Real-time molecular cycling: Mitochondria generate ATP → MtCK converts Creatine to PCr → PCr diffuses across cytosol → Myofibrillar/Neuronal CK resynthesizes ATP under load.
Multi-week compartment saturation modeling: Muscle uptake (SLC6A8) vs slow Blood-Brain Barrier (BBB) transport.
| Target Domain | Observed Effect | Bioenergetic Mechanism | Evidence Grade |
|---|---|---|---|
| Explosive Power (1–10s) | +5% to +15% peak wattage | Increased initial phosphocreatine availability delays reliance on glycolysis | High (Grade A) |
| Repeated High-Intensity Sprints | +12% to +20% work capacity | Accelerated mitochondrial ATP resynthesis between high-demand intervals | High (Grade A) |
| Sleep-Deprived Cognition | Moderate fatigue buffer | Preserves cerebral cortex bioenergetic homeostasis during metabolic stress | Moderate (Grade B) |
| Sarcopenia / Healthy Aging | Improves lean mass retention | Enhances cellular hydration, IGF-1 mRNA signaling & training volume tolerance | High (Grade A) |
Distinguishing Benign Serum Creatinine vs. True Glomerular Filtration (eGFR):
- Serum Creatinine Spike: Supplementation naturally increases non-enzymatic degradation of creatine into creatinine by ~15-25%. This falsely skews creatinine-based eGFR equations downwards without actual renal damage.
- True Marker (Cystatin C): Serum Cystatin C is unaffected by dietary creatine intake or muscle mass and reflects pristine, genuine renal filtration.
- Intracellular Hydration: Causes 1–2 kg intracellular osmotic water draw in initial 7 days—beneficial for cellular proteolysis inhibition and mechanical signaling, not harmful extracellular edema.
Cerebral Phosphagen Dynamics & Blood-Brain Barrier (BBB):
Unlike skeletal muscle, brain tissue possesses endogenous creatine synthesis via AGAT and GAMT enzymes, and expresses low density of CRT (SLC6A8) transporters across the BBB. Consequently, brain creatine elevates more gradually (~5–10% over 4–8 weeks), delivering distinct resilience against acute cognitive exhaustion, hypoxia, and prolonged wakefulness.