Ordinary sweetener suppresses the immune system of the mouse – in high doses

The research suggests that the biological effects of sucralose — commonly used as a sugar substitute — go beyond flavor boosting.Credit: Yon Marsh/Alamy

High doses of sucralose – a powerful, calorie-free sugar substitute that is 600 times sweeter than sucrose – decreases immune response in mice, a study has found.

The researchers have not studied the effects of the sweetener in humans and say regular consumption of sucralose is unlikely to be harmful. But the results, published on March 15 in Nature1suggest that the sweetener has a clear biological effect beyond flavor boosting.

“There’s been a worldview that these sweeteners would just wash through our bodies — our tongues would taste them and nothing else would happen,” says Susie Swithers, a behavioral neuroscientist at Purdue University in West Lafayette, Indiana, who studies the health effects. of using artificial sweeteners and was not involved in the study. “This study is yet another piece of evidence that that’s completely untrue.”

While the authors call for more research to better understand the effects of the molecule on human health, they also suggest it could be used to suppress conditions that cause a hyperactive immune system.

“What an impressive piece of work,” says Guillaume Walther, a physiologist at the University of Avignon in France who studies the health effects of sucralose. “The rigor of the study and experiments in this paper is incredible.”

Immune disorder

Artificial sweeteners have come under scrutiny in recent decades as researchers have found that some sugar substitutes have biological effects, such as altering people’s gut microbes2.

To investigate whether sucralose also has an effect on the immune system, Fabio Zani, a molecular biologist at the Francis Crick Institute in London, and his colleagues conducted lab tests that exposed the sweetener to immune cells called T cells, which were taken from mice and humans. They found that the sweetener affected the T cells’ ability to replicate and specialize.

To see if the effect was the same in live animals, the researchers gave mice water bottles containing a dose of sucralose that is the rodent equivalent of the maximum safe intake in humans — a standard set by regulatory agencies such as the U.S. Food and Drug Administration. The mice had either a bacterial infection or a tumor, which allowed the team to see how well their immune systems were responding. The sweetener disrupted T-cell responses in the mice given sucralose, compared to mice in control groups given water or other sweeteners. When the team stopped giving the mice sucralose, their T cell responses started to recover.

The researchers didn’t test lower doses of sucralose, but it “seemed very clear to us that if we went much lower, we probably would have lost the effect altogether,” said study co-author Karen Vousden, a cancer biologist at The Francis Crick Institute. “We’re pretty sure that the amount people take in through their normal diet won’t have any effect.”

The sweetener appears to only affect T cells, not other immune cells, such as B cells or myeloid cells, and it does not accumulate in the T cells. Previous research has shown that sucralose may affect the fluidity of cell membranes, making it more difficult for T cells to communicate, the authors speculate.

Robert Rankin, executive director of the Calorie Control Council, a trade group that represents companies that produce low-calorie foods and beverages, notes that the study focused on mice and that the doses are higher than the amount humans would normally consume.

Sweet medicine

The effects of sucralose on the immune system are not inherently negative, says Vousden. The results highlight the possibility that the sweetener could one day be used therapeutically to treat autoimmune diseases, she says.

To test this theory in animals, the researchers gave high doses of the sweetener to mice bred to be prone to type 1 diabetes, an autoimmune disease that causes T cells to attack pancreatic cells. After about 30 weeks, only about a third of the mice given the sweetener developed diabetes; in contrast, all mice fed only water developed the condition.

Zani says that if future research found a similar effect in humans, he could see the sweetener administered alongside more conventional immunosuppressants. This could allow doctors to lower the dosage of the immunosuppressants. This direction of research is promising, says Walther, especially because sucralose is cheap to produce and is said to have fewer unwanted side effects.

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