{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:02:39Z","timestamp":1790193759065,"version":"4.1.0"},"reference-count":84,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T00:00:00Z","timestamp":1662336000000},"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":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The French chemist Michel Eug\u00e8ne Chevreul discovered creatine in meat two centuries ago. Extensive biochemical and physiological studies of this organic molecule followed with confirmation that creatine is found within the cytoplasm and mitochondria of human skeletal muscles. Two groups of investigators exploited these relationships five decades ago by first estimating the creatine pool size <jats:italic>in vivo<\/jats:italic> with <jats:sup>14<\/jats:sup>C and <jats:sup>15<\/jats:sup>N labelled isotopes. Skeletal muscle mass (kg) was then calculated by dividing the creatine pool size (g) by muscle creatine concentration (g\/kg) measured on a single muscle biopsy or estimated from the literature. This approach for quantifying skeletal muscle mass is generating renewed interest with the recent introduction of a practical stable isotope (creatine\u2010(<jats:italic>methyl<\/jats:italic>\u2010d<jats:sub>3<\/jats:sub>)) dilution method for estimating the creatine pool size across the full human lifespan. The need for a muscle biopsy has been eliminated by assuming a constant value for whole\u2010body skeletal muscle creatine concentration of 4.3\u00a0g\/kg wet weight. The current single compartment model of estimating creatine pool size and skeletal muscle mass rests on four main assumptions: tracer absorption is complete; tracer is all retained; tracer is distributed solely in skeletal muscle; and skeletal muscle creatine concentration is known and constant. Three of these assumptions are false to varying degrees. Not all tracer is retained with urinary isotope losses ranging from 0% to 9%; an empirical equation requiring further validation is used to correct for spillage. Not all tracer is distributed in skeletal muscle with non\u2010muscle creatine sources ranging from 2% to 10% with a definitive value lacking. Lastly, skeletal muscle creatine concentration is not constant and varies between muscles (e.g. 3.89\u20134.62\u00a0g\/kg), with diets (e.g. vegetarian and omnivore), across age groups (e.g. middle\u2010age, ~4.5\u00a0g\/kg; old\u2010age, 4.0\u00a0g\/kg), activity levels (e.g. athletes, ~5\u00a0g\/kg) and in disease states (e.g. muscular dystrophies, &lt;3\u00a0g\/kg). Some of the variability in skeletal muscle creatine concentrations can be attributed to heterogeneity in the proportions of wet skeletal muscle as myofibres, connective tissues, and fat. These observations raise serious concerns regarding the accuracy of the deuterated\u2010creatine dilution method for estimating total body skeletal muscle mass as now defined by cadaver analyses of whole wet tissues and <jats:italic>in vivo<\/jats:italic> approaches such as magnetic resonance imaging. A new framework is needed in thinking about how this potentially valuable method for measuring the creatine pool size <jats:italic>in vivo<\/jats:italic> can be used in the future to study skeletal muscle biology in health and disease.<\/jats:p>","DOI":"10.1002\/jcsm.13083","type":"journal-article","created":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T03:08:59Z","timestamp":1662347339000},"page":"2595-2607","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["D<sub>3<\/sub>\u2010creatine dilution for skeletal muscle mass measurement: historical development and current status"],"prefix":"10.1002","volume":"13","author":[{"given":"Cassidy","family":"McCarthy","sequence":"first","affiliation":[{"name":"Pennington Biomedical Research Center Louisiana State University System  Baton Rouge Los Angeles USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale","family":"Schoeller","sequence":"additional","affiliation":[{"name":"Biotechnology Center and Nutritional Sciences University of Wisconsin  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin C.","family":"Brown","sequence":"additional","affiliation":[{"name":"Pennington Biomedical Research Center Louisiana State University System  Baton Rouge Los Angeles USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Cristina","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Post\u2010graduate Program in Health and Behavior Catholic University of Pelotas  Pelotas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa N.","family":"Varanoske","sequence":"additional","affiliation":[{"name":"Military Nutrition Division US Army Research Institute of Environmental Medicine  Natick Massachusetts USA"},{"name":"Oak Ridge Institute for Science and Education  Oak Ridge Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devon","family":"Cataldi","sequence":"additional","affiliation":[{"name":"University of Hawaii Cancer Center  Honolulu Hawaii USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Shepherd","sequence":"additional","affiliation":[{"name":"University of Hawaii Cancer Center  Honolulu Hawaii USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1127-9425","authenticated-orcid":false,"given":"Steven B.","family":"Heymsfield","sequence":"additional","affiliation":[{"name":"Pennington Biomedical Research Center Louisiana State University System  Baton Rouge Los Angeles USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12959"},{"key":"e_1_2_7_3_1","first-page":"23","article-title":"Measurement of skeletal muscle: Laboratory and epidemiological methods","volume":"50","author":"Heymsfield SB","year":"1995","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1520-6300(1999)11:2<167::AID-AJHB4>3.0.CO;2-G"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(68)90089-9"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1970.28.3.264"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-197603000-00008"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00045.2014"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00122.2012"},{"key":"e_1_2_7_10_1","first-page":"231","article-title":"Sur la composition chimique du bouillon de viandes (on the chemical composition of meatbroth)","volume":"21","author":"Chevreul E","year":"1835","journal-title":"J Pharm Sci Access"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)88617-3"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj0210190"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.65.1686.401"},{"key":"e_1_2_7_14_1","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S0031-6997(24)01490-X","article-title":"Clinical pharmacology of the dietary supplement creatine monohydrate","volume":"53","author":"Persky AM","year":"2001","journal-title":"Pharmacol Rev"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2000.80.3.1107"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2016.12.002"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)35610-2"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)30910-9"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03002912"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/90.3.323"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-197805000-00001"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI102672"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI103521"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI104929"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1227\/01.NEU.0000204309.91666.06"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/0306312706075334"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2008.242"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.2165\/00007256-199418040-00005"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1996.81.1.232"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12970-017-0173-z"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-123-9-199511010-00014"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511551741"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/37.3.478"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00455.2016"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12278"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-020-01122-w"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)73109-8"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)87420-8"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)88347-8"},{"key":"e_1_2_7_40_1","volume-title":"Report of the task group on reference man. Icrp publication 23","author":"International Commission on Radiological Protection (ICRP)","year":"1975"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14071526"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-35-9015P"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)85209-7"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389203718666170606105108"},{"key":"e_1_2_7_45_1","first-page":"163","volume-title":"Encyclopedia of analystical science","author":"Smith\u2010Palmer T","year":"2019"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1922.2.4.586"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1042\/cs0810249"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-017-4315-6"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357\u2010022\u201000541\u20103"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP282227"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glab266"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP282558"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glab020"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/sms.13585"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplegacy.1946.145.4.571"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1982.sp014399"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/36.1.131"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI104319"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplegacy.1958.194.3.553"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1966.tb41170.x"},{"key":"e_1_2_7_61_1","doi-asserted-by":"crossref","first-page":"875","DOI":"10.18388\/abp.2004_3520","article-title":"Biochemical and clinical characteristics of creatine deficiency syndromes","volume":"51","author":"Sykut\u2010Cegielska J","year":"2004","journal-title":"Acta Biochim Pol"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc8855"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1908.sp001243"},{"key":"e_1_2_7_64_1","first-page":"11","article-title":"Human aging, muscle mass, and fiber type composition","volume":"50","author":"Lexell J","year":"1995","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"e_1_2_7_65_1","unstructured":"SagayamaH YamadaY KondoE TanabeY UchizawaA ShankaranM et al.Skeletal muscle mass can be estimated by creatine (methyl\u2010d3) dilution and is correlated with fat free mass in young active males. In review."},{"key":"e_1_2_7_66_1","first-page":"945","article-title":"Creatinine excretion: Variability and relationships to diet and body size","volume":"59","author":"Bleiler RE","year":"1962","journal-title":"J Lab Clin Med"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/105.4.428"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/35.8.1802"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1159\/000012837"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12268"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11695-020-05082-2"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/76.2.378"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajhb.23252"},{"key":"e_1_2_7_74_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glaa111"},{"key":"e_1_2_7_75_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4505"},{"key":"e_1_2_7_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2022.111714"},{"key":"e_1_2_7_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamda.2020.03.017"},{"key":"e_1_2_7_78_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00227.2003"},{"key":"e_1_2_7_79_1","first-page":"787","volume-title":"International symposium on nuclear activation techniques in the life sciences; vienna, austria; 22\u201326 may 1978","author":"Burkinshaw L","year":"1979"},{"key":"e_1_2_7_80_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1967.23.5.713"},{"key":"e_1_2_7_81_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.22094"},{"key":"e_1_2_7_82_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12353"},{"key":"e_1_2_7_83_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm4.10527"},{"key":"e_1_2_7_84_1","doi-asserted-by":"publisher","DOI":"10.1259\/bjr.20190327"},{"key":"e_1_2_7_85_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12899"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.13083","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcsm.13083","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.13083","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T07:59:58Z","timestamp":1754639998000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.13083"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,5]]},"references-count":84,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1002\/jcsm.13083"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.13083","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,5]]},"assertion":[{"value":"2022-06-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}