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Advances in stable isotope tracer methodology part 2: new thoughts about an “old” method—measurement of whole body protein synthesis and breakdown in the fed state
  1. Robert R Wolfe1,
  2. Sanghee Park1,
  3. Il-Young Kim2,
  4. Paul J Moughan3,
  5. Arny A Ferrando1
  1. 1 Department of Geriatrics, Reynolds Institute on Aging, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
  2. 2 Department of Molecular Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University School of Medicine, Incheon, Republic of Korea
  3. 3 Riddet Institute, Massey University, Palmerston North, New Zealand
  1. Correspondence to Dr. Robert R Wolfe; RWolfe2{at}


Whole-body protein turnover (protein synthesis, breakdown, and net balance) model enables quantification of the response to a variety of circumstances, including the response to meal feeding. In the fed state, the whole-body protein turnover model requires taking account of the contribution of absorbed tracee to the observed total appearance of tracee in the peripheral blood (exogenous appearance, RaEXO). There are different approaches to estimating RaEXO. The use of an intrinsically labeled dietary protein is based on the overriding assumption that the appearance in the peripheral circulation of a tracer amino acid incorporated into a dietary protein is exactly proportional to the appearance of absorbed tracee. The bioavailability approach is based on the true ileal digestibility of the dietary protein and the irreversible loss of the tracee in the splanchnic bed via hydroxylation of the tracee (phenylalanine). Finally, RaEXO can be estimated as the increase above the basal rate of appearance of the tracee using traditional tracer dilution methodology. In this paper, we discuss the pros and cons of each approach and conclude that the bioavailability method is the least likely to introduce systematic errors and is therefore the preferable approach.

  • muscle, skeletal
  • research design
  • amino acids

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  • Contributors RW collected and analyzed the data and wrote the manuscript. IK prepared the figure. SP, IK, PJM, and AAF collected and analyzed the data and edited the manuscript.

  • Funding IK: Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2018R1D1A1B07051053).

  • Competing interests RW has received honoraria and research grants from the National Cattleman’s Beef Association and is a shareholder in Essential Blends, LLC. RW is a consultant for Trivita LLC.

  • Provenance and peer review Not commissioned; internally peer reviewed.

  • Patient consent for publication Not required.

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