A standard calculation methodology for human doubly labeled water studies

John R Speakman^{1

2

3

4}, Yosuke Yamada^{5

6}, Hiroyuki Sagayama⁷, Elena S F Berman⁸, Philip N Ainslie⁹, Lene F Andersen¹⁰, Liam J Anderson^{9

11}, Lenore Arab¹², Issaad Baddou¹³, Kweku Bedu-Addo¹⁴, Ellen E Blaak¹⁵, Stephane Blanc^{16

17}, Alberto G Bonomi¹⁸, Carlijn V C Bouten¹⁹, Pascal Bovet²⁰, Maciej S Buchowski²¹, Nancy F Butte²², Stefan G J A Camps¹⁵, Graeme L Close⁹, Jamie A Cooper¹⁶, Seth A Creasy²³, Sai Krupa Das²⁴, Richard Cooper²⁵, Lara R Dugas²⁵, Cara B Ebbeling²⁶, Ulf Ekelund²⁷, Sonja Entringer^{28

29}, Terrence Forrester³⁰, Barry W Fudge³¹, Annelies H Goris¹⁵, Michael Gurven³², Catherine Hambly², Asmaa El Hamdouchi¹³, Marije B Hoos¹⁵, Sumei Hu³, Noorjehan Joonas³³, Annemiek M Joosen¹⁵, Peter Katzmarzyk³⁴, Kitty P Kempen¹⁵, Misaka Kimura⁶, William E Kraus³⁵, Robert F Kushner³⁶, Estelle V Lambert³⁷, William R Leonard³⁸, Nader Lessan³⁹, David S Ludwig²⁶, Corby K Martin³⁴, Anine C Medin^{10

40}, Erwin P Meijer¹⁵, James C Morehen^{9

41}, James P Morton⁹, Marian L Neuhouser⁴², Theresa A Nicklas²², Robert M Ojiambo^{43

44}, Kirsi H Pietiläinen⁴⁵, Yannis P Pitsiladis⁴⁶, Jacob Plange-Rhule¹⁴, Guy Plasqui⁴⁷, Ross L Prentice⁴², Roberto A Rabinovich⁴⁸, Susan B Racette²⁴, David A Raichlen⁴⁹, Eric Ravussin³⁴, Rebecca M Reynolds⁵⁰, Susan B Roberts²⁴, Albertine J Schuit⁵¹, Anders M Sjödin⁵², Eric Stice⁵³, Samuel S Urlacher⁵⁴, Giulio Valenti¹⁵, Ludo M Van Etten¹⁵, Edgar A Van Mil⁵⁵, Jonathan C K Wells⁵⁶, George Wilson⁹, Brian M Wood^{57

58}, Jack Yanovski⁵⁹, Tsukasa Yoshida⁵, Xueying Zhang^{1

2}, Alexia J Murphy-Alford⁶⁰, Cornelia U Loechl⁶⁰, Edward L Melanson^{23

61

62}, Amy H Luke⁶³, Herman Pontzer^{64

65}, Jennifer Rood³⁴, Dale A Schoeller⁶⁶, Klaas R Westerterp⁶⁷, William W Wong²²; IAEA DLW database group

Affiliations

¹ Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
² Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, UK.
³ State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
⁴ CAS Center of Excellence in Animal Evolution and Genetics, Kunming, China.
⁵ National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Tokyo, Japan.
⁶ Institute for Active Health, Kyoto University of Advanced Science, Kyoto, Japan.
⁷ Faculty of Health and Sport Sciences, University of Tsukuba, Ibaraki, Japan.
⁸ Berman Scientific Consulting, Mountain View, CA, USA.
⁹ Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, UK.
¹⁰ Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.
¹¹ Crewe Alexandra Football Club, Crewe, UK.
¹² David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
¹³ Unité Mixte de Recherche en Nutrition et Alimentation, CNESTEN- Université Ibn Tofail URAC39, Regional Designated Center of Nutrition Associated with AFRA/IAEA, Rabat, Morocco.
¹⁴ Department of Physiology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
¹⁵ Maastricht University, Maastricht, the Netherlands.
¹⁶ Nutritional Sciences, University of Wisconsin, Madison, WI, USA.
¹⁷ Institut Pluridisciplinaire Hubert Curien, CNRS Université de Strasbourg, UMR7178, Strasbourg, France.
¹⁸ Phillips Research, Eindhoven, the Netherlands.
¹⁹ Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, the Netherlands.
²⁰ Institute of Social and Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland.
²¹ Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Vanderbilt University, Nashville, TN, USA.
²² Department of Pediatrics, Baylor College of Medicine, USDA/ARS Children's Nutrition Research Center, Houston, TX, USA.
²³ Division of Endocrinology, Metabolism and Diabetes, University of Colorado Anschulz Medical Campus, Aurora, CO, USA.
²⁴ Friedman School of Nutrition Science and Policy, Tufts University, 150 Harrison Avenue, Boston, MA, USA.
²⁵ Department of Public Health Sciences, Parkinson School of Health Sciences and Public Health, Loyola University, Maywood, IL, USA.
²⁶ Boston Children's Hospital, Boston, MA, USA.
²⁷ Department of Sport Medicine, Norwegian School of Sport Sciences, Oslo, Norway.
²⁸ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Institute of Medical Psychology, Berlin, Germany.
²⁹ University of California, Irvine, Irvine, CA, USA.
³⁰ Solutions for Developing Countries, University of the West Indies, Mona, Kingston, Jamaica.
³¹ University of Glasgow, Glasgow, UK.
³² Department of Anthropology, University of California, Santa Barbara, Santa Barbara, CA, USA.
³³ Central Health Laboratory, Ministry of Health and Wellness, Port Louis, Mauritius.
³⁴ Pennington Biomedical Research Center, Baton Rouge, LA, USA.
³⁵ Department of Medicine, Duke University, Durham, NC, USA.
³⁶ Northwestern University, Chicago, IL, USA.
³⁷ Research Unit for Exercise Science and Sports Medicine, University of Cape Town, Cape Town, South Africa.
³⁸ Department of Anthropology, Northwestern University, Evanston, IL, USA.
³⁹ Imperial College London Diabetes Centre, Imperial College London, London, UK.
⁴⁰ Department of Nutrition and Public Health, Faculty of Health and Sport Sciences, University of Agder, 4630 Kristiansand, Norway.
⁴¹ The FA Group, Burton-Upon-Trent, Staffordshire, UK.
⁴² Division of Public Health Sciences, Fred Hutchinson Cancer Research Center and School of Public Health, University of Washington, Seattle, WA, USA.
⁴³ Moi University, Eldoret, Kenya.
⁴⁴ University of Global Health Equity, Kigali, Rwanda.
⁴⁵ Helsinki University Central Hospital, Helsinki, Finland.
⁴⁶ University of Brighton, Eastbourne, UK.
⁴⁷ Department of Nutrition and Movement Sciences, Maastricht University, Maastricht, the Netherlands.
⁴⁸ University of Edinburgh, Edinburgh, UK.
⁴⁹ Biological Sciences and Anthropology, University of Southern California, Los Angeles, CA, USA.
⁵⁰ Centre for Cardiovascular Sciences, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
⁵¹ University of Tilburg, Tilburg, the Netherlands.
⁵² Department of Nutrition, Exercise and Sports, Copenhagen University, Copenhagen, Denmark.
⁵³ Stanford University, Stanford, CA, USA.
⁵⁴ Department of Anthropology, Baylor University, Waco, TX, USA.
⁵⁵ Maastricht and Lifestyle Medicine Center for Children, Jeroen Bosch Hospital's-Hertogenbosch, Maastricht University, Maastricht, the Netherlands.
⁵⁶ Population, Policy and Practice Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, London, UK.
⁵⁷ University of California, Los Angeles, Los Angeles, CA, USA.
⁵⁸ Department of Human Behavior, Ecology, and Culture, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
⁵⁹ Growth and Obesity, Division of Intramural Research, NIH, Bethesda, MD, USA.
⁶⁰ Nutritional and Health Related Environmental Studies Section, Division of Human Health, International Atomic Energy Agency, Vienna, Austria.
⁶¹ Eastern Colorado VA Geriatric Research, Education and Clinical Center, Aurora, CO, USA.
⁶² Division of Geriatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁶³ Division of Epidemiology, Department of Public Health Sciences, Loyola University School of Medicine, Maywood, IL, USA.
⁶⁴ Evolutionary Anthropology, Duke University, Durham, NC, USA.
⁶⁵ Duke Global Health Institute, Duke University, Durham, NC, USA.
⁶⁶ Biotech Center and Nutritional Sciences, University of Wisconsin, Madison, WI, USA.
⁶⁷ School of Nutrition and Translational Research in Metabolism, University of Maastricht, Maastricht, the Netherlands.

PMID: 33665639
PMCID: PMC7897799
DOI: 10.1016/j.xcrm.2021.100203

A standard calculation methodology for human doubly labeled water studies

John R Speakman et al. Cell Rep Med. 2021.

. 2021 Feb 16;2(2):100203.

doi: 10.1016/j.xcrm.2021.100203.

Authors

Affiliations

¹ Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
² Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, UK.
³ State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
⁴ CAS Center of Excellence in Animal Evolution and Genetics, Kunming, China.
⁵ National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Tokyo, Japan.
⁶ Institute for Active Health, Kyoto University of Advanced Science, Kyoto, Japan.
⁷ Faculty of Health and Sport Sciences, University of Tsukuba, Ibaraki, Japan.
⁸ Berman Scientific Consulting, Mountain View, CA, USA.
⁹ Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, UK.
¹⁰ Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.
¹¹ Crewe Alexandra Football Club, Crewe, UK.
¹² David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
¹³ Unité Mixte de Recherche en Nutrition et Alimentation, CNESTEN- Université Ibn Tofail URAC39, Regional Designated Center of Nutrition Associated with AFRA/IAEA, Rabat, Morocco.
¹⁴ Department of Physiology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
¹⁵ Maastricht University, Maastricht, the Netherlands.
¹⁶ Nutritional Sciences, University of Wisconsin, Madison, WI, USA.
¹⁷ Institut Pluridisciplinaire Hubert Curien, CNRS Université de Strasbourg, UMR7178, Strasbourg, France.
¹⁸ Phillips Research, Eindhoven, the Netherlands.
¹⁹ Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, the Netherlands.
²⁰ Institute of Social and Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland.
²¹ Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Vanderbilt University, Nashville, TN, USA.
²² Department of Pediatrics, Baylor College of Medicine, USDA/ARS Children's Nutrition Research Center, Houston, TX, USA.
²³ Division of Endocrinology, Metabolism and Diabetes, University of Colorado Anschulz Medical Campus, Aurora, CO, USA.
²⁴ Friedman School of Nutrition Science and Policy, Tufts University, 150 Harrison Avenue, Boston, MA, USA.
²⁵ Department of Public Health Sciences, Parkinson School of Health Sciences and Public Health, Loyola University, Maywood, IL, USA.
²⁶ Boston Children's Hospital, Boston, MA, USA.
²⁷ Department of Sport Medicine, Norwegian School of Sport Sciences, Oslo, Norway.
²⁸ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Institute of Medical Psychology, Berlin, Germany.
²⁹ University of California, Irvine, Irvine, CA, USA.
³⁰ Solutions for Developing Countries, University of the West Indies, Mona, Kingston, Jamaica.
³¹ University of Glasgow, Glasgow, UK.
³² Department of Anthropology, University of California, Santa Barbara, Santa Barbara, CA, USA.
³³ Central Health Laboratory, Ministry of Health and Wellness, Port Louis, Mauritius.
³⁴ Pennington Biomedical Research Center, Baton Rouge, LA, USA.
³⁵ Department of Medicine, Duke University, Durham, NC, USA.
³⁶ Northwestern University, Chicago, IL, USA.
³⁷ Research Unit for Exercise Science and Sports Medicine, University of Cape Town, Cape Town, South Africa.
³⁸ Department of Anthropology, Northwestern University, Evanston, IL, USA.
³⁹ Imperial College London Diabetes Centre, Imperial College London, London, UK.
⁴⁰ Department of Nutrition and Public Health, Faculty of Health and Sport Sciences, University of Agder, 4630 Kristiansand, Norway.
⁴¹ The FA Group, Burton-Upon-Trent, Staffordshire, UK.
⁴² Division of Public Health Sciences, Fred Hutchinson Cancer Research Center and School of Public Health, University of Washington, Seattle, WA, USA.
⁴³ Moi University, Eldoret, Kenya.
⁴⁴ University of Global Health Equity, Kigali, Rwanda.
⁴⁵ Helsinki University Central Hospital, Helsinki, Finland.
⁴⁶ University of Brighton, Eastbourne, UK.
⁴⁷ Department of Nutrition and Movement Sciences, Maastricht University, Maastricht, the Netherlands.
⁴⁸ University of Edinburgh, Edinburgh, UK.
⁴⁹ Biological Sciences and Anthropology, University of Southern California, Los Angeles, CA, USA.
⁵⁰ Centre for Cardiovascular Sciences, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
⁵¹ University of Tilburg, Tilburg, the Netherlands.
⁵² Department of Nutrition, Exercise and Sports, Copenhagen University, Copenhagen, Denmark.
⁵³ Stanford University, Stanford, CA, USA.
⁵⁴ Department of Anthropology, Baylor University, Waco, TX, USA.
⁵⁵ Maastricht and Lifestyle Medicine Center for Children, Jeroen Bosch Hospital's-Hertogenbosch, Maastricht University, Maastricht, the Netherlands.
⁵⁶ Population, Policy and Practice Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, London, UK.
⁵⁷ University of California, Los Angeles, Los Angeles, CA, USA.
⁵⁸ Department of Human Behavior, Ecology, and Culture, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
⁵⁹ Growth and Obesity, Division of Intramural Research, NIH, Bethesda, MD, USA.
⁶⁰ Nutritional and Health Related Environmental Studies Section, Division of Human Health, International Atomic Energy Agency, Vienna, Austria.
⁶¹ Eastern Colorado VA Geriatric Research, Education and Clinical Center, Aurora, CO, USA.
⁶² Division of Geriatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁶³ Division of Epidemiology, Department of Public Health Sciences, Loyola University School of Medicine, Maywood, IL, USA.
⁶⁴ Evolutionary Anthropology, Duke University, Durham, NC, USA.
⁶⁵ Duke Global Health Institute, Duke University, Durham, NC, USA.
⁶⁶ Biotech Center and Nutritional Sciences, University of Wisconsin, Madison, WI, USA.
⁶⁷ School of Nutrition and Translational Research in Metabolism, University of Maastricht, Maastricht, the Netherlands.

PMID: 33665639
PMCID: PMC7897799
DOI: 10.1016/j.xcrm.2021.100203

Abstract

The doubly labeled water (DLW) method measures total energy expenditure (TEE) in free-living subjects. Several equations are used to convert isotopic data into TEE. Using the International Atomic Energy Agency (IAEA) DLW database (5,756 measurements of adults and children), we show considerable variability is introduced by different equations. The estimated rCO₂ is sensitive to the dilution space ratio (DSR) of the two isotopes. Based on performance in validation studies, we propose a new equation based on a new estimate of the mean DSR. The DSR is lower at low body masses (<10 kg). Using data for 1,021 babies and infants, we show that the DSR varies non-linearly with body mass between 0 and 10 kg. Using this relationship to predict DSR from weight provides an equation for rCO₂ over this size range that agrees well with indirect calorimetry (average difference 0.64%; SD = 12.2%). We propose adoption of these equations in future studies.

Keywords: doubly labeled water; free-living; total energy expenditure; validation.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

**Figure 1**
Comparison of published CO₂ production by doubly labeled water to that by standard method (A) Relationship between CO₂ production (L/d) for 5,756 individuals extracted from the original studies and the recalculated estimates using Equation 1. (B–D) Bland-Altman plots comparing the published rCO₂ for studies using (B) the Coward and Prentice equation, (C) the Schoeller et al. A6 equation, and (D) the Racette et al. compared with the standard Equation 1 derived from Sagayama et al. In all plots, dotted line is average difference, and solid blue lines are plus and minus 2 SDs. The red lines define the boundary for plus and minus 10% difference between methods. Data refer to 5,756 adult individuals uploaded into the IAEA DLW database (v3.1).

**Figure 2**
Comparison of published energy expenditure by DLW to that calculated by standard method (A) Relationship between the TEE (MJ/d) for 4,571 individual adults extracted from the original studies and the recalculated TEE using the Weir equation. (B) Bland-Altman plot comparing the published TEE with those generated using the recommended equation. Dotted line is average difference. Data refer to data for 4,571 adult individuals uploaded into the IAEA DLW database (v3.1). The sample size is lower than in Figure 1, because for some individuals, estimates of RQ or FQ were not available.

**Figure 3**
Dilution space ratio as a function of body mass and performance of new equation against indirect calorimetry (A) Dilution space ratios (the hydrogen dilution space N_d divided by the oxygen dilution space N_o) of 332 babies weighing <10 kg from the IAEA DLW database v 3.1 (open circles) combined with data from validation studies in preterm and full-term babies (gray circles). For the sample from the database, there was a linear relationship (blue dotted line that marginally failed to reach significance p = 0.08). We fitted an asymptotic exponential to the combined dataset (red line; r² = 6.4%; p < 0.03). (B) The results of validation studies of the DLW method in babies comparing the DLW estimates of CO₂ production (rCO₂) derived from a combination of Equations 9 and 10 presented here and rCO₂ measured by indirect calorimetry. There was a strong linear relationship fitted by least-squares regression—dotted blue line, with r² = 0.90.

See this image and copyright information in PMC

References

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1. Lifson N. Theory of use of the turnover rates of body water for measuring energy and material balance. J. Theor. Biol. 1966;12:46–74. - PubMed
1. Speakman J.R. Chapman and Hall; 1997. Doubly Labelled Water: Theory and Practice.
1. Nagy K.A. Laboratory of Biomedical and Environmental Sciences, University of California; 1983. The Doubly Labeled Water (3HH18O) Method: A Guide to Its Use.
1. Schoeller D.A., van Santen E. Measurement of energy expenditure in humans by doubly labeled water method. J. Appl. Physiol. 1982;53:955–959. - PubMed

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A standard calculation methodology for human doubly labeled water studies

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A standard calculation methodology for human doubly labeled water studies

Authors

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Abstract

Conflict of interest statement

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