Metabolic States of the Body: Fasting and Starvation

During the initial hours of fasting, the body depletes its glycogen stores as the primary energy source. Glycogen reserves are typically exhausted within 12–24 hours, depending on metabolic demands. Once depleted, the body shifts to breaking down stored triglycerides and structural proteins to maintain energy production and blood glucose levels.

After glycogen depletion, the body uses gluconeogenesis to maintain blood glucose. Glycerol from lipolysis and amino acids from protein breakdown serve as substrates for glucose synthesis in the liver. This process stabilizes blood glucose levels while the body shifts to alternative fuel sources like free fatty acids and ketone bodies.

Ketone bodies become the brain's primary fuel source during prolonged fasting lasting days to weeks. Due to their lipid solubility, ketone bodies cross cell membranes and the blood-brain barrier, providing up to two-thirds of the brain's energy requirements. This metabolic adaptation conserves muscle protein by reducing reliance on gluconeogenesis.

Free fatty acids released from lipolysis of triglycerides in adipose tissue undergo beta-oxidation to generate energy for muscle fibers and other body cells. Elevated plasma levels of free fatty acids also stimulate liver cells to produce ketone bodies, which serve as an alternative fuel source for tissues throughout the body.

As fasting continues without dietary amino acid influx, protein synthesis slows while structural proteins break down to release amino acids for gluconeogenesis. These amino acids undergo deamination in the liver to form glucose. However, the body attempts to spare muscle protein as much as possible to preserve muscle function and performance.

By the second day of fasting, lipolysis of triglycerides in adipose tissue releases both glycerol and free fatty acids. Glycerol serves as a key substrate for gluconeogenesis, helping stabilize blood glucose levels. Meanwhile, free fatty acids provide energy directly to tissues, reducing the body's immediate glucose demands.

The body transitions from glycogen to fat stores as glycogen reserves deplete within 12–24 hours. This shift involves increased lipolysis in adipose tissue, which releases free fatty acids for beta-oxidation and glycerol for gluconeogenesis. Simultaneously, ketone body production increases, providing an alternative fuel source that helps sustain energy metabolism.