Artificial Sweetener May Impair Cancer Treatment, Study Finds

Next time you are reaching out for that sweetener sachet for your tea or coffee, think again. Researchers from the University of Pittsburgh and UPMC Hillman Cancer Centre have uncovered a link between the consumption of sucralose, a common artificial sweetener, and a decreased effectiveness of immunotherapy in treating certain cancers.

The study, focusing on melanoma and non-small cell lung cancer patients, revealed that those who ingested high amounts of sucralose experienced a less favorable response to treatment and had lower survival rates compared to those who consumed less of the sweetener.

The investigation, which was published in the journal Cancer Discovery, part of the American Association for Cancer Research, found that mice fed sucralose showed a reduction in the effectiveness of immune checkpoint inhibitor therapies. These treatments, such as anti-PD1, boost T cell activity to more efficiently target and destroy cancer cells. The study's findings highlighted the crucial role of arginine, an amino acid important for T cell functionality, particularly in cancer scenarios.

The study's senior author, Diwakar Davar, M.D., an associate professor of medicine at Pitt and a medical oncologist and hematologist at UPMC Hillman Cancer Centre, along with lead author Abby Overacre, Ph.D., an assistant professor in the Department of Immunology at Pitt and UPMC Hillman, and their team, utilised mouse models to demonstrate how sucralose consumption impacts the gut microbiome. They observed shifts in the bacterial composition of the gut, favoring species that break down arginine, thus depleting its levels in the blood, tumor fluid, and stool, which, in turn, impaired T cell performance.

This alteration in gut microbiota composition, triggered by sucralose, led to a diminished capability of T cells to function as required. Overacre remarked, "When arginine levels were depleted due to sucralose-driven shifts in the microbiome, T cells couldn't function properly. As a result, immunotherapy wasn't as effective in mice that were fed sucralose."

Consequently, mice with diets high in sucralose faced larger tumors and decreased survival rates when undergoing anti-PD1 therapy for adenocarcinoma and melanoma. However, the adverse effects of sucralose were counteracted by supplementing the mice's diets with arginine or citrulline, which is converted into arginine within the body, restoring the efficacy of immunotherapy.

To explore the implications of their findings on human patients, the research team analyzed data from 132 individuals with advanced stages of melanoma or non-small cell lung cancer, all of whom were undergoing anti-PD1 therapy, either alone or in combination with chemotherapy. The patients provided detailed dietary histories, including their consumption of artificial sweeteners in beverages like coffee, tea, and diet soda.

The outcomes of this study suggest a significant interaction between dietary sucralose intake and the performance of immunotherapy in cancer patients. "We found that sucralose impeded the effectiveness of immunotherapies across a range of cancer types, stages, and treatment modalities," Davar stated.

This discovery opens up new avenues for potential treatments, including the design of prebiotics and targeted nutrient supplementation for patients with high sucralose consumption levels.

Furthermore, the research indicates that supplements increasing arginine levels could neutralize sucralose's negative impact on immunotherapy in mice. This approach presents a possible avenue for clinical trials to evaluate its applicability in treating human patients, suggesting a shift towards dietary considerations in cancer treatment planning.