Creatine Emerges as Mitochondrial Medicine Tool for Personalized Health

Creatine is gaining recognition as a mitochondrial theranostic agent with significant potential for predictive, preventive, and personalized medicine (PPPM). Beyond its traditional role in muscle energy metabolism, creatine demonstrates multiple protective effects on mitochondria including membrane stabilization, oxidative stress reduction, and support of mitochondrial biogenesis.

This mini-review synthesizes evidence showing creatine's multifaceted biological functions across physiological and pathological states. The authors highlight how creatine sustains ATP homeostasis through the creatine kinase-phosphocreatine system while influencing mitochondrial dynamics and redox balance. These effects make it valuable for diseases characterized by impaired bioenergetics, including neurodegenerative conditions, metabolic disorders, and age-related pathologies.

The review identifies four critical gaps limiting clinical translation: lack of standardized biomarkers for early bioenergetic deficits, limited incorporation into predictive risk models, insufficient personalization despite known individual variability, and underdeveloped clinical validation of advanced formulations. The authors propose creatine profiling through biofluids, tissue sampling, and magnetic resonance spectroscopy as minimally invasive approaches for early detection and patient stratification.

A clinical illustration demonstrates creatine's diagnostic potential in long COVID patients, where muscle and brain creatine levels measured by MRS revealed bioenergetic deficits not detected by standard tests. The authors envision personalized intervention strategies guided by molecular profiling to maximize efficacy while minimizing risk.

Integration with multi-omics data, computational modeling, and digital health monitoring could overcome existing barriers. By reframing creatine as a scalable, safe, and cost-effective component of mitochondrial medicine, this approach could support proactive health maintenance and disease prevention.