Total-body creatine pool size and skeletal muscle mass determination by creatine-(methyl-d3) dilution in rats
Abstract
There is currently no direct, facile method to determine total-body skeletal muscle mass for the diagnosis and treatment of skeletal muscle wasting conditions such as sarcopenia, cachexia, and disuse. We tested in rats the hypothesis that the enrichment of creatinine-(methyl-d(3)) (D(3)-creatinine) in urine after a defined oral tracer dose of D(3)-creatine can be used to determine creatine pool size and skeletal muscle mass. We determined 1) an oral tracer dose of D(3)-creatine that was completely bioavailable with minimal urinary spillage and sufficient enrichment in the body creatine pool for detection of D(3)-creatine in muscle and D(3)-creatinine in urine, and 2) the time to isotopic steady state. We used cross-sectional studies to compare total creatine pool size determined by the D(3)-creatine dilution method to lean body mass determined by independent methods. The tracer dose of D(3)-creatine (<1 mg/rat) was >99% bioavailable with 0.2-1.2% urinary spillage. Isotopic steady state was achieved within 24-48 h. Creatine pool size calculated from urinary D(3)-creatinine enrichment at 72 h significantly increased with muscle accrual in rat growth, significantly decreased with dexamethasone-induced skeletal muscle atrophy, was correlated with lean body mass (r = 0.9590; P < 0.0001), and corresponded to predicted total muscle mass. Total-body creatine pool size and skeletal muscle mass can thus be accurately and precisely determined by an orally delivered dose of D(3)-creatine followed by the measurement of D(3)-creatinine enrichment in a single urine sample and is promising as a noninvasive tool for the clinical determination of skeletal muscle mass.
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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., 2012
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Skeletal Muscle Mass Measured Noninvasively by D3-Creatine Dilution in Children and Term Infants
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- Authors
- 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., & Evans, W. J.
- Affiliations
- GlaxoSmithKline (United States) (US)
- KineMed (United States) (US)
- University of California, Berkeley (US)
- Corresponding author
- Stimpson, Stephen A.
- ORCID
- Venue
- Journal of Applied Physiology
- Publisher
- American Physiological Society
- Published
- 2012-06-01
- Volume
- 112
- Issue
- 11
- Pages
- 1940-1948
- ISSN
- 0161-7567 (ISSN-L)
- 8750-7587
- 1522-1601
- OpenAlex
- W2331564679
- Cited by
- 73
- References
- 28
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 8 · 2023: 7 · 2022: 4 · 2021: 7 · 2020: 5 · 2019: 3 · 2018: 4 · 2017: 5 · 2016: 1 · 2015: 10 · 2014: 6 · 2013: 5 · 2012: 2
- FWCI
- 3.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Applied Physiology (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, isotopic steady state, lean body mass, muscle atrophy, dexamethasone, sarcopenia, cachexia, disuse, muscle mass assessment
- MeSH terms
- Animals, Creatine, Male, Metabolic Clearance Rate, Methylation, Muscular Atrophy, Random Allocation, Rats, Sprague-Dawley, Muscle, Skeletal, Rats
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