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

Metabolism. 2017 Apr;69:120-129. doi: 10.1016/j.metabol.2016.12.010. Epub 2016 Dec 20.


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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Amino Acids / blood
  • Amino Acids, Essential / therapeutic use*
  • Cross-Over Studies
  • Dietary Supplements*
  • Double-Blind Method
  • Female
  • Forced Expiratory Volume
  • Healthy Volunteers
  • Humans
  • Insulin / metabolism
  • Leucine / therapeutic use
  • Male
  • Middle Aged
  • Phenylalanine / metabolism
  • Protein Biosynthesis / drug effects*
  • Pulmonary Disease, Chronic Obstructive / metabolism*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Whey Proteins / metabolism


  • Amino Acids
  • Amino Acids, Essential
  • Insulin
  • Whey Proteins
  • Phenylalanine
  • Leucine