What is the role of creatine (creatine monohydrate) in enhancing athletic performance, particularly in individuals with impaired renal function or neuromuscular diseases?

Role of Creatine Monohydrate

Athletic Performance Enhancement

Creatine monohydrate improves high-intensity repeated sprint performance, enhances training capacity, increases muscle strength and power, and promotes lean body mass gains in athletes. 1

Mechanisms and Benefits in Athletes

• Creatine supplementation increases muscle creatine stores, which accelerates phosphocreatine resynthesis during high-intensity exercise 1
• It reduces perception of fatigue and enhances repeated sprint performance, skill execution, and fine motor control 1
• Chronic supplementation supports training adaptations including increased muscle strength, power, and lean body mass 1
• May also support brain function, though this requires further investigation 1

Evidence-Based Dosing Protocol for Athletes

Loading phase: 20 g/day divided into four equal doses for 5-7 days 1

Maintenance phase: 3-5 g/day as a single dose for the duration of supplementation 1

• Lower-dose approaches (2-5 g/day for 28 days) may avoid the associated 1-2 kg body mass increase that occurs with loading 1
• Concurrent consumption with mixed protein/carbohydrate (~50 g each) may enhance muscle creatine uptake via insulin stimulation 1
• Approximately 4-6 weeks are required following cessation for creatine levels to return to baseline 1

Important Considerations for Athletes

• Expect a potential 1-2 kg body mass increase after creatine loading, primarily from water retention associated with increased intramuscular total creatine 1, 2
• No negative health effects follow appropriate supplementation protocols in healthy individuals 1, 3
• Creatine supplementation up to 8 weeks with high doses has not been associated with major health risks; low-dose supplementation for 5 years showed no adverse effects 2

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Use in Impaired Renal Function

Creatine supplementation is contraindicated in individuals with impaired renal function (creatinine clearance <60 mL/min) and must be discontinued immediately if evidence of renal dysfunction develops. 1, 4

Critical Renal Function Considerations

• The majority (>90%) of ingested creatine is removed from plasma by the kidney and excreted in urine 5
• While studies in normal healthy individuals show kidneys can excrete creatine and creatinine without adversely altering renal function, this situation differs dramatically in persons with impaired glomerular filtration or inherent renal disease 5
• If a patient is taking creatine and has evidence of renal dysfunction, it is necessary to discontinue this supplement 1

Diagnostic Complexity in Creatine Users

A critical pitfall: Creatine supplementation artificially elevates serum creatinine without indicating true renal dysfunction, making standard kidney function assessment unreliable 4, 6

• Serum creatinine is profoundly affected by muscle mass because creatinine is produced from muscle catabolism 4, 6
• The combination of strength training and creatine supplementation can artificially elevate serum creatinine levels without indicating true renal dysfunction 4
• Standard eGFR equations (MDRD, CKD-EPI, Cockcroft-Gault) were not validated in populations with exceptionally high muscle mass or creatine supplementation, leading to systematic underestimation of true GFR 4, 6

Assessment Algorithm for Suspected Renal Dysfunction in Creatine Users

1. Stop creatine supplementation immediately 4
2. Ensure adequate hydration to prevent dehydration from falsely elevating creatinine and reducing GFR 4
3. Repeat renal function testing in 2-4 weeks after creatine washout 4
4. Consider cystatin C-based eGFR calculation, which is more accurate than creatinine-based equations in individuals with altered muscle mass 4, 6
5. If eGFR remains <45 mL/min/1.73 m² after creatine washout, refer to nephrology for comprehensive evaluation including cystatin C-based eGFR, urinalysis, urine protein-to-creatinine ratio, and renal ultrasound 4

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Use in Neuromuscular Diseases

The evidence for creatine supplementation in neuromuscular diseases is mixed, with some benefit demonstrated in Duchenne and Becker's muscular dystrophy, but no clear benefit established for routine use. 1, 7, 8

Duchenne and Becker's Muscular Dystrophy

• Clinical trials have shown improved function, fat-free mass, and some evidence of improved bone health with creatine monohydrate supplementation 7
• Studies using the mdx model of Duchenne muscular dystrophy found evidence of enhanced mitochondrial function, reduced intracellular calcium, and improved performance 7
• However, an RCT of creatine in DMD failed to show a clear benefit, and no formal recommendations for creatine use were established by expert consensus 1

Other Neuromuscular Conditions

• Myotonic dystrophy and inherited neuropathies (e.g., Charcot-Marie-Tooth): Improvements in function have not been significant 7
• Mitochondrial cytopathies: Some studies showed improved muscle endurance and body composition, yet other studies did not find significant improvements 7
• McArdle's disease (myophosphorylase deficiency): Lower-dose creatine supplementation improved exercise capacity, yet higher doses showed some indication of worsened function 7

Clinical Application in Neuromuscular Disease

• Therapeutic benefits may occur by preventing ATP depletion, stimulating protein synthesis or reducing protein degradation, and stabilizing biological membranes 8
• Larger randomized controlled trials using homogeneous patient groups and objective, clinically relevant outcome variables are needed to determine whether creatine supplementation will be of therapeutic benefit 7
• Given the lack of consensus and mixed evidence, creatine supplementation in neuromuscular diseases should be approached cautiously and only after careful consideration of potential benefits versus risks 1, 7

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Safety Profile and Contraindications

Absolute Contraindications

• Creatinine clearance <60 mL/min 4
• Pre-existing chronic kidney disease 4
• Evidence of renal dysfunction during supplementation 1

Relative Contraindications and Cautions

• Pregnancy: Evidence is lacking for safety in pregnant women 3
• Dehydration: Ensure adequate hydration during supplementation 4
• Nephrotoxic medications: Assess for concurrent use 4

Common Side Effects

• Gastrointestinal distress is reported in some individuals, particularly at high doses, but such effects are dose-dependent and not universally experienced 3
• Claims that creatine leads to dehydration or muscle cramps during exercise are largely unsupported by controlled studies; in fact, creatine may reduce the incidence of muscle cramps and assist in maintaining thermoregulatory balance 3

Long-Term Safety Concerns

• The question of whether long-term creatine supplementation (months to years) has any deleterious effects on renal structure or function cannot be answered definitively at this time 5
• Physicians should be aware that the safety of long-term creatine supplementation, in regard to effects on the kidneys, cannot be guaranteed 5
• More information is needed on possible changes in blood pressure, protein/albumin excretion, and glomerular filtration in athletes who are habitual users 5