What does your body do when it runs out of glycogen?

October 19, 2025 •

3 min read

After 90-120 minutes of moderate to high-intensity exercise, glycogen stores can be significantly depleted. When that happens, what does your body do when it runs out of glycogen? The body initiates a complex series of metabolic shifts to find alternative fuel sources and prevent a complete energy collapse.

Quick Summary

Once your body's preferred carbohydrate reserves are gone, it shifts metabolic pathways to rely on stored fat for energy. This adaptation involves breaking down fat into fatty acids and converting them into ketones, providing an alternative fuel source for the brain and muscles.

Key Points

Initial Fatigue: When glycogen is depleted, a sudden and profound drop in energy and exercise performance, often called 'hitting the wall' or 'bonking,' occurs due to the lack of the body's preferred quick-burning fuel.
Fat Mobilization: After glycogen is gone, the body initiates the breakdown of its large fat reserves (adipose tissue) into fatty acids and glycerol to be used for energy.
Ketone Production for the Brain: The liver begins converting fatty acids into ketone bodies, which provide an essential alternative fuel source for the brain when glucose levels are low.
Gluconeogenesis for Survival: In prolonged states of low glucose, the body can create new glucose from non-carbohydrate sources like glycerol and certain amino acids to fuel vital organs, potentially breaking down muscle protein.
Transition Symptoms: The metabolic switch can cause temporary, flu-like symptoms known as the 'keto flu,' including fatigue, headache, and irritability, as the body adapts to its new fuel source.
Performance Shift: The body's reliance on slower-burning fat means a decrease in performance for high-intensity, anaerobic activities, which are primarily fueled by glucose from glycogen.

The Body's Primary Fuel Source and the Initial Collapse

Glycogen is the body's primary, readily available energy source, formed by linking together glucose molecules. It is stored primarily in the liver and muscles. Muscle glycogen is used locally to fuel muscle contractions, particularly during high-intensity exercise, while liver glycogen is used to maintain stable blood glucose levels for the brain and other tissues. Endurance athletes are most familiar with the feeling of running low on this stored energy, a phenomenon known as "hitting the wall" or "bonking". This initial stage of glycogen depletion is marked by a dramatic loss of energy, sudden fatigue, and a reduced capacity to perform at the previous intensity. The brain, which relies heavily on glucose for fuel, becomes particularly affected, leading to mental fogginess and impaired focus.

The Metabolic Shift to Fat and Ketones

When the body can no longer rely on its glycogen reserves for sufficient energy, it triggers a metabolic shift to use its much larger fat stores. This transition involves a complex sequence of hormonal and enzymatic changes.

How the Body Burns Fat

Fat Mobilization: Hormones signal adipose (fat) tissue to release stored triglycerides. These triglycerides are broken down into fatty acids and glycerol.
Fatty Acid Oxidation: Fatty acids are transported via the bloodstream to muscle cells. Inside the muscle cells, they are broken down through a process called beta-oxidation to produce acetyl-CoA, which enters the Krebs cycle to generate ATP, the cell's energy currency. This process requires more oxygen and is slower than burning glucose, which is why it cannot support high-intensity exercise as effectively.

The Creation of Ketones

Since the brain cannot directly use fatty acids for fuel, a secondary adaptation occurs. When fat is the primary energy source and glucose levels are low, the liver increases its production of ketone bodies from acetyl-CoA through a process called ketogenesis. These ketones, including acetoacetate and beta-hydroxybutyrate, are then released into the bloodstream and can be used by the brain and other organs for energy. This state is known as ketosis and is a key metabolic adaptation to prolonged low-carbohydrate intake or fasting.

Gluconeogenesis: The Emergency Backup

Even when in ketosis, some tissues still require glucose. The body's final defense mechanism is gluconeogenesis, the creation of "new" glucose from non-carbohydrate sources.

The Gluconeogenesis Process

Amino Acid Utilization: During prolonged starvation, the body can break down muscle protein into amino acids. Glucogenic amino acids can be converted into glucose by the liver.
Glycerol Conversion: The glycerol released from the breakdown of triglycerides can also be converted into glucose in the liver.
Lactate Recycling: Lactate produced during anaerobic metabolism in muscles can be sent to the liver and converted back to glucose via the Cori cycle.

This process is vital for the brain but comes at a cost, as it can lead to muscle tissue loss, particularly if adequate protein and fat stores are not available.

Comparison of Fuel Sources: Glycogen vs. Fat/Ketones


Feature	Glycogen (Carbohydrates)	Fat/Ketones (Fat Oxidation)
Energy Source	Preferred for high-intensity exercise	Used during moderate exercise, rest, and fasting
Energy Delivery	Very rapid	Slower, but sustained
Storage Capacity	Limited (approx. 2,000 kcal)	Very large, essentially unlimited
Brain Fuel	Primary fuel source (glucose)	Alternative fuel source (ketones)
Intensity Supported	High intensity and anaerobic activity	Low to moderate intensity, aerobic activity
Oxygen Requirement	Low (anaerobic glycolysis)	High (aerobic beta-oxidation)

Conclusion

The depletion of glycogen triggers a sophisticated, multi-staged metabolic response designed to prevent catastrophic energy failure. The body's first step is a noticeable dip in performance and energy, known as "bonking." It then swiftly shifts to burning its extensive fat stores, a slower but more sustainable energy source. Concurrently, the liver produces ketones to fuel the brain, which is crucial for maintaining cognitive function. Finally, the body can turn to protein (and glycerol) via gluconeogenesis to produce minimal necessary glucose. Understanding this process is vital for athletes to properly fuel for endurance events and for anyone seeking to optimize their metabolic health. Through strategic nutrition and training, the body can be conditioned to become more efficient at utilizing fat, enhancing endurance and metabolic flexibility.

Learn more about the metabolic states of the body from Oregon State University

Frequently Asked Questions

Glycogen is the body's storage form of glucose (sugar), serving as a readily available energy reserve. It is primarily stored in the liver and muscles.

The duration depends on several factors, including the intensity and duration of exercise, and your diet. For daily living, it can take 12-22 hours, while intense endurance exercise can deplete stores in as little as 90-120 minutes.

Commonly experienced by endurance athletes, 'hitting the wall' or 'bonking' is the sudden feeling of fatigue and energy loss that occurs when muscle glycogen stores are depleted during intense exercise.

Yes. When glycogen is depleted, your body switches to using fat as its main energy source by breaking down stored triglycerides into fatty acids that can be used for fuel.

The brain cannot directly use fatty acids for fuel. Instead, the liver converts fatty acids into ketone bodies, which can cross the blood-brain barrier and serve as an alternative energy source for the brain.

Gluconeogenesis is a metabolic process where the body creates new glucose from non-carbohydrate precursors, such as lactate, glycerol, and certain amino acids. This occurs primarily in the liver during periods of prolonged fasting or low-carbohydrate intake.

For trained athletes, intentional glycogen depletion can be part of a training strategy to improve fat adaptation. However, for most, it can lead to reduced performance and fatigue. For those with certain medical conditions like type 1 diabetes, uncontrolled ketone production can be dangerous.