Creatine and Liver Function: What Blood Tests Actually Show

Concerns about creatine and liver health surface less frequently than kidney fears but follow a similar logic: because creatine is a supplement that passes through the body's metabolic machinery, some assume it must place strain on the liver. The liver synthesizes creatine endogenously, along with the kidneys and pancreas, so the organ is directly involved in creatine metabolism. The question is whether exogenous supplementation imposes additional hepatic burden, and the clinical data answers it clearly.

How the Body Handles Creatine

Endogenous creatine synthesis is a two-step process. The first step occurs in the kidneys, where the enzyme AGAT (arginine-glycine amidinotransferase) produces guanidinoacetate from arginine and glycine. The second step occurs in the liver, where the enzyme GAMT (guanidinoacetate N-methyltransferase) methylates guanidinoacetate to produce creatine. The liver then releases creatine into the bloodstream for uptake by muscles, the brain, and other tissues.

When creatine is taken as a supplement, it is absorbed through the gastrointestinal tract and enters the bloodstream directly. This actually bypasses much of the hepatic synthesis pathway. Exogenous creatine downregulates endogenous production through a feedback mechanism, meaning the liver synthesizes less creatine when dietary intake is adequate. In this sense, supplementation may reduce the liver's biosynthetic workload rather than increase it.

Clinical Liver Function Markers

The standard blood tests for liver function include alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and bilirubin. Elevation of these enzymes above reference ranges indicates hepatic stress, inflammation, or damage. In clinical trials of creatine supplementation, these markers have been measured repeatedly.

Poortmans and Francaux (1999) included hepatic function markers in their comprehensive safety assessment of long-term creatine users. Liver enzymes remained within normal ranges, with no statistically significant differences between creatine users and non-users. This study, published in Medicine & Science in Sports & Exercise, was one of the first to systematically examine liver function in supplementing athletes.

The extensive review by Kreider et al. (2017) in the ISSN position stand compiled liver function data from multiple trials. Across studies spanning weeks to years, using doses from 3 g/day (maintenance) to 20 g/day (loading), hepatic enzymes consistently remained within clinical norms. The review found no evidence that creatine monohydrate supplementation adversely affects liver function.

Long-Term Hepatic Data

Kreider et al. (2003) published data from athletes supplementing with creatine for up to 21 months. Their comprehensive metabolic panels included liver function tests. After nearly two years of continuous supplementation, hepatic markers showed no deviation from baseline values or from matched non-supplementing controls. The study measured ALT, AST, ALP, and bilirubin at multiple time points throughout the supplementation period.

Schilling et al. (2001) conducted a retrospective analysis of health markers in college athletes who had used creatine for variable durations. Liver function was assessed through standard enzyme panels. No pattern of hepatic stress or damage was identified. The authors noted that chronic creatine supplementation at typical doses appeared to have no detrimental effect on liver function.

These long-term datasets are particularly relevant because liver damage from supplements and medications typically follows a dose-duration pattern. Hepatotoxic substances tend to produce progressive enzyme elevations with continued use. The absence of such a pattern across years of supplementation provides strong negative evidence against hepatotoxicity.

Why the Concern Exists

The liver concern likely arises from two sources. First, a general assumption that any supplement taken regularly must burden the liver because the liver is the body's primary detoxification organ. This reasoning is overly broad. The liver processes everything in the bloodstream, including amino acids from food, glucose, lipids, and medications. The question is whether a specific substance causes damage, not whether it passes through hepatic metabolism.

Second, creatine is sometimes conflated with anabolic steroids in public perception. Oral anabolic steroids (particularly C-17 alpha-alkylated compounds) are known hepatotoxins that can cause peliosis hepatis, cholestasis, and liver tumors. Creatine is not a steroid. It is an amino acid derivative produced naturally by the human body. The metabolic pathways, mechanisms of action, and safety profiles of creatine and anabolic steroids have nothing in common beyond both being sold as supplements in some contexts.

Exercise and Liver Enzymes: A Confounding Factor

One nuance worth understanding is that intense exercise itself can transiently elevate liver enzymes, particularly AST. Aspartate aminotransferase is present in both liver tissue and skeletal muscle. A hard training session can release AST from muscle cells, producing a lab value that appears to indicate liver stress but actually reflects muscle damage from exercise. This effect is well-documented and is independent of supplementation.

Clinicians evaluating liver enzymes in active individuals who take creatine should be aware of this confound. An isolated AST elevation in someone who trained heavily the day before blood work is more likely exercise-induced than supplement-induced. The pattern to watch for hepatic issues is concordant elevation of multiple liver-specific markers (ALT, GGT, bilirubin), not isolated AST elevations.

None of the controlled studies examining creatine and liver function found patterns suggestive of hepatic injury, even after accounting for exercise-related confounds.

Special Populations

Research in clinical populations provides additional context. Creatine has been studied in patients with Parkinson's disease, Huntington's disease, muscular dystrophies, and type 2 diabetes. Many of these patients are on multiple medications that are themselves hepatically metabolized. Even in these pharmacologically complex situations, adding creatine supplementation has not produced evidence of liver dysfunction.

Individuals with pre-existing liver disease represent an understudied population. As with kidney disease, the absence of data in diseased livers means caution is appropriate. Patients with hepatitis, cirrhosis, fatty liver disease, or other hepatic conditions should discuss creatine supplementation with their hepatologist or gastroenterologist. The safety data applies to healthy livers, and extrapolation to diseased organs requires physician guidance.

Comparing Creatine to Known Hepatotoxins

For context, consider substances that actually cause liver damage. Acetaminophen (Tylenol) is the leading cause of acute liver failure in the United States. Alcohol is the leading cause of chronic liver disease. Many prescription medications carry FDA black box warnings for hepatotoxicity. These substances produce measurable, reproducible patterns of liver enzyme elevation, histological damage, and clinical symptoms.

Creatine produces none of these patterns. No case of liver failure has been attributed to creatine supplementation. No controlled study has found even subclinical liver enzyme elevations attributable to creatine. The contrast between creatine's safety profile and that of genuinely hepatotoxic substances is stark.

Summary

The clinical evidence is unambiguous. Creatine monohydrate supplementation at established doses (3-5 g/day maintenance, up to 20 g/day during loading) does not adversely affect liver function. This conclusion is supported by direct measurement of hepatic enzymes (ALT, AST, GGT, ALP, bilirubin) across multiple controlled trials with supplementation periods ranging from weeks to years. The ISSN position stand, the most authoritative review of creatine safety data, confirms that no hepatotoxic effects have been observed.

The liver concern, while understandable as a general caution about supplements, is not supported by clinical data specific to creatine. The endogenous biosynthesis of creatine by the liver, and the downregulation of that synthesis during supplementation, suggest that exogenous creatine may actually reduce hepatic biosynthetic demand rather than increase it.