Cahill · Annual review of nutrition 2006 · narrative review · n=?

Fuel metabolism in starvation.

Cited 1329 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review and autobiographical perspective with mechanism-based reasoning

PubMed 16848698 · doi:10.1146/annurev.nutr.26.061505.111258 · record verified 2026-08-30

What was done

This is an autobiographical and scientific review detailing the historical evolution and physiological understanding of human fuel metabolism during prolonged starvation. The author recounts clinical observations from 1953 to subsequent research characterizing insulin, free fatty acids, glycerol, glucose, lactate, pyruvate, and D-beta-hydroxybutyrate using indirect calorimetry in near-steady starvation states.

What was found

The abstract provides a conceptual and historical overview rather than quantitative experimental data. It highlights that D-beta-hydroxybutyric acid is utilized by the brain to enable survival during prolonged starvation, and notes its proposed therapeutic potential for delivering cellular energy during ischemic and metabolic challenges, such as stroke, myocardial insufficiency, neonatal stress, genetic mitochondrial disorders, and physical fatigue.

Why it matters

The review synthesizes seminal historical insights into how ketone body metabolism sustains human brain function during prolonged nutrient deprivation, framing ketone utilization as a fundamental adaptive mechanism with broad therapeutic implications for metabolic and ischemic disorders.

Limits

The abstract is a narrative, autobiographical review containing no specific sample sizes, trial data, effect estimates, or quantitative metrics. Proposed therapeutic applications represent mechanistic hypotheses rather than clinical trial results within this text.

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