Common Sweetener Suppresses Mouse Immune System

High doses of sucralose — a potent, calorie-free sugar substitute that is 600 times sweeter than sucrose — reduce immune responses in mice, a study has found. The researchers did not investigate the sweetener’s effects in humans, and say that it is unlikely that normal consumption of sucralose is harmful. But the results, published on 15 March in Nature, suggest that the sweetener has a clear biological effect beyond stimulating taste.

“There has been this world view 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 with the research. “This study is yet another piece of evidence that that’s profoundly untrue.”

Although the authors call for more research to better understand any impacts of the molecule on people’s health, they also suggest that it could be used to tamp down conditions that cause a hyperactive immune system.

Artificial sweeteners have come under scrutiny over the past few decades, because researchers have found that some sugar substitutes have biological effects, such as altering people’s gut microbes.

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 carried out laboratory tests that exposed the sweetener to immune cells called T cells taken from mice and humans. 

They found that the sweetener impaired the T cells’ ability to replicate and specialize.

To see whether the effect was the same in living 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 authorities such as the US Food and Drug Administration. 

The mice had either a bacterial infection or a tumor, which allowed the team to see how responsive their immune systems were. The sweetener impaired T cell responses in the mice that were fed sucralose, compared with mice in control groups that were given either water or other sweeteners. When the team stopped giving the mice sucralose, their T cell responses began 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”, says study co-author Karen Vousden, a cancer biologist at The Francis Crick Institute. “We’re pretty confident that the amount that people take in their normal diet is not going to have any effect.”

The sweetener seems to impair only T cells, and not other immune cells, such as B cells or myeloid cells, and it doesn’t accumulate inside the T cells. Previous research has shown that sucralose can affect the fluidity of cell membranes, which might make it more difficult for T cells to communicate, the authors speculate.

Robert Rankin, executive director of the Calorie Control Council, a trade group representing companies that produce reduced-calorie food and beverages, notes that the study focused on mice and that the doses exceed the amount that people would typically consume.

Sucralose’s effects on the immune system aren’t inherently negative, Vousden says. The results highlight the possibility that the sweetener could one day be used therapeutically to treat autoimmune conditions, she says.

To test this theory in animals, the researchers gave high doses of the sweetener to mice that were bred to be predisposed to type 1 diabetes, an autoimmune condition that causes T cells to attack pancreatic cells. After about 30 weeks, only about one-third of the mice that were given the sweetener went on to develop diabetes; by contrast, all the mice that were given only water developed the condition.

Zani says that if future research were to find a similar effect in humans, he could see the sweetener being administered alongside more-conventional immunosuppressive drugs. This could allow physicians to lower the dosages of the immunosuppressive drugs. This avenue of research is promising, says Walther, especially because sucralose is cheap to manufacture and would have fewer unwanted side effects.

Sources:

Fabio Zani, Julianna Blagih, Tim Gruber et al. (2023). The dietary sweetener sucralose is a negative modulator of T cell-mediated responses. Nature. https://doi.org/10.1038/s41586-023-05801-6 

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