Intermittent Fasting (IF/TRE) for Stage IV Cancer
Also known as: IF, Time-restricted eating, TRE, 16:8 fasting, 5:2 diet
Fasting before chemotherapy may protect normal cells while sensitizing cancer cells through differential stress resistance.
Mechanism of Action
Fasting-induced IGF-1 reduction activates protective stress responses (FOXO, Nrf2) in normal cells but not in cancer cells (which have constitutively active growth signaling). This 'differential stress resistance' protects normal tissue during chemotherapy while cancer cells remain vulnerable.
General mechanism: Temporal caloric restriction. AMPK activation, mTOR inhibition, autophagy induction, SIRT1 activation, ketogenesis, differential stress resistance.
Current Evidence
Phase I/II studies show fasting (48-72h before chemo) reduces chemotherapy side effects. De Longo fasting-mimicking diet trials show feasibility. Differential stress resistance confirmed in human studies.
Clinical Status: Phase I/II for chemo-protective effects. Fasting-mimicking diet trials ongoing.
Safety Profile
Generally safe for healthy individuals. Contraindicated in eating disorders. ALS: caloric maintenance critical. Diabetics: medication adjustment needed.
Key Research Questions
- Can fasting-induced differential stress resistance improve chemotherapy efficacy?
- What fasting duration optimizes cancer cell sensitization?