Addition of carbohydrate or alanine to an essential amino acid mixture does not enhance human skeletal muscle protein anabolism

Abstract

In humans, essential amino acids (EAAs) stimulate muscle protein synthesis (MPS) with no effect on muscle protein breakdown (MPB). Insulin can stimulate MPS, and carbohydrates (CHOs) and insulin decrease MPB. Net protein balance (NB; indicator of overall anabolism) is greatest when MPS is maximized and MPB is minimized. To determine whether adding CHO or a gluconeogenic amino acid to EAAs would improve NB compared with EAA alone, young men and women (n = 21) ingested 10 g EAA alone, with 30 g sucrose (EAA+CHO), or with 30 g alanine (EAA+ALA). The fractional synthetic rate and phenylalanine kinetics (MPS, MPB, NB) were assessed by stable isotopic methods on muscle biopsies at baseline and 60 and 180 min following nutrient ingestion. Insulin increased 30 min postingestion in all groups and remained elevated in the EAA+CHO and EAA+ALA groups for 60 and 120 min, respectively. The fractional synthetic rate increased from baseline at 60 min in all groups (P < 0.05; EAA = 0.053 ± 0.018 to 0.090 ± 0.039% · h(-1); EAA+ALA = 0.051 ± 0.005 to 0.087 ± 0.015% · h(-1); EAA+CHO = 0.049 ± 0.006 to 0.115 ± 0.024% · h(-1)). MPS and NB peaked at 30 min in the EAA and EAA+CHO groups but at 60 min in the EAA+ALA group and NB was elevated above baseline longer in the EAA+ALA group than in the EAA group (P < 0.05). Although responses were more robust in the EAA+CHO group and prolonged in the EAA+ALA group, AUCs were similar among all groups for fractional synthetic rate, MPS, MPB, and NB. Because the overall muscle protein anabolic response was not improved in either the EAA+ALA or EAA+CHO group compared with EAA, we conclude that protein nutritional interventions to enhance muscle protein anabolism do not require such additional energy.

Conflict of interest statement

Author disclosures: E. L. Glynn, C. S. Fry, K. L. Timmerman, M. J. Drummond, E. Volpi, and B. B. Rasmussen, no conflicts of interest.

Figures

FIGURE 1

Study design. A primed, constant infusion of l-13C6- phenylalanine was begun at 0700 h followed by placement of arterial and venous femoral catheters. The study consisted of a basal period (baseline) followed by nutrient ingestion (EAA, EAA+ALA, or EAA+CHO) and 3 additional 60-min periods. In each period, ICG was infused to measure BF, blood samples were collected every 15 min, and muscle biopsies from the vastus lateralis were obtained at baseline (2) and 60 and 180 min following nutrient ingestion. Arrow indicates blood draw. BF, blood flow; EAA, essential amino acids; EAA+ALA, 10 g essential amino acids + 30 g alanine; EAA+CHO, 10 g essential amino acids + 30 g carbohydrate as sucrose; ICG, indocyanine green; X, muscle biopsy.

FIGURE 2

Leg BF (A), arterial insulin (B), and glucose concentrations (C) and leg glucose uptake (D) in young men and women following ingestion of EAA alone or with ALA or CHO. Values are mean ± SEM, n = 7/group. *Within-group difference from baseline, P < 0.05; †different from EAA, P < 0.05. BF, blood flow; EAA, essential amino acids; EAA+ALA, 10 g essential amino acids + 30 g alanine; EAA+CHO, 10 g essential amino acids + 30 g carbohydrate as sucrose.

FIGURE 3

Phenylalanine concentration in the artery (A), delivery to the leg (Fin) (B), transport into muscle (Fm,a) (C), and intracellular availability (D) following nutrient ingestion in young men and women. Values are mean ± SEM, n = 7/group, except EAA+ALA and EAA+CHO Fm,a and intracellular availability n = 6. *Within-group difference from baseline, P < 0.05; †different from EAA, P < 0.05. EAA, essential amino acids; EAA+ALA, 10 g essential amino acids + 30 g alanine; EAA+CHO, 10 g essential amino acids + 30 g carbohydrate as sucrose.

FIGURE 4

Phenylalanine utilization for protein synthesis (Fo,m) (A), release from proteolysis (Fm,o) (B), and net balance (C) following nutrient ingestion in young men and women. Values are mean ± SEM, n = 7/group, except EAA+ALA and EAA+CHO Fo,m and Fm,on = 6. *Within-group difference from baseline, P < 0.05; †different from EAA, P < 0.05. aDifferent from EAA, P = 0.06. EAA, essential amino acids; EAA+ALA, 10 g essential amino acids + 30 g alanine; EAA+CHO, 10 g essential amino acids + 30 g carbohydrate as sucrose.

FIGURE 5

Fractional synthetic rate postnutrient ingestion (A) and individual participant responses 60 min following nutrient ingestion (B) in young men and women. Values are mean ± SEM (A) and raw values (B). (A) n = 7/group (missing 1 data point, EAA+CHO 180 min; missing 1 data point, EAA+ALA 60 and 180 min). *Within-group difference from baseline, P < 0.05. (B) EAA and EAA+CHO, n = 7; EAA+ALA n = 6. Dotted line indicates group mean. EAA, essential amino acids; EAA+ALA, 10 g essential amino acids + 30 g alanine; EAA+CHO, 10 g essential amino acids + 30 g carbohydrate as sucrose.