Starvation refers to a physiological and pathological state in which there is complete deprivation of food intake, with water being the only essential substance consumed. It represents an extreme form of negative energy balance in which energy intake becomes zero while energy expenditure continues to sustain vital body functions.

The causes of starvation can be diverse and often complex. These include famine, prolonged political protests or hunger strikes, obstruction or lesions of the esophagus or stomach, severe psychiatric illness, or conditions that prevent food intake or absorption. If starvation persists for a prolonged period, it can ultimately lead to death within a few months, depending on the individual’s nutritional reserves.

Body composition significantly influences survival. A thin person succumbs to starvation earlier than an obese individual because fat stores act as a major energy reserve. Women generally tolerate starvation better than men due to a relatively higher proportion of body fat.
In modern physiological understanding, starvation is not simply “lack of food,” but a coordinated metabolic adaptation aimed at preserving vital organs, especially the brain and heart, for as long as possible.

The following changes are found to take place during starvation:

  1. Weight Changes

If a person does not ingest any calories, his caloric expenditure still continues. As a result, the body enters a state of negative energy balance, leading to gradual loss of body weight.
During early starvation, the body first utilizes adipose tissue, which serves as the primary energy reservoir. If starvation continues, progressively more structural tissues are affected.

The extent of tissue loss varies significantly among organs:

• Adipose tissue may be almost completely depleted.
• Liver, skeletal muscles, and gastrointestinal tract may lose approximately one-third of their mass.
• Heart size is also reduced due to muscle protein breakdown and decreased workload.
• The central nervous system (CNS) is relatively preserved, with only about 5% loss of mass, reflecting its priority in survival.

In addition, body water shifts occur early in starvation. Initial weight loss is partly due to depletion of glycogen stores, since glycogen is stored with water. Only later does true fat and protein loss dominate the weight reduction process.

  2. Carbohydrate Metabolism

Starvation produces rapid and predictable changes in carbohydrate metabolism:

• Liver glycogen falls rapidly to very low levels within the first 24 hours.
• A slight partial recovery may occur later due to gluconeogenesis, despite overall depletion.
• Muscle glycogen decreases more slowly than liver glycogen, but still declines significantly.

Once glycogen stores are exhausted, the body shifts to gluconeogenesis, which becomes the primary source of blood glucose. The major substrates include:

• Amino acids (especially alanine)
• Glycerol (from fat breakdown)
• Lactate (via Cori cycle)

Blood glucose levels remain relatively stable for the first 1–2 days but later may fall to around 50 mg/dL. A mild secondary rise may occur due to enhanced gluconeogenesis.

The brain initially depends entirely on glucose; however, during prolonged starvation, it partially adapts to ketone bodies, thereby reducing its glucose requirement and conserving body protein.

  3. Fat Metabolism

Once carbohydrate reserves are depleted, fat becomes the principal energy source. Fatty acids are mobilized from adipose tissue under hormonal influence:

• Increased glucagon
• Decreased insulin

This hormonal shift promotes lipolysis, releasing free fatty acids into the circulation.

A major consequence of prolonged fat metabolism is the development of ketosis, due to excessive formation of ketone bodies in the liver. These ketone bodies are utilized by peripheral tissues and, after adaptation, also by the brain.

Other important changes include:

• Possible development of fatty liver, due to altered lipid handling and deposition of neutral fats.
• Reduction in hepatic phospholipids.
• Progressive protein sparing effect as ketone bodies replace glucose as brain fuel.

  4. Protein Metabolism

Starvation leads to a negative nitrogen balance, since the body continues to break down proteins without dietary replacement.

Amino acids undergo deamination, producing:

• Ammonia (NH₃) → converted to urea in the liver
• Non-nitrogenous carbon skeleton → used for:
• Gluconeogenesis (glucose formation)
• Ketone body production (acetyl-CoA pathway)

The breakdown of body protein becomes increasingly important as starvation progresses, particularly for maintaining blood glucose levels.
A key measurement of protein loss is urinary nitrogen:

• 1 gram of urinary nitrogen ≈ 6.25 grams of tissue protein breakdown

  Stages of Nitrogen Excretion in Starvation

In prolonged fasting ending in death, protein metabolism shows characteristic stages reflected in urinary nitrogen excretion:

1. First 1–2 days
   Urinary nitrogen is low because energy is primarily derived from glycogen stores. Glycogen depletion is the dominant event.
2. 3rd–4th day (peak nitrogen loss)
   Urinary nitrogen rises sharply due to breakdown of labile proteins from organs such as the liver, pancreas, spleen, thymus, kidneys, and gastrointestinal tract.
3. Adaptive phase (protein conservation phase)
   Urinary nitrogen progressively falls to about 6 g/day, representing breakdown of approximately 37.5 g of protein per day.
• Fat becomes the main energy source
• R.Q falls close to 0.70
• Ketosis becomes prominent and protein is relatively spared
4. Terminal fat depletion phase
   After fat reserves are exhausted, protein breakdown increases again, and urinary nitrogen rises. Severe metabolic acidosis develops due to excess ketone bodies.
5. Pre-death phase
   Renal failure may occur, and urinary nitrogen may fall again due to reduced kidney function. This is typically seen just before death.

It is important to note that not all individuals pass through all stages in a strict sequence, as starvation outcomes vary depending on health status and metabolic reserves.

Additionally, in late starvation, there is progressive decline in cardiac output and blood pressure due to severe depletion of both fat and protein stores.

  5. Urinary Excretion of Non-Protein Nitrogenous Products During Starvation

1. Urea

• Initially increases due to protein breakdown
• Later decreases and remains below normal
• Reflects protein conservation during prolonged starvation

2. Ammonia

• Increases during ketosis
• Acts as a buffer in urine to help regulate blood pH
• Also contributes to sodium conservation
• Increased renal ammoniagenesis is a key adaptive response in metabolic acidosis

3. Creatinine and Creatine

• Creatinine excretion decreases
• Creatine excretion increases
• Total creatinine + creatine remains approximately constant
• Increased creatine reflects muscle breakdown and impaired energy metabolism in muscle tissue

6. Under-Nutrition

Under-nutrition, also called semi-starvation, is far more common than complete starvation. It occurs in situations such as famine, war, extreme poverty, or chronic illness.
It may also be seen in diseases including:

• Gastrointestinal disorders
• Anorexia nervosa
• Cancer
• Chronic infections

In under-nutrition, the diet is not only deficient in calories but often also lacks essential vitamins and minerals, leading to multiple nutritional deficiencies.

Chronic under-nutrition has systemic effects, including immune suppression, due to reduced lymphocyte activity and impaired protein synthesis.

  Clinical Features of Pure Under-Nutrition

Pure under-nutrition refers mainly to reduced calorie intake.

1. Body Weight and Physical Appearance

• Marked loss of body weight
• Predominant loss of fat with some protein depletion
• Condition of emaciation
• Muscle atrophy with visible ribs, prominent scapulae, thin limbs, and flattened buttocks
• Dry, inelastic skin
• In some cases, edema may occur, masking weight loss due to fluid retention

2. Metabolic Activity

• Overall metabolic rate decreases
• Reduced cardiac output and low blood pressure
• Subnormal body temperature
• Decreased basal metabolic rate (BMR)
• Reduced oxygen consumption due to lowered mitochondrial activity

3. Fatigue and Exercise Intolerance

• Severe fatigue and lack of physical endurance
• Reduced exercise tolerance due to muscle wasting and depleted glycogen stores

4. Hunger and Neurological Symptoms

• Persistent hunger
• Episodes of dizziness
• Possible hypoglycemic attacks in prolonged cases

5. Immunity and Disease Susceptibility

• Decreased resistance to tuberculosis and infections
• Reduced incidence of hypertension and diabetes mellitus
• Delayed wound healing due to impaired collagen synthesis and protein deficiency

6. Psychological and Behavioral Changes

• Mental apathy and depression
• Reduced intellectual performance and work capacity
• Irritability and impaired judgment in severe cases
• Appearance of premature aging due to energy deficiency
• Decreased moral drive and social withdrawal in advanced stages

In summary, starvation and under-nutrition represent profound metabolic adaptations in which the body sequentially shifts from carbohydrate utilization to fat oxidation and finally to protein catabolism, while simultaneously attempting to preserve vital organ function for survival.