Famine response

The famine response is how the body of a human or animal responds to malnutrition.

The body uses glucose as its main metabolic fuel if it is available. About 20% of the total energy consumption occurs in the brain. The rest of the glucose consumption fuels muscle tissue and red blood cells.

Glucose can be obtained directly from dietary sugars and carbohydrates. In the absence of dietary sugars and carbohydrates, it is obtained from the breakdown of glycogen. Glycogen is a readily-accessible storage form of glucose, stored in small quantities in the liver and muscles. The body's glycogen reserve can provide glucose for about 6 hours.

After the glycogen reserve is used up, glucose can be obtained from the breakdown of fats. Fats from adipose tissue are broken down into glycerol and free fatty acids. Glycerol can then be used by the liver as a substrate for gluconeogenesis, to produce glucose.

Fatty acids can be used directly as an energy source by most tissues in the body, except the brain, since fatty acids are unable to cross the blood-brain barrier. After the exhaustion of the glycogen reserve, and for the next 2-3 days, fatty acids are the principal metabolic fuel. Initially the brain continues to use glucose, because if a non-brain tissue is using fatty acids as its metabolic fuel, this switches off the use of glucose in the same tissue - thus when fatty acids are being broken down for energy, this makes all of the remaining glucose available for use by the brain.

However, the brain requires about 120 g. of glucose per day (equivalent to the sugar in 3 cans of soda), and at this rate the brain will quickly use up the body's remaining carbohydrate stores. However, the body has a "backup plan" which involves molecules known as ketone bodies. Ketone bodies are short-chain derivatives of fatty acids. These shorter molecules can cross the blood-brain barrier and can be used by the brain as an emergency metabolic fuel.

After 2-3 days of starvation, the liver begins to synthesize ketone bodies from precursors obtained from fatty acid breakdown. The brain uses these ketone bodies as fuel, thus cutting its requirement for glucose. After fasting for 3 days, the brain gets 30% of its energy from ketone bodies. After 4 days, this goes up to 70%.

The consumption of ketone bodies by the brain relieves some of the glucose requirement but does not abolish it altogether. The brain retains some need for glucose, because ketone bodies can be broken down for energy only in the mitochondria, and mitochondria are often too big to travel down the long thin processes of neurons to reach the synapses.

In fact, the production of ketone bodies cuts the brain's glucose requirement from 120 g per day to about 30 g per day. Of the remaining 30 g requirement, 20 g per day can be produced by the liver from glycerol (itself a product of fat breakdown). But this still leaves a deficit of about 10 g of glucose per day that must be supplied from some other source. This other source will be the body's own proteins.

After several days of fasting, all cells in the body begin to break down protein. This releases amino acids into the bloodstream, which can be converted into glucose by the liver. Since much of our muscle mass is protein, this phenomenon is responsible for the wasting away of muscle mass seen in starvation.

However, the body is not able to selectively decide which cells will break down protein and which will not. In effect, all cells will break down protein, and essential cells (such as lung cells) are just as likely to be broken down as nonessential cells (such as muscle cells). The problem is that proteins are essential to the structure and metabolism of the cell. Most cells cannot tolerate the loss of very much protein. Furthermore, about 2-3 g of protein has to be broken down to synthesise 1 g of glucose - so to make 10 g of glucose, about 20-30 g of protein is broken down each day to keep the brain alive.

Thus, after about 40 to 50 days of starvation, the loss of body protein affects the function of important organs, and death results, even if there are still fat reserves left unused. (In a leaner person, the fat reserves are depleted earlier, the protein depletion occurs sooner, and therefore death occurs sooner.)

The ultimate cause of death is generally cardiac arrhythmia or cardiac arrest brought on by tissue degradation and electrolyte imbalances, or else an infection due to weakening of the immune system.