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Effects of Short-Term Dietary Protein Restriction on Blood Amino Acid Levels in Young Men.

ABSTRACT: Pre-clinical studies show that dietary protein restriction (DPR) improves healthspan and retards many age-related diseases such as type 2 diabetes. While mouse studies have shown that restriction of certain essential amino acids is required for this response, less is known about which amino acids are affected by DPR in humans. Here, using a within-subjects diet design, we examined the effects of dietary protein restriction in the fasted state, as well as acutely after meal feeding, on blood plasma amino acid levels. While very few amino acids were affected by DPR in the fasted state, several proteinogenic AAs such as isoleucine, leucine, lysine, phenylalanine, threonine, tyrosine, and valine were lower in the meal-fed state with DPR. In addition, the non-proteinogenic AAs such as 1- and 3-methyl-histidine were also lower with meal feeding during DPR. Lastly, using in silico predictions of the most limiting essential AAs compared with human exome AA usage, we demonstrate that leucine, methionine, and threonine are potentially the most limiting essential AAs with DPR. In summary, acute meal feeding allows more accurate determination of which AAs are affected by dietary interventions, with most essential AAs lowered by DPR.

SUBMITTER: Sjoberg KA

PROVIDER: S-EPMC7468950 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Effects of Short-Term Dietary Protein Restriction on Blood Amino Acid Levels in Young Men.

Sjøberg Kim A KA Schmoll Dieter D Piper Matthew D W MDW Kiens Bente B Rose Adam J AJ

Nutrients 20200723 8

Pre-clinical studies show that dietary protein restriction (DPR) improves healthspan and retards many age-related diseases such as type 2 diabetes. While mouse studies have shown that restriction of certain essential amino acids is required for this response, less is known about which amino acids are affected by DPR in humans. Here, using a within-subjects diet design, we examined the effects of dietary protein restriction in the fasted state, as well as acutely after meal feeding, on blood plas ...[more]

PMID: 32717986

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Project description:Skeletal muscle disuse leads to atrophy, declines in muscle function, and metabolic dysfunction that are often slow to recover. Strategies to mitigate these effects would be clinically relevant. In a double-blind randomized-controlled pilot trial, we examined the safety and tolerability as well as the atrophy mitigating effect of a novel amino acid composition (AXA2678), during single limb immobilization. Twenty healthy young men were randomly assigned (10 per group) to receive AXA2678 or an excipient- and energy-matched non-amino acid containing placebo (PL) for 28d: days 1-7, pre-immobilization; days 8-15, immobilization; and days 16-28 post-immobilization recovery. Muscle biopsies were taken on d1, d8 (immobilization start), d15 (immobilization end), and d28 (post-immobilization recovery). Magnetic resonance imaging (MRI) was utilized to assess quadriceps muscle volume (Mvol), muscle cross-sectional area (CSA), and muscle fat-fraction (FF: the fraction of muscle occupied by fat). Maximal voluntary leg isometric torque was assessed by dynamometry. Administration of AXA2678 attenuated muscle disuse atrophy compared to PL (p < 0.05) with changes from d8 to d15 in PL: ΔMvol = -2.4 ± 2.3% and ΔCSA = -3.1% ± 2.1%, both p < 0.001 vs. zero; against AXA2678: ΔMvol: -0.7 ± 1.8% and ΔCSA: -0.7 ± 2.1%, both p > 0.3 vs. zero; and p < 0.05 between treatment conditions for CSA. During immobilization, muscle FF increased in PL but not in AXA2678 (PL: 12.8 ± 6.1%, AXA2678: 0.4 ± 3.1%; p < 0.05). Immobilization resulted in similar reductions in peak leg isometric torque and change in time-to-peak (TTP) torque in both groups. Recovery (d15-d28) of peak torque and TTP torque was also not different between groups, but showed a trend for better recovery in the AXA2678 group. Thrice daily consumption of AXA2678 for 28d was found to be safe and well-tolerated. Additionally, AXA2678 attenuated atrophy, and attenuated accumulation of fat during short-term disuse. Further investigations on the administration of AXA2678 in conditions of muscle disuse are warranted. Clinical Trial Registration: https://clinicaltrials.gov, identifier: NCT03267745.

Dataset Information

Effects of Short-Term Dietary Protein Restriction on Blood Amino Acid Levels in Young Men.

Publications

Effects of Short-Term Dietary Protein Restriction on Blood Amino Acid Levels in Young Men.

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