Protein Type, Protein Dose, and Age Modulate Dietary Protein Digestion and Phenylalanine Absorption Kinetics and Plasma Phenylalanine Availability in Humans

Stefan H M Gorissen, Jorn Trommelen, Imre W K Kouw, Andrew M Holwerda, Bart Pennings, Bart B L Groen, Benjamin T Wall, Tyler A Churchward-Venne, Astrid M H Horstman, René Koopman, Nicholas A Burd, Cas J Fuchs, Marlou L Dirks, Peter T Res, Joan M G Senden, Jan M J M Steijns, Lisette C P G M de Groot, Lex B Verdijk, Luc J C van Loon, Stefan H M Gorissen, Jorn Trommelen, Imre W K Kouw, Andrew M Holwerda, Bart Pennings, Bart B L Groen, Benjamin T Wall, Tyler A Churchward-Venne, Astrid M H Horstman, René Koopman, Nicholas A Burd, Cas J Fuchs, Marlou L Dirks, Peter T Res, Joan M G Senden, Jan M J M Steijns, Lisette C P G M de Groot, Lex B Verdijk, Luc J C van Loon

Abstract

Background: Dietary protein ingestion stimulates muscle protein synthesis by providing amino acids to the muscle. The magnitude and duration of the postprandial increase in muscle protein synthesis rates are largely determined by dietary protein digestion and amino acid absorption kinetics.

Objective: We assessed the impact of protein type, protein dose, and age on dietary protein digestion and amino acid absorption kinetics in vivo in humans.

Methods: We included data from 18 randomized controlled trials with a total of 602 participants [age: 53 ± 23 y; BMI (kg/m2): 24.8 ± 3.3] who consumed various quantities of intrinsically l-[1-13C]-phenylalanine-labeled whey (n = 137), casein (n = 393), or milk (n = 72) protein and received intravenous infusions of l-[ring-2H5]-phenylalanine, which allowed us to assess protein digestion and phenylalanine absorption kinetics and the postprandial release of dietary protein-derived phenylalanine into the circulation. The effect of aging on these processes was assessed in a subset of 82 young (aged 22 ± 3 y) and 83 older (aged 71 ± 5 y) individuals.

Results: A total of 50% ± 14% of dietary protein-derived phenylalanine appeared in the circulation over a 5-h postprandial period. Casein ingestion resulted in a smaller (45% ± 11%), whey protein ingestion in an intermediate (57% ± 10%), and milk protein ingestion in a greater (65% ± 13%) fraction of dietary protein-derived phenylalanine appearing in the circulation (P < 0.001). The postprandial availability of dietary protein-derived phenylalanine in the circulation increased with the ingestion of greater protein doses (P < 0.05). Protein digestion and phenylalanine absorption kinetics were attenuated in older when compared with young individuals, with 45% ± 10% vs. 51% ± 14% of dietary protein-derived phenylalanine appearing in the circulation, respectively (P = 0.001).

Conclusions: Protein type, protein dose, and age modulate dietary protein digestion and amino acid absorption kinetics and subsequent postprandial plasma amino acid availability in vivo in humans. These trials were registered at clinicaltrials.gov as NCT00557388, NCT00936039, NCT00991523, NCT01317511, NCT01473576, NCT01576848, NCT01578590, NCT01615276, NCT01680146, NCT01820975, NCT01986842, and NCT02596542, and at http://www.trialregister.nl as NTR3638, NTR3885, NTR4060, NTR4429, and NTR4492.

Keywords: healthy aging; muscle mass maintenance; muscle protein synthesis; sarcopenia; splanchnic extraction.

Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.

Figures

FIGURE 1
FIGURE 1
Rate of appearance of dietary protein–derived phenylalanine (A) as well as cumulative plasma phenylalanine appearance over time in percentages (B) and over the entire 0–5-h postprandial period (B, insert) in participants who consumed 23 ± 5, 24 ± 7, and 26 ± 11 g intrinsically labeled whey (n = 137), casein (n = 393), and milk (n = 72) protein, respectively. Values are means ± SEMs. Labeled means without a common letter differ, P < 0.05. Ra, rate of appearance.
FIGURE 2
FIGURE 2
Rate of appearance of dietary protein–derived phenylalanine (A) and cumulative plasma phenylalanine appearance over time in percentages (B), and estimated amount of dietary protein–derived amino acids that appeared in the circulation in grams (C) in participants who consumed intrinsically labeled whey protein (n = 76) by tertile of protein dose in grams per kilogram of BM (0.23 ± 0.04 vs. 0.29 ± 0.01 vs. 0.35 ± 0.04 g/kg BM). Values are means ± SEMs. Labeled means without a common letter differ, P < 0.05. BM, body mass; Ra, rate of appearance; T, tertile.
FIGURE 3
FIGURE 3
Rate of appearance of dietary protein–derived phenylalanine (A) and cumulative plasma phenylalanine appearance over time in percentages (B) and estimated amount of dietary protein–derived amino acids that appeared in the circulation in grams (C) in participants who consumed intrinsically labeled casein (n = 359) by tertile of protein dose in grams per kilogram of BM (0.24 ± 0.01 vs. 0.28 ± 0.02 vs. 0.44 ± 0.07 g/kg BM). Values are means ± SEMs. Labeled means without a common letter differ, P < 0.05. BM, body mass; Ra, rate of appearance; T, tertile.
FIGURE 4
FIGURE 4
Rate of appearance of dietary protein–derived phenylalanine (A) and cumulative plasma phenylalanine appearance over time in percentages (B) and estimated amount of dietary protein–derived amino acids that appeared in the circulation in grams (C) after the ingestion of 22 ± 5 g intrinsically labeled casein in young (n = 82) and older (n = 83) men. Values are means ± SEMs. *Different from young men, P < 0.05. Ra, rate of appearance; T, tertile.

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