Whey Protein Hydrolysate Increases Amino Acid Uptake, mTORC1 Signaling, and Protein Synthesis in Skeletal Muscle of Healthy Young Men in a Randomized Crossover Trial

Abstract

Background: Muscle protein synthesis (MPS) can be stimulated by ingestion of protein sources, such as whey, casein, or soy. Protein supplementation can enhance muscle protein synthesis after exercise and may preserve skeletal muscle mass and function in aging adults. Therefore, identifying protein sources with higher anabolic potency is of high significance.

Objective: The aim of this study was to determine the anabolic potency and efficacy of a novel whey protein hydrolysate mixture (WPH) on mechanistic target of rapamycin complex 1 (mTORC1) signaling and skeletal MPS in healthy young subjects.

Methods: Ten young men (aged 28.7 ± 3.6 y, 25.2 ± 2.9 kg/m2 body mass index [BMI]) were recruited into a double-blind two-way crossover trial. Subjects were randomized to receive either 0.08 g/kg of body weight (BW) of WPH or an intact whey protein (WHEY) mixture during stable isotope infusion experiments. Fractional synthetic rate, leucine and phenylalanine kinetics, and markers of amino acid sensing were assessed as primary outcomes before and 1-3 h after protein ingestion using a repeated measures mixed model.

Results: Blood leucine concentration, delivery of leucine to muscle, transport of leucine from blood into muscle and intracellular muscle leucine concentration significantly increased to a similar extent 1 h after ingestion of both mixtures (P < 0.05). Phosphorylation of S6K1 (i.e. a marker of mTORC1 activation) increased equally by ∼20% 1-h postingestion (P < 0.05). Ingestion of WPH and WHEY increased mixed MPS similarly in both groups by ∼43% (P < 0.05); however, phenylalanine utilization for synthesis increased in both treatments 1-h postingestion but remained elevated 3-h postingestion only in the WPH group (P < 0.05).

Conclusions: We conclude that a small dose of WPH effectively increases leucine transport into muscle, activating mTORC1 and stimulating MPS in young men. WPH anabolic potency and efficacy for promoting overall muscle protein anabolism is similar to WHEY, an intact protein source. This trial was registered at clinicaltrials.gov as NCT03313830.

Keywords: amino acid transport; anabolic signaling; human muscle protein turnover; hyperaminoacidemia; leucine; muscle protein anabolism; whey protein.

Copyright © American Society for Nutrition 2019.

Figures

FIGURE 1

Consolidated Standards of Reporting Trials (CONSORT) diagram of study recruitment, enrollment, randomization, follow-up, and analysis. Abbreviations: WHEY, intact whey protein beverage; WPH, whey protein hydrolyzed beverage.

FIGURE 2

Schematic showing infusion study design. Fractional synthesis rate was determined using muscle biopsies taken from the participant on postabsorptive status (basal period) and 1 h and 3 h from protein ingestion (treatment period). Abbreviations: ICF, informed consent procedure; iDEXA, dual-energy X-ray absorptiometry; WHEY, intact whey protein beverage; WPH, whey protein hydrolyzed beverage.

FIGURE 3

Branched-chain and phenylalanine amino acid blood concentrations before and after whey protein hydrolyzed beverage (WPH) and intact whey protein beverage (WHEY) ingestion in young men. A) valine, B) leucine, C) isoleucine, and D) phenylalanine. Values are means ± SEs, n = 10. Line with * denotes difference from basal for all time points with no difference between groups, P < 0.05.

FIGURE 4

Blood flow A), glucose B), lactate C), and insulin D) concentration before and after whey protein hydrolyzed beverage (WPH) and intact whey protein beverage (WHEY) ingestion in young men. Values are means ± SEs, n = 10. *Denotes difference from basal with no difference between groups, P < 0.05.

FIGURE 5

Leucine kinetics after whey protein hydrolyzed beverage (WPH) and intact whey protein beverage (WHEY) ingestion in young men. A) arterial concentration, B) delivery and C) transport into the muscle, and D) intracellular concentrations in the basal state (basal) and 1 and 3 h following mixture ingestion. Each time point represents hourly averages. Values are means ± SEs, n = 10. *Significantly different from basal; P < 0.05; a significant difference between groups.

FIGURE 6

Phenylalanine kinetics after whey protein hydrolyzed beverage (WPH) and intact whey protein beverage (WHEY) ingestion in young men. A) Fractional synthesis rate (FSR) in the basal state (basal) and 1 and 3 h following mixture ingestion, B) FSR in the basal state and 3 h following mixture ingestion, C) intracellular amino acids utilization (om) indicating protein synthesis, and D) release from proteolysis (mo), reflecting protein breakdown following ingestion of WPH and WHEY in young men. Values are means ± SEs, n = 10. *Significantly different from basal; P < 0.05.

FIGURE 7

Phenylalanine net balance in the basal state and at 3-h postingestion for subjects given intact whey protein beverage (WHEY) and whey protein hydrolyzed beverage (WPH) mixture in young men. Values are means ± SEs, n = 10. No difference was observed between the 2 groups.