A review of fasting effects on the response of cancer to chemotherapy

Background & aims: Studies suggest that fasting before or during chemotherapy may induce differential stress resistance, reducing the adverse effects of chemotherapy and enhancing the efficacy of drugs. In this article, we review the effects of fasting, including intermittent, periodic, water-only short-term fasting, and caloric restriction on the responsiveness of tumor cells to cytotoxic drugs, their protective effect on normal cells, and possible mechanisms of action. Methods: We could not perform a systematic review due to the wide variation in the study population, design, dependent measures, and outcomes (eg, type of cancer, treatment variation, experimental setting, etc.). However, a systematic approach to search and review literature was used. The electronic databases PubMed (MEDLINE), Scopus, and Embase were searched up to July 2020. Results: Fasting potentially improves the response of tumor cells to chemotherapy by (1) repairing DNA damage in normal tissues (but not tumor cells); (2) upregulating autophagy flux as a protection against damage to organelles and some cancer cells; (3) altering apoptosis and increasing tumor cells' sensitivity to the apoptotic stimuli, and preventing apoptosis-mediated damage to normal cells; (4) depleting regulatory T cells and improving the stimulation of CD8 cells; and (5) accumulating unfolded proteins and protecting cancer cells from immune surveillance. We also discuss how ‘fasting-mimicking diet’ as a modified form of fasting enables patients to eat a low calorie, low protein, and low sugar diet while achieving similar metabolic outcomes of fasting. Conclusion: This review suggests the potential benefits of fasting in combination with chemotherapy to reduce tumor progression and increase the effectiveness of chemotherapy. However, with limited human trials, it is not possible to generalize the findings from animal and in vitro studies. More human studies with adequate sample size and follow-ups are required to confirm these findings