Table 2

Targeting tumor glycolysis through carbohydrate restriction

Factors promoting glycolysisCHO restriction as a metabolic strategy to target these factors
High blood glucose levels (Up-regulation of glycolytic enzymes)Blood glucose ↓, fatty acids ↑ (Fatty acids inhibit key glycolytic enzymes)
HypoxiaBlood glucose ↓, ketones ↑ (Poor nutrient supply to hypoxic cells; hypoxic cells unable to efficiently oxidize ketones)
Oncogenic signaling (Insulin/IGF-1-PI3K-Akt-mTOR)Blood glucose ↓, insulin ↓ (Counteracts PI3K pathway; also activates AMPK, inhibiting mTOR)
Ketones ↑ (Class I and II HDAC inhibitors)
Inflammation (High blood glucose levels and ROS promote inflammatory cytokine release)Blood glucose ↓ (Decreases ROS and inflammation)