Does taking creatine (a dietary supplement) increase serum creatinine levels in individuals with normal kidney function?

Does Creatine Supplementation Increase Serum Creatinine?

Yes, creatine supplementation does increase serum creatinine levels by approximately 0.2-0.3 mg/dL, but this elevation is a false signal that does not represent actual kidney damage or dysfunction. 1, 2, 3

Mechanism of the False Elevation

The increase in serum creatinine occurs because creatine spontaneously converts to creatinine through non-enzymatic degradation, not because of kidney impairment. 1, 2 This is a critical distinction:

• Creatine → Creatinine conversion is a chemical process, independent of kidney function 2
• In a controlled study, creatine supplementation (20g/day for 5 days, then 5g/day for 30 days) increased serum creatinine from 1.03 to 1.27 mg/dL, yet measured GFR using 51Cr-EDTA clearance remained completely unchanged (81.6 vs 82.0 mL/min/1.73m²) 1, 3
• This demonstrates that elevated creatinine from supplementation does not reflect reduced glomerular filtration 2, 3

Why This Creates Diagnostic Confusion

eGFR formulas incorporating serum creatinine are unreliable in patients with high muscle mass or those taking creatine supplements. 1 The problem compounds because:

• Standard laboratory reports automatically calculate eGFR based on serum creatinine, which will falsely suggest kidney dysfunction 1
• This can lead to misdiagnosis of chronic kidney disease when none exists 1
• The elevation may trigger unnecessary nephrology referrals, medication adjustments, or discontinuation of beneficial therapies 1

How to Distinguish False from True Kidney Dysfunction

When evaluating someone on creatine supplements with elevated creatinine, use these alternative assessments:

• Measure cystatin C-based eGFR, which is unaffected by muscle mass or creatine supplementation and provides accurate kidney function assessment 1, 2
• Check for proteinuria/albuminuria - its absence strongly suggests false elevation rather than true kidney disease 1, 2
• Obtain urinalysis with microscopy looking for hematuria, cellular casts, or acanthocytes that would indicate intrinsic kidney disease 1
• Consider direct GFR measurement (such as 51Cr-EDTA clearance or iothalamate clearance) rather than creatinine-based estimates 2

Safety Evidence in Healthy Individuals

Multiple controlled studies demonstrate that creatine supplementation does not cause actual kidney dysfunction in healthy individuals, even with long-term use. 2, 4 Specifically:

• A systematic review and meta-analysis found creatine supplementation did not significantly alter serum creatinine levels in a clinically meaningful way and did not alter plasma urea values 5
• Studies ranging from 5 days to 5 years with doses from 5-30 g/day showed no significant effects on kidney function indices in healthy athletes 6
• The 2023 narrative review in Nutrients concluded that creatine supplements are safe for human consumption based on studies using reliable kidney function assessment methods 4

Who Should Avoid Creatine

Creatine supplementation should be avoided in individuals with pre-existing chronic kidney disease or risk factors for renal dysfunction (diabetes, hypertension). 1, 2 The nephrology community specifically recommends:

• Kidney donors with solitary kidneys should not use creatine due to critical need to preserve remaining renal function 1
• Patients with GFR <45 mL/min/1.73m² should avoid creatine entirely 1
• Avoid combining creatine with nephrotoxic medications (NSAIDs, certain antibiotics) as this may unmask subclinical kidney stress 1

Common Pitfalls to Avoid

• Do not discontinue ACE inhibitors or ARBs based solely on creatinine elevation in someone taking creatine - small elevations up to 30% from baseline with RAS blockers should not prompt medication discontinuation in the absence of volume depletion 7, 2
• Do not use 24-hour urine creatinine clearance as it is less accurate than prediction equations and subject to collection errors 1
• Do not rely on serum creatinine alone - it should never be used to assess kidney function due to multiple confounding factors 1
• Remember that eGFR calculations assume steady-state conditions and are invalid when creatinine is acutely elevated from non-renal causes like creatine supplementation 1

Practical Management Algorithm

If you encounter elevated creatinine in someone taking creatine:

1. First, check urinalysis and spot urine albumin-to-creatinine ratio - if normal, this strongly suggests false elevation 1
2. Order cystatin C-based eGFR to get accurate kidney function assessment 1, 2
3. If diagnostic uncertainty persists, discontinue creatine and recheck serum creatinine in 1-2 weeks to assess true baseline 1
4. Maintain consistent hydration before testing and avoid intense exercise 24 hours prior, as muscle breakdown releases creatinine 1