Is creatine supplementation safe for healthy adults, and what are the contraindications for individuals with renal or hepatic disease, hypertension, diabetic nephropathy, pregnancy, or in adolescents/children?

Is Creatine Safe?

Creatine supplementation is safe for healthy adults at recommended doses (3-5 g/day), but should be avoided in individuals with pre-existing renal disease, diabetic nephropathy, hypertension with reduced kidney function (eGFR <45 mL/min/1.73 m²), pregnancy, and those with a solitary kidney. 1, 2, 3

Safety Profile in Healthy Adults

Creatine monohydrate has been extensively studied with over 500 peer-reviewed publications demonstrating relative safety at recommended maintenance doses of 3-5 g/day or 0.1 g/kg body weight/day. 2 Clinical trials with controlled designs consistently show that creatine supplementation does not impair kidney function in healthy individuals when used at these doses. 4

• Loading doses of 20 g/day for 5-7 days followed by maintenance dosing of 3 g/day have been studied for periods up to several months without adverse effects on liver or kidney function in healthy populations. 5, 3
• The most common side effect is transient water retention during early supplementation, which is physiologic rather than pathologic. 2, 5

Critical Contraindications

Renal Disease and Risk Factors

Individuals with pre-existing kidney disease or risk factors for renal dysfunction must avoid creatine supplementation. 3

• Patients with eGFR <45 mL/min/1.73 m² should not use creatine, as this represents moderate-to-severe chronic kidney disease where preservation of remaining renal function is paramount. 1
• Those with diabetic nephropathy (particularly with urinary albumin >300 mg/g creatinine) should avoid creatine entirely. 6, 1
• Individuals with hypertension and reduced kidney function are at increased risk and should not supplement. 3

Solitary Kidney

The American Journal of Kidney Diseases explicitly discourages creatine supplementation in kidney donors and individuals with a solitary kidney due to the critical need to preserve remaining renal function. 1 This recommendation stems from the principle that any substance with uncertain long-term effects should be avoided when renal reserve is already compromised.

Pregnancy

Creatine supplementation is not recommended during pregnancy due to lack of safety data in this population. 6

Diagnostic Pitfall: Elevated Serum Creatinine

A critical caveat is that creatine supplementation increases serum creatinine by 0.2-0.3 mg/dL through non-pathologic conversion of creatine to creatinine, which can falsely suggest kidney dysfunction. 1

• eGFR calculations based on serum creatinine become unreliable during creatine supplementation because they assume steady-state conditions. 1
• If kidney function assessment is needed during supplementation, use cystatin C-based eGFR or measured GFR rather than creatinine-based estimates. 1
• A single elevated creatinine in the context of creatine supplementation does not establish chronic kidney disease diagnosis. 1

Special Populations

Children and Adolescents

The safety of creatine in children and adolescents has not been established through rigorous clinical trials. 7 While no specific guideline explicitly contraindicates use in this age group, the lack of long-term safety data warrants caution.

Older Adults

Creatine supplementation has been shown to produce beneficial effects in older populations without adverse renal effects when used at recommended doses. 2, 3

Hepatic Impairment

The FDA label for creatine products warns to avoid use in patients with severe hepatic impairment (Child-Pugh Class C) and use lower doses in moderate hepatic impairment (Child-Pugh Class B). 8

Monitoring Recommendations

For individuals who choose to supplement despite borderline kidney function:

• Discontinue creatine immediately if diagnostic uncertainty about kidney function arises. 1
• Repeat serum creatinine and GFR measurements 1-2 weeks after cessation to assess true baseline kidney function. 1
• Avoid combining creatine with nephrotoxic medications such as NSAIDs, which can further compromise renal function. 1
• Ensure blood pressure is well-controlled (<130/80 mmHg) before considering supplementation in at-risk individuals. 1

Drug Interactions

When patients are taking ACE inhibitors or ARBs, small increases in creatinine (up to 30% from baseline) may occur and should not prompt medication discontinuation in the absence of volume depletion. 6, 1 However, this physiologic effect can be confused with creatine-induced creatinine elevation, complicating clinical assessment.

Long-Term Safety Considerations

Few trials have investigated long-term use exceeding 10 g/day for extended periods. 7 One case report documented acute renal failure in a 20-year-old man taking 20 g/day for four weeks, though causality remains uncertain. 7 When combined with other supplements or taken at higher than recommended doses for several months, isolated cases of liver and renal complications have been reported. 5