Advantame vs Sucralose: which is worse?

What is Advantame?

Advantame is the newest FDA-approved synthetic sweetener, approved in 2014. Like neotame, it is a structural derivative of aspartame but with a vanillin-derived substituent. It is approximately 20,000 times sweeter than sucrose — the most potent sweetener currently approved for food use in the US.

What is Sucralose?

Sucralose is a synthetic non-caloric sweetener made by selectively chlorinating three hydroxyl groups in sucrose (table sugar). Despite being derived from sugar, the chlorination makes it non-digestible: most passes through the body without being metabolized. It is approximately 600 times sweeter than sucrose.

Documented risks

Advantame: Advantame is the newest approved high-intensity sweetener with the least post-approval safety data. The FDA approval was based on extensive pre-market animal studies showing no significant toxicity, carcinogenicity, reproductive toxicity, or neurotoxicity at relevant doses. EFSA approved it for EU use in 2014, finding no safety concerns based on the submitted data. Like other synthetic sweeteners, advantame has not been studied for long-term effects in large human populations post-approval. The same gut microbiome and glucose tolerance concerns raised for other sweeteners (aspartame, sucralose, acesulfame K) have not been specifically studied for advantame, though the class-wide concerns are relevant. Given its 2014 approval date, independent long-term safety studies are still limited.

Sucralose: A 2023 study published in Nature Medicine found that sucralose-1,6-hexanediacid — a gut-derived metabolite of sucralose — enhanced T-cell immune activity in vitro. The researchers found that sucralose exposure in certain doses could potentially affect immune function. However, this was an early-stage study and its clinical implications for humans are not established. A 2021 Cell study found that sucralose and other non-nutritive sweeteners altered gut microbiome composition and glucose tolerance in human participants who were non-habitual sweetener users. The study found sucralose consumption was associated with glucose intolerance changes in some individuals, suggesting gut microbiome-mediated effects on metabolism. A 2016 study in the International Journal of Occupational and Environmental Health found sucralose consumption was associated with higher leukemia incidence in male mice at high lifetime doses. This finding prompted significant concern, though regulators noted the doses used far exceeded typical human intake. Chlorinated compounds: sucralose contains chlorine atoms in its structure. Critics have argued this makes it similar to organochlorine compounds, some of which are known carcinogens. Regulatory agencies have reviewed this and do not consider the chlorine in sucralose equivalent to organochlorine pollutants; the chlorinated positions are not metabolically active. However, high-temperature cooking with sucralose can generate chlorinated compounds. EFSA's 2017 re-evaluation concluded sucralose is safe and non-carcinogenic at its ADI of 15 mg/kg body weight. The FDA ADI of 5 mg/kg/day provides a substantial safety margin relative to typical consumer intake from Splenda use.