Is Creatine a Natural Supplement?
Yes, creatine is a naturally occurring compound synthesized endogenously in the liver, kidneys, and pancreas from amino acids (glycine, arginine, and methionine), and is also naturally present in dietary sources like meat and fish. 1
Natural Origin and Metabolism
- Creatine is produced naturally by the human body at approximately 1-2 grams per day, primarily in the liver and kidneys, making it an endogenous compound rather than a foreign substance. 1
- Dietary intake of creatine occurs naturally through consumption of skeletal and cardiac muscle tissue (meat and fish), which contains creatine that is absorbed and utilized by the body. 1
- Creatine spontaneously converts to creatinine in muscle tissue through a non-enzymatic process, which is then filtered by the kidneys and excreted in urine. 2
Safety Profile in Healthy Individuals
Creatine supplementation is safe for healthy individuals without pre-existing kidney disease, based on multiple controlled clinical trials showing no actual impairment of kidney function. 2, 3
- Multiple controlled studies demonstrate that creatine supplementation does not cause actual kidney dysfunction in healthy individuals, even with long-term use ranging from 5 days to 5 years at doses of 5-30 g/day. 2, 4
- A systematic review and meta-analysis found that creatine supplementation did not significantly alter serum creatinine levels or plasma urea values in a clinically meaningful way that indicates kidney damage. 5
- Short-term and long-term creatine supplementation had no significant effects on glomerular filtration rate in healthy athletes and bodybuilders without underlying kidney disease. 4
Critical Caveat: False Elevation of Serum Creatinine
The most important clinical pitfall is that creatine supplementation increases serum creatinine by 0.2-0.3 mg/dL through spontaneous conversion to creatinine, NOT through kidney damage, which can lead to misdiagnosis of kidney disease. 6, 2
- In a controlled study, creatine supplementation (20g/day) increased serum creatinine from 1.03 to 1.27 mg/dL while measured GFR using 51Cr-EDTA clearance remained completely unchanged (81.6 vs 82.0 mL/min/1.73m²), proving the elevation was false. 2
- eGFR formulas incorporating serum creatinine are unreliable in patients with high muscle mass or those taking creatine supplements, as they assume steady-state conditions that don't exist with supplementation. 6
- This false elevation can lead to over-diagnosis of chronic kidney disease with serious personal and public health consequences, including unnecessary restrictions and anxiety. 7
Contraindications: When to Avoid Creatine
Creatine supplementation should be avoided entirely in patients with pre-existing chronic kidney disease (GFR <45 mL/min/1.73m²), those with a solitary kidney, and individuals taking potentially nephrotoxic medications. 6, 2, 7
- The American Journal of Kidney Diseases explicitly discourages creatine supplementation in kidney donors with solitary kidneys due to the critical need to preserve remaining renal function. 6
- Patients with GFR <45 mL/min/1.73m² should avoid creatine entirely, as the safety profile in this population has not been adequately established. 6
- Animal studies in rats with cystic kidney disease showed that creatine supplementation worsened disease progression, evidenced by greater kidney weights, increased cyst scores, and lower creatinine clearances, suggesting particular caution in individuals with or at risk for renal disease. 8
- Combining creatine with NSAIDs or other nephrotoxic medications should be avoided, as this may unmask subclinical kidney stress. 6
Proper Assessment of Kidney Function During Supplementation
If kidney function assessment is needed in someone taking creatine, use cystatin C-based eGFR or direct GFR measurement methods, NOT creatinine-based estimates. 6, 2
- Cystatin C-based eGFR is not affected by muscle mass or creatine supplementation and provides a more accurate alternative for estimating kidney function. 2
- Check urinalysis with microscopy and spot urine albumin-to-creatinine ratio—the absence of proteinuria strongly suggests false creatinine elevation rather than true kidney disease. 6, 2
- If diagnostic uncertainty exists, discontinue creatine supplementation immediately and repeat serum creatinine and GFR measurements within 1-2 weeks to assess true baseline kidney function. 6