What Creatine Does: Mechanism, Dosing, and Clinical Applications
Mechanism of Action
Creatine increases phosphocreatine stores within muscle cells, which enhances ATP production essential for muscle protein synthesis and high-intensity exercise performance. 1
- Creatine combines with phosphate to form phosphocreatine (creatine phosphate), a high-energy compound in the ATP-CP energy system 2, 3
- This system is critical for rapid energy production during speed and power activities 3
- In a 70 kg male, approximately 120 g of creatine exists in the body, with 95% stored in skeletal muscle 3
- Muscle creatine exists as 40% free creatine and 60% phosphocreatine 3
- Creatine also stimulates muscle protein synthesis (MPS) and may inhibit muscle protein breakdown (MPB) 1
Recommended Dosing Protocol
The British Journal of Sports Medicine recommends a loading phase of 20 g/day divided into four equal doses (5 g per dose) for 5-7 days, followed by a maintenance dose of 3-5 g/day as a single dose. 4
Loading Phase
- Dose: 20 g/day divided into four equal daily doses (5 g per dose) 4
- Duration: 5-7 days 4, 2
- Purpose: Rapidly saturate muscle creatine stores 4
- Expected effect: Body mass increase of 1-2 kg due to intracellular water retention 4
Maintenance Phase
- Dose: 3-5 g/day as a single dose 4, 5
- Duration: Continue for entire supplementation period 4
- Alternative approach: 2 g/day for 30 days can achieve similar muscle saturation without loading 2, 6
Optimization Strategy
- Consume creatine with ~50 g of protein and carbohydrate to enhance muscle uptake through insulin-mediated transport 4
- Muscle creatine levels return to baseline approximately 4-6 weeks after cessation 4
Clinical Effects and Benefits
Exercise Performance
- Enhances performance in high-intensity, short-duration exercise tasks that rely on the ATP-CP energy system 2, 7
- Particularly effective for repeated sprints with short recovery periods 2
- Increases lean body mass, muscle strength, and enhances fatigue resistance 6
- Performance improvements are most consistent in laboratory settings for short-duration, high-intensity activities 7
Special Populations
Older Adults: Creatine supplementation in older adults increases body mass, enhances fatigue resistance, increases muscle strength, and improves activities of daily living 6
- When combined with resistance training, produces greater increases in lean body mass, strength, and bone mineral density than training alone 6
- May improve cognitive processing that is impaired by aging or sleep deprivation 6
Vegetarians: Show the largest increases in muscle creatine due to very low dietary creatine intake at baseline 2
Critical Care: May have potential benefit in ICU patients with muscle wasting, though no ICU-specific studies exist yet 1
Contraindications and Precautions
Renal Considerations
- Creatine supplementation is not recommended for primary prevention in individuals with normal kidney function, but caution is warranted in those with existing renal impairment 1
- Only two case reports have linked creatine to decreased renal function 7
- In chronic kidney disease, creatinine (the breakdown product of creatine) is used as a marker of kidney function and muscle mass 1
Safety Profile
- Short-term supplementation (up to 8 weeks with high doses, up to 5 years with low doses) shows no major health risks 3
- Creatine is relatively well tolerated at recommended dosages (3-5 g/day or 0.1 g/kg body weight/day) 5
Common Adverse Effects
Reported side effects include 7:
Important Clinical Caveats
- Creatine is NOT useful for endurance sports—benefits are limited to high-intensity, short-duration activities 7
- Commercially marketed creatine products do not meet pharmaceutical quality control standards, raising concerns about impurities or inaccurate dosing 7
- The extent of muscle creatine increase is inversely related to pre-supplementation levels 2
- Creatine is not an anabolic steroid and does not contravene current doping regulations 2