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.

Effects of whey protein hydrolysate ingestion on post-exercise muscle protein synthesis compared with intact whey protein in rats

“…However, we have not measured the plasma amino acid levels earlier than 60 min after administration. Moro [22] indicated that the ingestion of WPH induced similar levels of aminoacidemia compared with that of intact whey protein, which is inconsistent with our hypothesis, so further study is necessary to confirm it.…”

“…These results indicated it is possible that not only the amino-acid composition but also the difference of molecular form, such as amino acids, peptides or protein, affect skeletal muscle metabolism. Recently, Moro [22] showed that the ingestion of WPH induced a greater transport and accumulation of leucine into muscle, which increased amino acid utilization for protein synthesis compared with the ingestion of intact whey protein. However, it is unclear which is more effective for stimulating MPS, WPH or intact whey protein.…”

Comparison of whole egg v. egg white ingestion during 12 weeks of resistance training on skeletal muscle regulatory markers in resistance-trained men

“…Post-exercise protein ingestion is suggested to increase MPS through the provision of sufficient amino acids, particularly leucine, thus activating the key anabolic signalling mechanism of the mechanistic target of rapamycin (mTOR) (3,4) . Consequently, dietary protein intake is considered an essential component in the optimisation of skeletal muscle adaptations to RT.…”

Nutritional Strategies to Offset Disuse-Induced Skeletal Muscle Atrophy and Anabolic Resistance in Older Adults: From Whole-Foods to Isolated Ingredients

“…Therefore, greater relative daily amounts (>2 g•kg −1 •BW•day −1 ), combined with novel isolated intact protein blends as well as protein sources containing high relative proportions of di-and tripeptides (i.e., protein hydrolysates), may be needed to facilitate greater protective effects on muscle during disuse. Indeed, whilst evidence is limited, protein hydrolysates have been observed to be superior to intact proteins, largely due to decreased splanchnic extraction, increased postprandial AA bioavailability and rapid appearance of EAAs, in particular leucine, into circulation [78,[91][92][93]. Moreover, WP hydrolysates have also been observed to augment a greater acute postprandial MPS response compared to intact protein sources in younger and older adults [78,91,93].…”

“…Indeed, whilst evidence is limited, protein hydrolysates have been observed to be superior to intact proteins, largely due to decreased splanchnic extraction, increased postprandial AA bioavailability and rapid appearance of EAAs, in particular leucine, into circulation [78,[91][92][93]. Moreover, WP hydrolysates have also been observed to augment a greater acute postprandial MPS response compared to intact protein sources in younger and older adults [78,91,93]. However, ultimately, more chronic investigations are required to assess the longer-term anabolic potential of protein hydrolysates compared with intact (whole) proteins, particularly during periods of disuse and inactivity.…”