Inverse relationship between brain glucose and ketone metabolism in adults during short-term moderate dietary ketosis: A dual tracer quantitative positron emission tomography study

Ketones (principally β-hydroxybutyrate and acetoacetate (AcAc)) are an important alternative fuel to glucose for the human brain, but their utilisation by the brain remains poorly understood. Our objective was to use positron emission tomography (PET) to assess the impact of diet-induced moderate ketosis on cerebral metabolic rate of acetoacetate (CMRa) and glucose (CMRglc) in healthy adults. Ten participants (35 ± 15 y) received a very high fat ketogenic diet (KD) (4.5:1; lipid:protein plus carbohydrates) for four days. CMRa and CMRglc were quantified by PET before and after the KD with the tracers, 11C-AcAc and 18F-fluorodeoxyglucose (18F-FDG), respectively. During the KD, plasma ketones increased 8-fold (p = 0.005) while plasma glucose decreased by 24% (p = 0.005). CMRa increased 6-fold (p = 0.005), whereas CMRglc decreased by 20% (p = 0.014) on the KD. Plasma ketones were positively correlated with CMRa (r = 0.93; p