Starvation: Metabolic Changes

Abstract

Animals, including humans, invoke a comprehensive programme of hormonal and metabolic adaptations that enable them to withstand prolonged periods of starvation. The brain is only capable of using glucose or ketone bodies as respiratory fuel. During prolonged starvation, the primary source of glucose is gluconeogenesis from amino acids arising from muscle proteolysis. To spare glucose use (and thus spare muscle protein) most tissues of the body utilise fat‐derived fuels (fatty acid and ketone bodies). As starvation progresses ketone bodies also become the major fuel of the brain, again reducing the need for glucose. High concentrations of ketone bodies result in significant ketonuria with ketones excreted as ammonium salts. The ammonia is derived from the catabolism of glutamine in the kidney with the carbon skeleton being recovered as glucose. This well‐orchestrated pattern of metabolism allows a consistent fuel supply to the brain and other tissues during prolonged starvation.

Key Concepts

  • Circulating glucose concentrations do not drop below 3.5 mmol L−1 even in prolonged starvation.
  • During starvation, the brain must be supplied with fuel in the form of glucose or ketone bodies.
  • Carbohydrate reserves are depleted after 24 h of starvation.
  • In prolonged starvation, gluconeogenesis provides the glucose oxidised by the brain.
  • The major substrates for gluconeogenesis are amino acids derived from skeletal muscle protein breakdown.
  • Circulating ketone body concentrations rise during prolonged starvation.
  • During starvation, most tissues utilise fatty acids and/or ketone bodies to spare glucose for the brain.
  • Glucose utilisation by the brain is decreased during prolonged starvation as the brain utilises ketone bodies as the major fuel.
  • High concentrations of ketone bodies result in significant excretion of ketones.
  • Urinary ketones are excreted as ammonium salts derived from the renal metabolism of glutamine with the carbon skeleton being recovered through renal gluconeogenesis.

Keywords: glucose; fatty acids; ketones; brain metabolism; insulin; amino acids

Figure 1. Origin of blood glucose and rates of whole body glucose utilisation during the five phases of glucose homeostasis.
Figure 2. Plasma fuel concentrations during prolonged starvation.
Figure 3. Interorgan fuel metabolism during prolonged starvation.
Figure 4. Daily urinary nitrogen excretion in a male subject who fasted for 38 days.
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Further Reading

Benedict FG (1915) A Study of Prolonged Fasting. Washington: Carnegie Institute.

Cahill GF Jr (1970) Starvation in man. New England Journal of Medicine 282: 668–675.

Cahill GF Jr (2006) Fuel metabolism in starvation. Annual Review of Nutrition 26: 1–22.

Keys A, Brozek J, Henschel A, Mickelsen O and Taylor HL (1950) The Biology of Human Starvation. Minneapolis: University of Minnesota Press.

Ruderman NB, Aoki TT and Cahill GF Jr (1976) Gluconeogenesis and its disorders in man. In: Hanson RW and Mehlman MA, (eds). Gluconeogenesis: Its Regulation in Mammalian Species, pp. 515–532. New York: John Wiley.

Wahren J and Ekberg K (2007) Splanchnic Regulation of Glucose Production. Annual Review of Nutrition 27: 329–345.

Winick M (1979) Hunger Disease: Studies by the Jewish Physicians in the Warsaw Ghetto. New York: John Wiley.

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Watford, Malcolm(Apr 2015) Starvation: Metabolic Changes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000642.pub2]