D3‐creatine dilution for skeletal muscle mass measurement: historical development and current status
Abstract
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…
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