Study Reveals Artificial Sweetener May Weaken Cancer Immunotherapy - Video

A new study published in Cancer Discovery, a journal of the American Association for Cancer Research, has found that high consumption of sucralose—a common artificial sweetener—may impair the effectiveness of immunotherapy in cancer patients. Researchers reported that patients with melanoma or non-small cell lung cancer who consumed high levels of sucralose had worse outcomes and reduced survival compared to those with lower intake.

Sucralose is widely used as a sugar substitute in diet sodas, coffee, and other low-calorie foods. While often chosen for its ability to help manage blood sugar and weight, this new research suggests it may have unintended consequences for cancer patients undergoing immune checkpoint inhibitor therapies such as anti-PD1 treatment.

To explore this link, researchers used mouse models of adenocarcinoma and melanoma. They found that sucralose disrupted the gut microbiome, increasing bacteria that degrade arginine-an amino acid critical for T cell function. This reduction in arginine led to less effective immune responses and poorer tumor control. “When arginine levels were depleted due to sucralose-driven shifts in the microbiome, T cells couldn’t function properly,” explained lead author Dr. Abby Overacre. “As a result, immunotherapy wasn’t as effective in mice that were fed sucralose.”

However, the researchers also discovered a promising workaround. Supplementing sucralose-fed mice with either arginine or citrulline—a compound that the body converts into arginine-restored the effectiveness of immunotherapy. “That’s why it’s so exciting that arginine supplementation could be a simple approach to counteract the negative effects of sucralose on immunotherapy,” Overacre added.

To test the relevance in humans, the team analyzed dietary data from 132 cancer patients undergoing anti-PD1 therapy. Those with higher reported intake of sucralose-containing foods and drinks had consistently poorer responses across various cancer types and treatment combinations.

A clinical trial is being planned to test citrulline supplementation in patients receiving immunotherapy.

Reference: Kristin M. Morder, Madison Nguyen, Drew N. Wilfahrt, Zakaria Larbi. Dahmani, Ansen BP. Burr, Bingxian Xie, Michael Morikone, Hector Nieves-Rosado, William G. Gunn, Drew E. Hurd, Hong Wang, Steven J. Mullett, Kaitlin Bossong, Stacy L. Gelhaus, Dhivyaa Rajasundaram, Lawrence P. Kane, Greg M. Delgoffe, Jishnu Das, Diwakar Davar, Abigail E. Overacre-Delgoffe; Sucralose consumption ablates cancer immunotherapy response through microbiome disruption.. Cancer Discov 2025; https://doi.org/10.1158/2159-8290.CD-25-0247