Characterization of human plasma proteome dynamics using deuterium oxide

Proteomics Clin Appl. 2014 Aug;8(7-8):610-9. doi: 10.1002/prca.201400038.


Purpose: High-throughput quantification of human protein turnover via in vivo administration of deuterium oxide ((2) H2 O) is a powerful new approach to examine potential disease mechanisms. Its immediate clinical translation is contingent upon characterizations of the safety and hemodynamic effects of in vivo administration of (2) H2 O to human subjects.

Experimental design: We recruited ten healthy human subjects with a broad demographic variety to evaluate the safety, feasibility, efficacy, and reproducibility of (2) H2 O intake for studying protein dynamics. We designed a protocol where each subject orally consumed weight-adjusted doses of 70% (2) H2 O daily for 14 days to enrich body water and proteins with deuterium. Plasma proteome dynamics was measured using a high-resolution MS method we recently developed.

Results: This protocol was successfully applied in ten human subjects to characterize the endogenous turnover rates of 542 human plasma proteins, the largest such human dataset to-date. Throughout the study, we did not detect physiological effects or signs of discomfort from (2) H2 O consumption.

Conclusions and clinical relevance: Our investigation supports the utility of a (2) H2 O intake protocol that is safe, accessible, and effective for clinical investigations of large-scale human protein turnover dynamics. This workflow shows promising clinical translational value for examining plasma protein dynamics in human diseases.

Keywords: Deuterium oxide; Heavy water; Plasma proteome; Protein dynamics; Protein turnover.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Proteins / metabolism*
  • Deuterium Oxide / blood
  • Deuterium Oxide / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Proteomics / methods*
  • Young Adult


  • Blood Proteins
  • Deuterium Oxide