A chemical associated with sucralose, the artificial sweetener sold as Splenda®, damaged DNA in laboratory experiments and disrupted a model of the intestinal lining. Those findings, published in 2023, raised questions about a little studied substance that researchers detected in some samples of the sweetener.
But the laboratory results are not the whole story. Subsequent testing and a major European safety assessment have added important context, including challenges to the idea that the chemical necessarily forms during digestion. The original experiments did not establish that ordinary sucralose consumption damages DNA in people, and European regulators concluded in 2026 that the sweetener remains safe under its currently authorized uses.
The Chemical Behind the Sucralose Concerns
The 2023 investigation focused on sucralose-6-acetate, a compound that is chemically related to sucralose but is not the same substance. It can occur during manufacturing and remain as an impurity in the finished sweetener. The researchers reported finding it at concentrations of up to 0.67% in commercial sucralose samples they analyzed.
Earlier work by the same team, published in 2018, had identified compounds that dissolve in fat in the urine and feces of rats given sucralose. The researchers interpreted those findings as evidence that the sweetener was being chemically altered inside the animals. Their subsequent work identified sucralose-6-acetate as one of the compounds of interest. This was animal research, not a demonstration of the same process in people.
“Our new work establishes that sucralose-6-acetate is genotoxic,” Susan Schiffman said when the findings were announced in 2023. Schiffman was the study’s corresponding author and an adjunct professor in the joint department of biomedical engineering at North Carolina State University and the University of North Carolina at Chapel Hill. “We also found that trace amounts of sucralose-6-acetate can be found in off-the-shelf sucralose, even before it is consumed and metabolized.”
The digestion claim has since been questioned. In its 2026 review, the European Food Safety Authority noted that the compounds detected in the rat study could have been impurities already present in the administered sucralose. Their appearance in urine and feces therefore did not necessarily establish that metabolism had produced them.
What the DNA Experiments Showed
To investigate potential harm, the researchers exposed cultured human blood cells to sucralose-6-acetate and examined indicators of genetic damage. These were in vitro experiments, meaning they took place outside a living organism rather than in people consuming the sweetener.
The team reported results consistent with genotoxicity, the ability to damage genetic material. Their screening indicated a pattern associated with breaks in DNA strands.
“In short, we found that sucralose-6-acetate is genotoxic, and that it effectively broke up DNA in cells that were exposed to the chemical,” Schiffman said.
The distinction between a laboratory effect and a health risk matters. Exposing cells directly to a chemical can reveal a potential hazard, but it does not, by itself, show whether eating a food exposes human tissues to enough of that chemical to cause the same damage. The 2023 experiments did not demonstrate such harm from everyday consumption.
Sucralose and the Gut Barrier
The researchers also investigated the intestinal lining, which helps regulate what passes from the digestive tract into the body. Using a laboratory system containing human intestinal tissue, they tested both sucralose and sucralose-6-acetate. Both impaired the barrier’s integrity under the experimental conditions.
“Other studies have found that sucralose can adversely affect gut health, so we wanted to see what might be happening there,” Schiffman said. “When we exposed sucralose and sucralose-6-acetate to gut epithelial tissues — the tissue that lines your gut wall — we found that both chemicals cause ‘leaky gut.’ Basically, they make the wall of the gut more permeable. The chemicals damage the ‘tight junctions,’ or interfaces, where cells in the gut wall connect to each other.
“A leaky gut is problematic, because it means that things that would normally be flushed out of the body in feces are instead leaking out of the gut and being absorbed into the bloodstream.”
The team then examined how exposure to sucralose-6-acetate changed gene activity in the intestinal cells.
“We found that gut cells exposed to sucralose-6-acetate had increased activity in genes related to oxidative stress, inflammation and carcinogenicity,” Schiffman said.
These findings described cellular responses in a laboratory model. Increased activity in genes associated with cancer does not mean that the experiment demonstrated cancer development, just as greater permeability in cultured tissue does not establish that normal sweetener use causes an intestinal disorder in people.
Why the Exposure Threshold Needs Context
Another concern raised by the researchers involved the amount of sucralose-6-acetate that someone might consume without realizing it.
“To put this in context, the European Food Safety Authority has a threshold of toxicological concern for all genotoxic substances of 0.15 micrograms per person per day,” Schiffman said. “Our work suggests that the trace amounts of sucralose-6-acetate in a single, daily sucralose-sweetened drink exceed that threshold. And that’s not even accounting for the amount of sucralose-6-acetate produced as metabolites after people consume sucralose.”
That comparison requires an important qualification. A threshold of toxicological concern is a conservative screening tool used to help identify chemicals that need closer assessment when detailed toxicity information is limited. Exceeding such a threshold is not equivalent to demonstrating that a drink causes DNA damage or disease. It is also different from the acceptable daily intake established specifically for sucralose.
The researchers nevertheless considered their findings serious enough to warrant reconsidering the sweetener’s safety.
“This work raises a host of concerns about the potential health effects associated with sucralose and its metabolites. It’s time to revisit the safety and regulatory status of sucralose, because the evidence is mounting that it carries significant risks. If nothing else, I encourage people to avoid products containing sucralose. It’s something you should not be eating.”
That warning expressed the research team’s position in 2023. Later assessments reached a different overall conclusion about the safety of approved uses.
What the 2026 Safety Review Found
In February 2026, the European Food Safety Authority published a comprehensive reassessment of sucralose. Its experts retained the acceptable daily intake of 15 milligrams per kilogram of body weight per day and found that estimated dietary exposure remained below that level across the population groups assessed. This intake represents an amount considered safe to consume daily over a lifetime.
The review did not overlook the 2023 research. It considered the reported DNA damage signals, including those involving sucralose-6-acetate, but judged the relevant screening evidence to have limited relevance for its assessment. After weighing laboratory, animal, and other evidence, the panel concluded that sucralose’s use as a food additive did not raise a genotoxicity concern.
In the United States, sucralose also remains approved for use as a food sweetener. The Food and Drug Administration states that its safety assessment included more than 110 studies addressing potential toxic effects, along with human clinical research.
Later Genetic Testing Adds Another Piece
A study published online in August 2026 in Food and Chemical Toxicology evaluated commercial grade sucralose using several genetic toxicity tests in cells and animals. The authors reported negative results in most assays, including tests for mutations and chromosome damage. A study in genetically modified mice also found no increase in the mutations being measured.
One test, known as a comet assay, did detect DNA damage signals in several tissues. The authors described complications in interpreting those results and concluded that the overall findings did not indicate genotoxicity. Several authors were affiliated with Tate & Lyle, while others worked for Intertek, making the study’s industry connections relevant context.
Importantly, this investigation tested commercial sucralose rather than directly repeating the 2023 experiments with isolated sucralose-6-acetate. The two studies therefore address related, but not identical, questions.
Human Studies Explore Other Biological Effects
Separate research has examined whether sucralose influences processes such as appetite. These studies do not establish DNA damage, but they help investigate how the sweetener interacts with the body.
In a randomized study published in Nature Metabolism in March 2025, 75 young adults consumed drinks containing sucralose, an equally sweet amount of sugar, or water on separate visits. Compared with sugar, sucralose increased reported hunger and blood flow in the hypothalamus, a brain region involved in appetite regulation. Compared with water, it increased hypothalamic blood flow but did not change hunger ratings. These were immediate responses, not evidence that sucralose caused lasting weight gain.
A systematic review published in August 2026 examined 23 randomized trials of sucralose and cardiometabolic outcomes in healthy adults. Results for blood sugar regulation were mixed: some studies reported unfavorable changes, while others found no effect. The review’s authors raised concerns about possible metabolic effects, underscoring that questions about appetite and glucose regulation are distinct from the original claim about DNA damage.
Heating Sucralose Raises a Separate Question
The European review also identified an unresolved issue involving prolonged exposure to high temperatures. Under some heating conditions, chlorine from sucralose may become incorporated into other compounds whose health effects remain uncertain.
For that reason, the panel could not confirm the safety of a proposed expansion of sucralose use in certain baked goods. It also noted that similar uncertainties can arise during baking or frying at home, where temperatures, cooking times, and amounts vary. This concern involves products that may form during heating, rather than a confirmation of the 2023 sucralose-6-acetate findings.
Taken together, the evidence supports a more specific conclusion than a blanket warning about DNA damage. The 2023 study reported potentially important effects in laboratory systems, while subsequent assessments have not established that ordinary sucralose consumption causes the same harm in people. Questions about particular compounds, exposure conditions, and other biological effects remain areas for investigation.