“…Building upon the knowledge generated by researchers utilizing heavy water for measurement of body water pool size (Hevesy & Hofer, ), energy expenditure (Lifson, Gordon, & McClintock, ; Schoeller & van Santen, ) and aspects of plant protein metabolism (Humphrey & Davies, , ), it was soon realized, through the dedicated work of Marc Hellerstein and Stephen Previs (working independently of each other), that D 2 O could overcome a number of the issues related to the use of traditional substrate‐specific stable isotope tracers. Administered either orally (Previs et al, ; Gasier, Fluckey, & Previs, ; Robinson et al, ; Gasier et al, ; MacDonald et al, ; Wilkinson et al, , ; Decaris et al, ) or intravenously (Emmanuel et al, ), continuously (Robinson et al, ; Brook et al, ; Decaris et al, ) or as a single bolus (MacDonald et al, ; Wilkinson et al, , ), D 2 O rapidly equilibrates with body water (within ∼20 min in rodents; Dufner et al, and up to 1–2 hr in adults humans (IAEA Human Health Series, )), this creates a homogenous, slowly turning over, precursor pool available for use by multiple substrates. The deuterium from the body water can then be incorporated onto different substrates at stable CH positions through biological reductions during de novo synthesis, and the metabolic flux of these substrate pools can be calculated from the measurement of the amount of the label that is incorporated (Hellerstein, ).…”