Ostojic Sergej M, Rátgéber László
Faculty of Health Sciences, University of Pecs, Pecs, Hungary.
Department of Nutrition and Public Health, University of Agder, Kristiansand, Norway.
EPMA J. 2025 Sep 1;16(3):541-553. doi: 10.1007/s13167-025-00420-9. eCollection 2025 Sep.
Creatine, traditionally recognized for its role in skeletal muscle energy metabolism, is increasingly emerging as a mitochondria-targeted theranostic agent with significant relevance to the framework of predictive, preventive, and personalized medicine (PPPM). However, several critical gaps currently limit its translation into clinical practice: (1) the lack of sensitive and standardized biomarkers for early detection of bioenergetic deficits, (2) limited incorporation of creatine profiling into predictive risk models, (3) insufficient personalization of supplementation strategies despite known interindividual variability in transporter function, endogenous synthesis, and tissue kinetics, and (4) underdeveloped clinical validation of advanced creatine formulations and delivery systems. This mini review addresses these unmet needs by consolidating evidence on creatine's multifaceted biological functions-including stabilization of mitochondrial membranes, regulation of oxidative stress, support of mitochondrial biogenesis, and modulation of apoptotic signaling-across physiological and pathological states. By sustaining ATP homeostasis via the creatine kinase-phosphocreatine system and influencing mitochondrial dynamics and redox balance, creatine represents both a therapeutic and diagnostic candidate for diseases characterized by impaired bioenergetics. From a PPPM perspective, creatine profiling through biofluids, tissue sampling, and advanced imaging (e.g., proton magnetic resonance spectroscopy) offers a minimally invasive approach for early detection, patient stratification, and monitoring of mitochondrial function. Personalized intervention strategies-guided by molecular and phenotypic profiling-have the potential to maximize efficacy and minimize risk, while creatine loading or depletion tests may serve as functional biomarkers of mitochondrial reserve capacity and supplementation responsiveness. Finally, integration of creatine-centered diagnostics and therapeutics with multi-omics data, computational modeling, and digital health monitoring could overcome existing translational barriers. By reframing creatine from a sports nutrition supplement to a scalable, safe, and cost-effective component of mitochondrial medicine, this review outlines a pathway to address current diagnostic, predictive, and therapeutic deficits, ultimately supporting proactive, systems-level approaches to health maintenance and disease prevention.
肌酸，传统上因在骨骼肌能量代谢中的作用而被认可，如今正日益成为一种针对线粒体的诊疗试剂，与预测、预防和个性化医学（PPPM）框架具有重要关联。然而，目前有几个关键差距限制了其转化为临床实践：（1）缺乏用于早期检测生物能量缺陷的灵敏且标准化的生物标志物；（2）肌酸谱分析在预测风险模型中的纳入有限；（3）尽管已知转运体功能、内源性合成和组织动力学存在个体差异，但补充策略的个性化不足；（4）先进的肌酸制剂和递送系统的临床验证不完善。本综述通过整合肌酸在生理和病理状态下多方面生物学功能的证据来满足这些未满足的需求，这些功能包括线粒体膜的稳定、氧化应激的调节、线粒体生物发生的支持以及凋亡信号的调节。通过肌酸激酶 - 磷酸肌酸系统维持ATP稳态并影响线粒体动力学和氧化还原平衡，肌酸代表了生物能量受损疾病的治疗和诊断候选物。从PPPM角度来看，通过生物流体、组织采样和先进成像（如质子磁共振波谱）进行肌酸谱分析，为早期检测、患者分层和线粒体功能监测提供了一种微创方法。由分子和表型谱分析指导的个性化干预策略有可能使疗效最大化并使风险最小化，而肌酸负荷或消耗测试可作为线粒体储备能力和补充反应性的功能生物标志物。最后，将以肌酸为中心的诊断和治疗与多组学数据、计算建模和数字健康监测相结合，可以克服现有的转化障碍。通过将肌酸从运动营养补充剂重新定义为线粒体医学中可扩展、安全且具有成本效益的成分，本综述概述了一条解决当前诊断、预测和治疗缺陷的途径，最终支持主动的、系统层面的健康维护和疾病预防方法。
