Sucralose May Hinder Cancer Treatment Effectiveness

A widely used alternative to regular sugar, sucralose is often chosen by individuals looking to reduce calorie intake or control their blood glucose levels. However, recent studies conducted by the University of Pittsburgh and UPMC Hillman Cancer Center indicate that this synthetic sweetener might not be ideal for those receiving cancer immunotherapy treatments.

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Published in the journal Cancer Discovery The research discovered that individuals with melanoma and non-small cell lung cancer who ingested large amounts of sucralose experienced a less favorable reaction to immunotherapy and had lower survival rates compared to those whose diets contained minimal quantities of this artificial sweetener.

Interestingly, supplements increasing the level of the amino acid arginine reduced the harmful impact of sucralose on immunotherapy in mice, an method that may soon be evaluated in human studies.

"Many people might easily suggest, 'Avoid drinking diet soda,' however, when individuals are undergoing treatment for cancer, they're already facing significant challenges, making it impractical to ask them to make major changes to their eating habits," explained lead researcher Abby Overacre, Ph.D., an assistant professor in the Department of Immunology at Pitt and UPMC Hillman.

We must connect with patients at their current stage. This is why it's very promising that addingarginine might offer an easy way to offset the harmful impacts of sucralose on immunotherapy.

The senior author, Dr. Diwakar Davar, an associate professor of medicine at Pitt and a medical oncologist and hematologist at UPMC Hillman, worked alongside Overacre and their group to demonstrate through mouse studies that the harmful effects of sucralose result from interference with intestinal microorganisms.

Sucralose altered the makeup of the mouse intestinal microbiota, boosting bacteria that break down arginine, leading to lower concentrations of this amino acid in the bloodstream, tumor fluid, and feces.

Immune checkpoint inhibitors like anti-PD1 enhance T cell activity, enabling these cells to better target and destroy cancerous cells. Arginine plays a crucial role in T cell functionality, particularly within the context of tumors.

when arginine levels dropped because of changes in the microbiome caused by sucralose, T cells didn’t work correctly," explained Overacre. "This led to reduced effectiveness of immunotherapy in mice that consumed sucralose.

In laboratory studies involving mice with adenocarcinoma and melanoma, incorporating sucralose into their food suppressed the effects of anti-PD1 treatment, resulting in bigger tumors and reduced lifespan. However, when mice that consumed sucralose were also provided with arginine or citrulline—substances that convert to arginine within the body—the success of immune-based therapy was regained.

To determine the applicability of these results to human beings, scientists examined 132 individuals diagnosed with advanced melanoma or non-small cell lung cancer who were treated exclusively with anti-PD1 medication or alongside chemotherapy. Participants completed comprehensive dietary history surveys that asked about their frequency of consuming artificial sweeteners in coffee, tea, and diet soft drinks.

we discovered that sucralose reduced the efficacy of immunotherapies in various kinds of cancers, at different stages, and with multiple treatment approaches," stated davar. "these findings suggest the potential for developing prebiotics, like specific nutritional supplements for individuals who have high intake of sucralose.

Scientists aim to conduct a clinical study to explore if taking citrulline supplements—which increase arginine concentrations more effectively than arginine alone—impact the intestinal bacteria community and the body’s ability to fight tumors in individuals.

They are also keen on examining the effects of alternative sweeteners like aspartame, saccharin, xylitol, and stevia on the immune system and effectiveness of immunotherapy treatments.

More information: Consuming sucralose impairs the effectiveness of cancer immunotherapy by disrupting the gut microbiome, Cancer Discovery (2025). DOI: 10.1158/2159-8290.CD-25-0247

Supplied by the University of Pittsburgh

This narrative first appeared on Medical Xpress .