Effects of Creatine Supplementation on the Body
Creatine monohydrate supplementation increases muscle phosphocreatine stores by approximately 20%, enhancing ATP production during high-intensity exercise, which improves strength, power, and lean body mass, with the primary side effect being 1-2 kg water weight gain. 1, 2
Mechanism of Action
Creatine functions by increasing phosphocreatine stores within muscle cells, which serves as a rapid energy reservoir for ATP resynthesis during intense physical activity 1, 2. The compound catalyzes the reversible reaction converting phosphocreatine, magnesium adenosine diphosphate (MgADP-), and hydrogen ions into MgATP2- and creatine, providing immediate energy for high-intensity movements 2. This biochemical enhancement allows muscles to maintain power output during brief periods of maximal effort 3.
Beyond energy metabolism, creatine may enhance muscle protein synthesis and inhibit muscle protein breakdown, though this effect is approximately 30% lower than traditional resistance exercise alone 4, 2.
Performance and Body Composition Effects
Creatine supplementation produces measurable improvements in high-intensity, short-duration exercise performance, particularly during repeated sprint activities. 1, 5
- Enhances training capacity and promotes chronic adaptations including increased muscle strength, power, and lean body mass 1
- Most effective for activities lasting less than 30 seconds that rely heavily on the ATP-phosphocreatine energy system 5, 6
- Increases body mass by 1-2 kg, primarily through water retention associated with increased intramuscular creatine stores 1, 6
- May increase muscle mass when combined with resistance training, though the initial weight gain is osmotic water retention 6
- Not effective for endurance sports or prolonged aerobic activities 5
Cognitive Effects
Creatine may support brain function by increasing phosphocreatine stores in cerebral tissue 1, 4. Studies demonstrate that cognitive processing impaired by sleep deprivation or aging can improve with supplementation 7. Higher brain creatine concentrations are associated with enhanced neuropsychological performance 7.
Recommended Supplementation Protocol
Loading phase: 20 g/day divided into four equal 5g doses for 5-7 days 1, 2, 5
Maintenance phase: 3-5 g/day as a single dose for the duration of supplementation 1, 2
Alternative low-dose approach: 2-5 g/day for 28 days avoids water retention while effectively increasing muscle creatine stores 1, 2
Optimization strategy: Consume creatine with approximately 50g each of protein and carbohydrates to enhance muscle uptake via insulin stimulation 1, 2
Washout period: Creatine levels return to baseline approximately 4-6 weeks after cessation 1, 4
For healthy recreational athletes, supplementation should not exceed 2.5-3 g/day (approximately the daily turnover rate) 3. For athletes undergoing high-intensity training, maximum supplementation should be less than 5-6 g/day for less than 2 weeks under medical supervision 3. Doses exceeding 6 g/day should be considered therapeutic intervention and prescribed only by physicians for proven deficiency or severe stress conditions 3.
Safety Profile and Side Effects
Short-term creatine supplementation (up to 8 weeks) has not been associated with major health risks when following appropriate protocols. 6, 8
Common side effects:
- Transient water retention during early supplementation (1-2 kg weight gain) 1, 8
- Possible gastrointestinal distress including diarrhea 5
- Reports of cramping, dehydration, and dizziness, though causality is unclear 5
Potential concerns requiring caution:
- May decrease renal function, though only two case reports exist in the literature 5
- Creatine supplementation can affect glomerular filtration rate (GFR) assessment by altering exogenous creatinine generation, but does not affect actual kidney function 4
- When combined with other supplements or taken at higher than recommended doses for several months, cases of liver and renal complications have occurred 8
- Possible feedback inhibition of endogenous creatine synthesis with prolonged use 3
- Potential influence on insulin production 3
Critical caveat: Commercially marketed creatine products do not meet pharmaceutical quality control standards, raising concerns about impurities or inaccurate dosing 5. Creatine monohydrate is the most extensively studied form; other variants like creatine ethyl ester have not demonstrated added benefits 8.
Clinical Interpretation of Laboratory Values
When interpreting creatine phosphokinase (CPK) levels in individuals taking creatine, recognize that levels above 3000 U·L⁻¹ can occur after maximal resistance exercise without pathological significance 1. CPK levels reflect enzyme activity rather than total enzyme content and may peak 24-120 hours post-exercise 1. Individual factors including muscle mass, ethnicity, and exercise intensity significantly influence baseline enzyme levels 1.
Special Populations
In older adults, creatine supplementation (independent of exercise) increases body mass, enhances fatigue resistance, increases muscle strength, and improves activities of daily living 7. When combined with resistance training in elderly populations, creatine produces greater increases in bone mineral density than resistance training alone 7. These benefits are particularly relevant given age-related decreases in muscle creatine, muscle mass, bone density, and strength 7.