Assessing muscle protein synthesis rates in vivo in humans: the deuterated water (2H2O) method

Holwerda, Andrew M.; Atherton, Philip J.; Smith, Kenneth; Wilkinson, Daniel J.; Phillips, Stuart M.; van Loon, Luc J.C.

Abstract

Skeletal muscle tissue is in a constant state of turnover, with muscle tissue protein synthesis and breakdown rates ranging between 1-2 % across the day in vivo in humans. Muscle tissue remodeling is largely controlled by the up- and down-regulation of muscle tissue protein synthesis rates. Research studies generally apply stable isotope labeled amino acids to assess muscle protein synthesis rates in vivo in humans. Following labeled amino acid administration in a laboratory setting, muscle tissue samples are collected over several hours to assess the incorporation rate of these labeled amino acids in muscle tissue protein. To allow quantification of bulk muscle protein synthesis rates over more prolonged periods, the use of deuterated water methodology has regained much interest. Ingestion of daily boluses of deuterium oxide (2H2O) results in 2H-enrichment of the body water pool. The available 2H-atoms become incorporated into endogenously synthesized alanine primarily through transamination of pyruvate in the liver. With 2H-alanine widely available to all tissues, it becomes incorporated into de novo synthesized tissue proteins. Assessing the increase in tissue protein-bound 2H-alanine enrichment in muscle biopsy samples over time allows for calculation of muscle protein synthesis rates over several days or even weeks. As the deuterated water method allows for assessment of muscle tissue protein synthesis rates under free living conditions in non-laboratory settings, there is an increasing interest in its application. This manuscript describes the theoretical background of the deuterated water method and offers a comprehensive tutorial to correctly apply the method to determine bulk muscle protein synthesis rates in vivo in humans.

Citation

Holwerda, A. M., Atherton, P. J., Smith, K., Wilkinson, D. J., Phillips, S. M., & van Loon, L. J. (2024). Assessing muscle protein synthesis rates in vivo in humans: the deuterated water (2H2O) method. Journal of Nutrition, 154(11), 3177-3189. https://doi.org/10.1016/j.tjnut.2024.09.012

• Journal Article Type: Article
• Acceptance Date: Sep 10, 2024
• Online Publication Date: Sep 14, 2024
• Publication Date: 2024-11
• Deposit Date: Nov 26, 2024
• Publicly Available Date: Nov 26, 2024
• Journal: Journal of Nutrition
• Print ISSN: 0022-3166
• Electronic ISSN: 1541-6100
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 154
• Issue: 11
• Pages: 3177-3189
• DOI: https://doi.org/10.1016/j.tjnut.2024.09.012
• Public URL: https://nottingham-repository.worktribe.com/output/39978822
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0022316624010290?via%3Dihub