Can Fatty acids and Ketone Bodies Fuel Cancer? Many people claim that some cancers, especially prostate cancer, can use fatty acids and ketone bodies for energy (ATP production) and that ketogenic metabolic therapy will not work for cancers that can use fatty acids for energy. Research shows that all major cancers depend on the oxygen independent fermentation of the sugar glucose and the amino acid glutamine for energy. Multiple defects in the structure and function of cancer cell mitochondria are responsible for the dependency on fermentation for energy (doi.org/10.1007/s10863-025-1…). These mitochondrial defects reduce energy through oxygen-driven respiration (OxPhos) even in the presence of oxygen thus creating the well-documented addiction of cancer cells to glucose and glutamine for growth. Cancer cells need glucose and glutamine not only to produce energy but also for the synthesis of RNA & DNA. Fatty acids and ketone bodies require oxidation in functional mitochondria for energy production and cannot be fermented or used for RNA or DNA synthesis as can glucose and glutamine. Consequently, fatty acids and ketone bodies cannot replace glucose and glutamine as fuels for ATP synthesis in cancer (doi.org/10.1016/j.isci.2020.…). Fatty acids often accumulate in the cancer cell cytoplasm as lipid droplets because they cannot be effectively oxidized for energy. Please see the beautiful pictures of lipid droplet accumulation in different cancers (rdcu.be/dIhNT). It is important to know, however, that fatty acids can enhance mitochondrial uncoupling. Uncoupling is like pumping air into a tire that contains holes. Uncoupling increases oxygen consumption and the fermentation of glucose and glutamine thus making it appear as if cancer cells can use fatty acids for energy. No evidence has been presented showing that fatty acids or ketone bodies can drive dysregulated tumor cell growth in the absence of glucose and glutamine.