Caramel Color IV vs Saccharin: which is worse?

What is Caramel Color IV?

Caramel Color IV (Class IV caramel, E150d) is a food coloring made by heating sugar with both ammonium and sulfite compounds. This production method creates a unique set of reactive byproducts, notably 4-methylimidazole (4-MEI), which has been linked to cancer in animal studies. It is the most widely used caramel coloring in beverages like Coca-Cola and Pepsi.

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

Caramel Color IV: The primary concern with Caramel Color IV is 4-methylimidazole (4-MEI), a byproduct of the ammonia-sulfite caramel production process. The National Toxicology Program (NTP) found that 4-MEI caused lung cancer in male and female mice at high doses in 2-year bioassay studies, leading to California listing 4-MEI as a known carcinogen under Proposition 65 in 2011. The Prop 65 safe harbor level is 29 micrograms 4-MEI per day (the level that would cause 1 additional cancer per 100,000 people over a 70-year lifetime). CSPI testing in 2011-2012 found Coca-Cola and Pepsi sold in California contained 4-MEI levels that, at typical consumption rates, would exceed this threshold — triggering voluntary reformulation by both companies to reduce 4-MEI in their US products. The FDA reviewed 4-MEI and concluded that typical exposure levels 'are not a safety concern.' EFSA's evaluation found the NTP findings concerning but noted the margin of safety at typical European exposure levels. The cancer mechanism in mice involves high doses that may not extrapolate to typical human cola consumption.

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.