Fasting-mimicking diets (FMD) — comprising cyclic fasting or calorie-restricted low-protein and low-carbohydrate diets — enhance or supplement antitumor therapies in mice by reducing blood glucose, insulin and IGF1, and inhibiting cancer cell growth and proliferation. Vernieri et al. report the results of a first-in-human clinical trial investigating the safety, feasibility and biological effects of FMD in 101 patients with cancer receiving standard-of-care antitumor therapies. Patients underwent a median of 4 FMD cycles (5-day FMD followed by 16–23 days refeeding) alongside chemotherapy (73 patients), endocrine therapy (13), immunotherapy (3), targeted therapy (2), radiotherapy (1), radionucleotide therapy (1) and best supportive care (8). Grade 3/4 FMD-related adverse event incidence was 12.9% (90% CI 7.8–19.7%), and global compliance rate to FMD was 91.8%. FMD reduced median plasma glucose (−18.6%, range −63.1% to +67.8%), insulin (−50.7%, range −91.3% to +69.7%) and serum IGF1 (−30.3%, range −72.3% to +139.8%) independently of cancer type, stage and treatment. In two patient subsets (38 patients with various cancer types and 13 patients with advanced triple-negative breast cancer), FMD also reduced immunosuppressive monocyte populations while increasing effector T cell and natural kill cell populations. Interim analysis of pre-FMD and post-FMD tumor biopsy samples from 22 patients with breast cancer enrolled in the separate DigesT trial demonstrated intratumoral effects of FMD: glucose, insulin and IGF1 levels were reduced, tumor-infiltrating T cell and other immune cell populations were increased, and T cell cytotoxicity was increased. These results suggest that FMD is safe and feasible, although care must be taken to select patients not underweight or at risk of malnourishment. These findings also highlight the importance of ongoing and future clinical trials investigating FMD in cancer treatment.
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