Creatine ( methyl -d 3 ) dilution in urine for estimation of total body skeletal muscle mass: accuracy and variability vs. MRI and DXA

• Published in: Journal of applied physiology (1985) Vol. 124; no. 1; pp. 1 - 9
• Main Authors: Clark, Richard V., Walker, Ann C., Miller, Ram R., O’Connor-Semmes, Robin L., Ravussin, Eric, Cefalu, William T.
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.01.2018
• Series: Aging and Exercise
• Subjects: Accuracy; Aging; Body mass; Body size; Chronic illnesses; Congestive heart failure; Creatine; Creatinine; Deuteration; Dilution; Dual energy X-ray absorptiometry; Energy measurement; Estimates; Fasting; Lean body mass; Liquid chromatography; Magnetic resonance imaging; Mass spectrometry; Mass spectroscopy; Muscles; Musculoskeletal system; NMR; Nuclear magnetic resonance; Skeletal muscle; Urine; muscle mass; dual-energy X-ray absorptiometry; creatinine; lean mass; creatine
• ISSN: 8750-7587; 1522-1601; 1522-1601
• DOI: 10.1152/japplphysiol.00455.2016

A noninvasive method to estimate muscle mass based on creatine ( methyl-d 3 ) (D 3 -creatine) dilution using fasting morning urine was evaluated for accuracy and variability over a 3- to 4-mo period. Healthy older (67- to 80-yr-old) subjects ( n = 14) with muscle wasting secondary to aging and four patients with chronic disease (58–76 yr old) fasted overnight and then received an oral 30-mg dose of D 3 -creatine at 8 AM ( day 1). Urine was collected during 4 h of continued fasting and then at consecutive 4- to 8-h intervals through day 5. Assessment was repeated 3–4 mo later in 13 healthy subjects and 1 patient with congestive heart failure. Deuterated and unlabeled creatine and creatinine were measured using liquid chromatography–tandem mass spectrometry. Total body creatine pool size and muscle mass were calculated from D 3 -creatinine enrichment in urine. Muscle mass was also measured by whole body MRI and 24-h urine creatinine, and lean body mass (LBM) was measured by dual-energy X-ray absorptiometry (DXA). D 3 -creatinine urinary enrichment from day 5 provided muscle mass estimates that correlated with MRI for all subjects ( r = 0.88, P < 0.0001), with less bias [difference from MRI = −3.00 ± 2.75 (SD) kg] than total LBM assessment by DXA, which overestimated muscle mass vs. MRI (+22.5 ± 3.7 kg). However, intraindividual variability was high with the D 3 -creatine dilution method, with intrasubject SD for estimated muscle mass of 2.5 kg vs. MRI (0.5 kg) and DXA (0.8 kg). This study supports further clinical validation of the D 3 -creatine method for estimating muscle mass. NEW & NOTEWORTHY Measurement of creatine ( methyl-d 3 ) (D 3 -creatine) and D 3 -creatinine excretion in fasted morning urine samples may be a simple, less costly alternative to MRI or dual-energy X-ray absorptiometry (DXA) to calculate total body muscle mass. The D 3 -creatine enrichment method provides estimates of muscle mass that correlate well with MRI, and with less bias than DXA. However, intraindividual variability is high with the D 3 -creatine method. Studies to refine the spot urine sample method for estimation of muscle mass may be warranted.