Declines in muscle protein synthesis account for short-term muscle disuse atrophy in humans in the absence of increased muscle protein breakdown

Background: We determined the short-term (i.e. 4days) impacts of disuse atrophy in relation to muscle protein turnover [acute fasted-fed muscle protein synthesis (MPS)/muscle protein breakdown (MPB) and integrated MPS/estimated MPB]. Methods: Healthy men (N=9, 22±2years, body mass index 24±3kgm−2) underwent 4day unilateral leg immobilization. Vastus lateralis (VL) muscle thickness (MT) and extensor strength and thigh lean mass (TLM) were measured. Bilateral VL muscle biopsies were collected on Day 4 at t=−120, 0, 90, and 180min to determine integrated MPS, estimated MPB, acute fasted-fed MPS (l-[ring-13C6]-phe), and acute fasted tracer decay rate representative of MPB (l-[15N]-phe and l-[2H8]-phe). Protein turnover cell signalling was measured by immunoblotting. Results: Immobilization decreased TLM [pre: 7477±1196g, post: 7352±1209g (P0.05). Conclusions: Human skeletal muscle disuse atrophy is driven by declines in MPS, not increases in MPB. Pro-anabolic therapies to mitigate disuse atrophy would likely be more effective than therapies aimed at attenuating protein degradation

Co-ingesting milk fat with micellar casein does not affect postprandial protein handling in healthy older men

Background & aim: Dietary protein digestion and absorption plays an important role in modulating postprandial muscle protein synthesis. The impact of co-ingesting other macronutrients with dietary protein on protein digestion and absorption and the subsequent muscle protein synthetic response remains largely unexplored. This study investigated the impact of co-ingesting milk fat with micellar casein on dietary protein-derived amino acid appearance in the circulation and the subsequent postprandial muscle protein synthetic response in healthy older men. Methods: Twenty-four healthy, older males ( age: 65 ± 1 y, BMI: 25.7 ± 0.5 kg/m2 ) received a primed continuous infusion of L-[ring-2H5]-phenylalanine and L-[1–13C]-leucine and ingested 20 g intrinsically L-[1–13C]-phenylalanine and L-[1–13C]-leucine-labeled casein with ( PRO + FAT; n = 12 ) or without ( PRO; n = 12 ) 26.7 g milk fat. Plasma samples and muscle biopsies were collected in both the postabsorptive and postprandial state. Results: Release of dietary protein-derived phenylalanine into the circulation increased following protein ingestion ( P < 0.001 ) and tended to be higher in PRO compared with PRO + FAT ( Time × Treatment P = 0.076 ). No differences were observed in dietary protein-derived plasma phenylalanine availability ( 52 ± 2 vs 52 ± 3% in PRO vs PRO + FAT, respectively; P = 0.868 ). Myofibrillar protein synthesis rates did not differ between treatments, calculated using either the L-[ring-2H5]-phenylalanine ( 0.036 ± 0.003 vs 0.036 ± 0.004 %/h after PRO vs PRO + FAT, respectively; P = 0.933 ) or L-[1–13C]-leucine ( 0.051 ± 0.004 vs 0.046 ± 0.004 %/h, respectively; P = 0.480 ) tracer. In accordance, no differences were observed in myofibrillar protein-bound L-[1–13C]-phenylalanine enrichments between treatments ( 0.018 ± 0.002 vs 0.014 ± 0.001 MPE, respectively; P = 0.173 ). Conclusion: Co-ingesting milk fat with micellar casein does not impair protein-derived phenylalanine appearance in the circulation and does not modulate postprandial myofibrillar protein synthesis rates. Clinical Trial Registration Number: NCT01680146 ( http://www.clinicaltrials.gov/

The Muscle Protein Synthetic Response to the Ingestion of a Plant-Derived Protein Blend Does Not Differ from an Equivalent Amount of Milk Protein in Healthy Young Males

Background: Plant-derived proteins are considered to have lesser anabolic properties when compared with animal-derived proteins. The attenuated rise in muscle protein synthesis rates following ingestion of plant-derived compared with animal-derived protein has been, at least partly, attributed to deficiencies in specific amino acids such as leucine, lysine, and/or methionine. Combining different plant-derived proteins could provide plant-derived protein blends with a more balanced amino acid profile.Objectives: This study aimed to compare postprandial muscle protein synthesis rates following the ingestion of 30 g milk protein with a 30 g blend combining wheat, corn, and pea protein in healthy young men.Methods: In a randomized, double-blind, parallel-group design, 24 young males (aged 24 ± 4 y) received a primed continuous l-[ring-13C6]-phenylalanine infusion after which they ingested 30 g milk protein (MILK) or a 30 g plant-derived protein blend combining 15 g wheat, 7.5 g corn, and 7.5 g pea protein (PLANT-BLEND). Blood and muscle biopsies were collected frequently for 5 h to assess postprandial plasma amino acid profiles (secondary outcome) and subsequent muscle protein synthesis rates (primary outcome). Data were analyzed by 2-factor repeated measures ANOVA and 2-samples t tests.Results: MILK increased plasma essential amino acid concentrations more than PLANT-BLEND over the 5 h postprandial period (incremental AUC = 151 ± 31 compared with 79 ± 12 mmol·300 min·L−1, respectively; P Conclusions: Ingestion of 30 g plant-derived protein blend combining wheat-, corn-, and pea-derived protein increases muscle protein synthesis rates in healthy young males. The muscle protein synthetic response to the ingestion of 30 g of this plant-derived protein blend does not differ from the ingestion of an equivalent amount of a high-quality animal-derived protei

Consumption of high-leucine-containing protein bar following breakfast impacts aminoacidemia and subjective appetite in older persons

Background: Limited data are available examining dietary interventions for optimizing protein and leucine intake to stimulate muscle protein synthesis (MPS) in older humans. Objectives: We aimed to investigate the aminoacidemia and appetite responses of older adults after consuming breakfast, a meal frequently consumed with high-carbohydrate and below-par amounts of protein and leucine for stimulating MPS. Methods: Five men and 3 women (means ± SD; age: 74 ± 7 y, BMI: 25.7 ± 4.9 kg/m2, fat- and bone-free mass: 63 ± 7 kg) took part in this experiment in which they consumed breakfasts with low-protein (LP = 13 ± 2 g), high-protein (HP = 32 ± 5 g), and LP followed by a protein- and leucine-enriched bar formulation 2 h later (LP + Bar = 29 ± 2 g). The LP, HP, and LP + Bar breakfast conditions contained 519 ± 86 kcal, 535 ± 83 kcal, and 739 ± 86 kcal, respectively. Blood samples were drawn for 6 h and analyzed for amino acid, insulin, and glucose concentrations. Visual analog scales were assessed for hunger, fullness, and desire to eat. Results: The net AUC for essential amino acid (EAA) exposure was similar between the LP + Bar and HP conditions but greater in the HP condition compared with the LP condition. Peak leucinemia was higher in the LP + Bar condition compared with the HP, and both were greater than the LP condition. Net leucine exposure was similar between HP and LP + Bar, and both were greater than LP. Hunger was similarly reduced in LP + Bar and HP, and LP + Bar resulted in a greater hunger reduction than LP. Both LP + Bar and HP resulted in greater net fullness scores than LP. Conclusions: Consuming our bar formulation increased blood leucine availability and net exposure to EAAs to a similar degree as consuming a high-protein meal. High-protein at breakfast results in a greater net exposure to EAAs and leucine, which could support MPS in older persons. This study was registered at clinicaltrials.gov as NCT03712761

The effect of oral essential amino acids on incretin hormone production in youth and ageing

The effect of substantive doses of essential amino acids (EAA) on incretin and insulin production, and the impact of age upon this effect, is ill‐defined. Methods: A 15‐g oral EAA drink was administered to young (N = 8; 26 ± 4.4 years) and older (N = 8; 69 ± 3.8 years) healthy volunteers. Another group of younger volunteers (N = 9; 21 ± 1.9 years) was given IV infusions to achieve equivalent plasma amino acids (AA) profiles. Plasma AA, insulin, glucagon‐like peptide‐1 (GLP‐1) and glucose‐dependent insulinotropic peptide (GIP) were quantified over 2 hours. Results: In younger recruits, EAA‐induced rapid insulinaemia and aminoacidaemia with total amino acids(AA), EAA and branched chain amino acids (BCAA) matched between oral and IV groups. Insulin peaked at 39 ± 29 pmol L−1 at 30 minutes following oral feeding compared to 22 ± 9 pmol L−1 at 60 minutes following IV feeding (P: NS). EAA peaked at 3395 μmol L−1 at 45 minutes during IV infusion compared to 2892 μmol L−1 following oral intake (Feeding effect: P < 0.0001. Oral vs IV feeding: P: NS). There was an 11% greater increase in insulin levels in the 120 minutes duration of the study in response to oral EAA as opposed to IV EAA. GIP increased following oral EAA (452 pmol L−1 vs 232 pmol L−1, P < 0.05). Age did not impact insulin or incretins production. Conclusion: Postprandial rises in EAA levels lead to rapid insulinaemia which is higher with oral compared with IV EAA, that is attributed more to GIP and unaffected by age. This finding supports EAA, on their own or as part of high‐protein meal, as nutritive therapeutics in impaired glycaemia and ageing