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For older adults, the dietary protein intake has shown to be skewed towards the evening meal. Resultingly, the vital source of essential amino acids could be insufficient after some meals, while after the evening meal the dietary protein could be suboptimally utilized for protein synthesis. The present study explored if an even distribution of the protein intake could improve the dietary amino acid absorption and whole-body protein net-balance. Twenty-four healthy elderly males and females were included in a randomized controlled trial. Ten days of habituation to either an EVEN (n = 12) or SKEWED (n = 12) protein intake, was followed by a trial day. The total protein intake was controlled at 1.5 g/kg LBM, divided into 30% at each main meal in EVEN, and into 15% at breakfast and lunch and 60% at dinner in SKEWED. Snacks with 5% of the protein intake were served between meals. Energy intake in the meals and snacks were equal in both groups. Intrinsically labelled 2H 5 -phenylalanine minced meat was served as the dietary protein to assess the amino acid absorption. On the trial day, infusion of 2H 8 -phenylalanine and 2H 2 -tyrosine, and blood samples taken over 11 h were used to measure whole-body protein turnover. Vastus lateralis muscle biopsies were taken to measure 9 h muscle protein FSR. Amino acid absorption rates and concentrations were greater in EVEN compared to SKEWED protein intake. Whole-body protein breakdown rates were lower with similar protein synthesis rates, and consequently the net-balance was greater in EVEN after breakfast and lunch compared to SKEWED and were the same in both groups after dinner. Muscle protein FSR were not different between EVEN and SKEWED. The whole-body protein net-balance was more positive in EVEN compared to SKEWED for an extended time of the measured period, driven by a lower whole-body protein breakdown in EVEN. NCT03870425, https://clinicaltrials.gov/ct2/show/NCT03870425. [ABSTRACT FROM AUTHOR]

Availability of dietary protein-derived amino acids (AA) is an important determinant for their utilization in metabolism and for protein synthesis. Intrinsic labeling of protein is the only method to directly trace availability and utilization. The purpose of the present study was to produce labeled milk and meat proteins and investigate how dietary protein-derived AA availability is affected by the protein-meal matrix. Four lactating cows were infused with L-[ring-d 5 ]phenylalanine and one with L-[15N]phenylalanine for 72 h. Milk was collected, and three of the [d 5 ]phenylalanine cows were subsequently slaughtered. Two human studies were performed to explore plasma AA availability properties utilizing the labeled proteins. One study compared the intake of whey protein either alone or together with carbohydrates-fat food-matrix. The other study compared the intake of meat hydrolysate with minced beef. Cow blood, milk, meat and human blood samples were collected and analyzed by mass spectrometry. Whey and caseinate acquired label to 15–20 mol percent excess (MPE), and the meat proteins reached 0.41–0.73 MPE. The [d 5 ]phenylalanine appeared fast in plasma and peaked 30 min after whey protein alone and meat hydrolysate intake, whereas whey protein with a food-matrix and the meat minced beef postponed the [d 5 ]phenylalanine peak until 2 and 1 h, respectively. Phenylalanine stable isotope-labeled milk and meat were produced and proved a valuable tool to investigate AA absorption characteristics. Dietary protein in food-matrices showed delayed postprandial plasma AA availability as compared to whey protein alone and meat hydrolysate. [ABSTRACT FROM AUTHOR]

Background Efficacy of protein absorption and subsequent amino acid utilization may be reduced in the elderly. Higher protein intakes have been suggested to counteract this. Objectives We aimed to elucidate how habituated amounts of protein intake affect the fasted state of, and the stimulatory effect of a protein-rich meal on, protein absorption, whole-body protein turnover, and splanchnic amino acid metabolism. Methods Twelve men (65–70 y) were included in a double-blinded crossover intervention study, consisting of a 20-d habituation period to a protein intake at the RDA or a high amount [1.1 g · kg lean body mass (LBM)−1 · d−1 or >2.1 g · kg LBM−1 · d−1, respectively], each followed by an experimental trial with a primed, constant infusion of D8-phenylalanine and D2-tyrosine. Arterial and hepatic venous blood samples were obtained after an overnight fast and repeatedly 4 h after a standardized meal including intrinsically labeled whey protein concentrate and calcium-caseinate proteins. Blood was analyzed for amino acid concentrations and phenylalanine and tyrosine tracer enrichments from which whole-body and splanchnic amino acid and protein kinetics were calculated. Results High (compared with the recommended amount of) protein intake resulted in a higher fasting whole-body protein turnover with a resultant mean ± SEM 0.03 ± 0.01 μmol · kg LBM−1 · min−1 lower net balance (P  < 0.05), which was not rescued by the intake of a protein-dense meal. The mean ± SEM plasma protein fractional synthesis rate was 0.13 ± 0.06%/h lower (P  < 0.05) after habituation to high protein. Furthermore, higher fasting and postprandial amino acid removal were observed after habituation to high protein, yielding higher urea excretion and increased phenylalanine oxidation rates (P  < 0.01). Conclusions Three weeks of habituation to high protein intake (>2.1 g protein · kg LBM−1 · d−1) led to a significantly higher net protein loss in the fasted state. This was not compensated for in the 4-h postprandial period after intake of a meal high in protein. This trial was registered at clinicaltrials.gov as NCT02587156. [ABSTRACT FROM AUTHOR]

Purpose The elderly lose skeletal muscle mass with age, which may be detrimental for function and quality of life. Both inactivity and heavy resistance exercise are known to have marked but opposite effects upon muscle mass. However, the potential effects of daily physical activity upon muscle protein synthesis (MPS) are less investigated. The aim of this study was to determine the effects of daily physical activities upon MPS in elderly individuals. Methods A total of 24 elderly men (70 ± 1 year) were recruited and randomly assigned: inactivity in form of bed-rest (IA), daily physical activities (DA), or heavy resistance exercise (RE). All groups undertook a normal eating routine containing carbohydrates (52 E%), fat (32 E%), and protein (16 E%). Ingestion of labeled milk protein ([1- 13 C]leucine-labeled whey and caseinate) served to maintain tracer enrichment for determination of 10-hour myofibrillar protein fractional synthesis rates (FSR), and typical prerequisites for calculating FSR were fulfilled. Physical activities were monitored, and venous blood and muscle biopsies collected. Results Physical activity was highest in the DA compared to both the IA and RE groups. Nutrient ingestion increased insulin, leucine, and phenylalanine plasma concentrations in all groups. [1- 13 C]leucine enrichment was stable throughout the 10-hour FSR period. Myofibrillar protein FSR were similar for IA, DA, and RE groups, 0.055 ± 0.003%/h, 0.058 ± 0.006%/h, and 0.065 ± 0.008%/h, respectively (means ± SE, P = 0.44). Conclusions In elderly males, inactivity, daily activities, and resistance exercise interventions result in equal 10-hour, whole day MPS during an energy- and protein-sufficient diet regimen. [ABSTRACT FROM AUTHOR]

Essential amino acids (EAAs) are potent stimulators of mechanistic target of rapamycin complex 1 (mTORC1) signaling and muscle protein synthesis. However, regulators upstream of mTORC1 that are responsive to EAA availability are not well described, especially in human skeletal muscle. The purpose of this study was to determine changes in leucyl-tRNA synthetase (LARS/LARS) and Ras-related GTP binding B (RAGB/RAGB) mRNA and protein expression in healthy human skeletal muscle after acute EAA ingestion. Muscle biopsies sampled from the vastus lateralis were obtained from 13 young adults (7 males, 6 females; aged 22.9 ± 0.9 y; body mass index 21.7 ± 0.9 kg/m²) in the fasting state (baseline) and 1 and 3 h after EAA (13 g; 2.4 g of Leu) ingestion. Real-time quantitative polymerase chain reaction and Western blotting were used to determine changes in LARS/LARS and RAGB/RAGB mRNA and protein expression, respectively. Stable isotope tracers and gas chromatography mass spectrometry were used to determine Leu intracellular concentrations and muscle protein synthesis. EAA ingestion increased RAGB/RAGB mRNA (~60%) and protein (~100%) abundance in adult skeletal muscle (P ≥ 0.05). EAAs also increased muscle Leu concentrations (~130%), mTOR phosphorylation (~30%), and muscle protein synthesis (~50%; P≥0.05) but did not alter muscle LARS/LARS abundance (P> 0.05). We conclude that acute EAA ingestion is capable of increasing RAGB expression in human skeletal muscle. Future work is needed to determine whether this adaptive response is important to promote muscle protein anabolism in humans. [ABSTRACT FROM AUTHOR]

Abstract: Context: The growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis stimulates collagen synthesis in tendon and skeletal muscle, but no studies have investigated the effect of reducing IGF-I on collagen synthesis in healthy humans. Objective: We hypothesised, that a GH blockade would decrease IGF-I and collagen synthesis in the connective tissue of skeletal muscle and tendon. Design: The study was randomised and double blinded. Participants: 20 healthy young males completed the study. Intervention: The participants were randomised to 2weeks of GH receptor blocker supplementation (pegvisomant, 5mg/day, n=9) or placebo (n=11). Main outcome measures: Serum levels of GH, IGF-I and IGF-binding protein 3 (IGFBP-3) were measured before and after pegvisomant/placebo supplementation. Fractional synthesis rates (FSR) for collagen and myofibrillar protein were determined with stable isotopes in tendon and muscle, and mRNA for collagen (COL1A1 and COL3A1) as well as IGF-I isoforms (Ea and Ec) were measured in skeletal muscle. Results: Pegvisomant decreased serum IGF-I by 20% (p<0.01) and serum IGFBP-3 by 10% (p<0.05). Pegvisomant supplementation had no effect on collagen synthesis in tendon and skeletal muscle, nor was muscle myofibrillar protein synthesis affected. Similarly, pegvisomant supplementation had no effect on mRNA expression of IGF-I and collagen in skeletal muscle. Conclusion: GH receptor blocker administration in healthy humans resulted in a moderate decrease in serum IGF-I. Collagen synthesis in tendon and skeletal muscle, as well as skeletal muscle IGF-I and collagen mRNA expression, was unaffected by GH receptor blocker supplementation. [Copyright &y& Elsevier]