Fasting-Mimicking Diet Shows Promise in Boosting Anti-Tumor Immunity in Cancer Patients

A clinical trial published in Cancer (search)Search disease Discovery, a journal of the American Association for Cancer Research, indicates that a fasting-mimicking diet (FMD) is safe and may modulate metabolism and boost anti-tumor immunity in cancer patients receiving standard-of-care therapy. The study, involving 101 patients with various cancer types, found that short-term, severe calorie restriction resulted in biological effects that could be helpful in cancer treatment.

Safety and Feasibility of Fasting-Mimicking Diet

The FMD regimen consisted of a five-day, low-carbohydrate, low-protein, plant-derived diet, providing up to 600 Kcal on day 1 and up to 300 Kcal on days 2-5, totaling up to 1,800 Kcal. This cycle was repeated every three to four weeks for up to eight cycles. The trial demonstrated a 91.8 percent compliance rate, with only 12.9 percent of patients experiencing severe FMD-related adverse events, the most common being fatigue.

"Our results from a first-in-human clinical trial showed that a scheme of severe short-term calorie restriction was safe and biologically active in patients, and that its activity likely involved the activation of immune responses," said Claudio Vernieri, MD, PhD, a medical oncologist at Fondazione IRCCS Istituto Nazionale dei Tumori and the director of the Metabolic Reprogramming in Solid Tumors program at IFOM.

Metabolic and Immunological Effects

The study revealed significant metabolic changes, including a median reduction of 18.6 percent in plasma glucose, 50.7 percent in serum insulin, and 30.3 percent in serum IGF-1 (search)Search target concentrations. These metabolic modifications mirror those observed in preclinical models, where calorie restriction is associated with potent anti-tumor effects.

Furthermore, analysis of 38 patients at the end of a five-day FMD cycle showed a significant decrease in circulating immunosuppressive myeloid subpopulations and an increase in activated CD8+ T cells. These effects occurred independently of concomitant anti-tumor therapies and were also observed in a small group of healthy volunteers.

Impact on Tumor Microenvironment

An interim analysis of the DigesT trial, involving early-stage breast cancer (search)Search disease and melanoma (search)Search disease patients, revealed a significant increase in tumor-infiltrating CD8+ T cells and other changes, indicating a functional shift toward an anti-tumor immune microenvironment following FMD. This suggests that the FMD-induced immunomodulatory effects are coherent, originating in the blood and propagating to the tumor.

"Severe calorie restriction generated a metabolic ‘shock’ that activated several populations of immune cells that could boost the antitumor activity of standard antineoplastic treatments," said Licia Rivoltini, MD, head of the Immunotherapy of Human Tumors Unit at Fondazione IRCCS Istituto Nazionale dei Tumori.

Future Directions

While the study demonstrates the safety and potential benefits of FMD, the authors acknowledge that it does not allow for conclusions on the anti-tumor efficacy of calorie restriction due to the heterogeneous patient population and varied concomitant anti-cancer (search)Search disease therapies. New clinical trials, including the BREAKFAST trial, have been initiated to investigate the anti-tumor effects of FMD in cancer patients.

Filippo de Braud, MD, director of the Oncology and Hematology Department of Fondazione IRCCS Istituto Nazionale dei Tumori and professor of medical oncology at the University of Milan, commented on the importance of the reversible weight loss observed during the study, excluding the risk of progressive weight loss and malnourishment, which can reduce the efficacy of anti-cancer (search)Search disease therapies and survival.