Doubly labeled water

Doubly labeled water is water in which both the hydrogen and the oxygen have been partly or completely replaced (i.e. labeled) with an uncommon isotope of these elements for tracing purposes.

In practice, for both practical and safety reasons, almost all recent applications of the "doubly labeled water" (DLW) method use water labeled with heavy but non-radioactive forms of each element (deuterium, ²H; and oxygen-18, ¹⁸O). In theory, radioactive heavy isotopes of the elements could be used for such labeling; this was the case in many early applications of the method.^{[citation needed]}

In particular, DLW can be used for a method to measure the average daily metabolic rate of an organism over a period of time (often also called the Field metabolic rate, or FMR, in non-human animals). This is done by administering a dose of DLW, then measuring the elimination rates of ²H and ¹⁸O in the subject over time (through regular sampling of heavy isotope concentrations in body water, by sampling saliva, urine, or blood). At least two samples are required: an initial sample (after the isotopes have reached equilibrium in the body), and a second sample some time later. The time between these samples depends on the size of the animal. In small animals, the period may be as short as 24 hours; in larger animals (such as adult humans), the period may be as long as 14 days.

The method was invented in the 1950s by Nathan Lifson and colleagues^[1][2] at the University of Minnesota. However, its use was restricted to small animals until the 1980s because of the high cost of oxygen-18. Advances in mass spectrometry during the 1970s and early 1980s reduced the amount of isotope required, which made it feasible to apply the method to larger animals, including humans.^[3] The first application to humans was in 1982,^[4] by Dale Schoeller, over 25 years after the method was initially discovered. A complete summary of the technique is provided in a book by British biologist John Speakman.^[5]