Sucralose May Undermine Cancer Immunotherapy, Pitt–UPMC Study Warns

Researchers at the University of Pittsburgh and UPMC Hillman Cancer Center have found that sucralose, a popular artificial sweetener, can weaken the effectiveness of cancer immunotherapy. Their study, published under the title “Sucralose consumption ablates cancer immunotherapy response through microbiome disruption”, shows both animal and human data indicating negative outcomes for patients who consume high amounts of this sweetener.

Sucralose is an artificial sweetener derived from sugar but chemically modified so the body does not metabolize it for calories. It is about 600 times sweeter than regular sugar and is commonly used in diet sodas, sugar-free desserts, baked goods, and packaged foods. Unlike some other sweeteners, sucralose remains stable under heat, making it popular for cooking and baking.

Regulatory agencies like the U.S. Food and Drug Administration (FDA) have approved sucralose for use as a non-nutritive sweetener, though ongoing research explores its potential effects on metabolism, gut microbiome, and health outcomes.¹

The research by University of Pittsburgh and UPMC is published in the Journal Cancer Discovery, a publication of the American Association.

During a press release, UPMC said, "The study found that patients with melanoma and non-small c that patients with melanoma and non-small cell lung cancer who consumed high levels of sucralose had worse response to immunotherapy and poorer survival than those with diets low in artificial sweetener."

Using mouse models of melanoma and adenocarcinoma, the team found that adding sucralose to the diet disrupted the gut microbiome, increasing bacterial species that degrade arginine — a key amino acid for T-cell function.

“When arginine levels were depleted due to sucralose-driven shifts in the microbiome, T cells couldn’t function properly,” said lead author Abby Overacre, assistant professor in the Department of Immunology at Pitt and UPMC Hillman Cancer Center.

As a result, immune checkpoint inhibitor therapies such as anti-PD1, which rely on T-cell activation to kill cancer cells, were less effective. This led to larger tumors and poorer survival in sucralose-fed mice. The team also tested arginine and citrulline supplementation, which successfully restored immunotherapy effectiveness.

To see if these findings applied to humans, they analyzed diet questionnaires from 132 patients with advanced melanoma or nonsmall cell lung cancer receiving immunotherapy and found that those with high sucralose consumption had worse responses and lower survival.

“We need to meet patients where they are. 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 said.

Senior author Dr. Diwakar Davar emphasized that the results "raise the possibility of designing prebiotics, such as targeted nutrient supplementation for patients who consume high levels of sucralose.”

The researchers now plan to test citrulline supplements in clinical trials and study the impact of other sweeteners, including aspartame, saccharin, xylitol, and stevia, on immunotherapy outcomes.

References

1. U.S. Food and Drug Administration. Additional Information about High-Intensity Sweeteners Permitted for Use in Food in the United States. Last updated May 19, 2023. https://www.fda.gov/food/food-additives-petitions/aspartame-and-other-sweeteners-food

2. University of Pittsburgh School of Medicine, “Sucralose Could Make Cancer Treatment Less Effective,” UPMC Hillman Cancer Center News, July 31, 2025. https://www.medschool.pitt.edu/news/sucralose-could-make-cancer-treatment-less-effective?utm_source=chatgpt.com

(Rh/Eth/ARC/MSM)