Research paper
Owen OE, Morgan AP, Kemp HG, Sullivan JM, Herrera MG, Cahill GF Jr. Brain metabolism during fasting. Journal of Clinical Investigation. 1967 Oct;46(10):1589-1595. doi:10.1172/JCI105650
Why we cite it
The paper sets out a paradox: studies after brief postabsorptive periods had found glucose "the only significant energy-yielding substrate consumed by brain", yet people can fast longer than their carbohydrate and protein could supply it; "This study was designed to clarify the apparent paradox". (Corrected 2026-09-10 from "Study that overturned the prevailing assumption that the brain is an obligate glucose consumer": obligate is not in the paper and overturned is the library's verdict.) By catheterizing cerebral blood vessels in three obese patients after 5–6 weeks of starvation, demonstrated that ketone bodies (beta-hydroxybutyrate and acetoacetate) replace glucose as the predominant brain fuel during prolonged fasting. The authors argue this is how humans conserve muscle protein during starvation (survival "necessitates maximal sparing of nitrogen depots, of which the major portion is muscle"), and that ketone use means "fat products may even satisfy the central nervous system's substrate requirement, and therefore circumvent the need for gluconeogenesis and concomitant nitrogen depletion" (hedge restored 2026-09-10 from "the brain's ketone use reduces the need for gluconeogenesis from amino acids").