What Does Your Body Use When It Runs Out of Glycogen?

December 20, 2025 •

4 min read

Approximately 80-85% of a healthy adult's energy reserves are stored as fat. When the body's primary immediate fuel source, glycogen, is depleted during prolonged exercise or fasting, it initiates a critical metabolic shift to sustain energy production. This article will explain what does your body use when it runs out of glycogen.

Quick Summary

When glycogen stores are depleted, the body shifts to alternative fuel sources, primarily breaking down stored fat for energy through lipolysis and beta-oxidation. The liver also produces new glucose via gluconeogenesis and creates ketone bodies to power the brain and other tissues.

Key Points

Fat Reserves: When glycogen is depleted, the body primarily burns its plentiful stores of fat through lipolysis and beta-oxidation to generate energy.
Gluconeogenesis: The liver can produce new glucose from non-carbohydrate sources like lactate, glycerol, and amino acids to supply energy to the brain and red blood cells.
Ketone Bodies: During prolonged fasting, the liver can create ketone bodies from fat to serve as an alternative energy source for the brain and other tissues.
Protein Catabolism: The body only breaks down protein from muscle tissue as a last resort for energy during severe calorie deficits, as it is a slow and inefficient process.
Metabolic Shift: This process, known as 'hitting the wall' in endurance sports, signifies the body's transition from using glycogen for high-intensity energy to relying on fat, which provides a slower, more sustained fuel.
Prioritized Fueling: The body uses a specific hierarchy of fuels: immediate glucose, then stored glycogen, followed by fats, and finally, muscle protein during severe deprivation.

Glycogen is the body's stored form of carbohydrates, a complex polymer of glucose molecules found primarily in the liver and muscles. Muscle glycogen serves as a localized energy source for immediate use during physical activity, while liver glycogen is released into the bloodstream to maintain stable blood glucose levels for the brain and other organs. However, these glycogen stores are limited and can be exhausted after a prolonged period of intense exercise or fasting. When this occurs, the body is forced to pivot its metabolic machinery to burn alternative fuels. This shift is what is commonly referred to as "hitting the wall" by endurance athletes, a phenomenon characterized by intense fatigue and a dramatic drop in performance.

The Metabolic Shift: Tapping Into Fat Reserves

For most people, the body's most abundant energy reserve is stored fat, also known as adipose tissue. Once glycogen is gone, fat becomes the body's primary long-term fuel source. Fat is an extremely energy-dense fuel, providing more than twice the calories per gram compared to carbohydrates.

Lipolysis and Beta-Oxidation

The process of using fat for energy involves several key steps:

Lipolysis: During this initial phase, the body releases hormones like glucagon and adrenaline, which activate enzymes called lipases to break down stored triglycerides in fat cells into free fatty acids and glycerol.
Transport: The released fatty acids are then transported through the bloodstream to tissues that need energy, such as the muscles and heart.
Beta-Oxidation: Inside the mitochondria of the muscle cells, the fatty acids are broken down into smaller molecules called acetyl-CoA. This acetyl-CoA is then fed into the Krebs cycle to produce a large amount of adenosine triphosphate (ATP), the body's immediate energy currency.

Gluconeogenesis: Making New Glucose

Even when fat becomes the primary fuel, certain parts of the body, most notably the brain and red blood cells, have a constant and non-negotiable need for glucose. The liver and, to a lesser extent, the kidneys address this by producing new glucose through a process called gluconeogenesis, or "new glucose formation".

Glucogenic Substrates

Gluconeogenesis can produce glucose from non-carbohydrate sources, including:

Lactate: Produced by muscles during anaerobic glycolysis, lactate can be transported to the liver and converted back into glucose through the Cori cycle.
Glycerol: The glycerol backbone, released from the breakdown of triglycerides during lipolysis, can be used as a substrate by the liver to synthesize glucose.
Glucogenic Amino Acids: Certain amino acids, derived from the breakdown of proteins, can be used by the liver for glucose synthesis.

Ketone Bodies: An Alternative Fuel for the Brain

During prolonged fasting or a very low-carbohydrate diet, the liver can produce a special type of fuel called ketone bodies through a process called ketogenesis. This occurs when there is an excess of acetyl-CoA generated from the beta-oxidation of fatty acids.

Ketones, primarily acetoacetate and beta-hydroxybutyrate, are water-soluble molecules that can be used by the brain and other tissues for energy when glucose is scarce.
This provides a crucial energy safety net for the brain, which cannot directly use fatty acids for fuel. The liver, interestingly, produces ketones but cannot use them for energy itself due to a missing enzyme.

Comparing the Body's Fuel Sources


Feature	Carbohydrates (Glycogen)	Fat	Protein (Amino Acids)
Availability	Limited, stored in liver and muscle	Plentiful, stored in adipose tissue	Abundant, but primarily used for building tissue
Energy Density	Lower (4 kcal/gram)	Highest (9 kcal/gram)	Lower (4 kcal/gram)
Speed of Breakdown	Very fast, ideal for high-intensity activity	Slower, requires more oxygen	Slow, only as a last resort
Primary Role	Immediate, high-intensity energy	Long-term, low-to-moderate intensity energy	Tissue repair and growth
Utilization When Glycogen is Low	Initial source until depleted	Primary energy source	Used for gluconeogenesis during starvation

The Role of Protein Catabolism

When the body's glycogen and fat stores are insufficient, it turns to protein as a last resort for energy. The breakdown of muscle tissue (protein catabolism) releases amino acids that can be converted into glucose via gluconeogenesis. This is not an efficient or desirable process, as it leads to the loss of lean muscle mass. During starvation, the body tries to preserve muscle for as long as possible, but it will eventually turn to it for survival. This muscle wasting is a clear indicator of a severe energy deficit.

Conclusion

When the body runs out of its readily available glycogen stores, it is a metabolic signal to shift into a different mode of energy production. This switch prioritizes the use of abundant fat reserves for general energy needs, while the liver works to provide vital glucose to the brain and other organs through gluconeogenesis and ketone body production. Only in extreme and prolonged states of deprivation does the body resort to breaking down its own muscle tissue. Understanding this metabolic hierarchy is crucial for athletes managing their fueling strategies and for anyone interested in the science of nutrition and weight management. For further reading, an in-depth review on glycogen metabolism for athletes and coaches is available from the National Institutes of Health.

Frequently Asked Questions

Leading up to full glycogen depletion, the body begins a gradual shift, increasing its reliance on fat for fuel while conserving its remaining carbohydrates. For endurance athletes, this transition can be signaled by a feeling of fatigue and the need to slow down.

After glycogen stores are low, the body increases its rate of fat oxidation for energy. However, fat burns less efficiently, so performance may decrease. For long-term fat loss, maintaining a consistent calorie deficit is key, not just depleting glycogen.

Yes, breaking down muscle protein for energy is not ideal. This process, known as catabolism, leads to muscle wasting and is reserved for states of prolonged starvation or severe carbohydrate restriction when other fuel sources are unavailable.

The time it takes to deplete glycogen stores depends on the intensity and duration of activity, as well as an individual's fitness level. For intense, prolonged exercise like a marathon, it can take a couple of hours. During normal daily activity, stores are replenished regularly.

Athletes can manage their glycogen stores through proper nutrition and training. Strategies include carbohydrate loading before a major event, consistently consuming enough carbohydrates in their diet, and refueling during prolonged exercise with carbohydrate-rich snacks or gels.

Glycogenolysis is the breakdown of existing glycogen stores into glucose, primarily in the liver and muscles. Gluconeogenesis is the creation of 'new' glucose from non-carbohydrate sources, such as lactate or amino acids, mainly occurring in the liver.

The brain cannot directly use fatty acids for fuel because they cannot cross the blood-brain barrier. Instead, it relies on glucose and, when glucose is scarce, can utilize ketone bodies produced by the liver from fat.