Sucralose, an artificial sweetener used in many diet sodas and sugar-free foods, is often chosen by people who want to cut calories or manage blood sugar.
But new research from the University of Pittsburgh and UPMC Hillman Cancer Center suggests it might not be the best choice for cancer patients receiving certain immune-based treatments.
The study, published in Cancer Discovery, looked at people with melanoma or non-small cell lung cancer—two common but serious forms of cancer.
Researchers found that patients who consumed a lot of sucralose responded less well to immunotherapy and had shorter survival times compared to those who ate little or no sucralose.
Immunotherapy, particularly immune checkpoint inhibitors like anti-PD1 drugs, works by boosting the activity of T cells—key immune system soldiers that can attack and kill cancer cells.
For T cells to work properly, they need certain nutrients, including the amino acid arginine. The new study showed that sucralose can disrupt this process by changing the gut microbiome—the community of bacteria living in our intestines.
In experiments with mice, scientists found that sucralose shifted the balance of gut bacteria toward species that break down arginine.
This led to lower arginine levels in the blood, tumor tissue, and stool. With less arginine available, T cells couldn’t function at full strength, and the cancer treatment became less effective.
As a result, mice fed sucralose had larger tumors and shorter survival times when treated with anti-PD1 therapy.
But there was a silver lining: when the researchers gave these mice supplements of arginine or citrulline (a compound the body converts into arginine), the effectiveness of the cancer treatment returned to normal.
This finding could be important for real-world patients. “It’s not easy to tell cancer patients to suddenly stop drinking diet soda or eating products with sucralose,” says lead author Dr. Abby Overacre.
“They already have enough challenges. That’s why it’s exciting that something as simple as an arginine supplement could help offset the problem.”
To see if the mouse findings applied to humans, the research team examined data from 132 patients with advanced melanoma or non-small cell lung cancer who were receiving anti-PD1 therapy, with or without chemotherapy.
Each patient filled out a questionnaire about their diet, including how often they consumed artificial sweeteners in drinks like coffee, tea, or diet soda.
The results matched the mouse experiments: people who reported higher sucralose intake had worse responses to immunotherapy across different cancer types and treatment plans. Senior author Dr. Diwakar Davar says these findings open the door to new strategies, such as providing targeted nutrient supplements for patients who regularly consume sucralose.
The team now hopes to run a clinical trial to test whether citrulline supplements—which raise arginine levels even more effectively than arginine itself—can improve immune function and treatment results in patients.
They also plan to study how other sugar substitutes, such as aspartame, saccharin, xylitol, and stevia, affect the immune system and cancer therapy.
This study highlights a potentially important link between diet, the gut microbiome, and the effectiveness of cancer immunotherapy. While the research doesn’t prove that all cancer patients should avoid sucralose, it raises valid concerns—especially for those undergoing immune-based treatments.
The finding that arginine or citrulline supplements can reverse the negative effects in mice is promising and could lead to practical, patient-friendly solutions. However, this is still early research.
The human data relied on dietary questionnaires, which can be imprecise, and more controlled clinical trials will be needed to confirm cause and effect.
If future trials support these results, oncologists might start advising patients on artificial sweetener intake or providing specific supplements to protect treatment effectiveness.
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