Source: Kreider, R.B.; Stout, J.R. Creatine in Health and Disease. Nutrients 2021, 13, 447.

Main Themes:

• Review article explores creatine's therapeutic potential beyond its ergogenic benefits.
• Authors discuss creatine's metabolic effects, energy availability, and implications for diseases involving the creatine kinase/phosphocreatine system.

Key Ideas and Facts:

Metabolic Role:

• "Creatine and phosphagens play a critical role in providing energy through the creatine kinase (CK) and PCr system. The free energy yielded from the enzymatic degradation of adenosine triphosphate (ATP) [...] serves as a primary fuel to replenish ATP for cellular metabolism."

Therapeutic Potential:

Creatine Synthesis Deficiencies:

• "Long-term, high-dose creatine supplementation in individuals with creatine synthesis [disorders] can increase brain creatine and PCr levels and reduce the severity of deficits associated with these disorders."

Heart Health:

• "[...]current evidence suggests that phosphocreatine administration and possibly creatine supplementation support heart metabolism and health, particularly during ischemic challenges."

Neuroprotection:

• "[...] prophylactic creatine supplementation may reduce the severity of brain ischemia and therefore may have some therapeutic benefits in individuals at risk to stroke."

Other Potential Applications:

• Pregnancy: Emerging research suggests creatine supplementation during pregnancy may support fetal development, brain health, and potentially reduce complications related to birth asphyxia.
• Depression: Preliminary evidence suggests that creatine supplementation might have antidepressant effects, possibly by influencing brain energy metabolism. More research is needed to determine its therapeutic efficacy.
• Fertility, Skin Health, Glucose Management: Research indicates potential benefits of creatine in improving sperm motility and fertility, enhancing skin health, and supporting healthy glucose management in individuals with diabetes.

Limitations and Future Directions:

• Research on long-term effects of high-dose creatine supplementation in certain populations, like those with neurodegenerative diseases, is inconclusive.
• Further investigation is necessary to fully elucidate the therapeutic potential of creatine in various clinical contexts and to establish optimal dosages and treatment durations.