Trajectories of Brain Lactate and Re-visited Oxygen-Glucose Index Calculations Do Not Support Elevated Non-oxidative Metabolism of Glucose Across Childhood

Brain growth across childhood is a dynamic process associated with specific energy requirements. A disproportionately higher rate of glucose utilization (CMRglucose) compared with oxygen consumption (CMRO2) was documented in children’s brain and suggestive of non-oxidative metabolism of glucose. Several candidate metabolic pathways may explain the CMRglucose-CMRO2 mismatch, and lactate production is considered a major contender. The ~33% excess CMRglucose equals 0.18 mol glucose/g/min and predicts lactate release of 0.36 mol/g/min. To validate such scenario, we measured the brain lactate concentration (Lac) in 65 children to determine if indeed lactate accumulates and is high enough to 1) account for the glucose consumed in excess of oxygen and 2) support a high rate of lactate efflux from the young brain. Across childhood, brain Lac was lower than predicted, and below the range for adult brain. In addition, we re-calculated the CMRglucose-CMRO2 mismatch itself by using updated lumped constant values. The calculated cerebral metabolic rate of lactate indicated a net influx of 0.04 mol/g/min, or in terms of CMRglucose, of 0.02 mol glucose/g/min. Accumulation of Lac and calculated efflux of lactate from brain are not consistent with the increase in non-oxidative metabolism of glucose. In addition, the value for the lumped constant for 18Ffluorodeoxyglucose has a high impact on calculated CMRglucose and use of updated values alters or eliminates the CMRglucose-CMRO2 mismatch in developing brain. We conclude that the presently-accepted notion of non-oxidative metabolism of glucose during childhood must be revisited and deserves further investigations.