{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T17:35:23Z","timestamp":1789925723456,"version":"4.0.1"},"reference-count":12,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,6,25]],"date-time":"2013-06-25T00:00:00Z","timestamp":1372118400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>We recently validated in cross\u2010sectional studies a new method to determine total body creatine pool size and skeletal muscle mass based on D<jats:sub>3<\/jats:sub>\u2010creatine 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\u2010tandem mass spectrometry (LC\u2010MS\/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 D<jats:sub>3<\/jats:sub>\u2010creatine on subsequent, longitudinal measurements of change in muscle mass.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Rats were given an oral tracer dose of D<jats:sub>3<\/jats:sub>\u2010creatine (1.0\u00a0mg\/kg body weight) at 10 and 17\u00a0weeks of age. LC\u2010MS\/MS was used to determine urinary D<jats:sub>3<\/jats:sub>\u2010creatine, and urinary D<jats:sub>3<\/jats:sub>\u2010creatinine enrichment, at time intervals after D<jats:sub>3<\/jats:sub>\u2010creatine administration. Total body creatine pool size was calculated from urinary D<jats:sub>3<\/jats:sub>\u2010creatinine enrichment at isotopic steady state 72\u00a0h after administration of D<jats:sub>3<\/jats:sub>\u2010creatine tracer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At 10\u00a0weeks of age, rat lean body mass (LBM) measured by quantitative magnetic resonance correlated with creatine pool size (<jats:italic>r<\/jats:italic>\u2009=\u20090.92, <jats:italic>P<\/jats:italic>\u2009=\u20090.0002). Over the next 7\u00a0weeks, the decline in urinary D<jats:sub>3<\/jats:sub>\u2010creatinine enrichment was slow and linear, with a rate constant of 2.73\u2009\u00b1\u20090.06\u00a0%\/day. Subtracting background urinary D<jats:sub>3<\/jats:sub>\u2010creatinine enrichment from the elevated enrichment following a second dose of D<jats:sub>3<\/jats:sub>\u2010creatine at 17\u00a0weeks permitted repeat calculations of creatine pool size. As at 10\u00a0weeks, 17\u2010week LBM correlated with creatine pool size (<jats:italic>r<\/jats:italic>\u2009=\u20090.98, <jats:italic>P<\/jats:italic> &lt;0.0001). In addition, the change in creatine pool size was correlated with the change in LBM during the 7\u00a0weeks of rat growth between measurements (<jats:italic>r<\/jats:italic>\u2009=\u20090.96, <jats:italic>P<\/jats:italic> &lt;0.0001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The LC\u2010MS\/MS\u2010based D<jats:sub>3<\/jats:sub>\u2010creatine dilution method can be applied repeatedly to measure total body creatine skeletal muscle mass change in longitudinal study.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s13539-013-0110-1","type":"journal-article","created":{"date-parts":[[2013,6,24]],"date-time":"2013-06-24T13:01:35Z","timestamp":1372078895000},"page":"217-223","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Longitudinal changes in total body creatine pool size and skeletal muscle mass using the D<sub>3<\/sub>\u2010creatine dilution method"],"prefix":"10.1002","volume":"4","author":[{"given":"Stephen A.","family":"Stimpson","sequence":"first","affiliation":[{"name":"Muscle Metabolism Discovery Performance Unit, Metabolic Pathways and Cardiovascular Therapeutic Area GlaxoSmithKline  27709 Research Triangle Park NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Leonard","sequence":"additional","affiliation":[{"name":"Platform Sciences and Technology GlaxoSmithKline  Research Triangle Park NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa G.","family":"Clifton","sequence":"additional","affiliation":[{"name":"Muscle Metabolism Discovery Performance Unit, Metabolic Pathways and Cardiovascular Therapeutic Area GlaxoSmithKline  27709 Research Triangle Park NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Poole","sequence":"additional","affiliation":[{"name":"Muscle Metabolism Discovery Performance Unit, Metabolic Pathways and Cardiovascular Therapeutic Area GlaxoSmithKline  27709 Research Triangle Park NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott M.","family":"Turner","sequence":"additional","affiliation":[{"name":"KineMed, Inc.  Emeryville CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd W.","family":"Shearer","sequence":"additional","affiliation":[{"name":"Muscle Metabolism Discovery Performance Unit, Metabolic Pathways and Cardiovascular Therapeutic Area GlaxoSmithKline  27709 Research Triangle Park NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja S.","family":"Remlinger","sequence":"additional","affiliation":[{"name":"Muscle Metabolism Discovery Performance Unit, Metabolic Pathways and Cardiovascular Therapeutic Area GlaxoSmithKline  27709 Research Triangle Park NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard V.","family":"Clark","sequence":"additional","affiliation":[{"name":"Muscle Metabolism Discovery Performance Unit, Metabolic Pathways and Cardiovascular Therapeutic Area GlaxoSmithKline  27709 Research Triangle Park NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc K.","family":"Hellerstein","sequence":"additional","affiliation":[{"name":"KineMed, Inc.  Emeryville CA"},{"name":"Department of Nutritional Sciences and Toxicology University of California at Berkeley  Berkeley CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Evans","sequence":"additional","affiliation":[{"name":"Muscle Metabolism Discovery Performance Unit, Metabolic Pathways and Cardiovascular Therapeutic Area GlaxoSmithKline  27709 Research Triangle Park NC"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,6,25]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/37.3.478"},{"key":"e_1_2_6_3_1","author":"Hunter A","year":"1928","journal-title":"The biological distribution of creatine and creatinine. Creatine and creatinine"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470122952.ch4"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2000.80.3.1107"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00122.2012"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)35610-2"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1970.28.3.264"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(68)90089-9"},{"key":"e_1_2_6_10_1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0021-9258(18)51421-6","article-title":"Rate of formation and disappearance of body creatine in normal animals","volume":"138","author":"Bloch K","year":"1941","journal-title":"J Biol Chem"},{"key":"e_1_2_6_11_1","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/S0021-9258(17)30910-9","article-title":"The hydrolysis of phophocreatine and the origin of urinary creatinine","volume":"168","author":"Borsook H","year":"1947","journal-title":"J Biol Chem"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.18.1_Part_1.32"},{"key":"e_1_2_6_13_1","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0021-9258(18)35561-3","article-title":"The effect of methyltestosterone on the rate of synthesis of creatine","volume":"173","author":"Hoberman HD","year":"1948","journal-title":"J Biol Chem"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1007%2Fs13539-013-0110-1","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s13539-013-0110-1","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T02:48:21Z","timestamp":1696906101000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s13539-013-0110-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,6,25]]},"references-count":12,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2013,9]]}},"alternative-id":["10.1007\/s13539-013-0110-1"],"URL":"https:\/\/doi.org\/10.1007\/s13539-013-0110-1","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,6,25]]},"assertion":[{"value":"2013-04-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-05-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-06-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}