Oxidative stress and metabolic flipping CancerDialysis
Author: Sture Hobro
The accelerated metabolism in cancer cells produces a large amount of Reactive Oxygen Spices (ROS) that is countered (redox balance) by an increased utilization of glutathione that needs NADPH for antioxidant production. The increased need for NADPH is met with upregulated glycolysis and glucose, and if glucose is scarce, by increased glutaminolysis and glutamine dependence.
Ketones cannot be used to produce NADPH. Furthermore, when cancer cells are forced to produce energy (ATP) from ketones, this must be done in the mitochondria. Mitochondria in cancer cells are typically few, deformed and dysfunctional in cancer. Furthermore, when ATP is produced in the mitochondria of cancer cells, ROS is increased in cancer cells. Both radio and chemo therapies work mainly by increasing ROS in cancer cells. CancerDialysis works by reducing cancer cell’s ability to handle ROS.
Figure, Schematic ROS handling in healthy cells vs Cancer cells.
A. If ROS is produced, it must be reduced with antioxidants. Accumulated levels of ROS lead to cell death. Therefore, an increased production of ROS must unconditionally be met with an increased production of antioxidants.
B. Typically, healthy cells produce low levels of ROS and can produce antioxidants in more ways than cancer cells can. Furthermore, the use of ketones for ATP reduces ROS production in healthy cells.
C. Cancer cells have a much larger production of ROS and must produce more antioxidants to survive. This is mainly done through glutathione, which is a major antioxidant pathway that can remove ROS. However, the glutathione pathway needs NADPH that is mainly produced both from glycolysis and glutaminolysis.
D. It has been hypothesized that ketogenic condition increases ROS in cancer cells through both reduced glucose levels (a result of KC) and through increased mitochondrial ATP production through mitochondria) When a KC is achieved through CancerDialysis, cancer comes into a problematic situation. Increased ATP from mitochondria leads to increased ROS in cancer. Simultaneously, the potential to handle ROS with antioxidants through the glutathione pathway is reduced when the production of NADPH from glucose and glutamine is hampered during CancerDialysis.
See also
https://lnkd.in/dSeUP-ri
