Study Reveals Common Sweetener May Undermine Cancer Treatments

A widely used artificial sweetener, favored by many, appears to diminish the effectiveness of cancer therapies.

Research from the University of Pittsburgh indicates that sucralose, a no-calorie sweetener, could impair immunotherapy effectiveness in patients with melanoma and non-small cell lung cancer.

Initially created in the 1970s for individuals dealing with obesity and diabetes, sucralose—more commonly recognized as Splenda—has found its way into countless products. It’s now included in over 4,500 food and drink items, such as diet sodas and low-calorie snacks, and holds about 30 percent of the sweetener market in the United States.

Cancer patients undergoing immunotherapy, a treatment designed to activate the immune system against cancer cells, might opt for diet beverages or sugar-free snacks, thinking they’re making healthier choices.

However, findings suggest that sucralose can diminish beneficial gut bacteria while allowing harmful bacteria to thrive. This imbalance negatively affects digestion, nutrient absorption, and immune cell training, as well as serotonin production and inflammation control.

Dr. Diwakar Davar, an oncologist and hematologist at UPMC, mentioned, “We found that sucralose impeded the effectiveness of immunotherapies across various cancer types and treatment stages.” He added that these results could pave the way for developing prebiotics or nutrient supplements for patients who consume high levels of sucralose.

The research team utilized mouse models—some with lung cancer and others with melanoma—to explore how sucralose impacted their gut microbiomes, discovering that the sweetener disrupted their delicate balance.

This disruption led to a decrease in key amino acids like arginine, essential for immune cell function. It also caused dysfunction in CD8+ T cells, crucial for combating cancer, and weakened responses to anti-PD-1 immunotherapies, which include well-known drugs such as Keytruda and Opdivo.

Dr. Abby Overacre, an immunology professor at the university, noted, “When arginine levels decreased due to sucralose-induced microbiome changes, T cells couldn’t function properly. Consequently, immunotherapy was less effective in mice given sucralose.”

To gauge the implications for humans, they surveyed 132 advanced cancer patients—91 with melanoma and 41 with lung cancer—regarding their sucralose intake, alongside 25 individuals at high risk for melanoma recurrence.

Participants reported drinking diet sodas, sweetening coffee and tea with sucralose, and consuming low-calorie snacks. They defined high intake as over 0.16 mg per kilogram of body weight daily, which for a 155-pound individual is less than one packet of Splenda.

Those with melanoma and lung cancer consuming the defined amount of sucralose showed a 3.2 times higher risk of faster cancer progression and less tumor shrinkage following immunotherapy.

Patients at risk of melanoma recurrence who consumed similar amounts of sucralose also exhibited a higher likelihood of cancer reoccurrence after treatment and showed fewer signs of a robust immune response to tumors.

Experiments with mice revealed that microbiome disruption from sucralose was key to changes in cancer-fighting T cells, which were deprived of arginine. When researchers transferred fecal matter from mice fed sucralose to untreated mice, the latter exhibited a similarly poor immune response to immunotherapy.

Interestingly, when scientists supplemented low arginine levels using citrulline—an amino acid found in foods like melons and legumes—T cells were able to recover their cancer-fighting capabilities, resist immunotherapy, and experience tumor reduction.

These findings have been published in the journal Cancer Discovery. Dr. Overacre remarked, “Telling patients to stop drinking diet soda is easy, but those undergoing cancer treatment are already facing enough challenges, so a drastic dietary change may not be feasible.”

She emphasized the importance of meeting patients where they are and expressed excitement about the potential of arginine supplementation as a straightforward solution to mitigate sucralose’s adverse effects on immunotherapy.

The team aims to initiate a clinical trial to examine whether citrulline supplements, which elevate arginine levels more effectively than arginine itself, can influence gut microbiomes and enhance the immune response against tumors in patients.