Brain metabolism during fasting

Summary

This is one of the foundational studies in fuel-substrate biology of human starvation. Three obese subjects underwent five to six weeks of medically supervised starvation while researchers catheterized cerebral blood vessels to measure substrate uptake by the brain. The study established the central observation that during prolonged fasting, β-hydroxybutyrate and acetoacetate progressively displace glucose as the brain's predominant fuel — a finding that overturned the prevailing assumption that the brain had an absolute glucose obligation. The arteriovenous-difference measurements demonstrated that ketone bodies could supply the majority of cerebral oxidative metabolism after multi-week fasting. The paper sits upstream of Cahill 1970, which integrated this brain-substrate work with the broader picture of whole-body fuel adaptation during human starvation, and it remains the cleanest direct measurement of human brain ketone utilization in the published literature decades later.