Sucralose under the microscope: what is known about the persistence of sweetener E955 - from the environment to DNA

Sucralose (E955) is the "star" of zero-calorie products and children's yogurts, but in 2025, its reputation is being tested again. A large review in Nutrients collected data from three risk areas at once - environmental, oxidative stress, and genomic safety - and came to a restrained conclusion: the substance is extremely stable in nature, behavioral and metabolic shifts have been noted in certain organisms, and its derivatives can exhibit genotoxicity. The authors call for more careful use and better monitoring of sucralose traces in water and food.

Background of the study

Sucralose (E955) is one of the most widely used non-caloric sweeteners in beverages and "diet" products. Historically, its safety was assessed by classical toxicological criteria (acute/subacute toxicity, carcinogenicity at high doses), and regulators established acceptable daily intake. But in recent years, data has accumulated that does not cover the previous limits: sucralose is chemically stable, is almost not metabolized by humans, goes into wastewater and is found in natural reservoirs and even in drinking water. That is, we are talking not only about personal dietetics, but also about the environmental exposure of the entire population - in small doses, but chronically.

In parallel, signals about sucralose by-products have emerged. First, the industrial precursor of sucralose, sucralose-6-acetate, has been found in traces in finished batches and its possible formation in the gastrointestinal tract is discussed; genotoxic effects have been shown for this molecule in model systems. Second, chlorine-containing derivatives have been described during heating and in transformation processes, raising questions about the thermal stability and safety of baked goods/hot drinks with sweetener. Finally, a number of studies note microbiota shifts and signs of oxidative stress against the background of sucralose - effects of small doses that classical tests may not have detected.

Hence the motivation for the review: to collect disparate data on three "risk lines" - environmental stability, oxidative stress and genomic safety - to assess their quality and consistency and to understand where revisions of technological specifications, monitoring of impurities (including sucralose-6-acetate) are needed, and where new studies of long-term exposure to low doses and the impact on vulnerable groups (pregnant/nursing women, children, patients on multiple pharmacotherapy) are needed. The general vector is from a narrowly nutritional view to an interdisciplinary one: a food additive that is stable in the environment and produces reactive derivatives requires a more sophisticated risk assessment than just "zero calorie content".

What exactly was discussed in the review

• Environmental stability and "family resemblance" to organochlorines. Sucralose is a chlorinated carbohydrate; due to the "chlorine shield" it is little destroyed and remains in aquatic ecosystems for a long time. A number of works describe behavioral, metabolic and even genomic changes in aquatic organisms with chronic exposure to trace concentrations.
• Microbiota and oxidative stress. Experiments have recorded shifts in the composition of microbial communities (in the environment and in humans) and signs of oxidative stress - another argument in favor of caution when widely using the sweetener.
• Transformations and degradation products. When heated and metabolized by microbes, sucralose can produce toxic by-products (including dioxins/tetrachlorodibenzofurans under model conditions), which increases environmental concerns.
• The most alarming is sucralose-6-acetate. The industrial precursor of E955 was found in a number of commercial samples; theoretically, it can also be formed in the intestine. Genotoxicity (clastogenic effect) and an effect on the expression of genes associated with inflammation and carcinogenesis (e.g., MT1G, SHMT2) have been shown for it. There is also evidence of inhibition of CYP1A2/CYP2C19, which potentially changes the metabolism of other substances. Even trace amounts can exceed the benchmark of 0.15 μg/person/day.

The review also included "human" contexts. Sucralose is found in breast milk and is able to pass through the placental barrier - the question of the safety of formulas for pregnant and lactating women remains open. At the same time, in classic short-term toxicological tests, E955 looked "safe" for a long time, and the discussion is currently heated up by new data on persistence, by-products and effects on microbiota/stress pathways.

Why the topic is important right now

• Increased consumption of zero-calorie products after the Covid years and the “sugar zero” trend.
• Increased environmental pressure: treatment plants do a poor job of removing persistent organochlorine compounds, and background concentrations in water are slowly increasing.
• Vulnerable groups: pregnant/lactating women, young children, patients on polypharmacy (risk of drug interactions via CYP).

What does this mean for consumers?

• Sweeteners are not a "free" sweet. If you choose "sugar-free" drinks, do not make them a daily basis of the diet; alternate with water/unsweetened tea.
• Pregnancy/lactation: if possible, reduce the frequency of products with E955, especially thermally processed ones (baked goods, hot drinks with “sweet” syrups).
• Look at the whole diet: more whole foods and fewer ultra-sweet flavors - this reduces overall "sweet cravings" and the need for sweeteners.

(These tips are not a substitute for medical advice; for special diets, consult your doctor.)

What should industry and regulators do?

• Monitor and disclose sucralose and sucralose-6-acetate levels in beverages/foods; where possible, stricter process specifications for impurities.
• Pumping wastewater treatment: cathodic dehalogenation technologies and others are already being tested to destroy persistent organochlorine molecules.
• Support independent research on long-term low-dose effects, effects on microbiota, and cumulative sweetener + heat + GI effects.

Limitations of evidence

• The review brings together a variety of studies: cell lines, aquatic models, limited human data - this is not a direct assessment of cancer risks in consumers.
• Not every “finding in a sample” is equal to clinical harm: doses, duration, and accompanying factors are important.
• But where we are talking about persistent compounds and genotoxic derivatives, the precautionary principle is appropriate - and this is exactly what the authors propose.

Conclusion

Sucralose itself and especially its acetylated precursor raise questions about environmental sustainability, oxidative stress, and genomic safety. It’s too early to panic, but reducing the “sugar-free” routine, improving water purification, and demanding transparency on impurities is a smart strategy for the coming years.

Source: Tkach VV, Morozova TV, Gaivão IOM, et al. Sucralose: A Review of Environmental, Oxidative and Genomic Stress. Nutrients. 2025;17(13):2199. https://doi.org/10.3390/nu17132199