Updated systematic assessment of human, animal and mechanistic evidence demonstrates lack of human carcinogenicity with consumption of aspartame

• Published in: Food and chemical toxicology Vol. 172; p. 113549
• Main Authors: Borghoff, Susan J., Cohen, Sarah S., Jiang, Xiaohui, Lea, Isabel A., Klaren, William D., Chappell, Grace A., Britt, Janice K., Rivera, Brianna N., Choski, Neepa Y., Wikoff, Daniele S.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2023
• Subjects: Animals; Aspartame - toxicity; Carcinogenesis; Carcinogenicity Tests; Carcinogens - toxicity; Humans; Reproducibility of Results; Sweetening Agents - toxicity
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2022.113549

Aspartame has been studied extensively and evaluated for its safety in foods and beverages yet concerns for its potential carcinogenicity have persisted, driven primarily by animal studies conducted at the Ramazzini Institute (RI). To address this controversy, an updated systematic review of available human, animal, and mechanistic data was conducted leveraging critical assessment tools to consider the quality and reliability of data. The evidence base includes 12 animal studies and >40 epidemiological studies reviewed by the World Health Organization which collectively demonstrate a lack of carcinogenic effect. Assessment of >1360 mechanistic endpoints, including many guideline-based genotoxicity studies, demonstrate a lack of activity associated with endpoints grouped to key characteristics of carcinogens. Other non-specific mechanistic data (e.g., mixed findings of oxidative stress across study models, tissues, and species) do not provide evidence of a biologically plausible carcinogenic pathway associated with aspartame. Taken together, available evidence supports that aspartame consumption is not carcinogenic in humans and that the inconsistent findings of the RI studies may be explained by flaws in study design and conduct (despite additional analyses to address study limitations), as acknowledged by authoritative bodies. •A systematic review was conducted to assess the potential carcinogenicity hazard associated with consumption of aspartame.•Animal and epidemiological studies consistently demonstrate lack of carcinogenicity with aspartame consumption.•Review of >1300 mechanistic datasets demonstrated overall lack of genotoxicity or other plausible biologically cancer pathways.•Collective evidence supports that aspartame consumption is not carcinogenic in humans.