When the body is deprived of food, it enters a specialized metabolic state where energy needs must be met by internal reserves. This state triggers a highly orchestrated sequence of fuel switching designed for survival. The primary objective of this metabolic shift is to maintain a steady supply of energy for the brain, the body’s most sensitive and demanding organ. The body prioritizes the conservation of muscle protein by cycling through its carbohydrate, fat, and protein stores. This process involves transitioning from fast-burning, readily available fuels to more concentrated, long-term energy sources.
Phase 1: Depleting Carbohydrate Reserves
The body’s first energy source to be tapped is glucose, which is stored in the form of glycogen, a large, branching polysaccharide. The liver holds a reserve of glycogen that is quickly mobilized to maintain stable blood sugar levels for the entire body. This initial phase begins almost immediately after the last meal’s nutrients are absorbed.
The process of breaking down stored glycogen into usable glucose is called glycogenolysis. Liver glycogen is the most important supply at this stage, while muscle glycogen is generally reserved for the muscle cells’ own needs. The total amount of stored glycogen is relatively small, providing only about 8,000 kilojoules of energy in a typical adult.
These carbohydrate reserves are quickly exhausted, and this first phase typically lasts between 12 and 24 hours of complete fasting. Once liver glycogen is depleted, the body must rapidly establish alternative pathways to generate glucose. This is necessary because certain cells, like red blood cells, rely exclusively on glucose for fuel. This depletion marks the end of the body’s reliance on its most accessible, short-term energy reservoir.
Phase 2: Shifting to Fat Stores
Once carbohydrate reserves are exhausted, the body enters its second and most prolonged phase, shifting its metabolism to utilize fat stores. Adipose tissue is the most abundant and energy-dense fuel reserve, containing significantly more stored energy compared to glycogen. This transition is initiated by a drop in insulin and a rise in hormones like glucagon and epinephrine.
The breakdown of stored fat, known as lipolysis, cleaves triglycerides into fatty acids and glycerol. Fatty acids become the principal fuel source for most tissues, including skeletal muscle, the heart, and the liver. These fatty acids undergo beta-oxidation, which generates acetyl-CoA that feeds into the citric acid cycle for energy production.
The glycerol component, unlike fatty acids, is sent to the liver where it is converted into glucose through gluconeogenesis. This mechanism provides a small, but steady, non-carbohydrate source of glucose to the bloodstream. By switching most tissues to fat-based energy, the body effectively spares any remaining circulating glucose for the central nervous system. This reliance on fat allows for survival over extended periods.
Phase 3: Tapping into Structural Protein
The body attempts to conserve structural proteins, but must inevitably break down protein to meet the demand for glucose that fat cannot directly satisfy. This catabolism involves the dismantling of non-essential cellular and muscle protein. The purpose is to harvest the component amino acids, not to use the proteins themselves for general energy.
These amino acids, primarily alanine and glutamine, are transported to the liver and kidneys. They serve as the main raw material for gluconeogenesis, the creation of new glucose. This process is necessary to generate the basal amount of glucose still required by the central nervous system, even after metabolic adaptation.
The breakdown of protein leads to muscle wasting and compromises the function of structural and enzymatic proteins in the body. While some protein catabolism occurs in the initial phases to support gluconeogenesis, the widespread breakdown of structural protein is a marker of severe, late-stage starvation. This shift signifies a metabolic failure to conserve lean mass, which ultimately leads to organ dysfunction.
The Body’s Priority: Fueling the Brain
The brain’s specialized metabolism presents a unique challenge during starvation because it cannot directly use fatty acids for fuel. To bridge this gap, the liver initiates ketogenesis, converting the fatty acids released during lipolysis into ketone bodies. The primary ketone bodies produced are beta-hydroxybutyrate and acetoacetate, which successfully cross the blood-brain barrier.
The brain adapts to utilize these ketone bodies as a substitute for glucose. This metabolic adaptation allows the brain to derive up to 70% of its energy from ketones during prolonged starvation. This shift becomes significant after about three days of fasting, dramatically reducing the brain’s daily requirement for glucose.
By relying heavily on ketones, the brain decreases the total amount of glucose the body needs to produce each day. This glucose-sparing effect protects muscle tissue, as it lowers the demand for gluconeogenesis from amino acids. The ability of the brain to switch its fuel preference is the most important factor in prolonging survival during extended periods without food.