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Artificial Sweetener Metabolite Breaks DNA

A person putting sweetener in their drink.
Credit: Towfiqu barbhuiya / Unsplash.
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Scientists at the North Carolina State University found that a chemical compound produced through the digestion of a common artificial sweetener causes damage to DNA. The research is published in the Journal of Toxicology and Environmental Health, Part B.

Growing research on adverse effects of artificial sweeteners

Warnings around the health impact of consuming sugar has led many people to replace it in their diets with low calorie artificial sweetener alternatives, also known as non-sugar sweeteners (NSSs). However, a growing number of studies in the scientific literature are suggesting that there may be a cost behind this seemingly “healthy” swap.    

Recent research on artificial sweeteners

In May, the World Health Organization (WHO) published new guidance on the use of non-sugar sweeteners (NSS), in which it recommends they are not to be used to control body weight or reduce the risk of non-communicable diseases (NCD). A few days later, researchers from the Institute for Food Systems Biology at the Technical University of Munich published new data demonstrating that even an “average” NSS intake can affect immune cells in the blood. A 2022 study of >100,000 adults suggested that artificial sweeteners are associated with an increased risk of cancer.

A team of researchers led by Dr. Susan Schiffman, adjunct professor in the joint department of biomedical engineering at North Carolina State University and the University of North Carolina at Chapel Hill, published new data demonstrating that a chemical formed when we metabolize a commonly used sweetener – sucralose – is genotoxic.

What does genotoxic mean?

Agents that are genotoxic can directly or indirectly cause damage to DNA. This is achieved through the agent adversely affecting enzymes that are key to DNA replication processes.  

Sucralose-6-acetate breaks DNA strands

Previous research by Schiffman and colleagues identified that, when sucralose is ingested in rats, several fat-soluble compounds are produced in the gut, including sucralose-6-acetate. The team were concerned, as compounds that easily dissolve in fat are more likely to “stick around” in the body. This contradicts the reported findings of studies that were presented to gain regulatory approvals for sucralose, which claimed that it was not broken down in the body.

The new study involved a series of in vitro experiments where human blood cells were exposed to sucralose-6-acetate to assess genotoxicity markers using a high-throughput screening tool and a micronucleus test.

“Our new work establishes that sucralose-6-acetate is genotoxic,” says Schiffman. Data suggest that the mechanism through which this genotoxicity occurs is via the production of DNA strand breaks.

The team also conducted in vitro tests exposing gut tissue to the compound. “Other studies have found that sucralose can adversely affect gut health, so we wanted to see what might be happening there,” Schiffman describes. “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.”

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When leaky gut occurs, molecules that would typically be excreted from the body instead leak out of the gut and are absorbed into the blood stream.

The researchers used RNA-sequencing to analyze the transcriptome of human intestinal tissue after exposure to sucralose-6-acetate. They found a significantly increased expression of genes known to be associated with inflammation, oxidative stress and cancer.

Calls for revisiting the regulatory status of sucralose

Schiffman and colleagues could detect trace amounts of sucralose-6-acetate directly in off-the-shelf sucralose. This suggests the compound may be in the product itself, rather than simply being produced through its metabolism. “This work raises a host of concerns about the potential health effects associated with sucralose and its metabolites,” says Schiffman. “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.”

Reference: Schiffman SS, Scholl EH, Furey TS, Nagle HT. Toxicological and pharmacokinetic properties of sucralose-6-acetate and its parent sucralose: in vitro screening assays. J Toxicol Environ Health Part B. 2023:1-35. doi: 10.1080/10937404.2023.2213903

This article is a rework of a press release issued by North Carolina State University. Material has been edited for length and content.