Longitudinal changes in total body creatine pool size and skeletal muscle mass using the D3‐creatine dilution method
Open accessAbstract
Background We recently validated in cross‐sectional studies a new method to determine total body creatine pool size and skeletal muscle mass based on D3‐creatine dilution from an oral dose and detection of urinary creatinine enrichment by isotope ratio mass spectrometry (IRMS). Routine clinical use of the method in aging and disease will require repeated application of the method, with a more widely available technology than IRMS, to enable determination of change in skeletal muscle mass in longitudinal studies. We therefore adapted the method to liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) technology, and sought to establish proof of concept for the repeated application of the method in a longitudinal study. Because the turnover of creatine is slow, it was also critical to determine the impact of background enrichment from an initial dose of oral D3‐creatine on subsequent, longitudinal measurements of change in muscle mass. Methods Rats were given an oral tracer dose of D3‐creatine (1.0 mg/kg body weight) at 10 and 17 weeks of age. LC‐MS/MS was used to determine urinary D3‐creatine, and urinary D3‐creatinine enrichment, at time intervals after D3‐creatine administration. Total body creatine pool size was calculated from urinary D3‐creatinine enrichment at isotopic steady state 72 h after administration of D3‐creatine tracer. Results At 10 weeks of age, rat lean body mass (LBM) measured by quantitative magnetic resonance correlated with creatine pool size (r = 0.92, P = 0.0002). Over the next 7 weeks, the decline in urinary D3‐creatinine enrichment was slow and linear, with a rate constant of 2.73 ± 0.06 %/day. Subtracting background urinary D3‐creatinine enrichment from the elevated enrichment following a second dose of D3‐creatine at 17 weeks permitted repeat calculations of creatine pool size. As at 10 weeks, 17‐week LBM correlated with creatine pool size (r = 0.98, P <0.0001). In addition, the change in creatine pool size was correlated with the change in LBM during the 7 weeks of rat growth between measurements (r = 0.96, P <0.0001). Conclusion The LC‐MS/MS‐based D3‐creatine dilution method can be applied repeatedly to measure total body creatine skeletal muscle mass change in longitudinal study.
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There is a strong correlation (R=0.952) between lean mass by QMR and creatine pool size calculated by D3-creatine enrichment in urine in both single and repeat dosing.
“A strong correlation (R = 0.952) between lean mass by quantitative magnetic resonance (QMR) and creatine pool size as calculated by D3-creatine enrichment in urine in both single and repeat dosing was shown (Stimpson et al., 2012, 2013).”
From Myosteatosis in the Context of Skeletal Muscle Function Deficit: An Interdisciplinary Workshop at the National Institute on Aging (2020) · cites this paper as Stimpson et al., 2013
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Cites
Creatine and Creatinine Metabolism
Wyss, M., & Kaddurah-Daouk, R. (2000) · Physiological Reviews · doi:10.1152/physrev.2000.80.3.1107 · Cited by 2,950 · see citing works
Measurement of muscle mass in humans: validity of the 24-hour urinary creatinine method.
Heymsfield, S., Arteaga, C., McManus, C., Smith, J., & Moffitt, S. (1983) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/37.3.478 · Cited by 902 · see citing works
Creatine: Biosynthesis, Regulation, and Function
Walker, J. B. (1979) · Advances in enzymology and related areas of molecular biology/Advances in enzymology and related subjects · doi:10.1002/9780470122952.ch4 · Cited by 496 · see citing works
THE HYDROLYSIS OF PHOSPHOCREATINE AND THE ORIGIN OF URINARY CREATININE
Borsook, H., & Dubnoff, J. W. (1947) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)30910-9 · Cited by 160 · see citing works
Creatine Metabolism in Skeletal Muscle
Fitch, C. D., Shields, R. P., Payne, W. F., & Dacus, J. V. (1968) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)93544-1 · Cited by 134 · see citing works
(1928) · Nature · doi:10.1038/122766b0 · Cited by 133 · see citing works
RATE OF FORMATION AND DISAPPEARANCE OF BODY CREATINE IN NORMAL ANIMALS
Bloch, K., Schoenheimer, R., & Rittenberg, D. (1941) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)51421-6 · Cited by 119 · see citing works
Hoberman, H. D., Sims, E. A. H., & Peters, J. H. (1948) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)35610-2 · Cited by 114 · see citing works
Stimpson, S. A., Turner, S. M., Clifton, L. G., Poole, J. C., Mohammed, H. A., Shearer, T. W., Waitt, G. M., Hagerty, L. L., Remlinger, K. S., Hellerstein, M. K., et al. (2012) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00122.2012 · Cited by 73 · see citing works
Self-citationMeasurement of muscle mass in humans by isotopic dilution of creatine-14C
Kreisberg, R. A., Bowdoin, B. A., & Meador, C. K. (1970) · Journal of Applied Physiology · doi:10.1152/jappl.1970.28.3.264 · Cited by 53 · see citing works
Creatine metabolism in skeletal muscle
Fitch, C. D., Lucy, D. D., Bornhofen, J. H., & Dalrymple, G. V. (1968) · Neurology · doi:10.1212/wnl.18.1_part_1.32 · Cited by 50 · see citing works
THE EFFECT OF METHYLTESTOSTERONE ON THE RATE OF SYNTHESIS OF CREATINE
Hoberman, H. D., Sims, E. A. H., & Engstrom, W. W. (1948) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)35561-3 · Cited by 38 · see citing works
Muscle mass determination by isotopic dilution of creatine-14C
Meador, C. K., Kreisberg, R. A., Friday, J. P., Bowdoin, B. A., Coan, P. N., Armstrong, J. M., & Hazelrig, J. B. (1968) · Metabolism · doi:10.1016/0026-0495(68)90089-9 · Cited by 22 · see citing works
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Self-citationClark, R. V., Walker, A. C., O'Connor-Semmes, R. L., Leonard, M. S., Miller, R. R., Stimpson, S. A., Turner, S. M., Ravussin, E., Cefalu, W. T., Hellerstein, M. K., et al. (2014) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00045.2014 · Cited by 176 · see citing works
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Coen, P. M., Huo, Z., Tranah, G. J., Barnes, H. N., Zhang, X., Wolff, C. A., Wu, K., Cawthon, P. M., Hepple, R. T., Toledo, F. G. S., et al. (2024) · Aging Cell · doi:10.1111/acel.14118 · Cited by 17 · see citing works
- Authors
- Stimpson, S. A., Leonard, M. S., Clifton, L. G., Poole, J. C., Turner, S. M., Shearer, T. W., Remlinger, K. S., Clark, R. V., Hellerstein, M. K., & Evans, W. J.
- Affiliations
- GlaxoSmithKline (United States) (US)
- KineMed (United States) (US)
- Corresponding author
- Stimpson, Stephen A.
- ORCID
- Venue
- Journal of Cachexia Sarcopenia and Muscle
- Publisher
- Wiley
- Published
- 2013-06-25
- Volume
- 4
- Issue
- 3
- Pages
- 217-223
- ISSN
- 2190-5991 (ISSN-L)
- 2190-6009
- PMC
- PMC3774916
- OpenAlex
- W2007189319
- Cited by
- 59
- References
- 13
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 5 · 2022: 4 · 2021: 4 · 2020: 4 · 2019: 5 · 2018: 4 · 2017: 4 · 2016: 6 · 2015: 8 · 2014: 7
- FWCI
- 4.06
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Cachexia Sarcopenia and Muscle (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Health Sciences › Medicine › Physiology › Body Composition Measurement Techniques
- Keywords
- skeletal muscle mass, longitudinal assessment, lean body mass, rats
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