Impact of habituated dietary protein intake on fasting and postprandial whole-body protein turnover and splanchnic amino acid metabolism in elderly men: a randomized, controlled, crossover trial

Research output: Contribution to journalArticlepeer-review


  • Grith Højfeldt
  • Jacob Bülow
  • Jakob Agergaard
  • Ali Asmar
  • Peter Schjerling
  • Lene Simonsen
  • Jens Bülow
  • Gerrit Van hall

Colleges, School and Institutes

External organisations

  • Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery M81, Bispebjerg Hospital, Copenhagen, Denmark
  • Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Copenhagen, Rigshospitalet, Copenhagen, Denmark
  • Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Bispebjerg Bakke 23, building 8, 1st floor, 2400, Copenhagen NV, Denmark.
  • Department of Clinical Physiology and Nuclear Medicine, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark
  • Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Clinical Metabolomics Core Facility, Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.


Background: Efficacy of protein absorption and subsequent amino acid utilization may be reduced in the elderly. Higher protein intakes have been suggested to counteract this.

Objectives: We aimed to elucidate how habituated amounts of protein intake affect the fasted state of, and the stimulatory effect of a protein-rich meal on, protein absorption, whole-body protein turnover, and splanchnic amino acid metabolism.

Methods: Twelve men (65–70 y) were included in a double-blinded crossover intervention study, consisting of a 20-d habituation period to a protein intake at the RDA or a high amount [1.1 g · kg lean body mass (LBM)−1 · d−1 or >2.1 g · kg LBM−1 · d−1, respectively], each followed by an experimental trial with a primed, constant infusion of D8-phenylalanine and D2-tyrosine. Arterial and hepatic venous blood samples were obtained after an overnight fast and repeatedly 4 h after a standardized meal including intrinsically labeled whey protein concentrate and calcium-caseinate proteins. Blood was analyzed for amino acid concentrations and phenylalanine and tyrosine tracer enrichments from which whole-body and splanchnic amino acid and protein kinetics were calculated.

Results: High (compared with the recommended amount of) protein intake resulted in a higher fasting whole-body protein turnover with a resultant mean ± SEM 0.03 ± 0.01 μmol · kg LBM−1 · min−1 lower net balance (P < 0.05), which was not rescued by the intake of a protein-dense meal. The mean ± SEM plasma protein fractional synthesis rate was 0.13 ± 0.06%/h lower (P < 0.05) after habituation to high protein. Furthermore, higher fasting and postprandial amino acid removal were observed after habituation to high protein, yielding higher urea excretion and increased phenylalanine oxidation rates (P < 0.01).

Conclusions: Three weeks of habituation to high protein intake (>2.1 g protein · kg LBM−1 · d−1) led to a significantly higher net protein loss in the fasted state. This was not compensated for in the 4-h postprandial period after intake of a meal high in protein.

This trial was registered at as NCT02587156.


Original languageEnglish
Pages (from-to)1468-1484
Number of pages17
JournalThe American journal of clinical nutrition
Issue number6
Early online date25 Jul 2020
Publication statusPublished - Dec 2020


  • habitual protein intake, recommended protein intake, protein turnover, protein breakdown, whole-body protein turnover, intrinsically labeled proteins, stable-isotope tracers, whey protein, caseinate protein