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.

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

Nutrition & Metabolism ◽

10.1186/s12986-019-0417-9 ◽

2019 ◽

Vol 16 (1) ◽

Cited By ~ 1

Author(s):

Kyosuke Nakayama ◽

Ryoichi Tagawa ◽

Yuri Saito ◽

Chiaki Sanbongi

Keyword(s):

Protein Synthesis ◽

Whey Protein ◽

Muscle Protein ◽

Protein Hydrolysate ◽

Muscle Protein Synthesis ◽

Control Group ◽

Water Control ◽

Significant Treatment ◽

Post Exercise ◽

Whey Protein Hydrolysate

Abstract Background It is well known that ingestion of protein sources can stimulate muscle protein synthesis (MPS). The intake of whey protein is highly effective especially for accelerating MPS. Whey protein hydrolysate (WPH) can raise postprandial plasma concentration of amino acids, which impact stimulation of MPS more rapidly and highly than intact whey protein. However, it is unclear which is more effective for stimulating MPS, WPH or intact whey protein. The aim of the present study was to compare the effects of the WPH and whey protein on MPS in rats after exercise. Methods Rats were first subjected to a 2 h. swimming protocol. After this, in experiment 1, we evaluated time-dependent changes in the fractional synthetic rate (FSR) of the triceps muscle in Male Sprague-Dawley rats after ingestion of intact whey protein (30, 60, 90 or 120 min after ingestion). Then in experiment 2, at the time point that the results of Experiment 1 revealed postprandial FSR was highest (60 min after ingestion), we measured the FSR after ingestion of the WPH or whey protein at two different doses (0.5 or 2.0 g protein/kg body weight), or with deionized water (control), again after exercise. Plasma components and mammalian target of rapamycin (mTOR) signaling were also measured. Results In experiment 1, postprandial FSR was highest 60 min after whey protein was administered. In experiment 2, the FSR 60 min after ingestion of the WPH was higher than that of whey protein (significant treatment main effect). Moreover, at a lower dose, only the WPH ingestion caused greater MPS and phosphorylated 4E-binding protein 1 (4E-BP1) levels compared with the control group. Conclusion These results indicate that ingestion of the WPH was associated with greater post-exercise MPS compared with intact whey protein, especially at lower doses.

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Coingestion of Carbohydrate and Protein Hydrolysate Stimulates Muscle Protein Synthesis during Exercise in Young Men, with No Further Increase during Subsequent Overnight Recovery

Journal of Nutrition ◽

10.3945/jn.108.092924 ◽

2008 ◽

Vol 138 (11) ◽

pp. 2198-2204 ◽

Cited By ~ 58

Author(s):

Milou Beelen ◽

Michael Tieland ◽

Annemie P. Gijsen ◽

Hanne Vandereyt ◽

Arie K. Kies ◽

...

Keyword(s):

Protein Synthesis ◽

Muscle Protein ◽

Protein Hydrolysate ◽

Muscle Protein Synthesis ◽

Young Men

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Minimal whey protein with carbohydrate stimulates muscle protein synthesis following resistance exercise in trained young men

Applied Physiology Nutrition and Metabolism ◽

10.1139/h07-076 ◽

2007 ◽

Vol 32 (6) ◽

pp. 1132-1138 ◽

Cited By ~ 73

Author(s):

Jason E. Tang ◽

Joshua J. Manolakos ◽

Greg W. Kujbida ◽

Paul J. Lysecki ◽

Daniel R. Moore ◽

...

Keyword(s):

Protein Synthesis ◽

Resistance Exercise ◽

Whey Protein ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Young Men ◽

Skeletal Muscle Protein ◽

Double Blind ◽

Exercise Period ◽

The Impact

Whey protein is a supplemental protein source often used by athletes, particularly those aiming to gain muscle mass; however, direct evidence for its efficacy in stimulating muscle protein synthesis (MPS) is lacking. We aimed to determine the impact of consuming whey protein on skeletal muscle protein turnover in the post-exercise period. Eight healthy resistance-trained young men (age = 21 ± 1 .0 years; BMI = 26.8 ± 0.9 kg/m2 (means ± SE)) participated in a double-blind randomized crossover trial in which they performed a unilateral leg resistance exercise workout (EX: 4 sets of knee extensions and 4 sets of leg press; 8–10 repetitions/set; 80% of maximal), such that one leg was not exercised and acted as a rested (RE) comparator. After exercise, subjects consumed either an isoenergetic whey protein plus carbohydrate beverage (WHEY: 10 g protein and 21 g fructose) or a carbohydrate-only beverage (CHO: 21 g fructose and 10 g maltodextran). Subjects received pulse-tracer injections of l-[ring-2H5]phenylalanine and l-[15N]phenylalanine to measure MPS. Exercise stimulated a rise in MPS in the WHEY-EX and CHO-EX legs, which were greater than MPS in the WHEY-RE leg and the CHO-RE leg (all p < 0.05), respectively. The rate of MPS in the WHEY-EX leg was greater than in the CHO-EX leg (p < 0.001). We conclude that a small dose (10 g) of whey protein with carbohydrate (21 g) can stimulate a rise in MPS after resistance exercise in trained young men that would be supportive of a positive net protein balance, which, over time, would lead to hypertrophy.

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Minimal whey protein with carbohydrate stimulates muscle protein synthesis following resistance exercise in young men.

The FASEB Journal ◽

10.1096/fasebj.21.6.lb108-a ◽

2007 ◽

Vol 21 (6) ◽

Author(s):

Joshua Manolakos ◽

Jason Tang ◽

Greg Kujbida ◽

Paul Lysecki ◽

Daniel Moore ◽

...

Keyword(s):

Protein Synthesis ◽

Resistance Exercise ◽

Whey Protein ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Young Men

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Faculty Opinions recommendation of Effect of age on basal muscle protein synthesis and mTORC1 signaling in a large cohort of young and older men and women.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725380242.793518281 ◽

2016 ◽

Author(s):

James Timmons ◽

Iain Gallagher

Keyword(s):

Protein Synthesis ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Older Men ◽

Large Cohort ◽

Men And Women ◽

Mtorc1 Signaling ◽

Older Men And Women ◽

Effect Of Age

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Leucine or carbohydrate supplementation reduces AMPK and eEF2 phosphorylation and extends postprandial muscle protein synthesis in rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00242.2011 ◽

2011 ◽

Vol 301 (6) ◽

pp. E1236-E1242 ◽

Cited By ~ 46

Author(s):

Gabriel J. Wilson ◽

Donald K. Layman ◽

Christopher J. Moulton ◽

Layne E. Norton ◽

Tracy G. Anthony ◽

...

Keyword(s):

Protein Synthesis ◽

Test Meal ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Adenosine Monophosphate ◽

Energy Status ◽

Sprague Dawley ◽

Translation Elongation ◽

Cellular Energy ◽

Mtorc1 Signaling

Muscle protein synthesis (MPS) increases after consumption of a protein-containing meal but returns to baseline values within 3 h despite continued elevations of plasma amino acids and mammalian target of rapamycin (mTORC1) signaling. This study evaluated the potential for supplemental leucine (Leu), carbohydrates (CHO), or both to prolong elevated MPS after a meal. Male Sprague-Dawley rats (∼270 g) trained to consume three meals daily were food deprived for 12 h, and then blood and gastrocnemius muscle were collected 0, 90, or 180 min after a standard 4-g test meal (20% whey protein). At 135 min postmeal, rats were orally administered 2.63 g of CHO, 270 mg of Leu, both, or water (sham control). Following test meal consumption, MPS peaked at 90 min and then returned to basal ( time 0) rates at 180 min, although ribosomal protein S6 kinase and eIF4E-binding protein-1 phosphorylation remained elevated. In contrast, rats administered Leu and/or CHO supplements at 135 min postmeal maintained peak MPS through 180 min. MPS was inversely associated with the phosphorylation states of translation elongation factor 2, the “cellular energy sensor” adenosine monophosphate-activated protein kinase-α (AMPKα) and its substrate acetyl-CoA carboxylase, and increases in the ratio of AMP/ATP. We conclude that the incongruity between MPS and mTORC1 at 180 min reflects a block in translation elongation due to reduced cellular energy. Administering Leu or CHO supplements ∼2 h after a meal maintains cellular energy status and extends the postprandial duration of MPS.

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