This sweetener could make cancer treatment less effective

Sucralose, a common sugar substitute used by people who want to reduce their calorie intake and control blood sugar levels, could make cancer treatment less effective.

Research from the University of Pittsburgh and the UPMC Hillman Cancer Center (USA) suggests that this artificial sweetener may not be the best option for patients undergoing cancer immunotherapy.

The study, published in the journal Cancer Discovery , found that patients with melanoma and a type of non-small cell lung cancer who consumed high levels of sucralose had a worse response to immunotherapy and lower survival than those with diets low in the artificial sweetener.

Surprisingly, supplements that increased levels of the amino acid arginine mitigated the negative effects of sucralose in immunotherapy in mice, an approach that could now be tested in clinical trials.

The research was conducted in mouse models to demonstrate that the negative effects of sucralose are driven by the alteration of gut bacteria.

Sucralose altered the composition of the mouse gut microbiome , increasing arginine-degrading bacterial species, which reduced arginine levels in blood, tumor fluid, and feces.

Immunotherapy with immune checkpoint inhibitors, such as anti-PD1, works by increasing the activity of T cells so they can more effectively destroy cancer cells. Arginine is essential for T cell function, especially in cancer.

"When arginine levels were reduced due to changes in the microbiome caused by sucralose, T cells couldn't function properly," explains researcher Abby Overacre. "As a result, immunotherapy wasn't as effective in the sucralose-fed mice."

In mouse models of adenocarcinoma and melanoma, the addition of sucralose to the diet inhibited anti-PD1 therapy, resulting in larger tumors and decreased survival. However, when researchers administered arginine or citrulline (which is metabolized into arginine in the body) to sucralose-fed mice, the immunotherapy's effectiveness was restored.

To assess the relevance of these data to humans, they analyzed 132 patients with advanced melanoma or non-small cell lung cancer who received anti-PD1 therapy alone or in combination with chemotherapy. The patients completed detailed questionnaires about their dietary history , including questions about how often they consumed artificial sweeteners in coffee, tea, and diet soda.

" We found that sucralose impeded the effectiveness of immunotherapies across various cancer types, stages, and treatment modalities ," says lead author Diwakar Davar. "These observations raise the possibility of designing prebiotics, such as targeted nutritional supplements, for patients who consume high levels of sucralose."

Researchers hope to launch a clinical trial investigating whether citrulline supplements (which increase arginine levels more than arginine itself) affect the gut microbiome and antitumor immune response in patients.

They are also interested in studying how other sugar substitutes, such as aspartame, saccharin, xylitol, and stevia , affect the immune system and response to immunotherapy.