Is most of the liver's glycogen storage depleted during an overnight fast? Understanding your body's energy shift

November 18, 2025 •

4 min read

During a typical overnight fast, anywhere from 60% to 80% of the liver's glycogen is utilized to maintain stable blood sugar levels. This critical process prevents hypoglycemia and ensures a constant fuel supply for the brain, directly answering the question: is most of the liver's glycogen storage depleted during an overnight fast?

Quick Summary

An overnight fast significantly depletes the liver's glycogen reserves to provide glucose for the brain, while muscle glycogen remains largely intact. This metabolic shift is tightly regulated by hormones and prepares the body for alternative energy sources if fasting continues.

Key Points

Significant Depletion: Most of the liver's glycogen storage is depleted during an overnight fast, typically losing 60-80% of its reserves.
Brain's Primary Fuel: The brain's constant need for glucose is the main reason for liver glycogen depletion during sleep and other short-term fasts.
Muscle Glycogen Preserved: Muscle glycogen is reserved for localized muscle energy and remains largely untouched during an overnight fast, as it cannot be released into the bloodstream.
Metabolic Switch to Fat: As liver glycogen is depleted, the body transitions to burning fat (ketogenesis) and producing glucose from non-carb sources (gluconeogenesis).
Hormonal Control: Hormones like glucagon signal the liver to release glucose from its glycogen stores to maintain stable blood sugar levels.
Individual Factors: The exact rate and extent of depletion depend on diet, recent exercise, and an individual's metabolic health.

The Body's Energy Reserves: A Primer

To comprehend what happens during an overnight fast, one must first understand the body's energy storage system. Glycogen is the primary storage form of glucose, a readily available fuel source. While the body stores glycogen in both the liver and muscles, these reserves serve fundamentally different purposes, a distinction crucial for understanding the impact of fasting.

The Liver's Crucial Role in Maintaining Blood Glucose

During a fast, the liver acts as the body's central glucose regulator. After the absorption of a recent meal, blood glucose levels begin to drop. In response, the pancreas releases the hormone glucagon, which signals the liver to break down its stored glycogen (a process called glycogenolysis) and release glucose into the bloodstream. This steady release of glucose is essential for maintaining the normal physiological range of blood sugar, preventing a state of hypoglycemia that could compromise brain function. The brain's high and continuous demand for glucose, even during sleep, is the primary driver of liver glycogen depletion overnight.

The Extent of Overnight Depletion

Research confirms that a substantial portion of the liver's glycogen is used up during a typical 8- to 12-hour overnight fast. Estimates suggest that 60% to 80% of hepatic glycogen is consumed to fuel the brain and other glucose-dependent tissues. For example, a liver starting with approximately 90 grams of glycogen may end the night with only about 20 grams remaining. The precise depletion rate can vary based on factors like an individual's diet and prior physical activity levels.

Liver Glycogen vs. Muscle Glycogen: A Comparison

While the liver is working to supply the entire body, muscle glycogen remains largely untouched during an overnight fast. This is because muscle cells lack the specific enzyme (glucose-6-phosphatase) required to release glucose into the bloodstream. Muscle glycogen is reserved for the muscle's own energy needs during activity. This specialized function highlights why muscle reserves don't contribute to systemic glucose regulation. The following table summarizes the key differences:


Feature	Liver Glycogen	Muscle Glycogen
Primary Role	Regulates blood glucose levels for the entire body.	Provides energy for the specific muscle it's stored in.
Glucose Release	Yes, glucose can be released into the bloodstream.	No, glucose cannot be released into the bloodstream.
Overnight Depletion	Substantial (60-80%) to maintain blood sugar.	Minimal, reserved for muscular activity.
Total Storage	Approximately 100-120g in a healthy adult.	Much higher overall (400-500g), dependent on muscle mass and training.

The Metabolic Shift: From Glucose to Fat

After the liver's glycogen reserves are significantly diminished—typically after about 18 to 24 hours of fasting—the body undergoes a significant metabolic shift. The primary mechanism for glucose production, glycogenolysis, is replaced by two key processes:

Gluconeogenesis: The liver begins producing new glucose from non-carbohydrate sources, such as amino acids and glycerol. This helps maintain minimum blood glucose levels for the brain and red blood cells.
Lipolysis and Ketogenesis: As insulin levels fall and glucagon rises, fat stores are broken down into fatty acids (lipolysis). In the liver, these fatty acids are converted into ketone bodies, which can serve as an alternative energy source for many organs, including a large portion of the brain. This process, known as ketogenesis, becomes the dominant fuel source during prolonged fasting.

Factors Influencing Glycogen Depletion

The rate and extent of liver glycogen depletion are not static. Key factors include:

Diet: A high-carbohydrate diet will result in higher baseline glycogen stores, prolonging the time before significant depletion occurs. Conversely, a very low-carb diet can lead to lower stores and a faster transition to ketosis.
Exercise: High-intensity exercise can deplete both liver and muscle glycogen, accelerating the need for replenishment or alternative fuel sources. Training status also plays a role, as trained athletes can store more muscle glycogen.
Metabolic Health: Conditions such as insulin resistance can affect the body's ability to store and utilize glycogen efficiently, altering the fasting metabolic response.

Conclusion

In summary, a typical overnight fast does indeed deplete a large portion of the liver's glycogen stores, primarily to supply the brain with glucose. While this is a normal physiological process, it is important to remember that muscle glycogen is spared. The body has evolved intricate mechanisms, including hormonal regulation and the ability to transition to fat burning, to ensure energy homeostasis during periods without food. This adaptability is fundamental to our survival and is a major reason why overnight fasting is a manageable and natural part of daily life.

For additional scientific context on the metabolic response to fasting, see the NCBI Bookshelf entry on the physiology of fasting.

Frequently Asked Questions

The liver is the body's central glucose regulator because, unlike muscle cells, liver cells contain the enzyme necessary to release glucose into the bloodstream, making it available to all other organs.

The primary purpose is to maintain stable blood glucose levels for the brain, which relies on a constant glucose supply to function properly, even while you are sleeping.

Yes, as the liver's glycogen stores diminish over several hours, the body increases fat burning (lipolysis) and begins converting fat into ketones to be used for energy.

Once liver glycogen is fully depleted, the body increases gluconeogenesis (creating glucose from non-carb sources) and relies more heavily on fat-derived ketone bodies for energy.

No, an overnight fast is a short-term fast where liver glycogen is the primary energy source. Extended fasting, lasting 24 hours or more, relies more on fat metabolism and gluconeogenesis after glycogen stores are exhausted.

In a well-fed individual, liver glycogen typically lasts between 18 and 24 hours. After an overnight fast, a significant portion is gone, but some reserves typically remain.

Yes, an intense workout can deplete both muscle and liver glycogen, which means the body will have lower reserves at the start of an overnight fast and may transition to other fuel sources sooner.