A recent clinical trial has highlighted the potential benefits of a fasting-mimicking diet (FMD) for cancer patients, showing it to be safe, feasible, and capable of modulating metabolism and enhancing antitumor immunity. The study, published in Cancer Discovery, involved 101 patients with various tumor types who were undergoing standard anticancer therapies.
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 through 5, totaling up to 1,800 Kcal over five days. This cycle was repeated every three or four weeks for up to eight consecutive cycles, followed by a refeeding period of 16 to 23 days without specific dietary restrictions.
Key findings from the trial include a global compliance rate of 91.8% across all FMD cycles and a low incidence of severe FMD-related adverse events (12.9%), with fatigue being the most common. The study confirmed that short-term severe calorie restriction is safe, feasible, and well-tolerated by the majority of patients, regardless of tumor type or concomitant antitumor therapies.
Metabolically, the FMD regimen led to significant reductions in median plasma glucose concentration (18.6%), serum insulin (50.7%), and serum IGF-1 (30.3%) in 99 evaluable patients. These metabolic modifications remained stable over eight consecutive cycles, mirroring those induced by calorie restriction in preclinical models associated with potent antitumor effects.
Immunologically, the FMD resulted in a significant decrease in circulating immunosuppressive myeloid subpopulations and an increase in activated CD8+ T cells in 38 patients analyzed at the end of a five-day FMD cycle. These effects were observed independently of concomitant antitumor therapies and were also noted in a small group of healthy volunteers.
An interim analysis of another ongoing trial (DigesT) in early-stage breast cancer and melanoma patients revealed a significant increase in tumor-infiltrating CD8+ T cells and other changes indicating a functional switch toward an antitumor immune microenvironment following FMD.
The study's authors emphasize the potential of calorie restriction as a safe, inexpensive, and effective approach that could be easily combined with standard antineoplastic therapies. However, they acknowledge the study's limitations, including the inability to draw conclusions on the antitumor efficacy of calorie restriction due to the heterogeneous group of patients enrolled.
New clinical trials, including the BREAKFAST trial, have been initiated to further investigate the antitumor effects of the FMD dietary approach in cancer patients, aiming to understand if the metabolic and immunological effects induced by calorie restriction can improve the efficacy of antineoplastic therapies and prolong the life expectancy of cancer patients.
This research was funded by Fondazione IRCCS Istituto Nazionale dei Tumori, Associazione Italiana per la Ricerca sul Cancro (AIRC), and the European Union Framework Program Horizon 2020, with support from the Italian Ministry of Health.