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

Publication ,  Journal Article
Duffy, JS; Caldwell, HG; Hoiland, RL; Howe, CA; Smith, KJ; Bain, AR; MacLeod, DB; Ainslie, PN; Gibbons, TD
Published in: J Cereb Blood Flow Metab
December 7, 2025

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.

Duke Scholars

Published In

J Cereb Blood Flow Metab

DOI

EISSN

1559-7016

Publication Date

December 7, 2025

Start / End Page

271678X251400247

Location

United States

Related Subject Headings

  • Neurology & Neurosurgery
  • 3209 Neurosciences
  • 3202 Clinical sciences
  • 1109 Neurosciences
  • 1103 Clinical Sciences
  • 1102 Cardiorespiratory Medicine and Haematology
 

Citation

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Duffy, J. S., Caldwell, H. G., Hoiland, R. L., Howe, C. A., Smith, K. J., Bain, A. R., … Gibbons, T. D. (2025). Brain glucose extraction is fixed at 10% despite twofold variability in resting cerebral blood flow in healthy humans. J Cereb Blood Flow Metab, 271678X251400247. https://doi.org/10.1177/0271678X251400247
Duffy, Jennifer S., Hannah G. Caldwell, Ryan L. Hoiland, Connor A. Howe, Kurt J. Smith, Anthony R. Bain, David B. MacLeod, Philip N. Ainslie, and Travis D. Gibbons. “Brain glucose extraction is fixed at 10% despite twofold variability in resting cerebral blood flow in healthy humans.J Cereb Blood Flow Metab, December 7, 2025, 271678X251400247. https://doi.org/10.1177/0271678X251400247.
Duffy JS, Caldwell HG, Hoiland RL, Howe CA, Smith KJ, Bain AR, et al. Brain glucose extraction is fixed at 10% despite twofold variability in resting cerebral blood flow in healthy humans. J Cereb Blood Flow Metab. 2025 Dec 7;271678X251400247.
Duffy, Jennifer S., et al. “Brain glucose extraction is fixed at 10% despite twofold variability in resting cerebral blood flow in healthy humans.J Cereb Blood Flow Metab, Dec. 2025, p. 271678X251400247. Pubmed, doi:10.1177/0271678X251400247.
Duffy JS, Caldwell HG, Hoiland RL, Howe CA, Smith KJ, Bain AR, MacLeod DB, Ainslie PN, Gibbons TD. Brain glucose extraction is fixed at 10% despite twofold variability in resting cerebral blood flow in healthy humans. J Cereb Blood Flow Metab. 2025 Dec 7;271678X251400247.
Journal cover image

Published In

J Cereb Blood Flow Metab

DOI

EISSN

1559-7016

Publication Date

December 7, 2025

Start / End Page

271678X251400247

Location

United States

Related Subject Headings

  • Neurology & Neurosurgery
  • 3209 Neurosciences
  • 3202 Clinical sciences
  • 1109 Neurosciences
  • 1103 Clinical Sciences
  • 1102 Cardiorespiratory Medicine and Haematology