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Background: Dietary protein ingestion stimulates muscle protein synthesis by providing amino acids to the muscle. The magnitude and duration of the postprandial increase in muscle protein synthesis rates are largely determined by dietary protein digestion and amino acid absorption kinetics.Objective: We assessed the impact of protein type, protein dose, and age on dietary protein digestion and amino acid absorption kinetics in vivo in humans.Methods: We included data from 18 randomized controlled trials with a total of 602 participants [age: 53 ± 23 y; BMI (kg/m2): 24.8 ± 3.3] who consumed various quantities of intrinsically l-[1-13C]-phenylalanine-labeled whey (n = 137), casein (n = 393), or milk (n = 72) protein and received intravenous infusions of l-[ring-2H5]-phenylalanine, which allowed us to assess protein digestion and phenylalanine absorption kinetics and the postprandial release of dietary protein-derived phenylalanine into the circulation. The effect of aging on these processes was assessed in a subset of 82 young (aged 22 ± 3 y) and 83 older (aged 71 ± 5 y) individuals.Results: A total of 50% ± 14% of dietary protein-derived phenylalanine appeared in the circulation over a 5-h postprandial period. Casein ingestion resulted in a smaller (45% ± 11%), whey protein ingestion in an intermediate (57% ± 10%), and milk protein ingestion in a greater (65% ± 13%) fraction of dietary protein-derived phenylalanine appearing in the circulation (P < 0.001). The postprandial availability of dietary protein-derived phenylalanine in the circulation increased with the ingestion of greater protein doses (P < 0.05). Protein digestion and phenylalanine absorption kinetics were attenuated in older when compared with young individuals, with 45% ± 10% vs. 51% ± 14% of dietary protein-derived phenylalanine appearing in the circulation, respectively (P = 0.001).Conclusions: Protein type, protein dose, and age modulate dietary protein digestion and amino acid absorption kinetics and subsequent postprandial plasma amino acid availability in vivo in humans. These trials were registered at clinicaltrials.gov as NCT00557388, NCT00936039, NCT00991523, NCT01317511, NCT01473576, NCT01576848, NCT01578590, NCT01615276, NCT01680146, NCT01820975, NCT01986842, and NCT02596542, and at http://www.trialregister.nl as NTR3638, NTR3885, NTR4060, NTR4429, and NTR4492. [ABSTRACT FROM AUTHOR]

This study examined postprandial plasma insulin and glucose responses after co-ingestion of an insulinotropic protein (Pro) hydrolysate with and without additional free leucine with a single bolus of carbohydrate (Cho). Male patients with long-standing Type 2 diabetes (n = 10) and healthy controls (n = 10) participated in 3 trials in which plasma glucose, insulin, and amino acid responses were determined after the ingestion of beverages of different composition (Cho: 0.7 g/kg carbohydrate, Cho+Pro: 0.7 g/kg carbohydrate with 0.3 g/kg protein hydrolysate, or Cho+Pro+Leu: 0.7 g/kg carbohydrate, 0.3 g/kg protein hydrolysate and 0.1 g/kg free leucine). Plasma insulin responses [expressed as area under the curve (AUC)] were 141 and 204% greater in patients with Type 2 diabetes and 66 and 221% greater in the controls in the Cho+Pro and Cho+Pro+Leu trials, respectively, compared with those in the Cho trial (P < 0.05). The concomitant plasma glucose responses were 15 and 12% lower in the patients with Type 2 diabetes and 92 and 97% lower in the control group in the Cho+Pro and Cho+Pro+Leu trials, respectively, compared with those in the Cho trial (P < 0.05). Plasma leucine concentrations correlated with the insulin response in all subjects (r = 0.43, P < 0.001). We conclude that co-ingestion of a protein hydrolysate with or without additional free leucine strongly augments the insulin response after ingestion of a single bolus of carbohydrate, thereby significantly reducing postprandial blood glucose excursions in patients with long-standing Type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Increasing arginine (Arg) availability reduces atrophy in cultured skeletal muscle cells. Supplementation with its metabolic precursor citrulline (Cit) is more effective at improving skeletal muscle Arg concentrations. Objective: We tested the hypothesis that Cit supplementation would attenuate skeletal muscle atrophy and loss of function during hindlimb immobilization in mice. Methods: Male C57BL/6JArc mice underwent 14 d of unilateral hindlimb immobilization/plaster casting and were supplemented with ~0.81 g Cit ⋅ kg-1⋅ d-1 (CIT group) or Ala (ALA group) mixed into their food. The uncasted contralateral limb (internal control) and an uncasted group (CON) served as controls. Muscle atrophy was evaluated with mass, fiber area, and in situ muscle function. Results: Tibialis anterior (TA) muscle mass [ALA: 37.6 ± 0.92 mg; CIT: 38.3 ± 1.25 mg] and peaktetanic force (ALA: 1150 ± 38.5 mN; CIT: 1150 ± 52.0 mN) were lower (P < 0.001 ) in the ALA (53.9 ± 0.42 mg) and CIT (1760 ± 28.5 mN) groups than in the CON group. No difference was found between ALA and CIT groups for TA mass, fiber area, or peak force. The mRNA expression of the nitric oxide synthase 2, inducible (Nos2; ~15-fold) and B-cell chronic lymphoid leukemia/ lymphoma 2/adenovirus E1 B 19 kDa interacting protein 3 (Bnip3; ~17-fold) genes and the ratio of microtubule-associated protein light chain 3BII to3BI (LC3BI I:LC3BI) (50.5% ± 17.7%) were higher (P<0.05) in the ALA group than in the CON group, suggesting increased autophagy. In the CIT group, Bnip3 mRNA was lower (270%; P < 0.05) and Nos2 mRNA tended to be lower (245%; P= 0.05) than in the ALA group, whereas LC3BII:LC3BI was not different from the CON group. Conclusions: Cit treatment of male mice did not affect therapeutically relevant outcome measures such as skeletal muscle mass and peak muscle force after 14 d of hindlimb immobilization. [ABSTRACT FROM AUTHOR]

Impaired digestion and/or absorption of dietary protein lowers postprandial plasma amino acid availability and, as such, could reduce the postprandial muscle protein synthetic response in the elderly. We aimed to compare in vivo dietary protein digestion and absorption and the subsequent postprandial muscle protein synthetic response between young and elderly men. Ten elderly (64 ± 1 y) and 10 young (23 ± 1 y) healthy males consumed a single bolus of 35 g specifically produced, intrinsically L-[1-13C] phenylalanine-labeled micellar casein (CAS) protein. Furthermore, primed continuous infusions with L-[ring-²H5]phenylalanine, L-[1-13C]leucine, and L-[ring-²H5]tyrosine were applied and blood and muscle tissue samples were collected to assess the appearance rate of dietary protein-derived phenylalanine in the circulation and the subsequent muscle protein fractional synthetic rate over a 6-h postprandial period. Protein ingestion resulted in a rapid increase in exogenous phenylalanine appearance in both the young and elderly men. Total exogenous phenylalanine appearance rates (expressed as area under the curve) were 39 ± 3 μmol·6 h·kg-1 in the young men and 38 ± 2 μmol·6 h·kg-1 in the elderly men (P = 0.73). In accordance, splanchnic amino acid extraction did not differ between young (72 ± 2%) and elderly (73 ± 1%) volunteers (P = 0.74). Muscle protein synthesis rates, calculated from the oral tracer, were 0.063 ± 0.006 and 0.054 ± 0.004%/h in the young and elderly men, respectively, and did not differ between groups (P = 0.27). We conclude that protein digestion and absorption kinetics and the subsequent muscle protein synthetic response following the ingestion of a large bolus of intact CAS are not substantially impaired in healthy, elderly men. [ABSTRACT FROM AUTHOR]

We investigated the effect of carbohydrate and protein hydrolysate ingestion on whole-body and muscle protein synthesis during a combined endurance and resistance exercise session and subsequent overnight recovery. Twenty healthy men were studied in the evening after consuming a standardized diet throughout the day. Subjects participated in a 2-h exercise session during which beverages containing both carbohydrate (0.15 g·kg-1·h-1)and a protein hydrolysate (0.15 g·kg-1·h-1) (C+P, n = 10) or water only (W, n = 10) were ingested. Participants consumed 2 additional beverages during early recovery and remained overnight at the hospital. Continuous i.v. infusions with L-[ring-13C6]-phenylalanine and L-[ring-2H2]-tyrosine were applied and blood and muscle samples were collected to assess whole-body and muscle protein synthesis rates. During exercise, whole-body and muscle protein synthesis rates increased by 29 and 48% with protein and carbohydrate coingestion (P < 0.05). Fractional synthetic rates during exercise were 0.083 ± 0.011 %/h in the C+P group and 0.056 ± 0.003%/h in the W group, (P < 0.05). During subsequent overnight recovery, whole-body protein synthesis was 19% greater in the C+P group than in the W group (P < 0.05). However, mean muscle protein synthesis rates during 9 h of overnight recovery did notdiffer between groups and were 0.056 ± 0.004%/h in the C+ P group and 0.057 ± 0.004%/h in the W group (P = 0.89). We conclude that, even in a fed state, protein and carbohydrate supplementation stimulates muscle protein synthesis during exercise. Ingestion of protein with carbohydrate during and immediately after exercise improves whole-body protein synthesis but does not further augment muscle protein synthesis rates during 9 h of subsequent overnight recovery. [ABSTRACT FROM AUTHOR]

Protein ingestion stimulates muscle protein synthesis and improves net muscle protein balance. Insulin resistance has been suggested to result in a reduced muscle protein synthetic response to food intake. As such, we hypothesized that type 2 diabetes patients have a impaired muscle protein synthetic response to food ingestion. To test this hypothesis, 10 male type 2 diabetes patients using their normal oral glucose-lowering medication (68 ± 2 y) and 10 matched, normoglycemic men 165 ± 2 y) were randomly assigned to 2 crossover treatments in which whole body and muscle protein synthesis were measured following the consumption of either carbohydrate (CHOI or carbohydrate with a protein hydrolysate (CHO+PRO). 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 balance and mixed muscle protein fractional synthetic rate over a 6-h period. Whole-body phenylalanine and tyrosine flux were higher after the CHO+PRO treatment compared with the CHO treatment in the diabetes and control group (P < 0.011. Protein balance was negative following CHO but positive following CHO+ PRO treatment in both groups. Muscle protein synthesis rates were higher in both groups following the CHO+PRO (0.086 ± 0.014%/h) treatment than in the CHO treatment 10.040 ± 0.003%/h; P < 0.01) with no difference between the diabetes patients and normoglycemic controls. We conclude that the muscle protein synthetic response to CHO or CHO+ PRO ingestion is not substantially impaired in longstanding, type 2 diabetes patients treated with oral blood glucose-lowering medication. [ABSTRACT FROM AUTHOR]

Our objective was to determine the impact of carbohydrate and/or protein ingestion before and after exercise on ribosomal protein S6 kinase (S6K1) and S6 phosphorylation status in human skeletal muscle tissue. Seven healthy, untrained men (22.5 +/- 0.9 y) were randomly assigned to 2 cross-over experiments. Before, immediately after, and 1 h after a single bout of resistance exercise, subjects consumed 0.3 g x kg(-1) carbohydrate with or without 0.3 g x kg(-1) protein hydrolysate (CHO+PRO and CHO, respectively). Muscle biopsies were taken before and immediately after exercise and after 1 and 4 h of postexercise recovery to determine 4E-BP1, S6K1 (both T(421)/S(424) and T(389)), and S6 phosphorylation status. Following resistance exercise, 4E-BP1 phosphorylation was reduced to a greater extent in the CHO treatment (-48 +/- 7%) than in the CHO+PRO treatment (-15 +/- 14%, P < 0.01). During recovery, 4E-BP1 phosphorylation increased in both experiments (P < 0.01), and tended to be higher in the CHO+PRO test (P = 0.08). S6K1 phosphorylation at T(421)/S(424) substantially increased following exercise and remained elevated during recovery with no differences between treatments. In contrast to the CHO treatment (-4 +/- 2%), S6K1 phosphorylation at T(389) was higher following exercise in the CHO+PRO treatment only (+78 +/- 2%, P < 0.01). During recovery, S6K1 phosphorylation at T(389) remained higher in CHO+PRO than in CHO (P < 0.05). S6 phosphorylation was substantially higher following exercise in the CHO+PRO (1.69 +/- 0.35) than in the CHO experiment (0.45 +/- 0.07, P < 0.01) and remained elevated during recovery (P < 0.05). We conclude that the availability of dietary protein further enhances phosphorylation of S6K1 during recovery from resistance type exercise. [ABSTRACT FROM AUTHOR]

Our objective was to determine the impact of carbohydrate and/or protein ingestion before and after exercise on ribosomal protein S6 kinase (S6K1) and S6 phosphorylation status in human skeletal muscle tissue. Seven healthy, untrained men (22.5 ± 0.9 y) were randomly assigned to 2 cross-over experiments. Before, immediately after, and 1 h after a single bout of resistance exercise, subjects consumed 0.3 g·kg-1 carbohydrate with or without 0.3 g·kg-1 protein hydrolysate (CHO+PRO and CHO, respectively). Muscle biopsies were taken before and immediately after exercise and after 1 and 4 h of postexercise recovery to determine 4E-BP1, S6K1 (both T421/S424 and T389), and S6 phosphorylation status. Following resistance exercise, 4E-BP1 phosphorylation was reduced to a greater extent in the CHO treatment (-48 ± 7%) than in the CHO+PRO treatment (-15 ± 14%, P< 0.01). During recovery, 4E-BP1 phosphorylation increased in both experiments (P< 0.01), and tended to be higher in the CHO+PRO test (P = 0.08). S6K1 phosphorylation at T421/S424 substantially increased following exercise and remained elevated during recovery with no differences between treatments. In contrast to the CHO treatment (-4 ± 2%), S6K1 phosphorylation at T389 was higher following exercise in the CHO+ PRO treatment only (+78 ± 2%, P < 0.01). During recovery, S6K1 phosphorylation at T389 remained higher in CHO+PRO than in CHO (P < 0.05). S6 phosphorylation was substantially higher following exercise in the CHO+ PRO (1.69 ± 0.351 than in the CHO experiment (0.45 ± 0.07, P < 0.01) and remained elevated during recovery (P < 0.05). We conclude that the availability of dietary protein further enhances phosphorylation of S6K1 during recovery from resistance type exercise. [ABSTRACT FROM AUTHOR]