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

J Nutr. 2019 Jul 1;149(7):1149-1158. doi: 10.1093/jn/nxz053.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acids / blood
  • Amino Acids / metabolism*
  • Blood Glucose / metabolism
  • Cross-Over Studies
  • Double-Blind Method
  • Humans
  • Hydrolysis
  • Insulin / metabolism
  • Lactic Acid / metabolism
  • Male
  • Mechanistic Target of Rapamycin Complex 1 / metabolism*
  • Muscle Proteins / biosynthesis*
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Signal Transduction / drug effects*
  • Whey Proteins / pharmacology*


  • Amino Acids
  • Blood Glucose
  • Insulin
  • Muscle Proteins
  • Whey Proteins
  • Lactic Acid
  • Mechanistic Target of Rapamycin Complex 1

Associated data

  • ClinicalTrials.gov/NCT03313830