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Novel Essential Amino Acid Supplements Following Resistance Exercise Induce Aminoacidemia and Enhance Anabolic Signaling Irrespective of Age: A Proof-of-Concept Trial.

ABSTRACT: We investigated the effects of ingesting a leucine-enriched essential amino acid (EAA) gel alone or combined with resistance exercise (RE) versus RE alone (control) on plasma aminoacidemia and intramyocellular anabolic signaling in healthy younger (28 ± 4 years) and older (71 ± 3 years) adults. Blood samples were obtained throughout the three trials, while muscle biopsies were collected in the postabsorptive state and 2 h following RE, following the consumption of two 50 mL EAA gels (40% leucine, 15 g total EAA), and following RE with EAA (combination (COM)). Protein content and the phosphorylation status of key anabolic signaling proteins were determined via immunoblotting. Irrespective of age, during EAA and COM peak leucinemia (younger: 454 ± 32 µM and 537 ± 111 µM; older: 417 ± 99 µM and 553 ± 136 µM) occurred ~60-120 min post-ingestion (younger: 66 ± 6 min and 120 ± 60 min; older: 90 ± 13 min and 78 ± 12 min). In the pooled sample, the area under the curve for plasma leucine and the sum of branched-chain amino acids was significantly greater in EAA and COM compared with RE. For intramyocellular signaling, significant main effects were found for condition (mTOR (Ser2481), rpS6 (Ser235/236)) and age (S6K1 (Thr421/Ser424), 4E-BP1 (Thr37/46)) in age group analyses. The phosphorylation of rpS6 was of similar magnitude (~8-fold) in pooled and age group data 2 h following COM. Our findings suggest that a gel-based, leucine-enriched EAA supplement is associated with aminoacidemia and a muscle anabolic signaling response, thus representing an effective means of stimulating muscle protein anabolism in younger and older adults following EAA and COM.

SUBMITTER: Lees MJ

PROVIDER: S-EPMC7400893 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Novel Essential Amino Acid Supplements Following Resistance Exercise Induce Aminoacidemia and Enhance Anabolic Signaling Irrespective of Age: A Proof-of-Concept Trial.

Lees Matthew J MJ Wilson Oliver J OJ Webb Erin K EK Traylor Daniel A DA Prior Todd T Elia Antonis A Harlow Paul S PS Black Alistair D AD Parker Paul J PJ Harris Nick N Cooke Michael M Balchin Christopher C Butterworth Mathew M Phillips Stuart M SM Ispoglou Theocharis T

Nutrients 20200712 7

We investigated the effects of ingesting a leucine-enriched essential amino acid (EAA) gel alone or combined with resistance exercise (RE) versus RE alone (control) on plasma aminoacidemia and intramyocellular anabolic signaling in healthy younger (28 ± 4 years) and older (71 ± 3 years) adults. Blood samples were obtained throughout the three trials, while muscle biopsies were collected in the postabsorptive state and 2 h following RE, following the consumption of two 50 mL EAA gels (40% leucine ...[more]

PMID: 32664648

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Project description:Background:The muscle protein anabolic response to contraction and feeding may be blunted in older adults. Acute bouts of exercise can improve the ability of amino acids to stimulate muscle protein synthesis (MPS) by activating mechanistic target of rapamycin complex 1 (mTORC1) signaling, but it is not known whether exercise training may improve muscle sensitivity to amino acid availability. Objective:The aim of this study was to determine if muscle protein anabolism is resistant to essential amino acids (EAAs) and whether resistance exercise training (RET) improves muscle sensitivity to EAA in healthy older adults. Methods:In a longitudinal study, 19 healthy older adults [mean ± SD age: 71 ± 4 y body mass index (kg/m2): 28 ± 3] were trained for 12 wk with a whole-body program of progressive RET (60-75% 1-repetition maximum). Body composition, strength, and metabolic health were measured pre- and posttraining. We also performed stable isotope infusion experiments with muscle biopsies pre- and posttraining to measure MPS and markers of amino acid sensing in the basal state and in response to 6.8 g of EAA ingestion. Results:RET increased muscle strength by 16%, lean mass by 2%, and muscle cross-sectional area by 27% in healthy older adults (P < 0.05). MPS and mTORC1 signaling (i.e., phosphorylation status of protein kinase B, 4E binding protein 1, 70-kDa S6 protein kinase, and ribosomal protein S6) increased after EAA ingestion (P < 0.05) pre- and posttraining. RET increased basal MPS by 36% (P < 0.05); however, RET did not affect the response of MPS and mTORC1 signaling to EAA ingestion. Conclusion:RET increases strength and basal MPS, promoting hypertrophy in healthy older adults. In these subjects, a small dose of EAAs stimulates muscle mTORC1 signaling and MPS, and this response to EAAs does not improve after RET. Our data indicate that anabolic resistance to amino acids may not be a problem in healthy older adults. This trial was registered at www.clinicaltrials.gov as NCT02999802.

Project description:BackgroundConventional nutritional supplements are not or only partly successful in inducing protein accretion in advanced cancer, suggesting an attenuated anabolic response. To prevent muscle wasting and its deleterious consequences, generating an anabolic response is crucial. Dietary essential amino acids (EAA) have anabolic properties in other wasting diseases; however, data in advanced cancer are lacking.Patients and methodsIn 13 patients with advanced nonsmall-cell lung cancer (NSCLC) (stage III and IV) and 11 healthy age-matched subjects, we measured protein synthesis and breakdown of the whole body, and net protein anabolism (difference between protein synthesis and breakdown) after intake of 14 g of free EAA with high leucine levels (EAA/leucine) versus a balanced amino acid mixture containing both EAA and non-EAA as present in whey protein, according to a randomized, double-blind, crossover design.ResultsProtein synthesis and net protein anabolism were higher after intake of the EAA/leucine than the balanced amino acid mixture (P < 0.001), independent of presence of cancer. A highly significant linear relationship between net protein anabolism and the amount of EAA available in the systemic circulation (R(2): 0.85, P < 0.001) was found in both groups. The presence of muscle or recent weight loss, systemic inflammatory response, or length of survival did not influence this relationship. High leucine levels in the EAA/leucine mixture was of no anabolic benefit.ConclusionsThere is no anabolic resistance or attenuated anabolic potential to intake of 14 g of EAA/leucine or balanced amino acid mixture in advanced (mainly stage III) NSCLC. The high anabolic potential of dietary EAA in cancer patients is independent of their nutritional status, systemic inflammatory response or disease trajectory, suggesting a key role of EAA in new nutritional approaches to prevent muscle loss, thereby improving outcome of patients with advanced cancer.ClinicaltrailsgovNCT01172314.

Dataset Information

Novel Essential Amino Acid Supplements Following Resistance Exercise Induce Aminoacidemia and Enhance Anabolic Signaling Irrespective of Age: A Proof-of-Concept Trial.

Publications

Novel Essential Amino Acid Supplements Following Resistance Exercise Induce Aminoacidemia and Enhance Anabolic Signaling Irrespective of Age: A Proof-of-Concept Trial.

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