Effect of fasting on cancer: A narrative review of scientific evidence

Abstract

Emerging evidence suggests that fasting could play a key role in cancer treatment by fostering conditions that limit cancer cells' adaptability, survival, and growth. Fasting could increase the effectiveness of cancer treatments and limit adverse events. Yet, we lack an integrated mechanistic model for how these two complicated systems interact, limiting our ability to understand, prevent, and treat cancer using fasting. Here, we review recent findings at the interface of oncology and fasting metabolism, with an emphasis on human clinical studies of intermittent fasting. We recommend combining prolonged periodic fasting with a standard conventional therapeutic approach to promote cancer-free survival, treatment efficacy and reduce side effects in cancer patients.

Keywords: cancer; diet; fasting; intermittent fasting; oncology; review.

FIGURE 1

Effect of prolonged fasting on different systems of the body on patients. During fasting, the breakdown of liver glycogen reserves (into glucose) and triglycerides (into glycerol and free fatty acids) occurs. The brain progressively adjusts using the ketone bodies in addition to glucose to satisfy its energy requirements, while other tissues use fatty acids for energy. Gluconeogenesis is fueled by ketone bodies created in the liver from fatty acids, fat‐derived glycerol, and amino acids during the ketogenic phase of fasting.

FIGURE 2

Mechanisms of fasting on cancer cells. Fasting suppresses glucose, IGF1, insulin, the MAPK pathway, and heme oxygenase 1 while increasing many autophagy‐regulating components (Atgs, LC3, Beclin1, p62, Sirt1, and LAMP2). Fasting causes cancer cells to release oxidative phosphorylation (OXPHOS) through aerobic glycolysis, which leads to an increase in reactive oxygen species (ROS), p53 activation, DNA damage, and cell death in response to chemotherapy. Fasting activates the autophagic process, which induces cell death through a variety of mechanisms. It also suppresses CD73 and CD39 expression and causes extracellular ATP accumulation, which inhibits Treg cells and the M2 phenotype while activating CD8+ cytotoxic T cells. Fasting also inhibits hemoxygenase 1. It accelerates cellular death and activates CD8+ cytotoxic T lymphocytes, which drive the apoptosis cycle once again.