Revisiting the Warburg Effect: Diet-Based Strategies for Cancer Prevention

Table 1

Mechanisms for antitumor effects of the ketogenic diet.

Physiological change	Mechanisms for antitumor effect
Reduce insulin level and signaling	Lower insulin levels reduce oncogenic signaling pathways: PI3K-PKB-mTOR, RAS-RAF-MAPK.
Decrease blood glucose	Glucose restriction sensitizes tumor cells to radiotherapy and chemotherapy.
Enhance fatty acids and ketone bodies	Preclinical inhibition of glycolysis through fatty acids and ketone bodies (Randle cycle) is problematic for tumor cells with dysfunctional mitochondria that rely on glycolysis for energy and antioxidant production.
Increase β-hydroxybutyrate	β-Hydroxybutyrate is an endogenous histone deacetylase inhibitor with the potential to epigenetically alter protein expression in tumors towards a less aggressive phenotype.
Increase decanoic acid (if medium chain triglyceride oil is part of the ketogenic diet)	Decanoic acid is a PPARg agonist and inhibits AMPA glutamate receptors, which are overexpressed by human glioblastoma cells.

Adapted from [77].