Neotame vs Sucralose: which is worse?

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.

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

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.

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.