U01.01.122 Fasting and starvation

Understanding the metabolic shifts that occur during different nutritional states is critical for the USMLE Step 1 exam. These states are categorized into fed, fasting, and starvation phases, each with specific physiological responses to maintain energy balance, particularly for the brain and red blood cells (RBCs).

Metabolic States and Their Physiological Responses

State	Main Focus	Key Metabolic Pathways	Key Hormones
Fed State (Post-meal)	Store energy and nutrients	– Glycolysis and aerobic respiration for energy. – Insulin stimulates storage of lipids, proteins, and glycogen.	– Insulin
Fasting (Between Meals)	Maintain blood glucose levels	– Hepatic glycogenolysis (major) – Hepatic gluconeogenesis – Adipose release of free fatty acids (FFA) (minor).	– Glucagon, Epinephrine
Starvation (Days 1–3)	Preserve glucose for brain and RBCs, spare protein	– Hepatic glycogenolysis – Adipose release of FFA – Muscles shift fuel use from glucose to FFA – Hepatic gluconeogenesis from lactate, alanine, glycerol, and propionyl-CoA	– Glucagon, Epinephrine
Starvation (After Day 3)	Maximize fat use, preserve vital protein	– Ketone bodies become primary energy source for the brain – Depletion of fat stores accelerates protein degradation, leading to organ failure and death.	– Glucagon, Epinephrine

Key Points to Remember

Primary Goal of Fasting and Starvation: The body prioritizes glucose supply to the brain and RBCs while minimizing protein degradation.
Fed State: Insulin promotes storage of energy (lipids, proteins, glycogen) via glycolysis and aerobic respiration.
Fasting: The liver releases glucose through glycogen breakdown and gluconeogenesis. Fatty acids are also released from adipose tissue, but only minor contributions come from fats at this stage.
Starvation (Days 1–3): Glycogen stores are depleted, and the body adapts by increasing ketone body production, utilizing fatty acids for energy. Muscles shift from using glucose to fatty acids. Hepatic gluconeogenesis sustains blood glucose levels.
Starvation (After Day 3): The brain increasingly relies on ketone bodies for energy. Once fat stores are depleted, vital protein degradation accelerates, leading to organ failure and death.
Energy Contribution Over Time: During prolonged starvation, the body increasingly relies on fat stores, with carbohydrates and protein providing less energy.

Metabolic Shifts and Energy Sources

Energy Contribution by Source (% Maximal Energy)

Time (Days of Starvation)	Carbohydrates	Proteins	Fats
Day 0 (Fed)	100% (glycogen)	0%	0%
Day 1-3 (Starvation)	50%	10%	40%
After Day 3 (Starvation)	0%	5%	95%

Summary

Day 1: Glycogen stores are depleted, and the liver increases gluconeogenesis from lactate, alanine, and glycerol. Muscle and liver shift from glucose to fatty acids as the primary energy source.
Day 3 and Beyond: The body shifts to using ketone bodies for brain fuel. As fat stores deplete, protein degradation accelerates, causing organ failure if starvation persists.

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