Figure 3.

The relationship between plasma ketones (shown here only as β-hydroxybutyrate; β-HB) and cerebral metabolic rate of ketones (CMR_β-HB; left hand y-axis) over a physiological range of plasma β-HB. In the original studies, two different methods were used to calculate CMR_β-HB: (i) PET (n=5 points collected close together in the bottom left of the graph between β-HB values of 0.0–0.2 mM; ○) [207], and (ii) arterio-venous difference taking into account cerebral blood flow – (n=26; ◇ [19]), and (n=10 controls □, and n=12 presumed Alzheimer’s disease ▲) [21]. Arterio-venous difference in brain β-HB uptake was reportedly the same in Alzheimer’s disease as in the controls [21]. Combined together, the 53 data points from these three studies provide the following equation of the line for CMR_β-HB over a plasma β-HB concentration range from 0.0–1.5 mM: y = 1.677x + 0.0454 (r = 0.638; p < 0.0001). The right hand y axis shows the percentage contribution of ketones to the energy requirements of the whole human brain over a physiological range of plasma β-HB. The intercept of ~18% of brain energy requirements being met by β-HB at a plasma β-HB concentration of 1.5 mM is corroborated by two additional papers that reported arterio-venous differences across the brain to derive CMR_β-HB for higher plasma β-HB values averaging 2 and 7 mM, achieved during β-HB infusion [20] and experimental starvation [22], respectively.