Acidosis

Acidosis is a blood pH below 7.4 1. It is a condition that can arise from various factors, including oxygen deficiency, low metabolism, and increased fatty acid oxidation 2. Acidosis is characterized by an increase in the mitochondrial NADH/NAD ratio, which has wide-reaching effects on the metabolic cascade, particularly at the level of the Krebs cycle and the electron transport chain 2.

Acidosis can be caused by adaptation to increased aerobic glycolysis or oxidative phosphorylation, leading to the generation of protons and a decrease in blood pH 4. This condition can promote the proliferation and aggressive phenotypes of cancer cells, particularly in areas with low oxygen levels 4. The Warburg Effect, which describes the increased glycolysis in cancer cells, is actually a driver of cancer, and acidosis precedes and causes subsequent genetic mutations 6.

The Randle cycle, which describes the increased fatty acid oxidation and fatty acid synthesis in response to acidosis, is a positive feedback cycle that can lead to a vicious circle of increased lactic acid production and further acidosis 7. This cycle can be broken by providing extra glucose, which can inhibit fatty acid oxidation and reduce lactic acid production 7.

Acidosis-driven adaptation can also trigger the emergence of aggressive tumor cell subpopulations that exhibit increased invasion, proliferation, and drug resistance 8. Furthermore, acidosis promotes immune escape, which maintains tumor growth 8.