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Artificial sweeteners may have unwanted effects on overall health. Dejan Beokovic/Stocksy
  • A new study indicates that high doses of the artificial sweetener sucralose reduce immune responses in mice.
  • Specifically, it lowers the activation of their T cells.
  • Researchers stress that typical consumption of sucralose by humans is not likely to be harmful.
  • In the future, researchers hope to examine whether high doses of this common sweetener could be used to dampen hyperactive immune systems.

Known by the brand name Splenda, sucralose is one of several artificial sweeteners approved for use in the United States. The calorie-free sugar substitute is 600 times sweeter than sugar.

The U.S. Food & Drug Administration approved sucralose for use as a general-purpose sweetener for foods in 1999.

Dr. Karen Vousden, a cancer biologist at the Francis Crick Institute, a biomedical research center in London, told Medical News Today that the members of her team were interested in the impact of diet on disease, so they decided to research sucralose.

“Across the globe, the consumption of sweeteners is increasing rapidly and careful studies by many regulatory agencies have shown them to be safe at the levels of [typical] consumption,” she said.

“[I]n recent years there have been reports that sweeteners may have more effects than previously thought, such as an effect on the gut microbiome. So, we carried out a study to look at the effects of some of these sweeteners in mice.”
— Dr. Karen Vousden

A paper on their work was recently published in Nature. It reveals the researchers found that sucralose suppresses the immune systems of mice when consumed in high doses.

The FDA established an acceptable daily intake (ADI) for sucralose of 5 milligrams per kilogram of body weight per day. The European Food Safety Authority (EFSA) established an ADI for sucralose of 15 mg per kg of body weight per day.

A packet of Splenda has 12 mg of sucralose. A 150-pound person can ingest 340 mg of sucralose a day and still meet the ADI in the United States.

For the tests undertaken for their study, the researchers gave mice access to water containing the rodent equivalent of the ADI recommended by the EFSA (.72 mg) and by the FDA (.17 mg).

The researchers performed several laboratory tests on the T cells, a type of white blood cells, of mice and humans to look at the possible effect of sucralose on the immune system.

In one instance, researchers gave mice either 0.17 or 0.72 mg of sucralose or the chemically unrelated sweetener sodium saccharin (NaS). Neither dose of sucralose nor NaS had any detectable effect on different types of cells.

In another test, researchers measured the homeostatic expansion of donor T cells in mice engineered to produce neither mature T cells nor B cells who were given sucralose. Only sucralose inhibited the proliferation of key cells of the adaptive immune system.

Overall, several different tests showed high sucralose exposure decreases T cell proliferation and differentiation.

Because sucralose is poorly absorbed, Dr. Vousden, the senior author of the study, told MNT, the team was surprised “the effect was so clear across multiple mouse models.”

“We were also surprised to see such a specific effect of sucralose on T-cells — none of the other sweeteners had this effect and sucralose did not seem to change the activity of other immune cells,” she explained.

“Importantly, this effect is fully reversible, and we only see this with very high doses of sucralose — much higher than those reached by people simply consuming food or drinks containing sucralose as part of a normal diet.”
— Dr. Karen Vousden

Previous research has shown that sucralose can affect the fluidity of cell membranes. This might make it more difficult for T cells to communicate, the authors speculate.

“We are still investigating the mechanism underlying this specificity,” Dr. Vousden said.

Researchers found up to 12 weeks of exposure to either dose of sucralose or NaS did not affect food intake or body weight in mice. Additionally, sucralose did not significantly affect fasting insulin levels or glucose tolerance in the mice.

In some studies, including one from 2008, sucralose has been shown to affect the gut microbiota. In this latest paper, however, researchers reported “no consistent shift in the bacterial species” in the stool of sucralose-treated mice.

Additionally, the researchers decided to look at whether sucralose could be used therapeutically to treat autoimmune conditions. To do this, they gave nonobese diabetic (NOD) mice sucralose.

Those mice showed lower frequencies of high blood sugar and delayed development of type 1 diabetes. This and another test indicates that sucralose supplementation may mitigate T cell-mediated autoimmune responses.

“We are now hoping to test whether high doses of sucralose could have similar effects in people [as they did in mice]. If this holds true, maybe therapeutical doses of sucralose could prove beneficial in patients suffering from certain autoimmune disease.”
— Dr. Karen Vousden

Dr. Fabio Cominelli, the director of the Digestive Health Research Institute at Case Western Reserve University School of Medicine in Ohio, found in a 2018 study that when ingested by mice, sucralose may have a harmful impact on the intestinal microbiota.

Dr. Cominelli, who was not involved in the current study, said he wasn’t sure why the researchers of this study did not observe major changes in the microbiome.

That said, he pointed out to MNT that the paper may lack relevance to scientists interested in the long-term impact of sucralose on humans because the rodent tests relied on doses of the sweetener that are much higher than what humans typically ingest.

Professor Daniel Davis, chair in immunology at Imperial College London, told the Science Media Centre that the paper is “hugely important” in showing that sucralose plays a role in the body.

He said more research is needed, however, to understand the impact sucralose has on humans.

“The research here focuses on mice and uses experiments designed to highlight any changes in T cell responsiveness,” he said.

“Whether any effects would be seen in human immune reactions to actual infections or in other disease settings remains to be tested. Also, the dose of sucralose used here to affect T cells is achievable in human blood but very high. The effect was reversible, so if further work shows any effects [on] human health, this would likely be prevented by a change in diet. It is also important that effects were specific to sucralose, and not seen with other sweeteners.”
— Prof. Daniel Davis

“Although scientists often say this, my overall view is that more research is sorely needed,” noted Prof. Davis.

Dr. Vousden stressed to MNT that their work does not “support the idea that normal sucralose consumption is immunosuppressive or that the levels of sucralose people are exposed to as part of a [typical] diet would have any effect.”