Individuals who consume the artificial sweetener sucralose may have reduced responsiveness to cancer immunotherapy, indicating that sweeteners could diminish treatment efficacy.

Immunotherapy enhances the immune system’s ability to identify and eliminate cancer cells, proving vital for many cancers. “When successful, it is highly effective. Patients can feel better, enjoy their lives, and survive for years,” states Abigail over Eichaldergoff from the University of Pittsburgh, Pennsylvania. “Regrettably, not all patients respond well; many cancer types benefit only a limited number of individuals.”

The reasons behind this are unclear, but numerous studies indicate that the gut microbiota plays a critical role in regulating immune responses; prior research has also demonstrated that artificial sweeteners can modify human gut microorganisms.

Consequently, Overacre and colleagues investigated the potential effects of artificial sweeteners on immunotherapy outcomes. They tracked the treatment results of 157 patients who underwent cancer immunotherapy for a minimum of three months. Among these, 91 had advanced melanoma, 41 had non-advanced non-small cell lung cancer, and 25 had melanoma that had been surgically excised but were at risk of recurrence.

Prior to treatment commencement, participants filled out a dietary questionnaire covering the previous month, enabling researchers to estimate their artificial sweetener intake.

Consumption exceeding 0.16 milligrams of sucralose per kilogram daily correlated with poorer treatment outcomes. Participants with advanced melanoma who ingested lower amounts of sucralose experienced longer survival rates, approximately five months more without cancer progression.

In the case of non-small cell lung cancer participants, the survival advantage was about 11 months. For those at higher risk of melanoma recurrence, reducing sucralose intake allowed them to remain cancer-free an additional six months compared to heavier consumers.

Similar outcomes were noted for participants who consumed more than 0.1 milligrams per kilogram daily of Acesulfame K, another artificial sweetener.

The US Food and Drug Administration (FDA) advises limiting sucralose intake to below 5 milligrams per kilogram daily. “Thus, the threshold which seems to reduce the effectiveness of immunotherapy is not half, or even 25%, but rather about 5% of the recommended daily amount,” states Diwakar Dabar from the University of Pittsburgh. “This suggests that even a small amount could have a detrimental effect.”

Additional experiments with mice bearing various types of tumors demonstrated that adding sucralose to their water during immunotherapy expedited tumor growth and decreased survival rates.

Genetic analysis revealed that immune cells activated by immunotherapy were less effective in mice provided with sucralose to combat cancer. Fecal analyses also indicated significant alterations in the rodent gut microbiota, notably increased activity in the metabolic pathway utilized by T cells to process arginine, a crucial amino acid.

The findings imply that sucralose may hinder immunotherapy by reducing arginine levels and modifying gut microbiota in ways that impair T-cell efficacy. Furthermore, experiments demonstrated that arginine supplementation improved survival rates in mice consuming sucralose, bringing them in line with those not consuming artificial sweeteners.

However, it remains uncertain if sucralose exerts similar effects on human gut microbiota and T-cell function. Josam Suez from Johns Hopkins University in Maryland notes, “It is incredibly challenging to derive findings based solely on human data, particularly regarding nutrition and food frequency surveys, while isolating specific impacts of non-nutritive sweeteners and isolating the effects of sucralose on clinical outcomes.”

“We invest considerable resources in the development of new medications, which is costly, challenging, and time-consuming,” remarks Davar. Discovering ways to enhance existing treatments, such as avoiding artificial sweeteners or using arginine supplements, presents a more straightforward and economical approach.

Nonetheless, further investigation is essential to determine if it genuinely enhances patient outcomes. “Hence, it is crucial to maintain support for these research priorities in a challenging funding landscape,” concludes Davar.