Recent research published in Cancer Discovery, a prestigious journal of the American Association for Cancer Research, reveals concerning findings regarding the consumption of sucralose among patients with melanoma and non-small cell lung cancer. The study indicates that individuals who consume high levels of this artificial sweetener experience a significantly worse response to immunotherapy treatments and exhibit poorer survival rates compared to those with low sucralose intake.
In a remarkable twist, the research team found that supplements designed to boost levels of the amino acid arginine could counteract the detrimental effects of sucralose on immunotherapy in animal models. This discovery opens the door for potential clinical trials to explore this promising approach further. Lead author Abby Overacre, Ph.D., an assistant professor in the Department of Immunology at Pitt and UPMC Hillman, emphasizes the challenges faced by cancer patients, stating, “It’s easy to say, ‘Stop drinking diet soda,’ but when patients are being treated for cancer, they are already dealing with enough.” She highlights the importance of finding realistic dietary adjustments for patients during their treatment.
Senior author Diwakar Davar, M.D., an associate professor of medicine at Pitt and a medical oncologist at UPMC Hillman, collaborated with Overacre and their research team to investigate the underlying mechanisms. Their studies using mouse models demonstrated that the negative impacts of sucralose are primarily due to its disruption of gut bacteria. Specifically, the consumption of sucralose altered the composition of the gut microbiome in mice, leading to an increase in bacterial species that degrade arginine. This shift resulted in a decrease in arginine levels in the blood, tumor fluid, and stool, which are critical for effective T cell function.
Immunotherapy, particularly immune checkpoint inhibitors like anti-PD1, relies on enhancing T cell activity to effectively target and destroy cancer cells. When the levels of arginine were diminished due to sucralose-induced changes in the microbiome, T cells struggled to perform optimally. Overacre explains, “As a result, immunotherapy wasn’t as effective in mice that were fed sucralose.” In their experiments, mice models of adenocarcinoma and melanoma showed inhibited anti-PD1 therapy when sucralose was added to their diet, resulting in larger tumors and significantly poorer survival outcomes.
In an encouraging turn, when researchers supplemented the diets of sucralose-fed mice with arginine or citrulline (which the body converts into arginine), the effectiveness of immunotherapy was restored. To further investigate the relevance of these findings in human patients, the research team analyzed data from 132 individuals with advanced melanoma or non-small cell lung cancer who were undergoing anti-PD1 therapy, either alone or in combination with chemotherapy. Patients provided detailed dietary histories, including their consumption of artificial sweeteners like sucralose.
Davar noted, “We found that sucralose impeded the effectiveness of immunotherapies across a range of cancer types, stages, and treatment modalities.” This observation raises the potential for designing prebiotics and targeted nutrient supplementation for patients who consume high amounts of sucralose. The researchers are hopeful about launching clinical trials to explore whether citrulline supplements, which may enhance arginine levels more effectively than arginine itself, can positively influence the gut microbiome and the immune response against tumors.
Additionally, the research team is keen to investigate how various other sugar substitutes, such as aspartame, saccharin, xylitol, and stevia, affect the immune system and the response to immunotherapy. This comprehensive approach could lead to significant advancements in cancer treatment strategies, particularly for patients who rely on artificial sweeteners in their diets.
The study was supported by numerous grants from the National Institutes of Health and other notable foundations, highlighting its importance and the need for further exploration in this critical area of cancer treatment.
