Principles, problems and a paradox with the measurement of energy expenditure of free-living subjects using doubly-labelled water.

Many aspects of the study of human nutrition would benefit from the ability to measure the energy which is expended by subjects as they go about their normal activities. The doubly-labelled water technique is a method which allows such measures to be made. The technique depends on the principle that a measure of carbon dioxide production is possible from the difference in the rates at which isotopic labels of hydrogen and oxygen are eliminated from the body. This simple explanation however conceals a host of assumptions. Several issues have emerged as important in the application of the technique to humans. These issues include first, the use of two samples (an initial and final sample) or multiple samples to estimate the rates of isotope elimination, and secondly the appropriate use of dilution spaces. This paper reviews the current status of the debates concerning these two issues. Paradoxically, improvements in our understanding of the technique, in the methods for calculating carbon dioxide production and in the accuracy of mass spectrometry, have not led to improvements in the accuracy of the technique. The mean deviation of estimates of carbon dioxide production using the technique from estimates made by conventional methods averages 7 per cent.