{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:08:58Z","timestamp":1792706938003,"version":"4.5.0"},"reference-count":10,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,4,16]],"date-time":"2018-04-16T00:00:00Z","timestamp":1523836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Muscle mass can be measured directly <jats:italic>in vivo<\/jats:italic> by isotope dilution, using Creatine\u2010(methyl\u2010d<jats:sub>3<\/jats:sub>) monohydrate (D<jats:sub>3<\/jats:sub>\u2010Cr) by mouth followed by measurement of the steady\u2010state enrichment of D<jats:sub>3<\/jats:sub>\u2010creatinine (D<jats:sub>3<\/jats:sub>\u2010Crn) in urine. Isotope dilution methods require knowledge of the amount of tracer delivered to the pool of interest. In a subset of human subjects, a small amount of orally administered D<jats:sub>3<\/jats:sub>\u2010Cr \u2018spills\u2019 into urine after absorption and prior to transport into skeletal muscle cells. The objectives were to develop a method to correct for spillage to compare the estimate of muscle mass by D<jats:sub>3<\/jats:sub>\u2010Cr dilution to other assessments of fat\u2010free mass.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Subjects (19 males, 23\u201381\u00a0years old; 20 females, 20\u201377\u00a0years old) ingested a single dose of 60\u00a0mg D<jats:sub>3<\/jats:sub>\u2010Cr and urine was collected prior to and daily for 4\u00a0days following the dose. Fasting morning urine samples was assessed for D<jats:sub>3<\/jats:sub>\u2010Cr, total Cr, D<jats:sub>3<\/jats:sub>\u2010Crn, and total Crn concentrations, as well as isotopic enrichments of D<jats:sub>3<\/jats:sub>\u2010Crn, by LC\/MS. The 24\u2010h urine collections over 3\u00a0days after the dose of D<jats:sub>3<\/jats:sub>\u2010Cr were also performed to determine D<jats:sub>3<\/jats:sub>\u2010Cr spillage. Total body water, fat mass, and fat\u2010free mass were assessed by bioelectrical impedance spectroscopy (BIS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Spillage of D<jats:sub>3<\/jats:sub>\u2010Cr in the urine was greater in women than men. D<jats:sub>3<\/jats:sub>\u2010Crn enrichment and the ratio of Cr\/Crn were used in an algorithm to calculate Cr pool size and muscle mass. Specifically, an algorithm was developed for the estimation of spillage based on the relationship between the fasting Cr\/Crn ratio and the cumulative proportion of the D<jats:sub>3<\/jats:sub>\u2010Cr dose excreted over 3\u00a0days based on 24\u2010h urine collections. Muscle mass corrected using the algorithm based on fasting urine levels correlated (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.9967, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001) with that corrected by measuring D<jats:sub>3<\/jats:sub>\u2010Cr dose excreted. Muscle mass measured by D<jats:sub>3<\/jats:sub>\u2010Crn enrichment also correlated (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.8579, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001, algorithm corrected) with that measured by 24\u2010h Crn excretion. Muscle mass measured by D<jats:sub>3<\/jats:sub>\u2010Cr dilution method correlated with intracellular water by BIS, whether using spillage corrected by the algorithm (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.9041, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001) or measured by 3\u00a0day D<jats:sub>3<\/jats:sub>\u2010Cr losses (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.91, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001) and similarly correlated with fat\u2010free mass by BIA (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.8857 and 0.8929, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The D<jats:sub>3<\/jats:sub>\u2010Cr dilution method is further validated here as a non\u2010invasive, easy\u2010to\u2010use test for measuring muscle mass. The technical issue of D<jats:sub>3<\/jats:sub>\u2010Cr spillage can be corrected for with a simple algorithm based on fasting spot urine samples. Muscle mass by Cr dilution potentially has broad applications in clinical and research settings.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12278","type":"journal-article","created":{"date-parts":[[2018,4,17]],"date-time":"2018-04-17T00:37:56Z","timestamp":1523925476000},"page":"540-546","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":97,"title":["Dilution of oral D<sub>3<\/sub>\u2010Creatine to measure creatine pool size and estimate skeletal muscle mass: development of a correction algorithm"],"prefix":"10.1002","volume":"9","author":[{"given":"Mahalakshmi","family":"Shankaran","sequence":"first","affiliation":[{"name":"Department of Nutritional Sciences and Toxicology University of California  Berkeley CA 94720 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregg","family":"Czerwieniec","sequence":"additional","affiliation":[{"name":"KineMed, Inc.  Emeryville CA 94608 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chancy","family":"Fessler","sequence":"additional","affiliation":[{"name":"KineMed, Inc.  Emeryville CA 94608 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po\u2010yin Anne","family":"Wong","sequence":"additional","affiliation":[{"name":"KineMed, Inc.  Emeryville CA 94608 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salena","family":"Killion","sequence":"additional","affiliation":[{"name":"KineMed, Inc.  Emeryville CA 94608 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott M.","family":"Turner","sequence":"additional","affiliation":[{"name":"KineMed, Inc.  Emeryville CA 94608 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc K.","family":"Hellerstein","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences and Toxicology University of California  Berkeley CA 94720 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences and Toxicology University of California  Berkeley CA 94720 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,4,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13539-013-0110-1"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00122.2012"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00045.2014"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00010.2013"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/37.3.478"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(75)90040-2"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-201x.1998.00395.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-011-0853-y"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejcn.2017.27"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12089"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcsm.12278","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.12278","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T16:06:46Z","timestamp":1695485206000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.12278"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,16]]},"references-count":10,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2018,6]]}},"alternative-id":["10.1002\/jcsm.12278"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.12278","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,16]]},"assertion":[{"value":"2017-06-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-12-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}