Validation of the doubly labeled water method using off-axis integrated cavity output spectroscopy and isotope ratio mass spectrometry

Edward L. Melanson, Tracy Swibas, Wendy M. Kohrt, Vicki A. Catenacci, Seth A. Creasy, Guy Plasqui, Loek Wouters, John R Speakman, Elena S. F. Berman

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15 Citations (Scopus)
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When the doubly-labeled water (DLW) method is used to measure total daily energy expenditure (TDEE), isotope measurements are typically performed using isotope ratio mass spectrometry (IRMS). New technologies, such as off-axis integrated cavity output spectroscopy (OA-ICOS) provide comparable isotopic measurements of standard waters and human urine samples, but the accuracy of carbon dioxide production (VCO2) determined with OA-ICOS has not been demonstrated. We compared simultaneous measurement of VCO2 obtained using whole-room indirect calorimetry (IC) with DLW-based measurements from IRMS and OA-ICOS. 17 subjects (10 female; 22 to 63 yrs.) were studied for 7 consecutive days in the IC. Subjects consumed a dose of 0.25 g H2(18)O (95% APE) and 0.14 g (2)H2O (99.8% APE) per kg of total body water, and urine samples were obtained on days 1 and 8 to measure average daily VCO2 using OA-ICOS and IRMS. VCO2 was calculated using both the plateau and intercept methods. There were no differences in VCO2 or TDEE measured by OA-ICOS or IRMS compared with IC when the plateau method was used. When the intercept method was used, VCO2 measured using OA-ICOS did not differ from IC, but VCO2 measured using IRMS was significantly lower than IC. Accuracy (~1-5%), precision (~8%), intraclass correlation coefficients (R=0.87-90), and root mean squared error (30-40 L/day) of VCO22 measured by OA-ICOS and IRMS were similar. Both OA-ICOS and IRMS produced measurements of VCO2 with comparable accuracy and precision when compared to IC.

Original languageEnglish
Pages (from-to)124-130
Number of pages7
JournalAmerican Journal of Physiology: Endocrinology and Metabolism
Issue number2
Early online date3 Oct 2017
Publication statusPublished - Feb 2018

Bibliographical note

This work was supported by an NIH Small Business Innovation (SBIR)
research Grant (R44 DK093362), as well as support from the Colorado Nutrition and Obesity Research Center (P30 DK048520) and the Colorado Clinical and Translational Science Institute (UL1 RR025780). Dr. Melanson is also supported by resources from the Geriatric Research, Education, and Clinical Center at the Denver VA Medical Center.


  • Journal Article
  • Adult
  • Humans
  • Oxygen Isotope
  • Deuterium
  • Respiratory Gas Exchange


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