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 more than 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 comprehensive systematic review of human, experimental animal and mechanistic data by Borghoff et al (2023) concluded that aspartame consumption is not carcinogenic in humans, as also supported by regulatory bodies that evaluated aspartame over the years.
The evidence base included 12 animal studies and over 40 epidemiological studies which collectively demonstrate a lack of carcinogenic effect of aspartame. Also, assessment of over 1360 mechanistic endpoints, including many guideline-based genotoxicity studies, demonstrate a lack of activity associated with endpoints grouped to key characteristics of carcinogens. Other mechanistic data do not provide evidence of a biologically plausible carcinogenic pathway associated with aspartame.
The review also discussed the inconsistent findings of the Ramazzini Institute studies, being the only cancer bioassays reporting potential adverse effects. As indicated by multiple authoritative bodies, including the European Food Safety Authority (EFSA) (2006, 2009, 2011, 2013), the U.S. Food and Drug Administration (FDA) (2006, 2007, 2014) and Food Standards Australia New Zealand (FSANZ) (2022), these reports of potential adverse effects can be explained by flaws in study design and conduct.
The epidemiological evidence synthesis integrated studies published following the publication of the WHO review by Rios-Leyvraz and Montez (2022), and an updated meta-analysis was conducted. No significant association between higher aspartame/ low/no calorie sweetener intake and overall risk of cancer, as well as breast or prostate cancer was found.
Based on the totality of the available data reviewed in this study, the authors conclude that evidence supports a lack of carcinogenic effects associated with aspartame consumption in humans.