The doubly labeled water method is particularly useful for measuring average metabolic rate (field metabolic rate) over relatively long periods of time (a few days or weeks), in subjects for which other types of direct or indirect calorimetric measurements of metabolic rate would be difficult or impossible. For example, the technique can measure the metabolism of animals in the wild state, with the technical problems being related mainly to how to administer the dose of isotope, and collect several samples of body water at later times to check for differential isotope elimination.
Most animal studies involve capturing the subject animals and injecting them, then holding them for a variable period before the first blood sample has been collected. This period depends on the size of the animal involved and varies between 30 minutes for very small animals to 6 hours for much larger animals. In both animals and humans, the test is made more accurate if a single determination of respiratory quotient has been made for the organism eating the standard diet at the time of measurement, since this value changes relatively little (and more slowly) compared with the much larger metabolic rate changes related to thermoregulation and activity.
Because the heavy hydrogen and oxygen isotopes used in the standard doubly labeled water measurement are non-radioactive, and also non-toxic in the doses used (see heavy water), the doubly labeled water measurement of mean metabolic rate has been used extensively in human volunteers, and even in infants and pregnant women. The technique has been used on over 200 species of wild animals (mostly birds, mammals and some reptiles). Applications of the method to animals have been reviewed. A paper by Pontzer, Yamada, Sagayama and colleagues in 2021 summarized the results of over 6400 measurements using the technique in humans aged between 8 days and 96 years old.
Doubly labeled water (HO) can also be used for unusually warm ice and unusually dense water, as it has a higher melting point than and is denser than either light water or what is normally meant by "heavy water" (HO). HO melts at 4.00~4.04 °C (39.2 °F~39.27 °F) and the liquid reaches its maximum density of 1.21684~1.21699 g/cm at 11.43~11.49 °C (52.57 °F~52.68 °F).