Caramel Color IV vs Neotame: 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 Neotame?

Neotame is a synthetic dipeptide sweetener — a derivative of aspartame with a 3,3-dimethylbutyl group added to block aspartame's metabolism, preventing the release of phenylalanine. This means it is safe for people with phenylketonuria (PKU), unlike aspartame. It is approximately 7,000-13,000 times sweeter than sucrose.

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.

Neotame: Neotame is one of the newer synthetic sweeteners with a shorter safety track record. A 2023 study published in Frontiers in Nutrition found that neotame damaged intestinal epithelial cells in vitro and disrupted the gut microbiome in mice — including reducing beneficial bacteria and increasing bacterial invasion of intestinal cells. The study observed effects at concentrations that could be achievable through high consumption of neotame-containing products. The FDA has set an ADI of 0.3 mg/kg/day, one of the lower sweetener ADIs, reflecting a conservative safety margin. Limited long-term human safety data exist compared to aspartame, acesulfame K, or saccharin, which have been used for decades. EFSA's 2010 opinion found no safety concern at permitted levels. The Frontiers in Nutrition 2023 gut study represents new concerning findings that warrant further investigation.