Characterization of human plasma proteome dynamics using deuterium oxide

Purpose: High-throughput quantification of human protein turnover via in vivo administration of deuterium oxide (²H₂O) 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 ²H₂O 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 ²H₂O intake for studying protein dynamics. We designed a protocol where each subject orally consumed weight-adjusted doses of 70% ²H₂O 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 ²H₂O consumption. Conclusions and clinical relevance: Our investigation supports the utility of a ²H₂O 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.