Humans usually eat a few times a day. This means that an individual's normal nutritional status cycles between two states, well‐fed and fasting. Biochemically, the source of glucose, which is far and away the preferred source of energy for the brain, defines these states. During the well‐fed state, the diet supplies glucose and the rest of the energy needed for protein synthesis. Between meals, the breakdown of glycogen and gluconeogenesis from amino acids supplies the glucose requirements. In more advanced cases of starvation, muscle protein is broken down more extensively for gluconeogenesis. In advanced stages of starvation, glucose metabolism is reduced and the brain metabolizes ketone bodies for energy.
The digestion of foodstuffs in and absorption from the intestinecharacterizes the well‐fed state, which lasts for about four hours after a meal. Free amino acids and glucose are absorbed and transported to the liver. Excess energy is converted to fat in the liver and transported, along with dietary fat, to the adipose tissues. The pancreas releases high levels of insulin in response to these events. Insulin signals the liver to convert glucose to glycogen, amino acids to protein, and fat to triglycerides. The adipose tissues synthesize and deposit fats. A deficiency of insulin is a cause of diabetes, characterized by excess levels of blood glucose. In this disease, glucose is not converted into glycogen or fat, so it remains in the circulation.
As the individual enters the fasting state, glycogen is broken down into glucose to supply energy for the tissues. Simultaneously, gluconeogenesis begins as amino acids, lactate, and pyruvate from metabolism are cycled into the formation of glucose. As fats are broken down, the fatty acids supply energy to the peripheral tissues, while the glycerol from breaking down the triacylglycerols is transported to the liver and converted to glucose. Gluconeogenesis becomes more important than glycogen breakdown after about 16 hours of fasting. Gluconeogenesis is maximal after about two days without food, at which time ketone bodies are made from fat and transported to the brain. This transition describes the beginning of starvation, which can last for six to ten weeks before death occurs. During starvation, the body breaks down amino acids for glucose; however, ketone bodies and fat supply most energy requirements. At this time, the body is in negative nitrogen balance, because the amount of nitrogen excreted due to protein breakdown exceeds the nitrogen eaten in food. The small amount of glucose made is supplied to brain, kidney, and red blood cells. The latter two tissues have no alternative energy sources; the brain uses both ketone bodies and glucose. When fat is gone, the only sources of energy available are amino acids from muscle. The carbon skeletons are metabolized, and the nitrogen is excreted. This situation cannot continue for very long. Eventually, the kidneys fail, or the heart muscle is broken down, and the individual dies.