Advantame vs Saccharin: 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 Saccharin?

Saccharin is the oldest artificial sweetener, discovered accidentally at Johns Hopkins in 1879. It is a sulfonamide compound approximately 300-400 times sweeter than sucrose with no caloric value. It has a slightly bitter metallic aftertaste at higher concentrations. Saccharin's sodium salt (sodium saccharin) is the form used in most food applications.

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.

Saccharin: Saccharin's carcinogenicity history is one of the most tumultuous in food regulatory history. In 1977, the FDA proposed banning saccharin after studies found it caused bladder cancer in rats at very high doses. Congress passed the Saccharin Study and Labeling Act, which put a moratorium on the ban and required a cancer warning label on saccharin products ('Use of this product may be hazardous to your health. This product contains saccharin which has been determined to cause cancer in laboratory animals.'). By 2000, saccharin was removed from the US National Toxicology Program's Report on Carcinogens after subsequent research determined that the bladder cancer in male rats was caused by a rat-specific mechanism — high pH, high protein, and calcium phosphate in rat urine — that does not apply to human urine. The cancer warning label requirement was repealed. IARC also removed saccharin from its Group 2B list in 1999. However, Canada maintained its ban on food use saccharin, citing continued precautionary concern. A 2022 study in Cell found saccharin was among the artificial sweeteners most significantly altering gut microbiome composition and glucose tolerance in previously non-sweetener-using participants. Saccharin showed the largest effect on glucose tolerance among the sweeteners studied (saccharin, sucralose, aspartame, stevia). Saccharin passes through the placenta and appears in breast milk, raising questions about infant exposure that have not been fully resolved.