America's Top Sweetener May Hinder Cancer Treatment

A widely used artificial sweetener called sucralose, which appears in both packet form and diet soft drinks, could potentially be unsuitable for individuals undergoing treatment. cancer treatment .

A research project conducted by the University of Pittsburgh and UPMC Hillman Cancer Center indicates that the widely used sweetener for individuals looking to reduce calorie intake or control their blood sugar might have unexpected effects. immunotherapy less effective.

Scientists discovered that individuals suffering from melanoma (The deadliest form of skin cancer) and non-small cell lung cancer (the most prevalent kind of lung cancer) individuals who ingested significant amounts of sucralose experienced less favorable outcomes from immunotherapy and lower survival rates compared to those whose diets contained smaller quantities of the sweetener.

Nevertheless, the research group found that supplements increasing the amount of the amino acid "arginine," which aids the body in producing protein, reduced the harmful impact of sucralose on immunotherapy in mice.

"it's simple to advise someone to stop consuming diet soda, yet when individuals are undergoing treatment for cancer, they're already facing significant challenges; therefore, requesting major changes to their diet might not be practical," stated Abby Overacre, the study's author and a professor of immunology at Pitt and UPMC Hillman, in a statement.

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.

Sucralose appears in some diet colas, low-sugar energy beverages, and sugar-free protein or energy snacks, along with numerous individual packages designed to add sweetness to tea and coffee.

The research group employed mouse models to demonstrate that the harmful effects of sucralose stem from interference with gut microbes. The synthetic sweetener was discovered to alter the balance of the mouse intestinal microbiome—the beneficial and detrimental bacteria residing in the digestive tract.

Sucralose promoted the growth of bacterial species that break down arginine, leading to lower concentrations of this amino acid in the bloodstream, tumor fluid, and feces.

Immunotherapy drugs such as anti-PD1 enhance T cell activity, enabling them to better target and destroy cancer cells. Arginine plays a crucial role in T cell functionality, especially within the context of cancer.

Due to reduced arginine levels caused by alterations in the gut bacteria triggered by sucralose, T cells were unable to operate effectively, making immunotherapy less successful in mice consuming sucralose, as reported by the scientists.

In laboratory mice with melanoma and adenocarcinoma—an aggressive form of cancer originating from glandular tissue—incorporating sucralose into their food reduced the effectiveness of anti-PD1 treatment. As a result, tumor growth increased and patient outcomes worsened.

"Currently, we recognize that the gut microbiome plays a crucial role in determining the effectiveness of immunotherapy for cancer patients. Nevertheless, the extent to which different diets or food additives influence this remains unclear. Studies have indicated that artificial sweeteners such as sucralose can decrease microbial diversity within the microbiome, even among individuals who are otherwise healthy," Overacre stated. .

So, we questioned if they could adversely affect the effectiveness of immunotherapy in cancer patients because of alterations in the gut microbiota.

Nevertheless, although their results indicate this possibility, when the scientists provided mice consuming sucralose with arginine or citrulline, which converts to arginine within the body, the success of immunotherapy was regained.

To determine how applicable these results are to humans, 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, covering their frequency of consuming artificial sweeteners in coffee, tea, and diet soft drinks.

"we discovered that sucralose reduced the efficacy of immunotherapies for various kinds of cancers, at different stages and with multiple treatments," stated diwakar davar, an author of the study and a pitt professor of medicine as well as an upmc hillman oncologist, in a release.

This suggests the potential for developing prebiotics, including specific nutritional supplements for individuals with high sucralose intake.

What constitutes a "high" amount of sucralose? As Overacre noted, "This was rather unexpected! We discovered that even minimal amounts of sucralose (0.16 mg per kg daily) could lead to poorer outcomes during immunotherapy treatment. For someone weighing 70 kg (approximately 155 pounds), this equates to under one packet of sweetener each day."

We observed that comparable low concentrations of sucralose produced the identical outcome in mice, and this effect could be reversed by modifying the gut microbiota or adding arginine back into the system.

Can the harm caused by sucralose be reversed? "Although we don't have all the answers right now, the quick response is probably yes. Earlier research has shown that individuals with good health who cease using artificial sweeteners often experience improvement in their blood sugar reactions, for instance. The question remains about how long the digestive system bacteria are affected adversely, and what steps can be taken to enhance this in the near future?"

The arginine that scientists utilized—or citrulline, which results in greater blood levels of arginine compared to arginine alone—is available as a dietary supplement in many supermarkets.

"The advantage of using arginine supplements is that they are simple to consume and generally well-tolerated, which makes them a suitable choice for individuals who are already on other medications," said Overacre.

Looking ahead, we might explore alternative methods to replenish the gut microbiome using fecal microbiota transplantation [in which a healthy individual's stool is transferred to a patient], adjustments in diet, or prebiotic supplements.

Could cutting down on sucralose in your daily intake not be the best approach over time? "If individuals are open and capable of adjusting their diets, this could definitely have benefits. Still, sucralose is frequently found in processed items, and numerous people aren’t aware they're ingesting it, which makes it more challenging to manage."

We look forward to conducting clinical trials in the coming years to investigate whether adding arginine or stopping sucralose completely could benefit more cancer patients receiving immunotherapy. Although taking an additional supplement means one more pill each day, the potential long-term benefits might make it worthwhile.

Scientists additionally intend to examine the effects of alternative sweeteners—such as aspartame, saccharin, xylitol, and stevia—on the immune system and effectiveness of immunotherapy treatments.

Do you have advice for a health-related article? What should we cover? Do you have a question regarding sucralose and cancer therapy? Please let us know through health@ .

Reference

Morder, K. M., Nguyen, M., Wilfahrt, D. N., Dahmani, Z. Larbi, Burr, A. BP., Xie, B., Morikone, M., Nieves-Rosado, H., Gunn, W. G., Hurd, D. E., Wang, H., Mullett, S. J., Bossong, K., Gelhaus, S. L., Rajasundaram, D., Kane, L. P., Delgoffe, G. M., Das, J., Davar, D., & Overacre-Delgoffe, A. E. (2025). Ingestion of sucralose impairs effectiveness of cancer immunotherapy via disturbance of gut microbes. Cancer Discovery . https://doi.org/10.1158/2159-8290.CD-25-0247

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