Hormonal Shifts During Starvation
When caloric intake drops to near zero, the endocrine system orchestrates a series of profound changes. The fed state, characterized by high insulin and low glucagon, is rapidly reversed.
Increased Glucagon
Glucagon, a hormone produced by the pancreas, is released in higher quantities as blood glucose levels fall. This crucial hormone primarily acts on the liver, where it stimulates the breakdown of stored glycogen into glucose, a process called glycogenolysis. After about 24 hours of fasting, these glycogen stores are exhausted, and glucagon's role shifts to promoting gluconeogenesis, the creation of new glucose from non-carbohydrate sources. Glucagon also stimulates lipolysis and ketogenesis, encouraging the use of fat for fuel.
Elevated Cortisol
Cortisol, a stress hormone from the adrenal glands, also sees a significant increase during starvation. Its actions include stimulating both gluconeogenesis and lipolysis. Cortisol's role extends to breaking down proteins from skeletal muscle to provide amino acids as a substrate for glucose production in the liver. High cortisol levels also inhibit the uptake of glucose by peripheral tissues, thereby sparing it for the brain.
Higher Ghrelin
Often called the 'hunger hormone,' ghrelin, produced primarily in the stomach, increases significantly during periods of caloric restriction. Elevated ghrelin signals the brain to increase appetite and food-seeking behavior, an evolutionary response to prompt eating.
Metabolic Pathways that Increase
In concert with the hormonal changes, the body activates several metabolic pathways to procure and utilize alternative fuel sources.
Enhanced Lipolysis and Fatty Acid Oxidation
As glycogen stores are depleted, the body increases its reliance on fat reserves. The process of lipolysis, the breakdown of triglycerides stored in adipose (fat) tissue, ramps up dramatically. This releases fatty acids into the bloodstream, which are then oxidized by most tissues (excluding the brain initially) for energy.
Accelerated Ketogenesis and Increased Ketone Bodies
In prolonged starvation, the liver converts fatty acids into ketone bodies, including acetoacetate and β-hydroxybutyrate, through a process called ketogenesis. These ketones can cross the blood-brain barrier and serve as a primary fuel source for the brain, significantly reducing its reliance on glucose. This shift is critical for preserving muscle mass, as it lessens the need for protein breakdown to produce glucose. A person in this state is in ketosis, which can be identified by the presence of ketones in the breath and urine.
Heightened Gluconeogenesis
Once liver glycogen is exhausted, typically within 24 hours, gluconeogenesis becomes the primary mechanism for maintaining a minimal level of blood glucose for glucose-dependent cells, like red blood cells. This process, taking place mainly in the liver, increases significantly during starvation, using amino acids (from protein breakdown) and glycerol (from fat breakdown) as its building blocks.
Rising Proteolysis and Ureagenesis
To supply the necessary amino acids for gluconeogenesis, the body increases proteolysis, the breakdown of proteins, primarily from skeletal muscle. While this is minimized by the brain's switch to ketones, it remains a critical source. The excess nitrogen from amino acid catabolism is converted to urea, a process called ureagenesis, which is then excreted by the kidneys. Consequently, blood urea nitrogen (BUN) levels can increase.
Comparison of Metabolic Stages in Starvation
| Feature | Early Starvation (First ~24 hours) | Prolonged Starvation (>24 hours) |
|---|---|---|
| Primary Fuel Source | Glycogen stores from liver and muscle | Fat reserves (fatty acids and ketones) |
| Dominant Hormone | Glucagon drives glycogenolysis | Glucagon and cortisol sustain gluconeogenesis and lipolysis |
| Glucose Production | Glycogenolysis is the main source | Gluconeogenesis from amino acids and glycerol takes over |
| Ketone Body Level | Low; ketogenesis is just beginning | High; ketogenesis provides major brain fuel |
| Protein Breakdown | Minimal; protein is relatively spared | Increased proteolysis to fuel gluconeogenesis |
| Metabolic Rate | Initially stable or slightly elevated | Decreases to conserve energy |
Conclusion
When the body faces starvation, it executes a complex, life-sustaining protocol orchestrated by a dramatic increase in hormones like glucagon, cortisol, and ghrelin. These hormonal shifts activate a sequence of metabolic processes that increase the breakdown of fat and, eventually, protein stores to provide energy. Key processes that increase include lipolysis, ketogenesis, and gluconeogenesis, ensuring the brain and other critical organs have a fuel supply. This adaptive metabolic switch allows for prolonged survival but comes at the cost of muscle mass over time as the body depletes its fat reserves. Understanding these increases provides insight into the body's remarkable resilience and is crucial for developing refeeding strategies in malnourished individuals.
For more detailed information on the physiology of starvation, consult academic resources such as this review available on the National Institutes of Health website: Adaptive Effects of Endocrine Hormones on Metabolism of Macronutrients during Fasting and Starvation: A Scoping Review.
