Revision of calculations in the doubly labeled water method for measurement of energy expenditure in humans

In the doubly labeled water (DLW) method for the measurement of energy expenditure in humans, the basis of the calculation for CO2 production is the difference between the products of the rate constants for the disappearance of 18O and 2H from body water (KO, and KD, respectively) and the matching isotope dilution spaces (NO and ND, respectively). Thus, omitting corrections for isotope fractionation, CO2 production = 0.5 (KONO-KDND). In this calculation, it is also customary to normalize observed NO and ND values to a fixed value for ND/NO. The increasing use of the method has resulted in the generation of substantially more information on the normal value for ND/NO than existed at the time the method was first developed, and recent work has suggested that revisions of the originally used value of 1.03 may now be deemed appropriate. Values of 1.034 or 1.0427 have recently been suggested, but when applied in energy expenditure studies these estimates would lead to significantly different expenditure measurements. It can, however, be shown from published work and direct experimental study that ND/NO values are method dependent, and for these reasons the lower revised value of 1.034 appears to be more acceptable. The possibility that particular populations may ultimately be shown to be different from 1.034 should not, however, be dismissed entirely, and for this reason we suggest that information derived in individual experiments could be used in a Bayesian fashion to generate new ND/NO estimates. The appropriate techniques are described.

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Energy expenditure by doubly labeled water: validation in humans and proposed calculation

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1986.250.5.r823 ◽

1986 ◽

Vol 250 (5) ◽

pp. R823-R830 ◽

Cited By ~ 67

Author(s):

D. A. Schoeller ◽

E. Ravussin ◽

Y. Schutz ◽

K. J. Acheson ◽

P. Baertschi ◽

...

Keyword(s):

Energy Expenditure ◽

Isotope Dilution ◽

Isotope Ratio Mass Spectrometry ◽

Co2 Production ◽

Doubly Labeled Water ◽

Adult Males ◽

Doubly Labeled Water Method ◽

The Difference ◽

Total Body ◽

Atom Percent Excess

To further validate the doubly labeled water method for measurement of CO2 production and energy expenditure in humans, we compared it with near-continuous respiratory gas exchange in nine healthy young adult males. Subjects were housed in a respiratory chamber for 4 days. Each received 2H2(18)O at either a low (n = 6) or a moderate (n = 3) isotope dose. Low and moderate doses produced initial 2H enrichments of 5 and 10 X 10(-3) atom percent excess, respectively, and initial 18O enrichments of 2 and 2.5 X 10(-2) atom percent excess, respectively. Total body water was calculated from isotope dilution in saliva collected at 4 and 5 h after the dose. CO2 production was calculated by the two-point method using the isotopic enrichments of urines collected just before each subject entered and left the chamber. Isotope enrichments relative to predose samples were measured by isotope ratio mass spectrometry. At low isotope dose, doubly labeled water overestimated average daily energy expenditure by 8 +/- 9% (SD) (range -7 to 22%). At moderate dose the difference was reduced to +4 +/- 5% (range 0-9%). The isotope elimination curves for 2H and 18O from serial urines collected from one of the subjects showed expected diurnal variations but were otherwise quite smooth. The overestimate may be due to approximations in the corrections for isotope fractionation and isotope dilution. An alternative approach to the corrections is presented that reduces the overestimate to 1%.

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Use of feces to estimate isotopic abundance in doubly labeled water studies in reindeer in summer and winter

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1997.273.4.r1451 ◽

1997 ◽

Vol 273 (4) ◽

pp. R1451-R1456 ◽

Cited By ~ 6

Author(s):

Geir Gotaas ◽

Eric Milne ◽

Paul Haggarty ◽

Nicholas J. C. Tyler

Keyword(s):

Energy Metabolism ◽

Energy Expenditure ◽

Rate Constants ◽

Total Energy Expenditure ◽

Body Water ◽

Doubly Labeled Water ◽

Isotopic Abundance ◽

Wild Mammals ◽

Doubly Labeled Water Method ◽

Free Ranging

The reliance on samples of blood or urine to estimate isotopic abundance in studies of energy metabolism using the doubly labeled water method has restricted application of the technique to animals that are either tame or easy to catch. This is generally not the case with large, free-ranging wild mammals. The use of feces as a source of body water in which to measure the concentration of isotopic markers was investigated in four female reindeer in summer and in winter.2H2O and H2 18O were injected to ∼160 parts per million excess. Samples of plasma and feces were then collected simultaneously for up to 456 h. Both isotopes were equilibrated with body water at 8 h postdose. There were no significant differences by animal between dilution spaces, rate constants, rates of CO2production, and total energy expenditure (TEE) calculated based on samples of plasma or feces in any trial. Mean TEE was 3.557 W/kg (SD 0.907, n = 4) in summer and 1.865 W/kg (SD 0.166, n = 4) in winter.

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Sensitivity of methods for calculating energy expenditure by use of doubly labeled water

Journal of Applied Physiology ◽

10.1152/jappl.1989.66.2.644 ◽

1989 ◽

Vol 66 (2) ◽

pp. 644-652 ◽

Cited By ~ 16

Author(s):

J. Seale ◽

C. Miles ◽

C. E. Bodwell

Keyword(s):

Energy Expenditure ◽

Weight Maintenance ◽

Carbon Dioxide Production ◽

Metabolizable Energy ◽

Doubly Labeled Water ◽

Calculation Methods ◽

Data Set ◽

Calculated Energy ◽

Doubly Labeled Water Method ◽

The Difference

Attempts to estimate human energy expenditure by use of doubly labeled water have produced three methods currently used for calculating carbon dioxide production from isotope disappearance data: 1) the two-point method, 2) the regression method, and 3) the integration method. An ideal data set was used to determine the error produced in the calculated energy expenditure for each method when specific variables were perturbed. The analysis indicates that some of the calculation methods are more susceptible to perturbations in certain variables than others. Results from an experiment on one adult human subject are used to illustrate the potential for error in actual data. Samples of second void urine, 24-h urine, and breath collected every other day for 21 days are used to calculate the average daily energy expenditure by three calculation methods. The difference between calculated energy expenditure and metabolizable energy on a weight-maintenance diet is used to estimate the error associated with the doubly labeled water method.

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Doubly labeled water method: in vivo oxygen and hydrogen isotope fractionation

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1986.251.6.r1137 ◽

1986 ◽

Vol 251 (6) ◽

pp. R1137-R1143 ◽

Cited By ~ 15

Author(s):

D. A. Schoeller ◽

C. A. Leitch ◽

C. Brown

Keyword(s):

Water Loss ◽

Isotope Fractionation ◽

Isotopic Fractionation ◽

Co2 Production ◽

Doubly Labeled Water ◽

Water Turnover ◽

Evaporative Water ◽

Equilibrium Control ◽

Doubly Labeled Water Method

The accuracy and precision of the doubly labeled water method for measuring energy expenditure are influenced by isotope fractionation during evaporative water loss and CO2 excretion. To characterize in vivo isotope fractionation, we collected and isotopically analyzed physiological fluids and gases. Breath and transcutaneous water vapor were isotopically fractionated. The degree of fractionation indicated that the former was fractionated under equilibrium control at 37 degrees C, and the latter was kinetically fractionated. Sweat and urine were unfractionated. By use of isotopic balance models, the fraction of water lost via fractionating routes was estimated from the isotopic abundances of body water, local drinking water, and dietary solids. Fractionated water loss averaged 23% (SD = 10%) of water turnover, which agreed with our previous estimates based on metabolic rate, but there was a systematic difference between the results based on O2 and hydrogen. Corrections for isotopic fractionation of water lost in breath and (nonsweat) transcutaneous loss should be made when using labeled water to measure water turnover or CO2 production.

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Relative dilution spaces of 2H- and 18O-labeled water in humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1994.267.4.e585 ◽

1994 ◽

Vol 267 (4) ◽

pp. E585-E590 ◽

Cited By ~ 66

Author(s):

S. B. Racette ◽

D. A. Schoeller ◽

A. H. Luke ◽

K. Shay ◽

J. Hnilicka ◽

...

Keyword(s):

Gender Difference ◽

Energy Expenditure ◽

Isotope Dilution ◽

Doubly Labeled Water ◽

Future Studies ◽

Average Ratio ◽

18O Isotope ◽

Doubly Labeled Water Method ◽

Improved Accuracy ◽

Space Ratio

The doubly labeled water method for measuring energy expenditure can be very sensitive to small differences in the ratio of the 2H to 18O isotope dilution spaces. Recently it has been suggested that the average ratio is higher than the 1.03 we previously recommended. We therefore combined the data from 99 recently studied subjects. Subjects (85 females and 14 males) were between the ages of 4 and 78 yr (mean = 34 yr) and between 10 and 52% (mean = 35%) fat. The average 2H-to-18O dilution space ratio was 1.034 +/- 0.014, which was very similar to the original assumption. As in recent reports, we did find that most of the variance (60%) was due to random analytic error and that there was no correlation between the dilution space ratio and age or body fat. However, in contrast to recent reports we found no evidence of a gender difference. Use of the constant dilution space ratio of 1.034 to recalculate CO2 product in published validation studies demonstrated improved accuracy, and thus the value of 1.034 is suggested for use in future studies.

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Comparison of Energy Intake in Toddlers Assessed by Food Frequency Questionnaire and Total Energy Expenditure Measured by the Doubly Labeled Water Method

Journal of the Academy of Nutrition and Dietetics ◽

10.1016/j.jand.2012.09.021 ◽

2013 ◽

Vol 113 (3) ◽

pp. 459-463 ◽

Cited By ~ 22

Author(s):

Clare E. Collins ◽

Tracy L. Burrows ◽

Helen Truby ◽

Philip J. Morgan ◽

Ian M.R. Wright ◽

...

Keyword(s):

Energy Expenditure ◽

Total Energy ◽

Energy Intake ◽

Food Frequency Questionnaire ◽

Total Energy Expenditure ◽

Doubly Labeled Water ◽

Food Frequency ◽

Doubly Labeled Water Method

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Validation of single-sample doubly labeled water method

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1989.256.2.r572 ◽

1989 ◽

Vol 256 (2) ◽

pp. R572-R576 ◽

Cited By ~ 2

Author(s):

M. D. Webster ◽

W. W. Weathers

Keyword(s):

Water Flux ◽

Passerine Bird ◽

Single Sample ◽

Co2 Production ◽

Doubly Labeled Water ◽

Water Turnover ◽

Sample Technique ◽

Doubly Labeled Water Method ◽

The One ◽

Sample Method

We have experimentally validated a single-sample variant of the doubly labeled water method for measuring metabolic rate and water turnover in a very small passerine bird, the verdin (Auriparus flaviceps). We measured CO2 production using the Haldane gravimetric technique and compared these values with estimates derived from isotopic data. Doubly labeled water results based on the one-sample calculations differed from Haldane values by less than 0.5% on average (range -8.3 to 11.2%, n = 9). Water flux computed by the single-sample method differed by -1.5% on average from results for the same birds based on the standard, two-sample technique (range -13.7 to 2.0%, n = 9).

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