Fasting-mimicking diets as a strategy to reprogram tumor metabolism: a systematic review

The fasting-mimicking diet (FMD) is a plant-based, low-calorie dietary intervention characterized by reduced carbohydrate, with an emphasis on complex carbohydrates, and protein intake, alongside increased fat intake, designed to replicate the metabolic effects of fasting. Increasing evidence suggests that FMD may modulate tumorigenic pathways, enhancing the efficacy of anticancer treatments while minimizing adverse effects and resistance. This systematic review aimed to evaluate the effects of FMD on tumor metabolism, both as a standalone intervention and in combination with conventional and experimental therapies, and to identify the underlying mechanisms involved. This review was registered in PROSPERO and conducted according to PRISMA guidelines. A comprehensive search of Embase, PubMed/MEDLINE, Scopus, Web of Science, and Science Direct was performed using the term “fasting-mimicking diet.” Inclusion criteria comprised preclinical studies in mice or rats that implemented ≥ 50% caloric restriction and assessed the impact of FMD on tumorigenesis rate, tumor count, volume or weight, survival rate, inflammatory and immune responses, oxidative stress, gene/protein expression linked to antitumor effects, or treatment-related toxicity. FMD alone was associated with delayed tumor progression, reduced metastasis, and downregulation of tumor-promoting biomarkers. When combined with chemotherapy, hormone therapy, targeted therapy, immunotherapy, or vitamin C, FMD enhanced antitumor efficacy through mechanisms involving oxidative stress modulation, improved antioxidant activity, autophagy regulation, and immune and inflammatory responses. These pathways contribute to the differential stress resistance observed in normal cells and increased vulnerability in tumor cells. Preclinical evidence suggests it can suppress tumor growth, reduce metastatic burden, and potentiate the therapeutic effects of multiple treatment modalities by modulating key metabolic pathways.