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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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 (CO2) determined with OA-ICOS has not been demonstrated. We compared simultaneous measurement CO2 obtained using whole-room indirect calorimetry (IC) with DLW-based measurements from IRMS and OA-ICOS. Seventeen subjects (10 female; 22 to 63 yr) were studied for 7 consecutive days in the IC. Subjects consumed a dose of 0.25 g H-2 O-18 (98% APE) and 0.14 g (H2O)-H-2 (99.8% APE) per kilogram of total body water, and urine samples were obtained on days 1 and 8 to measure average daily CO2 using OA-ICOS and IRMS. CO2 was calculated using both the plateau and intercept methods. There were no differences in CO2 measured by OA-ICOS or IRMS compared with IC when the plateau method was used. When the intercept method was used, CO2 using OA-ICOS did not differ from IC, but CO2 measured using IRMS was significantly lower than IC. Accuracy (similar to 1-5%), precision (similar to 8%), intraclass correlation coefficients (R = 0.87-90), and root mean squared error (30-40 liters/day) of CO2 measured by OA-ICOS and IRMS were similar. Both OA-ICOS and IRMS produced measurements of CO2 with comparable accuracy and precision compared with IC.

Original languageEnglish
Pages (from-to)E124-E130
Number of pages7
JournalAmerican Journal of Physiology : Endocrinology and Metabolism
Issue number2
Publication statusPublished - Feb 2018


  • adult
  • deuterium
  • humans
  • oxygen isotope
  • respiratory gas exchange
  • O-17-EXCESS
  • DELTA-O-18


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