Is creatine monohydrate safe for an adult with ankylosing spondylitis who has normal renal function (estimated glomerular filtration rate ≥60 mL/min/1.73 m²) and normal hepatic function, and what dosing and monitoring protocol should be used?

Creatine Monohydrate and Ankylosing Spondylitis

Creatine monohydrate supplementation is safe for adults with ankylosing spondylitis who have normal renal function (eGFR ≥60 mL/min/1.73 m²) and normal hepatic function, with standard dosing protocols and baseline monitoring of renal function. 1, 2, 3

Safety Profile in Normal Renal Function

The evidence strongly supports the safety of creatine supplementation in individuals with normal kidney function:

• Creatine monohydrate does not cause renal disease in healthy individuals with normal baseline kidney function, and reports of kidney damage associated with its use are extremely rare. 2, 3

• Multiple studies examining short-term (5 days), medium-term (9 weeks), and long-term (up to 5 years) creatine supplementation in athletes with normal renal function found no adverse effects on kidney function when monitored by clearance methods and urine protein excretion. 3

• The most common adverse effect is transient water retention during the early stages of supplementation, which is clinically insignificant in patients without heart failure or advanced kidney disease. 1

Recommended Dosing Protocol

Loading Phase (Optional):

• 0.3 g/kg/day for 5-7 days, divided into multiple doses throughout the day 1
• For a 70 kg adult: approximately 20 g/day divided into 4 doses of 5 g each

Maintenance Phase:

• 0.03 g/kg/day (typically 2-5 g/day for most adults) 1
• Loading doses are not necessary to increase intramuscular creatine stores; maintenance dosing alone will achieve the same effect over 3-4 weeks 1

Duration:

• Most commonly studied for 4-6 weeks, though long-term use up to 5 years has been documented without adverse effects in healthy individuals 1, 3

Monitoring Protocol

Baseline Assessment (Before Starting):

• Serum creatinine and calculated eGFR 2, 4
• Blood urea nitrogen (BUN) 2
• Urinalysis for proteinuria 4
• Liver function tests (AST, ALT) if planning prolonged use 1

Follow-up Monitoring:

• Recheck serum creatinine and eGFR at 4-6 weeks after initiation 4
• If creatinine rises, recognize that creatine supplementation transiently increases serum creatinine through increased creatine-to-creatinine conversion, which does not reflect true kidney dysfunction 2, 4
• Consider measuring cystatin C-based eGFR if there is concern about falsely elevated creatinine, as this provides a creatinine-independent assessment of true GFR 4

Critical Contraindications and Warnings

Absolute Contraindications:

• Chronic kidney disease (eGFR <60 mL/min/1.73 m²) 2
• Concurrent use of potentially nephrotoxic medications (NSAIDs, aminoglycosides, ACE inhibitors/ARBs in high doses) 2
• Pre-existing liver disease 1

Relative Contraindications:

• Very high protein diets (>2.8 g/kg/day) combined with creatine may increase BUN and create diagnostic confusion 2, 4
• Dehydration or volume depletion states 1

Special Considerations for Ankylosing Spondylitis

NSAID Interactions:

• If the patient with ankylosing spondylitis is taking NSAIDs regularly (as recommended by ACR/SAA guidelines for active AS), avoid combining with creatine supplementation due to the cumulative nephrotoxic potential. 5, 2
• The 2019 ACR/SAA guidelines strongly recommend NSAIDs as first-line treatment for active AS, and continuous NSAID therapy is conditionally recommended over on-demand use. 5
• If NSAIDs are being used continuously, creatine supplementation should be deferred or NSAIDs should be temporarily discontinued during creatine loading phases. 2

Monitoring in AS Patients on Biologics:

• Patients on TNF inhibitors or other biologics for AS do not have additional contraindications to creatine use, but baseline and follow-up renal monitoring remains essential 5

Common Pitfalls to Avoid

Misinterpreting Elevated Creatinine:

• Creatine supplementation increases serum creatinine by 0.2-0.3 mg/dL through non-pathologic conversion of creatine to creatinine, which falsely lowers calculated eGFR. 2, 4
• This does not represent true kidney damage; measured GFR by isotope methods (⁵¹Cr-EDTA clearance) remains unchanged. 4
• Do not discontinue creatine based solely on elevated serum creatinine without confirming true GFR decline through cystatin C-based eGFR or measured GFR. 4

Combining with High-Protein Diets:

• Athletes often consume high-protein diets (>2 g/kg/day) alongside creatine, which elevates BUN and can create false concern for kidney disease. 2, 4
• This combination is safe in individuals with normal baseline renal function but requires clear documentation to avoid diagnostic confusion. 4

Case Reports of Acute Tubular Necrosis:

• One case report documented acute tubular necrosis in an 18-year-old taking recommended doses of creatine monohydrate, though causality was not definitively established and the patient recovered fully after discontinuation. 6
• This represents an extremely rare idiosyncratic reaction, but underscores the importance of baseline and follow-up monitoring. 6

Product Selection

• Use only creatine monohydrate, as this is the most extensively studied formulation with established safety data. 1
• Other forms such as creatine ethyl ester have not demonstrated added benefits and lack long-term safety data. 1