Background:Colorectal cancer (CRC) is increasingly driven by metabolic dysregulation and lifestyle factors, creating a need for interventions that target cellular energy mechanics. This review explores the mechanistic rationale for intermittent fasting (IF) as a preventive strategy, which is predicated on the biological logic of autophagy, the internal quality control system of the cell. The central basis is that IF functions as a controlled metabolic stressor; by temporarily restricting nutrient availability, it forces a shift from glucose-dependent growth (anabolic) to stress-resistant repair (catabolic). At the molecular level, this shift is orchestrated by the AMPK‒mTOR axis. Fasting inhibits mTOR (which drives proliferation) and activates AMPK, which triggers autophagy to clear damaged organelles and mitigate oxidative stress. In early carcinogenesis, this process is fundamentally protective, acting as a "genomic caretaker" that removes the toxic debris and inflammation that fuel tumor initiation.

Main text:However, this review reveals a critical dual biological role of autophagy in colorectal tumor prevention and survival. While beneficial for prevention, established tumors can hijack this same recycling mechanism to survive the nutrient starvation induced by fasting, effectively using autophagy to fuel their own persistence and resist therapy. Therefore, while IF successfully counteracts the Warburg effect and reduces inflammation in preclinical models, its clinical success hinges on precision. The central challenge lies in defining the specific metabolic threshold; the exact dose of fasting required to trigger protection in healthy tissue without emboldening existing malignancies, particularly in varying mutational contexts such asKirsten rat sarcoma(KRAS). Conclusion:By withholding a continuous supply of nutrients from premalignant cells, intermittent fasting induces a systemic modification that promotes autophagy, an essential cellular maintenance process eliminating cellular waste and reorganizes the metabolic environment, diminishing the glycolytic flux that supports emerging tumours while simultaneously increasing fatty acid oxidation. The resultant metabolic pressure serves as a formidable physiological barrier, effectively inhibiting early-stage carcinogenesis. Critically, the absence of human dose response data and mutation-stratified trials represents a significant barrier to clinical translation, necessitating biomarker-driven patient selection strategies.