Brain glucose extraction is fixed at 10% despite twofold variability in resting cerebral blood flow in healthy humans

In the resting, non-stimulated brain, metabolic demands are met exclusively by the delivery and extraction of glucose and oxygen at an ~6:1 ratio. Amongst healthy people at rest, there is marked variability in resting global cerebral blood flow (CBF) yet remarkably stable concentrations of circulating glucose and oxygen. Thus, we would expect interindividual variability in resting CBF to be inversely related to oxygen and glucose extraction, maintaining oxidative glucose metabolism. Herein, we investigated the fundamental relationship between CBF and substrate extraction in 75 healthy adults (27.3 ± 4.8 years) with resting measures of CBF and cross-brain concentrations of oxygen and glucose. We observed that the marked interindividual variability in CBF (<500 to >1200 mL/min) is inversely related to oxygen extraction (R² = 0.85, p = 0.005) but not glucose extraction (R² = 0.30, p = 0.273). The metabolic rates of oxygen and glucose (CMRO₂ and CMRglc) are both directly correlated with CBF. However, there was a 1.6-fold greater slope for CMRglc-CBF, compared to CMRO₂-CBF (p = 0.040). These findings indicate that the resting brain extracts more oxygen when delivery is low, maintaining stable CMRO₂ and ATP production. Despite glucose being the primary oxidized substrate, the brain's ability to adjust its extraction is limited, making CMRglc more dependent on delivery.