Figure 3.

Molecular processes influenced by a ketogenic diet. (A) The low carbohydrate intake obtained through a ketogenic diet results in the decrement of glucose, insulin, and IGF-1. As a consequence, tumor-promoting pathways, like the PI3K/Akt pathway, are inhibited, as iss the production of ATP in dysfunctional mitochondria. (B) Ketone bodies can be metabolized by cancer cells only in presence of O₂. In the hypoxic condition typical of tumor cells, BHB cannot be metabolized due to the absence of SCOT, BDH1, and ACAT1. (C) BHB favors the gene transcription mediated by Nrf2, with the consequent production of glutathione able to detoxify cells from ROS. In addition, BHB inhibits the effects of several members of the HDAC family, thus inhibiting the proliferation and survival of cancer cells. In parallel, BHB-mediated HDAC-inhibition is responsible for the increase in the cytotoxic effects of chemotherapy on cancer cells.