Effectiveness of essential amino acid supplementation in stimulating whole body net protein anabolism is comparable between COPD patients and healthy older adults

Abstract

Background: The development of effective nutritional strategies in support of muscle growth for patients with chronic obstructive pulmonary disease (COPD) remains challenging. Dietary essential amino acids (EAAs) are the main driver of postprandial net protein anabolism. In agreement, EAA supplements in healthy older adults are more effective than supplements with the composition of complete proteins. In patients with COPD it is still unknown whether complete protein supplements can be substituted with only EAAs, and whether they are as effective as in healthy older adults.

Methods: According to a double-blind randomized crossover design, we examined in 23 patients with moderate to very severe COPD (age: 65±2 years, FEV₁: 40±2% of predicted) and 19 healthy age-matched subjects (age: 64±2 years), whether a free EAA mixture with a high proportion (40%) of leucine (EAA mixture) stimulated whole body net protein gain more than a similar mixture of balanced free EAAs and non-EAAs as present in whey protein (TAA mixture). Whole body net protein gain and splanchnic extraction of phenylalanine (PHE) were assessed by continuous IV infusion of L-[ring-²H₅]-PHE and L-[ring-²H₂]-tyrosine, and enteral intake of L-[¹⁵N]-PHE (added to the mixtures).

Results: Besides an excellent positive linear relationship between PHE intake and net protein gain in both groups (r=0.84-0.91, P<0.001), net protein gain was 42% higher in healthy controls and 49% higher in COPD patients after intake of the EAA mixture compared to the TAA mixture (P<0.0001). These findings could not be attributed to the high LEU content, as in both groups net protein gain per gram EAA intake was lower for the EAA mixture (P<0.0001). Net protein gain was higher in COPD patients for both mixtures due to a 40% lower splanchnic extraction (P<0.0001), but was similarly related to dietary PHE (i.e. EAA) plasma appearance.

Conclusions: In COPD patients, similarly to healthy older adults, free EAA supplements stimulate whole body protein anabolism more than free amino acid supplements with the composition of complete proteins. Therefore, free EAA supplements may aid in the prevention and treatment of muscle wasting in this patient population.

Keywords: COPD; Essential amino acid; Leucine; Protein turnover.

Figure 1

Study design. All participants were studied twice within one week (≥ one day apart) during a 6-hour infusion protocol, and received two different free amino acid mixtures according to a randomized crossover design.

Figure 2

Mean (± SE) (A) plasma EAA concentration after intake of the 14 g TAA and EAA mixtures in healthy controls (n=19) (B) plasma EAA concentration after intake of the 7 g TAA and EAA mixtures in COPD patients (n=23) (C) plasma LEU concentration after intake of the 14 g TAA and EAA mixtures in healthy controls (n=19) (D) plasma LEU concentration after intake of the 7 g TAA and EAA mixtures in COPD patients (n=23). Statistics were done using two-way repeated measures analysis of variance with “time” and “mixture” as factors used to compare differences between mixtures and over time. In both groups, and for the EAA as well as the LEU concentration: time effect, P<0.0001, mixture effect, P<0.0001, and time x mixture interaction, P<0.0001. EAA mixture significantly different from TAA mixture, ^****P<0.0001, ^**P<0.01, ^*P<0.05. TAA mixture: total amino acid mixture (balanced mixture of EAA and non-EAA). EAA mixture: essential amino acid mixture (balanced mixture of EAA and additional LEU). EAA: essential amino acid. LEU: leucine.

Figure 3

Mean (± SE) (A) plasma insulin concentration after intake of the 14 g TAA and EAA mixtures in healthy controls (n=19) (B) plasma insulin concentration after intake of the 7 g TAA and EAA mixtures in COPD patients (n=23). Statistics were done using two-way repeated measures analysis of variance with “time” and “mixture” as factors used to compare differences between mixtures and over time. Healthy controls: time effect, P<0.0001, mixture effect, P=0.0382, and no time x mixture interaction. COPD patients: time effect, P<0.0001, mixture effect, P=0.0290, and time x mixture interaction, P=0.0167. EAA mixture significantly different from TAA mixture, ^**P<0.01, ^*P<0.05. TAA mixture: total amino acid mixture (balanced mixture of EAA and non-EAA). EAA mixture: essential amino acid mixture (balanced mixture of EAA and additional LEU).

Figure 4

Correlation after intake of the TAA and EAA mixtures between whole body net protein gain and (A) PHE intake, in healthy controls (n=19) and COPD patients (n=23). Healthy: net protein gain = 0.45 × + 5.42, r=0.91, P<0.0001. COPD: net protein gain = 0.79 × EAA intake – 3.1, r=0.85, P<0.0001. Slopes are significantly different between groups, P<0.0001. (B) Dietary PHE plasma appearance after splanchnic extraction, in healthy controls (n=19) and COPD patients (n=23). Healthy: net protein gain = 0.90 × EAA intake – 2.58, r=0.96, P<0.0001. COPD: net protein gain = 0.99 × EAA intake – 1.81, r=0.97, P<0.0001. Slopes are similar between groups. (C) Change in PHE concentration, in controls (n=19) and COPD patients (n=23). Healthy: net protein gain = 0.32 × EAA intake + 22.76, r=0.53, P=0.0006. COPD: net protein gain = 0.36 × EAA intake + 24.93, r=0.45, P=0.0007. Slopes are similar between groups. Statistics were done using linear regression analysis and computation of Pearson’s correlation coefficient. Net protein gain, dietary PHE plasma appearance and change in PHE concentration are expressed as the 3h postprandial area under the curve. TAA mixture: total amino acid mixture (balanced mixture of EAA and non-EAA). EAA mixture: essential amino acid mixture (balanced mixture of EAA and additional LEU). PHE: phenylalanine. Net protein gain = protein synthesis – protein breakdown.

Figure 5

Mean (± SE) whole body net protein gain after intake of the TAA and EAA mixtures in healthy controls (n=19) and COPD patients (n=23) (A) per gram total AA intake (B) per gram EAA intake (C) per gram balanced EAA intake (=EAA intake minus additional LEU). Statistics were done using two-way measures analysis of variance with “group” and “mixture” as factors used to compare differences between groups and mixtures. Net protein gain per gram total AA intake: group effect, P<0.0001, mixture effect, P<0.0001, and no group x mixture interaction. Net protein gain per gram EAA intake: group effect, P=0.0005, mixture effect, P<0.0001, and no group x mixture interaction. Net protein gain per gram balanced EAA intake: group effect, P=0.0004, mixture effect, P<0.0001, and no group x mixture interaction. Net protein gain is expressed as the 3h postprandial area under the curve. EAA mixture significantly different from TAA mixture, ^****P<0.0001. TAA mixture: total amino acid mixture (balanced mixture of EAA and non-EAA). EAA mixture: essential amino acid mixture (balanced mixture of EAA and additional LEU). AA: amino acid. EAA: essential amino acid. PHE: phenylalanine. Net protein gain = protein synthesis – protein breakdown.