Evidence mapPaperPMID 24764133Full record

ArticleJournal of applied physiology (Bethesda, Md. : 1985)2014

Total body skeletal muscle mass: estimation by creatine (methyl-d3) dilution in humans.

Richard V Clark, Ann C Walker, Robin L O'Connor-Semmes, Michael S Leonard, Ram R Miller, Stephen A Stimpson, Scott M Turner, Eric Ravussin, William T Cefalu, Marc K Hellerstein and 1 more

Registry-linked trialAbstract read
In one paragraph

Article in Journal of applied physiology (Bethesda, Md. : 1985), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06811324 (The Effects of Tirzepatide Use on Muscle and Vascular Function Among Obese Older Adults), which is not on this map. Cited by 102 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
102citing papers in PubMed, 2 pooled it
5.4field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06811324 phase2recruitingstarted 2026, after this paper: background citation

The Effects of Tirzepatide Use on Muscle and Vascular Function Among Obese Older Adults

Ran2026Enrolled20Registered outcomes3Posted comparisons0ConditionsCardiovascular Function, GLP - 1, Obesity Prevention, Sarcopenia in ElderlyArmsTirzepatide
Open the trial in the graph
3 · Its place in the literature

Who cites it

102 citing papers in PubMed, 2 syntheses or guidelines pooled it, 173 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Application of the DJournal of cachexia, sarcopenia and muscle · 2023
    Trial
  6. Trial
  7. Creatine ( methyl-dJournal of applied physiology (Bethesda, Md. : 1985) · 2018
    Trial
  8. Trial
  9. Review
  10. Review
  11. Review
  12. Review
  13. Skeletal Muscle Mass Measured Noninvasively by DJournal of pediatrics. Clinical practice · 2025
    Article
  14. Article
  15. Article
  16. Review
  17. Sarcopenia: how to determine and manage.Knee surgery & related research · 2025
    Review
  18. Article
  19. Article
  20. Article

42 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 1 country.

Richard V ClarkMuscle Metabolism Discovery Performance Unit, Metabolic Pathways and Cardiovascular Therapeutic Area, GlaxoSmithKline R&D, Research Triangle Park, North Carolina; Richard.V.Clark@GSK.com.
Ann C WalkerMuscle Metabolism Discovery Performance Unit, Metabolic Pathways and Cardiovascular Therapeutic Area, GlaxoSmithKline R&D, Research Triangle Park, North Carolina;
Robin L O'Connor-SemmesMuscle Metabolism Discovery Performance Unit, Metabolic Pathways and Cardiovascular Therapeutic Area, GlaxoSmithKline R&D, Research Triangle Park, North Carolina;
Michael S LeonardMuscle Metabolism Discovery Performance Unit, Metabolic Pathways and Cardiovascular Therapeutic Area, GlaxoSmithKline R&D, Research Triangle Park, North Carolina;
Ram R MillerMuscle Metabolism Discovery Performance Unit, Metabolic Pathways and Cardiovascular Therapeutic Area, GlaxoSmithKline R&D, Research Triangle Park, North Carolina;
Stephen A StimpsonMuscle Metabolism Discovery Performance Unit, Metabolic Pathways and Cardiovascular Therapeutic Area, GlaxoSmithKline R&D, Research Triangle Park, North Carolina;
Scott M TurnerKineMed Inc., Emeryville, California;
Eric RavussinPennington Biomedical Research Center, Baton Rouge, Louisiana; and.
William T CefaluPennington Biomedical Research Center, Baton Rouge, Louisiana; and.
Marc K HellersteinDepartment of Nutritional Sciences and Toxicology, University of California, Berkeley, California.
William J EvansKineMed Inc., Emeryville, California;
GlaxoSmithKline (United States) · USKineMed (United States) · USPennington Biomedical Research Center · USResearch Triangle Park Foundation · USUniversity of California, Berkeley · US

Funding

Louisiana Clinical and Translational Science CenterU54GM104940 · LSU PENNINGTON BIOMEDICAL RESEARCH CTR · 2025 to 2025
$3.9M
NIGMS NIH HHS U54 GM104940
6 · The paper itself

Abstract

Current methods for clinical estimation of total body skeletal muscle mass have significant limitations. We tested the hypothesis that creatine (methyl-d3) dilution (D3-creatine) measured by enrichment of urine D3-creatinine reveals total body creatine pool size, providing an accurate estimate of total body skeletal muscle mass. Healthy subjects with different muscle masses [n = 35: 20 men (19-30 yr, 70-84 yr), 15 postmenopausal women (51-62 yr, 70-84 yr)] were housed for 5 days. Optimal tracer dose was explored with single oral doses of 30, 60, or 100 mg D3-creatine given on day 1. Serial plasma samples were collected for D3-creatine pharmacokinetics. All urine was collected through day 5. Creatine and creatinine (deuterated and unlabeled) were measured by liquid chromatography mass spectrometry. Total body creatine pool size and muscle mass were calculated from D3-creatinine enrichment in urine. Muscle mass was also measured by magnetic resonance imaging (MRI), dual-energy x-ray absorptiometry (DXA), and traditional 24-h urine creatinine. D3-creatine was rapidly absorbed and cleared with variable urinary excretion. Isotopic steady-state of D3-creatinine enrichment in the urine was achieved by 30.7 ± 11.2 h. Mean steady-state enrichment in urine provided muscle mass estimates that correlated well with MRI estimates for all subjects (r = 0.868, P < 0.0001), with less bias compared with lean body mass assessment by DXA, which overestimated muscle mass compared with MRI. The dilution of an oral D3-creatine dose determined by urine D3-creatinine enrichment provides an estimate of total body muscle mass strongly correlated with estimates from serial MRI with less bias than total lean body mass assessment by DXA.

Indexed as

AdultAgedAged, 80 and overBody CompositionChromatography, LiquidCreatineCreatinineFemaleHumansIndicator Dilution TechniquesMaleMass SpectrometryMiddle AgedMuscle, SkeletalCreatineCreatininecreatinecreatininelean body massmuscle mass

Identifiers

PMID24764133
PMCPMC4064374
OpenAlexW2145660772

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.