The Randle Cycle (Randle Effect)

The Randle Cycle, also known as the Randle Effect, is the inhibition of glucose oxidation by an excess of fatty acids, leading to decreased metabolic efficiency. Estrogen promotes this effect 1.

This phenomenon was first described by Philip Randle, who noted that increasing the amount of fat in the bloodstream decreases the ability of cells to metabolize glucose, resulting in decreased glucose tolerance, similar to diabetes 2. The Randle Cycle is characterized by the instantaneous diabetogenic effect of fatty acids, which blocks the use of glucose 3.

Research has shown that the Randle Cycle is linked to increased fatty acid oxidation (FAO), which can lead to a vicious cycle of decreased glucose metabolism and increased fatty acid synthesis (FAS) 2. This cycle is also associated with mitochondrial dysfunction, including hyperacetylation of mitochondrial proteins, overfeeding, and downregulation of Complex I of the electron transport chain (ETC) 7.

The Randle Cycle has been implicated in various diseases, including cancer, where it is linked to the Warburg Effect, a process in which cancer cells preferentially use glycolysis for energy production, even in the presence of oxygen 2. The Warburg-Randle Cycle, as proposed by Georgi Dinkov, captures the intimate relationship between glucose and fat oxidation in cancer cells 7.

In contrast, research has shown that providing extra glucose can break the Randle Cycle and improve metabolic function 6. Additionally, blocking systemic acidosis, such as with baking soda, has been shown to have profoundly therapeutic effects in cancer treatment 8.