharin, steviol glycosides, and sucralose do not pose a genotoxic or carcinogenic risk to humans.