Human brain β-hydroxybutyrate and lactate increase in fasting-induced ketosis

Ketones are known to constitute an important fraction of fuel for consumption by the brain, with brain ketone content generally thought to be low. However, the recent observation of 1-mmol/L levels of brain β-hydroxybutyrate (BHB) in children on the ketogenic diet suggests otherwise. The authors report the measurement of brain BHB and lactate in the occipital lobe of healthy adults using high field (4-T) magnetic resonance spectroscopy, measured in the nonfasted state and after 2- and 3-day fasting-induced ketosis. A 9-mL voxel located in the calcarine fissure was studied, detecting the BHB and lactate upfield resonances using a ¹H homonuclear editing sequence. Plasma BHB levels also were measured. The mean brain BHB concentration increased from a nonfasted level of 0.05 ± 0.05 to 0.60 ± 0.26 mmol/L (after second day of fasting), increasing further to 0.98 ± 0.16 mmol/L (after the third day of fasting). The mean nonfasted brain lactate was 0.69 ± 0.17 mmol/L, increasing to 1.47 ± 0.22 mmol/L after the third day. The plasma and brain BHB levels correlated well (r = 0.86) with a brain-plasma slope of 0.26. These data show that brain BHB rises significantly with 2- and 3-day fasting-induced ketosis. The lactate increase likely results from ketones displacing lactate oxidation without altering glucose phosphorylation and glycolysis.