The prevalence and impact of low skeletal muscle mass (SMM) across healthy and disease states has positioned body composition as an impactful research field over the past decade, with an exponential number of publications in various specialty journals. As such, the quest to develop accurate, precise and practical techniques to assess SMM is of major importance, albeit a significant barrier to overcome.

The creatine-(methyl-d₃) dilution, or D₃-creatine dilution (D₃-Cr) method, is an approach for SMM quantification of recent revitalization. It involves the consumption of deuterium-labelled (stable) isotopes to estimate the creatine pool size, and hence SMM, assuming a constant value for whole-body SMM creatine concentration.^{1, 2} A single fasting spot urine collection is needed 2- to 4-days after dosing, which is analysed using high-performance liquid chromatography. The growing interest in the use of D₃-Cr for body composition assessment is understandable. D₃-Cr is simple, safe, precise and of minimal subject burden including for neonates and bedridden/clinical populations; it is also practical for remote assessments.^{1, 3} Furthermore, SMM estimated from D₃-Cr is associated with physical performance, incidence of falls, fractures and mobility limitations in older adults.^{4, 5}

Notwithstanding the important positive aspects of the D₃-Cr method, it is not without limitations, which were addressed in a comprehensive review by McCarthy et al.¹ In this paper, the authors credit the decades of historical developments that led to the current use and understanding of the D₃-Cr method and consider its physiological premises. Further, they provide an intriguing and compelling discussion on methodological assumptions and therefore setbacks of the technique.¹ These include considerations regarding the validity of the D₃-Cr method, and the actual body composition compartment measured, with both topics interpreted considering modern evidence from skeletal muscle research. In a snapshot, the authors caution against the use of D₃-Cr as a reference method for SMM assessment, highlighting potential sources of measurement error. As with other body composition techniques, these are mainly related to inherent assumptions used to estimate/quantify the compartment of interest, in this case, SMM. D₃-Cr estimates SMM from creatine pool size, which in turn is impacted by physiological premises of D₃-Cr absorption, distribution, catabolism and excretion.¹ McCarthy et al.¹ further highlight that SMM creatine concentration is not constant and varies between muscles and muscle composition, age, disease states and dietary patterns.

As two of their key takeaway messages, McCarthy et al.¹ argue that D₃-Cr is not a direct measurement of SMM nor a direct measure of ‘functional’ muscle mass. Rather, D₃-Cr, as an indirect method, measures skeletal muscle contractile (myofibre) mass; it is therefore quantifying the muscle fibre component.¹ Muscle function derives mainly from myofibres but also includes the actions of other intact muscle tissue components. The relatively large contribution of myofibres to muscle function may explain the good associations observed between D₃-Cr-estimated SMM with functional/clinical outcomes, as shown in previously cited studies above.

The article by McCarthy et al.¹ challenges body composition researchers to improve and further develop the use of D₃-Cr for SMM estimation and provide suggestions on how this can be achieved. We anxiously await for further advances on the use and applicability of this technique, including its relevance and practicality in clinical settings.^6-8 Taking the article by McCarthy et al.¹ into consideration, this journey may be long and end in frustration.

在过去十年中，低骨骼肌质量 (SMM) 在健康和疾病状态下的流行和影响已将身体成分定位为一个有影响力的研究领域，各种专业期刊上的出版物呈指数级增长。因此，寻求开发准确、精确和实用的技术来评估 SMM 非常重要，尽管这是一个需要克服的重大障碍。

肌酸-(甲基-d ₃ ) 稀释或 D ₃ -肌酸稀释 (D ₃ -Cr) 方法是一种用于 SMM 量化近期恢复的方法。它涉及消耗氘标记的（稳定的）同位素来估计肌酸池大小，并因此估计 SMM，假设全身 SMM 肌酸浓度为恒定值。^{1, 2}给药后 2 至 4 天需要收集单次空腹尿液，使用高效液相色谱法进行分析。_{人们对使用 D 3} -Cr 进行身体成分评估的兴趣日益浓厚是可以理解的。3 _{_}-Cr 简单、安全、精确且受试者负担最小，包括新生儿和卧床/临床人群；它也适用于远程评估。^{1, 3}_{此外，根据 D 3} -Cr估计的 SMM与老年人的身体表现、跌倒发生率、骨折和行动受限有关。^{4, 5}

_{尽管 D 3} -Cr 方法具有重要的积极方面，但它并非没有局限性，McCarthy 等人在综合审查中解决了这些局限性。¹在本文中，作者归功于导致当前对 D ₃ -Cr 方法的使用和理解的数十年历史发展，并考虑了其生理学前提。此外，它们提供了关于方法论假设的有趣且令人信服的讨论，并因此提供了该技术的挫折。¹_{这些包括关于 D 3}有效性的考虑-Cr 方法和测量的实际身体成分隔室，这两个主题的解释都考虑了骨骼肌研究的现代证据。在快照中，作者告诫不要使用 D ₃ -Cr 作为 SMM 评估的参考方法，强调测量误差的潜在来源。与其他身体成分技术一样，这些主要与用于估计/量化感兴趣的隔间的固有假设有关，在本例中为 SMM。D ₃ -Cr 根据肌酸池大小估计 SMM，肌酸池大小又受 D ₃ -Cr 吸收、分布、分解代谢和排泄的生理前提影响。¹麦卡锡等人。^1个进一步强调 SMM 肌酸浓度不是恒定的，并且在肌肉和肌肉成分、年龄、疾病状态和饮食模式之间变化。

作为他们的两个关键外卖信息，麦卡锡等人。¹认为 D ₃ -Cr 不是 SMM 的直接测量值，也不是“功能性”肌肉质量的直接测量值。相反，D ₃ -Cr 作为一种间接方法，测量骨骼肌收缩（肌纤维）质量；因此，它正在量化肌肉纤维成分。¹肌肉功能主要来自肌纤维，但也包括其他完整肌肉组织成分的作用。肌纤维对肌肉功能的相对较大贡献可以解释在 D ₃ -Cr 估计的 SMM 与功能/临床结果之间观察到的良好关联，如上文先前引用的研究所示。

麦卡锡等人的文章。¹挑战身体成分研究人员改进和进一步开发 D ₃ -Cr 在 SMM 估计中的使用，并就如何实现这一目标提供建议。我们焦急地等待这项技术的使用和适用性的进一步进展，包括它在临床环境中的相关性和实用性。^6-8以 McCarthy 等人的文章为例。¹考虑到这一点，这段旅程可能会很漫长，并以挫折告终。