The Impact of Artificial Sweeteners on Cancer Treatment
Artificial sweeteners, widely used in food and beverages, have been found to potentially interfere with the effectiveness of cancer treatments. A study conducted by researchers at the University of Pittsburgh has revealed that sucralose, a popular zero-calorie sweetener known as Splenda, can weaken the impact of immunotherapy in patients with melanoma and non-small cell lung cancer.
Initially developed in the 1970s for individuals with obesity and diabetes, sucralose has become a common ingredient in over 4,500 food and drink products. It is particularly prevalent in diet sodas and low-calorie foods, making up 30% of the sweetener market in the United States. However, recent findings suggest that its widespread use may have unintended consequences for cancer patients undergoing immunotherapy.
Immunotherapy works by enhancing the immune system’s ability to identify and destroy cancer cells. Patients often opt for diet sodas or sugar-free snacks, believing these choices are healthier. However, the presence of sucralose in these products may be counterproductive. The sweetener has been shown to eliminate beneficial gut bacteria while allowing harmful strains to proliferate. This disruption can affect various bodily functions, including digestion, nutrient absorption, immune cell training, vitamin production, and inflammation reduction.
Dr. Diwakar Davar, a senior author of the study and an oncologist at UPMC, emphasized the implications of their findings: “We found that sucralose impeded the effectiveness of immunotherapies across a range of cancer types, stages, and treatment modalities. These observations raise the possibility of designing prebiotics, such as targeted nutrient supplementation for patients who consume high levels of sucralose.”
The research team used mouse models to investigate how sucralose affects the microbiome. They discovered that the sweetener disrupts the balance of gut bacteria, leading to reduced levels of essential amino acids like arginine. Arginine plays a critical role in fueling immune cells, and its depletion can result in dysfunctional CD8+ T cells, which are vital for fighting cancer. This disruption also diminishes the effectiveness of anti-PD-1 immunotherapy, a class of cancer treatments that includes drugs like Keytruda and Opdivo.
Dr. Abby Overacre, the lead author of the study and an immunology professor at Pitt and UPMC Hillman, explained the impact of sucralose on T cells: “When arginine levels were depleted due to sucralose-driven shifts in the microbiome, T cells couldn’t function properly. As a result, immunotherapy wasn’t as effective in mice that were fed sucralose.”
To determine the relevance of these findings in humans, the researchers surveyed 132 advanced cancer patients, including 91 with melanoma and 41 with lung cancer, as well as 25 people at high risk of melanoma recurrence. Participants reported consuming diet sodas, using artificial sweeteners in coffee and tea, and eating low-calorie snacks. High sucralose intake was defined as anything above 0.16 mg per kilogram of body weight per day. For a 155-lb person, this equates to less than a single packet of Splenda.
Patients with melanoma and lung cancer who consumed at least this amount of sucralose had a 3.2 times higher risk of their cancer progressing faster and experienced less tumor shrinkage in response to immunotherapy. Similarly, those at risk of melanoma recurrence showed a higher likelihood of cancer returning after surgery and immunotherapy, along with fewer signs of a robust immune response.
Experiments in mice revealed that the microbiome disruption caused by sucralose was the main factor behind the altered immune responses. When feces from sucralose-fed mice were transplanted into untreated mice, the latter exhibited similar poor immune responses. However, when scientists supplemented low arginine levels with citrulline—a compound found in melons, pumpkins, and legumes—T cells regained their ability to kill cancer cells, reversed resistance to immunotherapy, and tumors shrank.
The study’s findings were published in the journal Cancer Discovery. Dr. Overacre noted the practical implications: “It’s easy to say, ‘Stop drinking diet soda,’ but when patients are being treated for cancer, they are already dealing with enough, so asking them to drastically alter their diet may not be realistic. We need to meet patients where they are. 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 researchers plan to launch a clinical trial to explore whether citrulline supplements, which boost arginine levels more effectively than arginine itself, influence the gut microbiome and anti-tumor immune response in patients. Their work highlights the importance of considering dietary factors in cancer treatment and opens new avenues for improving patient outcomes through targeted interventions.
