How Is Creatine Processed by the Liver or Kidneys? A Comprehensive Guide

November 18, 2025 •

4 min read

The human body naturally produces its own supply of creatine, a nitrogenous organic acid, from amino acids. However, many people opt for creatine supplements to boost performance, which often leads to the question: is creatine processed by the liver or kidneys? Both organs play distinct and vital roles in the creatine pathway.

Quick Summary

Creatine synthesis is a two-step process involving both the kidneys and the liver. The kidneys begin the process, and the liver completes it. The kidneys are primarily responsible for filtering creatinine, the natural waste product of creatine, from the blood.

Key Points

Synthesis is a Joint Effort: Creatine is synthesized in both the kidneys and the liver, not exclusively by one organ.
The Kidneys Initiate Synthesis: The first step of creatine synthesis, converting arginine and glycine to guanidinoacetate (GAA), happens mostly in the kidneys.
The Liver Completes Synthesis: The second and final step, which turns GAA into creatine, takes place in the liver.
Kidneys Filter Creatinine: The kidneys are responsible for filtering creatinine, the waste product of creatine, from the bloodstream for excretion.
Generally Safe for Healthy Organs: Decades of research show that creatine supplementation does not harm the liver or kidneys in healthy individuals when taken at recommended doses.
High Creatinine Doesn't Mean Damage: Increased serum creatinine levels from creatine use are normal and do not indicate kidney damage in healthy people.
Consult a Doctor if Ill: Individuals with pre-existing kidney or liver conditions should consult a doctor before using creatine supplements.

The Dual-Role of the Kidneys and Liver in Creatine Synthesis

Creatine is not the sole domain of a single organ, but rather the result of a coordinated two-step process involving both the kidneys and the liver. This endogenous synthesis is crucial for maintaining the body's natural creatine pool, especially for individuals with low dietary intake.

Step 1: Initiation in the Kidneys

The initial reaction of creatine synthesis occurs primarily in the kidneys. This step involves the enzyme L-arginine:glycine amidinotransferase (AGAT), which transfers an amidino group from the amino acid arginine to another amino acid, glycine. The products of this reaction are ornithine and guanidinoacetate (GAA). GAA is an intermediate compound that is then released into the bloodstream.

Step 2: Completion in the Liver

After being synthesized in the kidneys, the intermediate GAA travels through the bloodstream to the liver. In the liver, the enzyme guanidinoacetate N-methyltransferase (GAMT) methylates GAA, using S-adenosylmethionine (SAM) as the methyl donor. This final step converts GAA into creatine. Once produced, the liver releases creatine back into the bloodstream for transport to high-energy-demand tissues, most notably skeletal muscle.

The Journey of Creatinine: From Muscle to Kidney Excretion

Creatinine is the waste product of creatine metabolism, and its journey is distinctly different from that of its precursor. Approximately 1-2% of the body's stored creatine is converted daily into creatinine, a spontaneous and non-enzymatic reaction.

Role of the Kidneys in Creatinine Excretion

The kidneys play the primary role in processing and eliminating creatinine. As a relatively small molecule, creatinine is freely filtered by the glomerulus within the kidneys. Unlike other substances, it is not significantly reabsorbed by the renal tubules, allowing for its efficient removal from the blood. The total amount of creatinine excreted is directly related to an individual's muscle mass. A common misconception arises from the fact that standard kidney function tests measure serum creatinine levels. Because creatine supplementation increases the overall creatine pool, it can lead to higher baseline creatinine levels, which may be misinterpreted as poor kidney function in healthy individuals. However, numerous studies have confirmed that creatine supplementation does not cause renal damage in healthy individuals.

The Creatine Metabolism Pathway: A Comparison


Process	Location	Primary Role	Precursors/Byproducts
Creatine Synthesis	Kidneys & Liver	Endogenous Production	Arginine, Glycine, GAA
Creatine Storage	Skeletal Muscle	Energy Reserve	Phosphocreatine
Creatinine Production	Muscles (Spontaneous)	Waste Product Formation	Breakdown of Creatine
Creatinine Excretion	Kidneys (Glomerulus)	Waste Elimination	Creatinine

Is Creatine Safe for Healthy Liver and Kidneys?

Decades of research have addressed the safety of creatine supplementation on organ function, yielding overwhelmingly positive results for healthy individuals. Case reports suggesting kidney damage are rare and typically involve individuals with pre-existing conditions or those taking excessive doses.

Scientific Evidence for Safety

Extensive Research: Hundreds of studies have examined creatine's safety, including long-term use, and found no evidence of harm to the liver or kidneys in healthy populations.
No Impact on Function: Systematic reviews have concluded that creatine supplementation does not significantly alter markers of renal function, such as serum creatinine and urea, in healthy subjects.
Proper Hydration: Creatine draws water into muscle cells, so maintaining adequate hydration is important, particularly during intense exercise. Insufficient hydration, rather than the supplement itself, can cause undue stress on the kidneys.

Creatine's Benefits to Liver Function Beyond its safety, creatine has even shown potential benefits for liver health in some contexts. Studies have found that creatine supplementation may help reduce fat accumulation and decrease homocysteine production in the liver, leading to beneficial effects in fatty liver conditions.

Considerations for Individuals with Pre-Existing Conditions For those with a history of liver or kidney disease, it is crucial to consult a healthcare professional before beginning creatine supplementation. While creatine is generally safe, any individual with compromised organ function should be cautious and seek medical advice, as their ability to process supplements or waste products may be affected.

A Summary of the Creatine Pathway

Here is a step-by-step breakdown of how creatine is handled within the body:

Amino acids (arginine and glycine) are used by the enzyme AGAT in the kidneys to produce GAA.
GAA is released from the kidneys into the bloodstream and travels to the liver.
In the liver, GAA is methylated by the enzyme GAMT to form creatine.
Creatine is released into the blood and transported to muscle tissue via specific transporters.
Once in the muscle, creatine is largely phosphorylated to phosphocreatine, an energy reserve.
Daily, a small percentage of creatine spontaneously breaks down into creatinine.
Creatinine is released from the muscles into the bloodstream.
The kidneys filter creatinine from the blood and excrete it in the urine.

Conclusion

In summary, the question "is creatine processed by the liver or kidneys" reveals a complex metabolic process involving both organs. Creatine is synthesized in a two-stage process, beginning in the kidneys and concluding in the liver. Its subsequent waste product, creatinine, is then filtered and eliminated by the kidneys. While a temporary increase in creatinine levels is a normal physiological response to supplementation and reflects increased muscle mass and supplement intake, extensive research confirms that creatine is safe for the liver and kidneys in healthy individuals when taken at recommended doses. For those with pre-existing conditions, consultation with a healthcare provider is always the safest approach. Understanding this metabolic pathway dispels myths and reinforces the safety of one of the most well-researched supplements available. For further reading, consult the International Society of Sports Nutrition's comprehensive position stand on creatine: Creatine in Health and Disease.

Frequently Asked Questions

For healthy individuals, creatine metabolism is not hard on the kidneys. The kidneys are well-equipped to handle the increased creatinine that results from supplementation. Concerns are primarily for those with pre-existing kidney disease.

No, extensive research has found no evidence that creatine supplementation at recommended doses causes liver damage in healthy individuals. In fact, some studies suggest it may offer potential benefits for liver health.

Yes, creatine supplementation can slightly increase serum creatinine levels, which is a key marker in kidney function tests. This can sometimes be misinterpreted as poor kidney function, but it is a normal physiological response in healthy individuals.

Creatinine is a waste product of creatine metabolism that is produced naturally by the muscles and freely filtered by the kidneys. It's an important diagnostic marker used to estimate kidney function.

A loading phase (higher initial dose) is not necessary for creatine supplementation to be effective. A lower, consistent daily dose of 3-5 grams will achieve the same results over a slightly longer period.

If you stop taking creatine, your phosphocreatine levels in the muscle will gradually return to their baseline over several weeks. Any associated water retention will also subside.

No, creatine is not an anabolic steroid. It is a naturally occurring compound in the body, made from amino acids. It works by helping to regenerate ATP for energy, not by mimicking hormones like steroids.