PITTSBURGH, July 30 — Cancer patients undergoing immunotherapy who consume sucralose, the artificial sweetener found in Splenda, appear to have a worse response to treatment, according to new research published today in Cancer Discovery. The study also suggests that supplementing with the amino acid arginine might help counteract these negative effects.
This discovery adds a significant piece to the puzzle of how the gut microbiome—the complex community of microorganisms in our digestive system—influences the effectiveness of cancer therapies. It seems sucralose disrupts beneficial gut bacteria, which are crucial for supporting immune function, including T cells, the key players in our immune defenses.
“What’s new in this study is that sucralose is promoting a microbiome that has few of the beneficial bacteria and more of the not so useful ones,” noted Magdalena Plebanski, an immunologist at RMIT University in Melbourne, Australia, who was not involved in the research. She added, “And that sucralose could potentially be negatively affecting T cells directly.”
Previous work had hinted at sucralose’s impact on immunotherapy, but the exact reasons remained elusive. To delve deeper, immunologist Abby Overacre and her team at the University of Pittsburgh investigated the gut microbiome in mice. They observed that mice fed sucralose, at levels comparable to human consumption, showed reduced gut microbiome diversity and lower levels of arginine.
“Artificial sweeteners reduced [gut microbiome] diversity, and along with that, reduced overall levels of arginine,” Overacre explained. “Arginine is very important for immune cell function, especially in cancer.”
These mice were bred to have similar cancers to the human patients in the study. Crucially, those that consumed sucralose exhibited a diminished response to immunotherapy, while mice fed regular table sugar did not show this effect.
To assess whether these findings translated to humans, the researchers surveyed 132 patients with advanced melanoma or non-small cell lung cancer undergoing anti-PD1 therapy, a common type of immunotherapy. Participants completed detailed dietary questionnaires, including inquiries about artificial sweetener consumption.
The findings indicated that even small amounts of sucralose could negatively impact immunotherapy outcomes.
“We identified a cutoff of approximately 0.07 milligrams per kilogram of body weight that segregated patients who did poorly compared to patients who didn’t,” stated medical oncologist Diwakar Davar of the University of Pittsburgh, a co-author of the study. He pointed out that this threshold is significantly lower than the U.S. Food and Drug Administration’s acceptable daily intake for sucralose, which is 5 milligrams per kilogram. For a 70-kilogram individual, this limit equates to roughly 22 cans of diet soda per day.
Despite the relatively small quantities involved, Overacre advised patients undergoing immunotherapy against drastic dietary overhauls. “Adding an arginine or citrulline supplement, which boosts arginine, is easy,” she suggested.
Andrew Ruplin, a clinical oncology pharmacist, offered a more cautious perspective. He recommended that patients discuss the implications of these findings with their oncologists to make informed decisions regarding supplementation.
“The data joins a growing body of evidence that the benefits and risks of immunotherapy may be altered by individual patient behaviors that were completely unknown to us previously,” Ruplin of the Fred Hutchinson Cancer Center in Seattle commented. However, he emphasized the need for further prospective human trials with larger patient cohorts and a broader range of cancers before these findings can be integrated into standard treatment protocols.
The research team plans to initiate clinical trials to explore whether supplements can indeed enhance the gut microbiome and improve anti-tumor immune responses. They also aim to investigate the effects of other sugar substitutes on immunotherapy efficacy.
