Reviewed and revised 29 January 2017
- An adaptive hypometabolic state
- Unlike most other species, human brains can also use ketones as fuel, so muscle (i.e. protein) can be relatively spared in favour of fat as the primary energy fuel during prolonged starvation
- Physiological goal to preserve plasma glucose levels for brain metabolism; the brain can also use ketones as a fuel
- Distinct from the stress response
- liver: glycogenolysis: glycogen -> glucose under action of glucose-6-phosphatase; gluconeogenesis: glycerol and gluconeogenic amino acids -> glucose
- decreased insulin, increased glucagon -> increased hepatic glycogenolysis, gluconeogenesis, amino acid uptake, ureagenesis & protein catabolism
- catecholamine secretion -> stimulation of lipolysis & glucogenolysis
- cortisol secretion -> enhanced extra-hepatic protein catabolism & hepatic utilisation of amino acids for gluconeogenesis
- glycogen stores are depleted by ~24h (8,000 kJ in 70kg male)
- remaining glucose shunted to brain, RBCs, inflammatory cells, wound tissue (glucose metabolism is shut down in other tissues)
- amino acid demand is met by skeletal muscle proteolysis
- respiratory quotient falls to 0.7 (CO2/O2 ratio when fat is catabolised)
- 500mL fluid deficit met through venous capacitance vessels in lower limb & increased ADH production.
48h to 2 weeks
- body starts to conserve protein
- FFAs & TG’s are used as fuel sources (in 70kg adult, there is enough energy for basal metabolism for 24 hrs)
- lipase in adipose tissue hydrolyses TG’s -> long chain FFA’s & glycerol
- some FFAs -> used directly
- some FFAs -> liver and metabolised to ketones (acetoacetic acid & beta hydroxybutyric acid) -> used by most tissues & as a back up substrate in the brain
- Cori cycle: allows lipid-derived energy in glucose to be shuttled to peripheral glycolytic tissues, which in turn send the lactate back to the liver for resynthesis to glucose.
- brain switches to ketoacids for fuel (30% of energy at 3 days, 70% by 4 days)
- with prolonged fasting amino acids from skeletal muscle become predominant substrate for gluconeogenesis
- reduced metabolic rate
- body weight reduced to about 85% of normal
- starvation occurs when fat stores are depleted and proteolysis is the only remaining energy source (occurs sooner in lean individuals)
STARVATION RESPONSE VERSUS STRESS RESPONSE COMPARISON
Key features of the starvation and stress responses compared and contrasted:
|Starvation response||Stress Response|
|Overview||Overall an adaptive hypometabolism whereby fat is used as the primary energy fuel and protein is relatively spared||Endogenous ‘stress’ mediators such as cortisol, catecholamines, GH, glucagon and cytokines are increased and contribute to the pattern of metabolism and mobilisation of the fuel required|
|Metabolic state||Hypometabolic state (initially marginal increase in catabolism)||Increased catabolism|
|Carbohydrates||Initially only marginal increase in glycogenolysis or gluconeogensis|
After 24-48hrs gluconeogenesis does increase from peripherally released amino acids
and glycerol (from lipolysis) to supply glucose dependent tissues e.g. brain, immune system and renal medulla
|Glycogenolysis, and gluconeogenesis increased|
Gluconeogenesis decoupled from hormone control so can increase blood glucose level
|Lipids||Initially an increase in lipolysis and ketosis with marginal increase in catabolism, glycogenolysis or gluconeogensis|
Beyond 48hrs ketosis occurs and FFAs are used for energy, which minimizes the need for amino acids and so preserves muscle
|Lipolysis with no increase in ketosis|
|Protein||Mobilisation of protein is passive as a result of decrease in insulin||Mobilisation of protein is an active process|
|Albumin||Stable albumin initially with decreased energy expenditure||Albumin levels drop precipitously|
(negative acute phase reactant)
|Active or passive?||Passive due to decrease in insulin|
(mobilization of protein, glucose and lipids)
(energy expenditure and mobilisation of protein)
(if adequate protein and energy stores)
CONSEQUENCES OF UNDERFEEDING IN THE CRITICALLY ILL
- Impaired immune function
- Increased incidence of infection
- Weakness and fatigue
- Decreased ventilatory drive
- Prolonged mechanical ventilation
- Poor wound healing
- Muscle breakdown
- Depression and apathy
- Prolonged ICU and hospital stay
References and Links
- Berger MM, Chioléro RL. Hypocaloric feeding: pros and cons. Curr Opin Crit Care. 2007 Apr;13(2):180-6. PMID: 17327740.
- Cahill GF Jr. Starvation in man. N Engl J Med. 1970 Mar 19;282(12):668-75. PMID: 4915800.
- Cahill GF Jr. Fuel metabolism in starvation. Annu Rev Nutr. 2006;26:1-22. PMID: 16848698.
- Finn PF, Dice JF. Proteolytic and lipolytic responses to starvation. Nutrition. 2006 Jul-Aug;22(7-8):830-44. PMID: 16815497.
- Fontaine E, Müller MJ. Adaptive alterations in metabolism: practical consequences on energy requirements in the severely ill patient. Curr Opin Clin Nutr Metab Care. 2011 Mar;14(2):171-5. PMID: 21178609.
- Palesty JA, Dudrick SJ. The goldilocks paradigm of starvation and refeeding. Nutr Clin Pract. 2006 Apr;21(2):147-54.PMID: 16556925
- Soeters MR, Soeters PB, Schooneman MG, Houten SM, Romijn JA. Adaptive reciprocity of lipid and glucose metabolism in human short-term starvation. Am J Physiol Endocrinol Metab. 2012 Dec 15;303(12):E1397-407. PMID: 23074240.