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 (CMR(glucose)) compared with oxygen consumption (CMR(O2)) was documented in children's brain and suggestive of non-oxidative metabolism of glucose. Several candidate metabolic pathways may explain the CMR(glucose)-CMR(O2) mismatch, and lactate production is considered a major contender. The ~33% excess CMR(glucose) equals 0.18 μmol glucose/g/min and predicts lactate release of 0.36 μmol/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 CMR(glucose)-CMR(O2) mismatch itself by using updated lumped constant values. The calculated cerebral metabolic rate of lactate indicated a net influx of 0.04 μmol/g/min, or in terms of CMR(glucose), of 0.02 μmol 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 [(18)F]fluorodeoxyglucose has a high impact on calculated CMR(glucose) and use of updated values alters or eliminates the CMR(glucose)-CMR(O2) 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.