Malignant
brain tumors are a significant health problem in children and adults and are often unmanageable. As a metabolic disorder involving the dysregulation of glycolysis and respiration, malignant
brain cancer is potentially manageable through changes in metabolic environment. A radically different approach to
brain cancer management is proposed that combines metabolic control analysis with the evolutionarily conserved capacity of normal cells to survive extreme shifts in physiological environment. In contrast to malignant
brain tumors that are largely dependent on glycolysis for energy, normal neurons and glia readily transition to
ketone bodies (
beta-hydroxybutyrate) for energy in vivo when
glucose levels are reduced. The bioenergetic transition from
glucose to
ketone bodies metabolically targets
brain tumors through integrated anti-inflammatory, anti-angiogenic, and pro-apoptotic mechanisms. The approach focuses more on the genomic flexibility of normal cells than on the genomic defects of
tumor cells and is supported from recent studies in orthotopic mouse
brain tumor models and in human pediatric
astrocytoma treated with dietary energy restriction and the
ketogenic diet.