Doubly Labeled Water

The ability to measure free-living energy expenditure is important given that most precise techniques require an individual to remain in a clinical setting for hours at a time. Therefore, the emergence of a novel technique that is noninvasive and allows a person to go about his or her normal daily activities moved the field of energy metabolism into a new era. This technique, the doubly labeled water method (DLW), is safe and straightforward, but technically complex.

Basically, DLW uses water labeled with two stable isotopes—oxygen-18 (H218O) and deuterium (D2O)—hence, the “double label.” These isotopes are safe and mix with the total body water pool just as any other type of water. After a baseline urine or saliva sample is taken, a measured dose of the water, containing a specific amount of each isotope relative to body weight or total fat-free mass (e.g., 0.1 g H218O/kg body weight and 0.08 g D2O/kg body weight) is given to the volunteer. Approximately five hours post dose, the DLW has equilibrated throughout the total body water pool and a urine or saliva sample is collected. Then, on any number of days following the dose, subsequent samples are collected and all samples are analyzed for the ratio of DLW to unlabeled water present in the urine or saliva using a mass spectrometer. A computer program is then used to analyze the rate of loss of each isotope from the total body water pool and the difference in the two rates is used to estimate the CO2 production, allowing for a precise estimate of total energy expenditure to be made.

The DLW method has been found to be accurate to within 3 to 6 percent of total energy expenditure measured using direct calorimetry, the most precise technique available. Thus, not only is it extremely accurate, but it also allows for individuals to carry on with their normal daily activities and does not require them to change their lifestyles in any real way. The fact that free-living energy expenditure is captured improves the accuracy of dietary measures by allowing for a comparison to be made between total energy expenditure and estimated energy intake. Unfortunately, the technical expertise required to analyze the samples as well as the cost of the DLW (upward of $200 per subject) makes the DLW method prohibitively expensive for many investigators in developing countries. Alternatives to the DLW method do exist, [Page 197]but what is gained in technical ease and cost is balanced by a loss in precision.

The main uses of the DLW are to measure energy expenditure in free-living persons, children or adults. It can also be used to more accurately assess body composition, by providing an estimate of total body water which can then be extrapolated to the amount of fat mass and lean body mass. A novel use of these isotopes is to more accurately assess breast milk intake by delivering a dose of the water to a breast-feeding mother and collecting urine samples from the infant. Finally, DLW has been used to compare food intake measures using the assumption that when a person is in energy balance, his or her energy intake equals his or her energy expenditure, so a measure of energy expenditure using DLW should indicate his or her usual energy intake.

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