Cancer Dialysis and hybrid cars/cells
Author: Sture Hobro
Everyone knows about hybrid cars that can be fueled either with electricity or gas. Few know that this is also true for human cells, which can work on glucose extracted from carbohydrates or ketones extracted from fat when glucose is scarce.
Healthy human cells can get energy (ATP) in two steps from glucose: partly from fermentation of glucose in glycolysis (~ 5% of ATP), and most energy comes from the TCA cycle and OXPHOS (~95% of ATP from glucose). This is depicted in Figure 1. In figure 2 you can see what happens when healthy cells use ketones instead.
Figures 3 and 4 depict cancer cells fueled either with glucose (2) during normal metabolic conditions or ketones (3) during starvation-like conditions.
In Figure 3, you also see how cancer cells have largely abandoned the use of the TCA cycle for energy production when utilizing glucose and rely heavily on an upregulated glycolysis for ATP (the Warburg effect).
This has consequences and cancer cells export a lot of hydrogen ions and lactate out from the cancer cell and creates a Tumor MicroEnvironment (TME) with a low pH and high lactate levels. This is an unfriendly environment for important immune cells. A second effect is that increased glycolysis gives rise to an abundance of substrate for antioxidant production in cancer cells.
When the cancer cell hybrid system is switched to work with ketones, (ketogenic conditions), figure 4, the export of hydrogen ions and lactate is stopped, and the content in TME is corrected. Simultaneously, the abundance of substrate for antioxidant production is reduced, and increased reliance on the TCA cycle is needed in the absence of glucose. This typically leads to increased oxidative stress in cancer cells since both the TCA cycle as such and more importantly, the ETC cycle where OXPHOS takes place, are compromised in most cancer cells.
Conclusion 1: Radio and chemo therapies work largely by increasing oxidative stress. By inducing a ketogenic condition with CancerDialysis this may augment those treatments by reducing cancer’s ability to counteract this – with increased antioxidant production. Less antioxidants can be produced by ketones!
Conclusion 2: For immune therapies the correction of TME will play a key role by reducing the alteration seen in the TME that reduce the effectiveness of important immune cells, and correcting pH and lactate levels may increase the response rate from immune therapies.
