Artificial sweetener's potential impact on cancer treatment efficacy underscored
In a groundbreaking study, researchers from the University of Pittsburgh and UPMC Hillman Cancer Center have found a potential link between the artificial sweetener sucralose and the success of cancer immunotherapy, particularly in patients with advanced melanoma and non-small cell lung cancer (NSCLC).
The study, published in Cancer Discovery, reveals that higher sucralose intake could correlate with an inferior response to immunotherapy and shorter progression-free survival in these patients. Specifically, those consuming more than 0.16 milligrams of sucralose per kilogram of body weight a day had significantly poorer outcomes.
The research, which involved both preclinical mouse models and prospective human studies, found that mice fed sucralose had weaker immune responses to anti-PD-1 immunotherapy, a common treatment for melanoma and lung cancer. In humans, higher sucralose intake corresponded with poorer tumor responses and outcomes during immunotherapy for advanced/metastatic melanoma and NSCLC.
The mechanism appears linked to sucralose-induced changes in the gut microbiome, which impair T-cell function critical to immunotherapy efficacy. Sucralose-fed mice showed a surge in gut bacteria that break down arginine, an amino acid essential for T cell metabolism and function. This reduction in arginine levels could make it harder for the immune system to attack tumors, even when boosted by immunotherapy.
However, there is a potential clinical intervention. Supplementing the mice's water with arginine or citrulline (which the body converts to arginine) reversed the negative effects of sucralose. The researchers plan to test citrulline in clinical trials, since it may raise arginine levels more effectively.
The study analyzed dietary data from 157 people receiving immune checkpoint inhibitor therapy. In advanced melanoma, patients in the low-sucralose group went a median of five months longer without their cancer progressing. In NSCLC, the difference was 11 months. Among patients at high risk of melanoma recurrence, the low-sucralose group stayed cancer-free for six months longer.
The study on sucralose and cancer immunotherapy was conducted on mice with melanoma or adenocarcinoma. Fecal microbiome transplants from healthy, treatment-responsive mice into sucralose-fed ones reversed the effect, suggesting the gut microbes themselves were the key intermediaries.
For cancer patients on immunotherapy, especially those with melanoma or NSCLC, cutting back on sucralose or finding ways to offset its effects could be a low-cost way to improve treatment outcomes. Arginine and citrulline are widely available as over-the-counter supplements.
While data are robust in preclinical models and supported by prospective patient cohorts, further clinical trials are needed to confirm these findings and validate arginine supplementation or dietary recommendations for patients receiving immunotherapy.
- The study published in Cancer Discovery links the artificial sweetener sucralose to inferior responses in cancer patients undergoing immunotherapy, especially those with advanced melanoma and non-small cell lung cancer.
- The research shows that higher sucralose intake could lead to shorter progression-free survival and poorer outcomes in these patients, with those consuming more than 0.16 milligrams per kilogram of body weight a day experiencing significantly poorer outcomes.
- The study found that mice fed sucralose had weaker immune responses to anti-PD-1 immunotherapy, a common treatment for melanoma and lung cancer, due to sucralose-induced changes in the gut microbiome that impair T-cell function critical to immunotherapy efficacy.
- A potential clinical intervention for the negative effects of sucralose on cancer immunotherapy is supplementing mice's water with arginine or citrulline, which can raise arginine levels and potentially reverse the negative effects of sucralose.
- The study, which analyzed dietary data from 157 people receiving immune checkpoint inhibitor therapy, shows that cutting back on sucralose or finding ways to offset its effects could be a low-cost way to improve treatment outcomes for cancer patients on immunotherapy, especially those with melanoma or NSCLC, as arginine and citrulline are widely available as over-the-counter supplements.
