Updated systematic assessment of human, animal and mechanistic evidence demonstrates lack of human carcinogenicity with consumption of aspartame.
Level 3 - non-randomized controlled study
Systematic review of observational epidemiological studies, animal bioassays, and in vitro mechanistic data.
PubMed 36493943 · doi:10.1016/j.fct.2022.113549
What was done
The authors conducted an updated systematic review evaluating human epidemiological, animal bioassay, and mechanistic data regarding aspartame carcinogenicity, utilizing critical assessment tools to rate study quality and reliability. The evaluated evidence base comprised 12 animal studies, more than 40 epidemiological studies (previously reviewed by the World Health Organization), and over 1,360 mechanistic endpoints, including guideline-based genotoxicity assays.
What was found
The abstract reports no numerical effect estimates, relative risks, or confidence intervals. The synthesis of the 12 animal studies and >40 epidemiological studies found an overall lack of carcinogenic effect. Analysis of >1,360 mechanistic endpoints showed a lack of activity across key characteristics of carcinogens, with non-specific endpoints (such as mixed findings for oxidative stress across species and tissues) failing to demonstrate a biologically plausible carcinogenic pathway. Discrepant positive findings from Ramazzini Institute animal studies were determined to be attributable to methodological and design flaws.
Why it matters
This review integrates toxicological, mechanistic, and epidemiological data streams to address persistent safety controversies around aspartame. It reinforces conclusions from major regulatory and authoritative bodies that dietary aspartame exposure does not pose a carcinogenic risk.
Limits
The abstract does not provide quantitative pooled effect sizes, confidence intervals, or heterogeneity metrics. The human evidence relies on observational epidemiological designs susceptible to residual confounding and exposure mismeasurement, and mechanistic findings for non-specific markers like oxidative stress were inconsistent across tissues and test models.
Cited by
- context Approximately 80% of studies evaluating aspartame show no effect on cancer risk.