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Deuterated water (2H2O, heavy water) labelling to investigate human cell dynamics in vivo - lessons in protocol design and toxicity from the current literature

Song, A; Zhang, Y; Busch, R; Asquith, B; Macallan, D (2025) Deuterated water (2H2O, heavy water) labelling to investigate human cell dynamics in vivo - lessons in protocol design and toxicity from the current literature. FRONTIERS IN IMMUNOLOGY, 16. p. 1544193. ISSN 1664-3224 https://doi.org/10.3389/fimmu.2025.1544193
SGUL Authors: Macallan, Derek Clive

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Abstract

The use of deuterated water (also known as ‘heavy water’) as a tracer to measure human in vivo cell proliferation rates for specific cell subsets has expanded significantly in recent years. Although there have been several published methods papers, investigators developing new applications may be confused by differences in study design and deuterated water dose/duration. Furthermore, this approach may be met with regulatory difficulties and participant concerns about toxicity. This scoping review explores lessons that can be learnt from the current literature on the use of deuterated water in human in vivo studies measuring cell proliferation. We identified 29 such studies involving 535 study participants, both healthy volunteers and those with specific clinical conditions. Wide variations in protocols were noted with doses ranging from 40-100 ml/day of pure deuterated water (or equivalent) and durations from 4-12 weeks. Study design usually reflected the kinetics of the cell of interest. No clinical toxicity signals were noted in any studies although four studies did report transient dizziness, a recognized symptom of changing water density. These published studies provide a strong safety signal for potential participants and regulatory authorities and can act as templates for the development of new research applications.

Item Type: Article
Additional Information: Copyright © 2025 Song, Zhang, Busch, Asquith and Macallan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Keywords: humans, deuterated water, deuterium, deuterium oxide, heavy water, cell proliferation
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: FRONTIERS IN IMMUNOLOGY
ISSN: 1664-3224
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
103865Z/14/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
220794/Z/20/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
G1001052Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
J007439Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
317040Seventh Framework Programmehttp://dx.doi.org/10.13039/501100004963
764698Horizon 2020https://doi.org/10.13039/501100007601
15012Horizon 2020https://doi.org/10.13039/501100007601
UNSPECIFIEDJefferiss TrustUNSPECIFIED
URI: https://openaccess.sgul.ac.uk/id/eprint/117517
Publisher's version: https://doi.org/10.3389/fimmu.2025.1544193

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