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

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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Short-Term Oxandrolone Administration Stimulates Net Muscle Protein Synthesis in Young Men

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.84.8.2705 ◽

1999 ◽

Vol 84 (8) ◽

pp. 2705-2711 ◽

Cited By ~ 52

Author(s):

M. Sheffield-Moore

Keyword(s):

Protein Synthesis ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Young Men ◽

Short Term

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Dileucine ingestion is more effective than leucine in stimulating muscle protein turnover in young males: a double blind randomized controlled trial

Journal of Applied Physiology ◽

10.1152/japplphysiol.00295.2021 ◽

2021 ◽

Author(s):

Kevin J. M. Paulussen ◽

Rafael A. Alamilla ◽

Amadeo F. Salvador ◽

Colleen F. McKenna ◽

Andrew T. Askow ◽

...

Keyword(s):

Protein Synthesis ◽

Protein Turnover ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Controlled Trial ◽

Young Men ◽

Double Blind ◽

Muscle Protein Turnover ◽

Breakdown Rates ◽

Over Time

Leucine is regarded as an anabolic trigger for the mTORC1 pathway and the stimulation muscle protein synthesis rates. More recently, there has been an interest in underpinning the relevance of BCAA-containing dipeptides and their intact absorption into circulation to regulate muscle anabolic responses. We investigated the effects of dileucine and leucine ingestion on postprandial muscle protein turnover. Ten healthy young men (age: 23±3 y) consumed either 2 g of leucine (LEU) or 2 g of dileucine (DILEU) in a randomized crossover design. The participants underwent repeated blood and muscle biopsy sampling during primed continuous infusions of L-[ring-13C6]phenylalanine and L-[15N]phenylalanine to determine myofibrillar protein synthesis (MPS) and mixed muscle protein breakdown rates (MPB), respectively. LEU and DILEU similarly increased plasma leucine net area under the curve (AUC; P = 0.396). DILEU increased plasma dileucine AUC to a greater extent than LEU (P = 0.013). Phosphorylation of Akt (P = 0.002), rpS6 (P <0.001) and p70S6K (P < 0.001) increased over time in both LEU and DILEU conditions. Phosphorylation of 4E-BP1 (P = 0.229) and eEF2 (P = 0.999) did not change over time irrespective of condition. Cumulative (0-180 min) MPS increased in DILEU (0.075±0.032 %⋅hour-1), but not in LEU (0.047±0.029 %⋅hour-1; P=0.023). MPB did not differ between LEU (0.043±0.030 %⋅h-1) and DILEU conditions (0.051±0.027 %⋅hour-1; P = 0.659). Our results showed that dileucine ingestion elevated plasma dileucine concentrations and muscle protein turnover by stimulating MPS in 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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Elderly Men Show a Diminished Sensitivity of the Dose Response of Muscle Protein Synthesis to Essential Amino Acids (EAA) Compared to Young Men

Clinical Science ◽

10.1042/cs106009p ◽

2004 ◽

Vol 106 (s50) ◽

pp. 9P-9P

Author(s):

DJR Cuthbertson ◽

J Babraj ◽

T Waddell ◽

K Smith ◽

MJ Rennie

Keyword(s):

Amino Acids ◽

Protein Synthesis ◽

Dose Response ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Young Men ◽

Essential Amino Acids ◽

Elderly Men

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Co-ingestion of leucine with protein does not further augment post-exercise muscle protein synthesis rates in elderly men

British Journal Of Nutrition ◽

10.1017/s0007114507812013 ◽

2008 ◽

Vol 99 (3) ◽

pp. 571-580 ◽

Cited By ~ 67

Author(s):

René Koopman ◽

Lex B. Verdijk ◽

Milou Beelen ◽

Marchel Gorselink ◽

Arie Nieuwenhuijzen Kruseman ◽

...

Keyword(s):

Physical Activity ◽

Protein Synthesis ◽

Muscle Protein ◽

Protein Hydrolysate ◽

Muscle Protein Synthesis ◽

Whole Body ◽

Elderly Men ◽

Body Protein ◽

Synthetic Rate ◽

Fractional Synthetic Rate

Leucine has been suggested to have the potential to modulate muscle protein metabolism by increasing muscle protein synthesis. The objective of this study was to investigate the surplus value of the co-ingestion of free leucine with protein hydrolysate and carbohydrate following physical activity in elderly men. Eight elderly men (mean age 73 ± 1 years) were randomly assigned to two cross-over treatments consuming either carbohydrate and protein hydrolysate (CHO+PRO) or carbohydrate, protein hydrolysate with additional leucine (CHO+PRO+leu) after performing 30 min of standardized physical activity. Primed, continuous infusions with l-[ring-13C6]phenylalanine and l-[ring-2H2]tyrosine were applied, and blood and muscle samples were collected to assess whole-body protein turnover as well as protein fractional synthetic rate in the vastus lateralis muscle over a 6 h period. Whole-body protein breakdown and synthesis rates were not different between treatments. Phenylalanine oxidation rates were significantly lower in the CHO+PRO+leu v. CHO+PRO treatment. As a result, whole-body protein balance was significantly greater in the CHO+PRO+leu compared to the CHO+PRO treatment (23·8 (sem 0·3) v. 23·2 (sem 0·3) μmol/kg per h, respectively; P < 0·05). Mixed muscle fractional synthetic rate averaged 0·081 (sem 0·003) and 0·082 (sem 0·006) %/h in the CHO+PRO+leu and CHO+PRO treatment, respectively (NS). Co-ingestion of leucine with carbohydrate and protein following physical activity does not further elevate muscle protein fractional synthetic rate in elderly men when ample protein is ingested.

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Protein coingestion stimulates muscle protein synthesis during resistance-type exercise

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00774.2007 ◽

2008 ◽

Vol 295 (1) ◽

pp. E70-E77 ◽

Cited By ~ 54

Author(s):

Milou Beelen ◽

René Koopman ◽

Annemie P. Gijsen ◽

Hanne Vandereyt ◽

Arie K. Kies ◽

...

Keyword(s):

Protein Synthesis ◽

Muscle Protein ◽

Protein Hydrolysate ◽

Muscle Protein Synthesis ◽

Nutritional Intervention ◽

Whole Body ◽

Exercise Session ◽

Body Protein ◽

Fed State ◽

Breakdown Rates

In contrast to the effect of nutritional intervention on postexercise muscle protein synthesis, little is known about the potential to modulate protein synthesis during exercise. This study investigates the effect of protein coingestion with carbohydrate on muscle protein synthesis during resistance-type exercise. Ten healthy males were studied in the evening after they consumed a standardized diet throughout the day. Subjects participated in two experiments in which they ingested either carbohydrate or carbohydrate with protein during a 2-h resistance exercise session. Subjects received a bolus of test drink before and every 15 min during exercise, providing 0.15 g·kg−1·h−1 carbohydrate with (CHO + PRO) or without (CHO) 0.15 g·kg−1·h−1 protein hydrolysate. Continuous intravenous infusions with l-[ ring-13C6]phenylalanine and l-[ ring-2H2]tyrosine were applied, and blood and muscle biopsies were collected to assess whole body and muscle protein synthesis rates during exercise. Protein coingestion lowered whole body protein breakdown rates by 8.4 ± 3.6% ( P = 0.066), compared with the ingestion of carbohydrate only, and augmented protein oxidation and synthesis rates by 77 ± 17 and 33 ± 3%, respectively ( P < 0.01). As a consequence, whole body net protein balance was negative in CHO, whereas a positive net balance was achieved after the CHO + PRO treatment (−4.4 ± 0.3 vs. 16.3 ± 0.4 μmol phenylalanine·kg−1·h−1, respectively; P < 0.01). In accordance, mixed muscle protein fractional synthetic rate was 49 ± 22% higher after protein coingestion (0.088 ± 0.012 and 0.060 ± 0.004%/h in CHO + PRO vs. CHO treatment, respectively; P < 0.05). We conclude that, even in a fed state, protein coingestion stimulates whole body and muscle protein synthesis rates during resistance-type exercise.

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Branched-Chain Amino Acid Fortification Does Not Restore Muscle Protein Synthesis Rates following Ingestion of Lower- Compared with Higher-Dose Mycoprotein

Journal of Nutrition ◽

10.1093/jn/nxaa251 ◽

2020 ◽

Vol 150 (11) ◽

pp. 2931-2941 ◽

Cited By ~ 1

Author(s):

Alistair J Monteyne ◽

Mariana O C Coelho ◽

Craig Porter ◽

Doaa R Abdelrahman ◽

Thomas S O Jameson ◽

...

Keyword(s):

Protein Synthesis ◽

Amino Acid ◽

G Protein ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Young Men ◽

Quadriceps Muscle ◽

Double Blind ◽

Protein Ingestion ◽

Branched Chain

ABSTRACT Background We have shown that ingesting a large bolus (70 g) of the fungal-derived, whole food mycoprotein robustly stimulates muscle protein synthesis (MPS) rates. Objective The aim of this study was to determine if a lower dose (35 g) of mycoprotein enriched with branched-chain amino acids (BCAAs) stimulates MPS to the same extent as 70 g of mycoprotein in resistance-trained young men. Methods Nineteen men [aged 22 ± 1 y, BMI (kg/m2): 25 ± 1] took part in a randomized, double-blind, parallel-group study. Participants received primed, continuous infusions of l-[ring-2H5]phenylalanine and ingested either 70 g mycoprotein (31.5 g protein; MYCO; n = 10) or 35 g BCAA-enriched mycoprotein (18.7 g protein: matched on BCAA content; ENR; n = 9) following a bout of unilateral resistance exercise. Blood and bilateral quadriceps muscle samples were obtained before exercise and protein ingestion and during a 4-h postprandial period to assess MPS in rested and exercised muscle. Two- and 3-factor ANOVAs were used to detect differences in plasma amino acid kinetics and mixed muscle fractional synthetic rates, respectively. Results Postprandial plasma BCAA concentrations increased more rapidly and to a larger degree in ENR compared with MYCO. MPS increased with protein ingestion (P ≤ 0.05) but to a greater extent following MYCO (from 0.025% ± 0.006% to 0.057% ± 0.004% · h−1 in rested muscle, and from 0.024% ± 0.007% to 0.072% ± 0.005% · h−1 in exercised muscle; P < 0.0001) compared with ENR (from 0.031% ± 0.003% to 0.043% ± 0.005% · h−1 in rested muscle, and 0.027% ± 0.005% to 0.052% ± 0.005% · h−1 in exercised muscle; P < 0.01) ingestion. Postprandial MPS rates were greater in MYCO compared with ENR (P < 0.01). Conclusions The ingestion of lower-dose BCAA-enriched mycoprotein stimulates resting and postexercise MPS rates, but to a lesser extent compared with the ingestion of a BCAA-matched 70-g mycoprotein bolus in healthy young men. This trial was registered at clinicaltrials.gov as 660065600.

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Impact of protein coingestion on muscle protein synthesis during continuous endurance type exercise

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00446.2010 ◽

2011 ◽

Vol 300 (6) ◽

pp. E945-E954 ◽

Cited By ~ 30

Author(s):

Milou Beelen ◽

Antoine Zorenc ◽

Bart Pennings ◽

Joan M. Senden ◽

Harm Kuipers ◽

...

Keyword(s):

Protein Synthesis ◽

Muscle Protein ◽

Protein Hydrolysate ◽

Muscle Protein Synthesis ◽

Whole Body ◽

Body Protein ◽

Oxidation Rates ◽

Breakdown Rates ◽

The Impact ◽

Muscle Biopsies

This study investigates the impact of protein coingestion with carbohydrate on muscle protein synthesis during endurance type exercise. Twelve healthy male cyclists were studied during 2 h of fasted rest followed by 2 h of continuous cycling at 55% Wmax. During exercise, subjects received either 1.0 g·kg−1·h−1 carbohydrate (CHO) or 0.8 g·kg−1·h−1 carbohydrate with 0.2 g·kg−1·h−1 protein hydrolysate (CHO+PRO). Continuous intravenous infusions with l-[ ring-13C6]phenylalanine and l-[ ring-2H2]tyrosine were applied, and blood and muscle biopsies were collected to assess whole body protein turnover and muscle protein synthesis rates at rest and during exercise conditions. Protein coingestion stimulated whole body protein synthesis and oxidation rates during exercise by 22 ± 3 and 70 ± 17%, respectively ( P < 0.01). Whole body protein breakdown rates did not differ between experiments. As a consequence, whole body net protein balance was slightly negative in CHO and positive in the CHO+PRO treatment (−4.9 ± 0.3 vs. 8.0 ± 0.3 μmol Phe·kg−1·h−1, respectively, P < 0.01). Mixed muscle protein fractional synthetic rates (FSR) were higher during exercise compared with resting conditions (0.058 ± 0.006 vs. 0.035 ± 0.006%/h in CHO and 0.070 ± 0.011 vs. 0.038 ± 0.005%/h in the CHO+PRO treatment, respectively, P < 0.05). FSR during exercise did not differ between experiments ( P = 0.46). We conclude that muscle protein synthesis is stimulated during continuous endurance type exercise activities when carbohydrate with or without protein is ingested. Protein coingestion does not further increase muscle protein synthesis rates during continuous endurance type exercise.

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