The French chemist Michel Eugène Chevreul discovered creatine in meat two centuries ago. Extensive biochemical and physiological studies of this organic molecule followed with confirmation that creatine is found within the cytoplasm and mitochondria of human skeletal muscles. Two groups of investigators exploited these relationships five decades ago by first estimating the creatine pool size in vivo with ¹⁴C and ¹⁵N labelled isotopes. Skeletal muscle mass (kg) was then calculated by dividing the creatine pool size (g) by muscle creatine concentration (g/kg) measured on a single muscle biopsy or estimated from the literature. This approach for quantifying skeletal muscle mass is generating renewed interest with the recent introduction of a practical stable isotope (creatine-(methyl-d₃)) dilution method for estimating the creatine pool size across the full human lifespan. The need for a muscle biopsy has been eliminated by assuming a constant value for whole-body skeletal muscle creatine concentration of 4.3 g/kg wet weight. The current single compartment model of estimating creatine pool size and skeletal muscle mass rests on four main assumptions: tracer absorption is complete; tracer is all retained; tracer is distributed solely in skeletal muscle; and skeletal muscle creatine concentration is known and constant. Three of these assumptions are false to varying degrees. Not all tracer is retained with urinary isotope losses ranging from 0% to 9%; an empirical equation requiring further validation is used to correct for spillage. Not all tracer is distributed in skeletal muscle with non-muscle creatine sources ranging from 2% to 10% with a definitive value lacking. Lastly, skeletal muscle creatine concentration is not constant and varies between muscles (e.g. 3.89–4.62 g/kg), with diets (e.g. vegetarian and omnivore), across age groups (e.g. middle-age, ~4.5 g/kg; old-age, 4.0 g/kg), activity levels (e.g. athletes, ~5 g/kg) and in disease states (e.g. muscular dystrophies, <3 g/kg). Some of the variability in skeletal muscle creatine concentrations can be attributed to heterogeneity in the proportions of wet skeletal muscle as myofibres, connective tissues, and fat. These observations raise serious concerns regarding the accuracy of the deuterated-creatine dilution method for estimating total body skeletal muscle mass as now defined by cadaver analyses of whole wet tissues and in vivo approaches such as magnetic resonance imaging. A new framework is needed in thinking about how this potentially valuable method for measuring the creatine pool size in vivo can be used in the future to study skeletal muscle biology in health and disease.

中文翻译：

---

用于骨骼肌质量测量的 D3-肌酸稀释：历史发展和现状

两个世纪前，法国化学家 Michel Eugène Chevreul 在肉类中发现了肌酸。对这种有机分子进行了广泛的生化和生理学研究，随后证实肌酸存在于人体骨骼肌的细胞质和线粒体中。五年前，两组研究人员首先利用¹⁴ C 和¹⁵估计体内肌酸池大小，利用了这些关系N 标记的同位素。然后通过将肌酸池大小 (g) 除以单次肌肉活检测量或从文献中估计的肌肉肌酸浓度 (g/kg) 来计算骨骼肌质量 (kg)。随着最近引入实用的稳定同位素（肌酸-（甲基-d ₃)) 用于估计整个人类寿命中肌酸池大小的稀释方法。假设全身骨骼肌肌酸浓度恒定为 4.3 g/kg 湿重，则无需进行肌肉活检。目前估计肌酸池大小和骨骼肌质量的单室模型基于四个主要假设：示踪剂吸收完全；示踪剂全部保留；示踪剂仅分布于骨骼肌；骨骼肌肌酸浓度已知且恒定。其中三个假设在不同程度上是错误的。并非所有示踪剂都被保留，尿液同位素损失范围为 0% 至 9%；需要进一步验证的经验方程用于校正溢出。并非所有示踪剂都分布在骨骼肌中，非肌肉来源的肌酸含量从 2% 到 10% 不等，但缺乏明确的数值。最后，骨骼肌肌酸浓度不是恒定的，并且随着肌肉（例如 3.89–4.62 g/kg）、饮食（例如素食和杂食）、不同年龄组（例如中年，~4.5 g/kg；老年）而变化, 4.0 g/kg)、活动水平（例如运动员，~5 g/kg）和疾病状态（例如肌肉萎缩症，<3 g/kg）。骨骼肌肌酸浓度的一些变化可归因于湿骨骼肌如肌纤维、结缔组织和脂肪的比例的异质性。体内方法，例如磁共振成像。需要一个新的框架来思考这种用于测量体内肌酸池大小的潜在有价值的方法如何在未来用于研究健康和疾病中的骨骼肌生物学。