What Depletes Creatine in the Body?: Understanding the Factors Behind Low Levels

October 6, 2025 •

5 min read

Approximately 95% of the body's creatine is stored in skeletal muscle, where it plays a central role in energy metabolism, particularly during high-intensity activities. So, what depletes creatine in the body? A variety of physiological and external factors can lead to a reduction in your body's creatine stores.

Quick Summary

Low creatine is caused by factors like dietary choices, reduced muscle mass from aging or disease, and impaired liver function, which hinders synthesis. Intense exercise also rapidly depletes phosphocreatine stores for energy.

Key Points

Low Dietary Intake: Vegetarians and vegans typically have lower muscle and blood creatine levels because they do not consume animal products, the main dietary source.
Reduced Muscle Mass: A decrease in muscle mass due to aging (sarcopenia), immobility, or muscle diseases directly reduces the body's capacity for creatine storage.
Liver Dysfunction: Since the liver is a primary site for creatine synthesis, diseases affecting liver function can significantly reduce the body's creatine production.
Intense Exercise: High-intensity, short-duration exercise rapidly depletes phosphocreatine (PCr) stores in muscles to provide immediate energy, necessitating time for recovery and replenishment.
Genetic Disorders: Rare genetic defects in the enzymes for creatine synthesis (AGAT, GAMT) or the creatine transporter (SLC6A8) can cause severe, chronic creatine depletion.
Medication Interactions: Some medications increase serum creatinine by interfering with kidney secretion, but this does not reflect a depletion of creatine stores. This is a crucial distinction from actual creatine depletion.
Hyperthyroidism: An overactive thyroid gland has been associated with lower circulating creatinine levels, likely due to alterations in muscle metabolism.

The Creatine Cycle: Synthesis, Storage, and Excretion

To understand what can cause low creatine levels, it is helpful to first understand how the body produces and utilizes it. Creatine is a nitrogenous organic acid that is synthesized from the amino acids glycine, arginine, and methionine.

Synthesis: The process primarily takes place in the kidneys, liver, and pancreas. The enzyme L-arginine:glycine amidinotransferase (AGAT) catalyzes the initial step in the kidneys, while the final methylation step is handled by guanidinoacetate N-methyltransferase (GAMT) in the liver.
Storage and Use: After synthesis, creatine is transported through the bloodstream to tissues with high energy demands, with about 95% ending up in skeletal muscle. Here, creatine kinase (CK) facilitates the conversion of creatine to phosphocreatine (PCr), a high-energy phosphate molecule that can quickly regenerate ATP during intense, short-burst exercise.
Excretion: The body continuously and non-enzymatically converts creatine into creatinine, a waste product that is filtered out of the blood by the kidneys and excreted in the urine. Creatinine levels are often measured in blood and urine to assess kidney function, but this can be a confounding factor when evaluating creatine depletion directly.

Primary Factors That Deplete Creatine

Low Dietary Intake

One of the most straightforward causes of low creatine stores is a diet lacking in its primary sources. Creatine is found almost exclusively in animal products, particularly red meat and fish.

Vegetarian and Vegan Diets: Individuals following these diets consume very little to no exogenous creatine, meaning they rely entirely on their body's endogenous synthesis. This often results in significantly lower baseline creatine levels in muscle, though not necessarily in the brain.
Malnutrition: A prolonged period of low protein intake, whether due to a restrictive diet or an underlying health issue, can also contribute to lower creatine levels. The amino acid precursors needed for synthesis are limited in these circumstances.

Reduced Muscle Mass (Sarcopenia)

Since the majority of creatine is stored in skeletal muscle, any condition that leads to a reduction in muscle mass will inherently decrease the body's creatine reserves.

Aging: As people age, a natural loss of muscle mass, known as sarcopenia, occurs, leading to lower creatine stores and circulating creatinine.
Lack of Exercise or Immobility: A sedentary lifestyle, as well as conditions causing immobility, reduces muscle mass and, consequently, creatine.
Muscle Disease: Certain diseases, such as muscular dystrophy, cause progressive muscle wasting, which results in low creatine levels.

Liver Disease

The liver is a key site for creatine synthesis. Chronic liver disease can significantly impair this function.

Impaired Production: Severe liver disease can reduce creatine production by as much as 50%, leading to lower creatine and creatinine levels.

Intense Exercise

While exercise is often associated with higher creatine uptake and storage, the very act of high-intensity activity causes a temporary depletion.

PCr System: During short, maximal bursts of exercise, the phosphocreatine (PCr) system is activated to rapidly regenerate ATP. This process quickly consumes available PCr, requiring time for replenishment. Over time, consistent heavy resistance training combined with adequate intake can increase overall creatine stores.

Medical Conditions and Medications Affecting Creatine Levels

Creatine Synthesis and Transport Defects

Rare genetic disorders can disrupt creatine metabolism, causing severe depletion and affecting organs like the brain and muscles. These include deficiencies in the enzymes AGAT or GAMT, or a defect in the creatine transporter (SLC6A8).

Hyperthyroidism

An overactive thyroid gland (hyperthyroidism) is associated with reduced serum creatinine levels. The exact mechanism is not fully understood, but it is believed to involve altered muscle metabolism.

Pregnancy

During pregnancy, an increased glomerular filtration rate (GFR) can lead to more efficient removal of creatinine by the kidneys. This can result in lower circulating creatinine levels, which is a normal physiological change and does not necessarily indicate a problem with creatine stores.

Medications and Creatinine Levels: An Important Distinction

This is a critical pharmacological point. While some medications are known to increase serum creatinine levels, they do so by inhibiting its renal secretion, not by depleting creatine stores. In fact, they can create a misleading reading of kidney function.

Examples: Common drugs like the antibiotic trimethoprim and the H2-blocker cimetidine can interfere with creatinine secretion.
Long-Term Kidney Damage: Separately, the prolonged use of drugs like NSAIDs can cause direct kidney damage, which would indirectly affect the body's ability to filter creatinine.

Comparison of Factors Affecting Creatine


Factor	Effect on Creatine Levels	Primary Mechanism
Vegetarian/Vegan Diet	Lower muscle and blood creatine levels	Reduced dietary intake of creatine from animal products.
Reduced Muscle Mass	Lower total body creatine stores	Less tissue available to store creatine (e.g., sarcopenia).
Liver Disease	Lower endogenous creatine production	Impaired function of the liver, a major site of synthesis.
Intense Exercise	Temporary depletion of PCr stores	Rapid use of phosphocreatine for ATP resynthesis.
Creatine Synthesis Defects	Chronically low creatine levels	Genetic issues with enzymes (AGAT, GAMT) or transport (SLC6A8).
Hyperthyroidism	Lower circulating creatine	Believed to be due to altered muscle metabolism.
Pregnancy	Lower circulating creatinine	Increased kidney filtration rate leads to greater excretion.

Conclusion

Creatine levels in the body are the result of a delicate balance between dietary intake, endogenous synthesis, storage in muscle tissue, and metabolism into creatinine for excretion. While intense exercise can temporarily deplete the high-energy form of creatine (PCr), long-term or chronic depletion is often linked to more significant underlying issues.

Key factors that can lead to depleted creatine stores include a lack of dietary intake, most notably in vegetarian and vegan diets, and a reduction in muscle mass due to aging, inactivity, or disease. Liver dysfunction can also inhibit the body's natural synthesis capabilities. It is crucial to distinguish between true creatine depletion and misleading creatinine test results caused by certain medications.

If you have concerns about consistently low creatine or creatinine levels, it is best to consult a healthcare professional. They can help determine the root cause, whether it's dietary, physiological, or related to an underlying medical condition. In cases of insufficient dietary intake, particularly for those on plant-based diets, supplementation with creatine monohydrate has been shown to be safe and effective for restoring levels.

Frequently Asked Questions

Yes, diet can cause low creatine levels. Vegetarians and vegans, who do not consume animal products like meat and fish, often have lower creatine stores because they rely solely on their body's internal synthesis.

Creatine is an amino acid stored in muscles for energy, while creatinine is the waste product created when creatine is metabolized. Creatinine is filtered by the kidneys and excreted in the urine. Measuring creatinine levels is often used to gauge kidney function, but can sometimes be misleading regarding actual creatine stores.

While not medically necessary for all, creatine supplementation can be particularly beneficial for vegetarians and vegans to increase their lower baseline muscle creatine stores. Studies have shown supplementation can enhance physical performance and cognitive function in this group.

Intense, short-duration exercise rapidly uses phosphocreatine (PCr), a high-energy form of creatine, for energy. This creates a temporary depletion of PCr, but consistent training and adequate creatine intake can lead to overall higher creatine storage over time.

The liver is one of the primary organs responsible for synthesizing creatine from amino acid precursors. Therefore, liver disease or impaired liver function can reduce the body's natural production of creatine, leading to lower levels.

Medical conditions that can lower creatine include muscle-wasting diseases like muscular dystrophy, chronic liver disease, genetic defects in creatine synthesis or transport, and hyperthyroidism.

Not directly. Certain medications, like trimethoprim and cimetidine, can increase serum creatinine levels by inhibiting its excretion by the kidneys. This does not mean creatine stores are being depleted, but rather that a test result may inaccurately reflect kidney function.