Starvation in Man

Summary

George Cahill's 1970 NEJM review remains the single most important paper ever written on human starvation metabolism. Drawing on his lab's careful in-patient studies of obese volunteers undergoing therapeutic fasts (then a common obesity treatment), Cahill mapped the day-by-day fuel transitions that allow humans to survive weeks-to-months of food deprivation: the shift from glucose to fatty acid oxidation in muscle within hours of the last meal, the rise of hepatic ketogenesis over the first few days, and — most consequentially — the progressive switch by the brain from preferring glucose to preferring β-hydroxybutyrate and acetoacetate as primary fuels. This brain-ketone adaptation is what protects body protein. Without it, prolonged fasting would deplete muscle within days through gluconeogenesis demand; with it, daily protein loss falls to a trickle, fat becomes the dominant fuel, and survival extends to the limits of fat reserves. The paper identifies insulin as the principal regulatory hormone of the transitions and remains the foundational citation for almost every modern paper on fasting physiology.