A common sweetener suppresses the immune system of mice – in high doses

Sugar free artificial sweeteners pictured on a spoon hovering over a glass cup and saucer of tea

Research suggests that the biological effects of sucralose — often used as a sugar substitute — go beyond taste stimulation.Credit: Yon Marsh/Alamy

High doses of sucralose — a potent calorie-free sugar substitute that’s 600 times sweeter than sucrose — reduce immune responses in mice, a study has found.

Researchers have not studied the effects of the sweetener in humans and say normal 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 taste stimulation.

“There was this worldview that these sweeteners would just pass 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 effects on health. to use artificial sweeteners and did not participate in the research. “This study is yet more proof that this is deeply wrong.”

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

“What impressive 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 article is incredible.”

Immune deficiency

Artificial sweeteners have come under intense scrutiny over the past few decades as researchers have found that some sugar substitutes have biological effects, such as altering gut microbes.2.

To find out if sucralose also has an effect on the immune system, Fabio Zani, a molecular biologist at the Francis Crick Institute in London, and his colleagues performed lab tests that exposed the sweetener to immune cells called T cells taken from mice and humans. They found that the sweetener impaired the ability of T cells to replicate and specialize.

To see if the effect was the same in live animals, the researchers gave the mice bottles of water 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 United States Food and Drug Administration. . The mice had either a bacterial infection or a tumour, which allowed the team to see how reactive their immune systems were. The sweetener altered T cell responses in mice fed sucralose, compared to mice in control groups that received 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 completely lost the effect,” says study co-author Karen Vousden, a cancer biologist at the Francis Crick Institute. “We’re pretty confident that the amount people eat in their normal diets won’t have any effect.”

The sweetener appears to only alter T cells, not other immune cells, such as B cells or myeloid cells, and it does not accumulate inside T cells. Previous research has shown that sucralose may affect the fluidity of cell membranes, which could 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 low-calorie foods and beverages, notes that the study focused on mice and that the doses exceed the amount that the people generally consume.

Alternative medicine

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 diseases, 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 disease that causes T cells to attack pancreatic cells. . After about 30 weeks, only about a third of the mice that received the sweetener developed diabetes; in contrast, all mice that received only water developed the disease.

Zani says if future research were to find a similar effect in humans, he could see the sweetener given alongside more conventional immunosuppressive drugs. This could allow doctors to reduce doses of immunosuppressive drugs. This line of research holds promise, Walther says, not least because sucralose is cheap to make and has fewer adverse side effects.

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