Creatine Supplementation and Creatinine: Why Your Lab Results Look High

If you take creatine and your doctor has flagged elevated creatinine or reduced eGFR on your blood work, this article explains what is happening and what it means. The short answer is that creatine supplementation predictably raises serum creatinine because creatinine is a direct metabolic byproduct of creatine. This increase does not indicate kidney damage. But the standard equations used to estimate kidney function interpret it as if it does, creating a diagnostic artifact that can lead to unnecessary concern, additional testing, and potentially inappropriate medical decisions.

The Biochemistry: Creatine to Creatinine

Creatine is stored primarily in skeletal muscle as free creatine and phosphocreatine. A fixed percentage of the total creatine pool, approximately 1.7% per day, undergoes non-enzymatic, irreversible conversion to creatinine. This is a spontaneous chemical reaction (cyclization and dehydration) that occurs at a rate proportional to the total body creatine pool.

When you supplement with creatine monohydrate, your intramuscular creatine stores increase from approximately 120 mmol/kg dry muscle to 140-160 mmol/kg dry muscle (the saturation point). With a larger creatine pool, the absolute amount of creatinine produced per day increases proportionally. This additional creatinine enters the bloodstream and is cleared by the kidneys through glomerular filtration. Serum creatinine rises because production increases, not because clearance decreases.

This distinction is fundamental. In kidney disease, serum creatinine rises because the kidneys cannot adequately filter and excrete creatinine. In creatine supplementation, serum creatinine rises because more creatinine is being produced. The kidneys are working normally in both cases, but in only one case (kidney disease) is the elevated creatinine a signal of pathology.

How eGFR Is Calculated and Why It Fails Here

The estimated glomerular filtration rate (eGFR) reported on standard metabolic panels is calculated using serum creatinine as the primary input variable. The most commonly used equations are the CKD-EPI equation and the older MDRD equation. Both work by mathematically relating serum creatinine to the rate at which the kidneys must be filtering blood to produce that creatinine level, adjusted for age, sex, and race.

These equations were developed and validated in non-supplementing populations. They assume that serum creatinine variation reflects variation in kidney filtration, not variation in creatinine production. In a typical clinical population, this assumption holds reasonably well. In a creatine-supplementing individual, it breaks down.

Consider a concrete example. A healthy 30-year-old male has a baseline serum creatinine of 1.0 mg/dL, producing an eGFR of approximately 100 mL/min/1.73m2 (normal). After starting creatine supplementation, his serum creatinine rises to 1.3 mg/dL due to increased creatinine production. The CKD-EPI equation now calculates an eGFR of approximately 76 mL/min/1.73m2. This falls into the "mildly decreased" category on many lab report reference ranges and may trigger clinical flags for stage 2 chronic kidney disease.

The man's kidneys have not changed. His actual GFR is still approximately 100 mL/min/1.73m2. The equation has produced a false result because its core assumption (that elevated creatinine reflects reduced filtration) is violated by creatine supplementation.

How to Get Accurate Results

Several approaches can provide accurate kidney function assessment in creatine users:

Cystatin C-based eGFR. Cystatin C is a small protein produced by all nucleated cells at a relatively constant rate. It is freely filtered by the kidneys and not affected by muscle mass, diet, or creatine supplementation. The CKD-EPI equation has a cystatin C-based variant that provides eGFR without relying on serum creatinine. This is the simplest solution: ask your physician to order a cystatin C level and calculate eGFR using the cystatin C equation.

Combined creatinine-cystatin C equation. The CKD-EPI combined equation uses both creatinine and cystatin C as inputs. In creatine users, the discordance between a high creatinine-based eGFR and a normal cystatin C-based eGFR immediately reveals the supplementation artifact. The combined equation produces a value closer to the true GFR.

24-hour urine creatinine clearance. This test measures the actual volume of blood the kidneys clear of creatinine per minute by collecting all urine produced over 24 hours and simultaneously measuring serum creatinine. Unlike the estimated equations, this test directly measures clearance rather than estimating it. In creatine users, the clearance will be normal because the kidneys are handling the increased creatinine load without difficulty.

Temporary cessation. Stopping creatine supplementation for 4-6 weeks before blood work allows creatine stores to deplete and creatinine production to return to baseline. This approach is definitive but impractical for regular monitoring and sacrifices the benefits of supplementation during the washout period.

What Poortmans and Francaux Found

Poortmans and Francaux (1999) directly addressed this issue in their landmark study published in Medicine & Science in Sports & Exercise. They measured actual GFR (not estimated) in creatine-supplementing athletes and found it to be normal. They also measured albumin excretion rate, another independent marker of kidney health, and found it to be normal. Their study demonstrated definitively that elevated serum creatinine in creatine users reflects increased creatinine production, not decreased kidney function.

This study remains one of the most important references for clinicians evaluating creatine users. It provides direct evidence that the kidney function concern triggered by elevated creatinine in this population is a diagnostic artifact, not a clinical finding.

Communicating With Your Healthcare Provider

The practical challenge for creatine users is that many physicians are unfamiliar with this artifact. A productive conversation might include the following points:

First, disclose creatine supplementation before blood work, not after results come back. Proactive disclosure frames the elevated creatinine as an expected finding rather than a surprise that triggers concern.

Second, explain the mechanism. Creatine is converted to creatinine in the body. Supplementation increases creatine stores, which increases creatinine production, which raises serum creatinine. The kidneys are not involved in this elevation.

Third, request a cystatin C level if your physician wants to verify kidney function. This provides an independent, creatine-unaffected measure of filtration.

Fourth, reference the Poortmans and Francaux study and the ISSN position stand. These peer-reviewed sources provide authoritative evidence that creatine does not impair kidney function in healthy individuals and that elevated creatinine in this context is expected and benign.

When Elevated Creatinine IS Concerning

Not every elevated creatinine in a creatine user can be dismissed as a supplementation artifact. If creatinine rises significantly above what supplementation alone would explain, or if other markers suggest kidney dysfunction (elevated BUN disproportionate to creatinine, proteinuria, abnormal urinalysis, hypertension, edema), these findings warrant genuine clinical evaluation regardless of supplementation status.

The expected creatinine elevation from creatine supplementation is modest. A rise of 0.1-0.3 mg/dL above the individual's pre-supplementation baseline is typical. Values significantly higher than this, or progressive increases over time, should not be automatically attributed to supplementation and may warrant investigation.

Creatine users who have not established a pre-supplementation creatinine baseline face a challenge: they cannot distinguish between the supplementation artifact and a genuine change. If you plan to use creatine long-term, obtaining baseline blood work before starting supplementation provides a reference point for future comparisons.

Summary

Creatine supplementation predictably elevates serum creatinine by 0.1-0.3 mg/dL because creatinine is a direct metabolic byproduct of creatine. This elevation produces falsely low eGFR values on standard metabolic panels, creating the appearance of kidney dysfunction where none exists. The solution is to use cystatin C-based GFR estimation, which is unaffected by creatine intake. Disclosure of supplementation to healthcare providers before blood work prevents misinterpretation and unnecessary clinical interventions.