This study investigates brain metabolism during prolonged fasting in three obese patients. Catheterization of cerebral vessels revealed that β-hydroxybutyrate and acetoacetate, ketone bodies, replaced glucose as the primary fuel for brain metabolism. A significantly low respiratory quotient was observed, suggesting a carboxylation mechanism for disposing of carbon from consumed substrates. The study found that the brain's glucose uptake was reduced to 0.26 mmol/L, and there was significant production of lactate and pyruvate. The authors discuss the sources of glucose synthesis during fasting, including nitrogen loss from urine, glycerol from adipose tissue, and lactate and pyruvate from glycolysis. They also highlight the importance of ketone body utilization in maintaining brain function during prolonged fasting. The findings suggest that fat products can satisfy the central nervous system's energy requirements, circumventing the need for gluconeogenesis and nitrogen depletion.This study investigates brain metabolism during prolonged fasting in three obese patients. Catheterization of cerebral vessels revealed that β-hydroxybutyrate and acetoacetate, ketone bodies, replaced glucose as the primary fuel for brain metabolism. A significantly low respiratory quotient was observed, suggesting a carboxylation mechanism for disposing of carbon from consumed substrates. The study found that the brain's glucose uptake was reduced to 0.26 mmol/L, and there was significant production of lactate and pyruvate. The authors discuss the sources of glucose synthesis during fasting, including nitrogen loss from urine, glycerol from adipose tissue, and lactate and pyruvate from glycolysis. They also highlight the importance of ketone body utilization in maintaining brain function during prolonged fasting. The findings suggest that fat products can satisfy the central nervous system's energy requirements, circumventing the need for gluconeogenesis and nitrogen depletion.