Sucralose, a popular sugar substitute found in everything from diet sodas to low-calorie desserts, may do more than just sweeten your food. A new study from the University of Pittsburgh and UPMC Hillman Cancer Center suggests it could also make certain cancer treatments less effective.
Publishing in Cancer Discovery, researchers found that patients with melanoma and non-small cell lung cancer who consumed high amounts of sucralose responded less effectively to immunotherapy and had poorer survival compared with those who consumed little to none.
The study traced the problem to the gut microbiome. In both mouse models and human data, sucralose altered the balance of gut bacteria, increasing species that break down the amino acid arginine, a key nutrient for T cell function. Since immunotherapy works by boosting T cells to fight cancer, this arginine depletion appeared to blunt the therapy’s effectiveness.
“When arginine levels were depleted due to sucralose-driven shifts in the microbiome, T cells couldn’t function properly,” said lead author Abby Overacre, Ph.D., assistant professor in the Department of Immunology at Pitt and UPMC Hillman. “As a result, immunotherapy wasn’t as effective in mice that were fed sucralose.”
But there’s a possible workaround. In mice, supplementing with arginine or citrulline (which the body converts into arginine) restored the effectiveness of immunotherapy despite sucralose intake.
“We need to meet patients where they are,” Overacre added. “That’s why it’s so exciting that arginine supplementation could be a simple approach to counteract the negative effects of sucralose on immunotherapy.”
The team also examined data from 132 patients with advanced melanoma or lung cancer undergoing treatment and found similar associations between sucralose intake and poorer responses across cancer types and therapies.
Next steps include clinical trials to test whether citrulline supplementation can offset these effects in patients. Researchers are also interested in exploring how other sweeteners, like aspartame, saccharin, xylitol and stevia, influence treatment outcomes.
This study was supported by the National Institutes of Health, the Damon Runyon Cancer Research Foundation and Gateway for Cancer Research.