What is Nitrogen Balance?
To understand why the body goes into negative nitrogen balance, one must first grasp the concept of nitrogen balance itself. Nitrogen is a fundamental component of amino acids, which are the building blocks of protein. Your body's nitrogen balance is a simple index used to assess protein metabolism by comparing the amount of nitrogen consumed (primarily from dietary protein) with the amount of nitrogen excreted (mainly as urea in urine, but also through feces and sweat).
There are three states of nitrogen balance:
- Positive Nitrogen Balance: This occurs when nitrogen intake exceeds nitrogen loss. It is the optimal state for growth and repair, seen during childhood, pregnancy, and tissue recovery from injury.
- Nitrogen Equilibrium: In healthy adults who are not growing or healing, nitrogen intake and loss are roughly equal. This indicates a stable, steady-state metabolism.
- Negative Nitrogen Balance: This is a catabolic state where nitrogen loss is greater than intake. It signifies that the body is breaking down more protein than it is synthesizing, leading to a net loss of body protein and muscle mass.
The Body's Metabolic Adaptation to Starvation
Starvation is the most extreme form of malnutrition, forcing the body to adopt a series of metabolic survival mechanisms. The body progresses through distinct phases, each marked by a shift in its primary fuel source.
Phase One: Glycogen Stores Depletion
In the initial 24 hours of fasting, the body uses its readily available energy sources. Liver and muscle glycogen, a stored form of glucose, is broken down via glycogenolysis to maintain blood sugar levels. This ensures the brain and red blood cells, which are heavily dependent on glucose, have a fuel supply.
Phase Two: Fat Stores Mobilization
After approximately 24-48 hours, glycogen stores are depleted. The body's metabolism shifts dramatically to utilize fat reserves from adipose tissue. Lipolysis breaks down triglycerides into fatty acids and glycerol. The liver converts the glycerol into glucose through gluconeogenesis, while the fatty acids are converted into ketone bodies through ketogenesis. Ketone bodies then become a primary energy source for many tissues, including a portion of the brain, significantly reducing the brain's glucose dependence. This is an adaptive mechanism designed to spare muscle protein as long as possible.
Phase Three: Protein and Muscle Catabolism
When fat reserves become exhausted, the body enters a final, dangerous stage of starvation. It is forced to break down its own functional proteins to create glucose. This protein catabolism primarily involves the breakdown of muscle tissue, including skeletal and heart muscle. Amino acids, particularly alanine and glutamine, are liberated from the muscle and transported to the liver where they are converted into glucose via gluconeogenesis. This process directly results in a negative nitrogen balance because nitrogen is being excreted from the body as urea, while zero protein is being consumed.
The Hormonal Triggers
Several hormones orchestrate the metabolic shifts during starvation:
- Glucagon: As blood glucose drops, the pancreas releases glucagon, which signals the liver to release stored glycogen and eventually to perform gluconeogenesis.
- Cortisol: Adrenal cortical hormones like cortisol are released during stress, enhancing protein breakdown and the conversion of amino acids to glucose.
- Insulin: Insulin levels drop dramatically during fasting. Since insulin is an anabolic hormone, its decrease contributes to the catabolic state where protein synthesis is inhibited.
- Growth Hormone: Levels of growth hormone also increase, stimulating lipolysis (fat breakdown) to further conserve protein.
Comparison of Metabolic States During Fasting
| Feature | Initial Fasting (0-24 hrs) | Prolonged Starvation (Days to Weeks) |
|---|---|---|
| Primary Fuel Source | Stored glycogen | Fat stores and ketone bodies |
| Secondary Fuel Source | None | Protein (muscle) |
| Main Metabolic Process | Glycogenolysis | Lipolysis and Ketogenesis |
| Nitrogen Balance | Close to equilibrium | Severely negative |
| Hormonal Profile | Decreased insulin, increased glucagon | Decreased insulin, increased glucagon and cortisol |
| Body Impact | Minimal | Muscle wasting, organ degradation |
The Physiological Consequences of Negative Nitrogen Balance
The consistent catabolism of protein during prolonged starvation leads to severe consequences:
- Muscle Wasting (Atrophy): The body has no choice but to break down muscle tissue to supply essential amino acids for glucose production. This leads to a significant loss of muscle mass, weakness, and fatigue.
- Organ Damage: Vital organs, including the heart, liver, and kidneys, are made of protein. When muscle reserves are depleted, the body begins breaking down organ tissue, compromising their function. The ultimate cause of death from starvation is often heart failure or arrhythmia resulting from tissue degradation and electrolyte imbalances.
- Impaired Immune Function: Protein is essential for producing antibodies and other immune system components. A lack of protein from severe negative nitrogen balance weakens the immune system, making the body highly susceptible to infections.
- Reduced Brain Function: While the brain adapts to use ketones, a small but critical amount of glucose is still required. When protein is broken down for this purpose, it can still lead to cognitive decline, irritability, and apathy.
Conclusion
The human body's entry into a negative nitrogen balance during starvation is not an anomaly but a meticulously orchestrated, though ultimately destructive, survival strategy. As the body exhausts its carbohydrate and fat reserves, it turns inward, cannibalizing its own functional proteins to produce life-sustaining glucose for the brain. This catabolic process, driven by shifts in hormones like glucagon and cortisol, leads to the tell-tale signs of muscle wasting and immune system collapse. Understanding why the body goes into negative nitrogen balance during starvation reveals the extreme lengths to which our biology will go to survive and underscores the severe, life-threatening nature of prolonged nutritional deprivation.
Visit the NCBI Bookshelf for a more in-depth look at the physiology of fasting.
