EAA Intake to Optimize Protein Anabolism in COPD

Weight loss commonly occurs in patients with chronic obstructive pulmonary disease (COPD), negatively influencing their quality of life, treatment response and survival. Loss of muscle protein is generally a central component of weight loss in COPD patients. Attempts to reverse muscle loss in COPD by supplying large amounts of protein or calories to these patients have been unsuccessful. Gains in muscle mass are difficult to achieve in COPD unless specific metabolic abnormalities are targeted. The investigators recently observed that alterations in protein metabolism are present in normal weight COPD patients. Elevated levels of protein synthesis and breakdown rates were found in this COPD group indicating that alterations are already present before muscle wasting occurs. Furthermore, reduced plasma essential amino acid (EAA) levels were observed in COPD patients. These reduced EAA plasma levels were significantly related with the presence of muscle wasting in COPD. Until now, limited research has been done examining protein metabolism and the response to feeding in patients with COPD. Previous studies support the concept of essential amino acids (EAA) as an anabolic stimulus in the young and elderly and in insulin resistant states. Until yet no information is present on the anabolic effects of EAA in elderly COPD patients. It is therefore our hypothesis that a high-leucine essential amino acids mixture specifically designed to stimulate protein anabolism will target the metabolic alterations of COPD patients. In the present study, the acute effects of an EAA nutritional supplement on whole body, muscle and liver protein metabolism will be examined in COPD patients and compared to a supplement consisting of a balanced mixture of total amino acids. The principal endpoints will be the extent of stimulation of whole body protein synthesis as this is the principal mechanism by which either amino acid or protein intake causes muscle anabolism, and the reduction in endogenous protein breakdown. Both endpoints will be assessed by isotope methodology which is thought to be the reference method.

In this study the investigators will test the following hypothesis: A high-leucine essential amino acid mixture (dose of 7.0 g EAA + 15 g carbohydrates) will stimulate protein anabolism to a greater extent than a standard balanced mixture of total (essential and non-essential) amino acids (dose of 6.7 g total AA + 15 g carbohydrates) in COPD patients. The principal endpoints will be the extent of stimulation of protein synthesis rate and the reduction in endogenous protein breakdown. The current project will provide information that will enable us to better understand the underlying metabolic mechanisms that regulate protein metabolism in patients with COPD.

7 g free amino acids provided as a one time bolus, including 15 g carbohydrates. As part of the total amount of essential amino acids 24% is leucine.

7 g free essential amino acids provided as a one time bolus, including 15 g carbohydrates. As part of the total amount of essential amino acids 40% is leucine.

Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement

Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement

Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement

Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement

Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement

Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement

Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement

Acute change from postabsorptive state after intake of essential amino acid + LEU vs total amino acid supplement

Inclusion Criteria: Diagnosis of chronic airflow limitation, defined as measured forced expiratory volume in one second (FEV1) less than 70% of reference FEV1 Shortness of breath on exertion Age 45 years and older Clinically stable condition and not suffering from respiratory tract infection or exacerbation of their disease (defined as a combination of increased cough, sputum purulence, shortness of breath, systemic symptoms such as fever, and a decrease in FEV1 > 10% compared with values when clinically stable in the preceding year) at least 4 weeks prior to the study Ability to lie in supine position for 6 hours Exclusion Criteria: Established diagnosis of malignancy Presence of fever within the last 3 days Established diagnosis of Diabetes Mellitus Untreated metabolic diseases including hepatic or renal disorder Presence of acute illness or metabolically unstable chronic illness Recent myocardial infarction (less than 1 year) Use of long-term oral corticosteroids or short course of oral corticosteroids in the preceding month before enrollment Any other condition according to the PI or study physicians would interfere with proper conduct of the study / safety of the patient Failure to give informed consent

Jonker R, Deutz NE, Erbland ML, Anderson PJ, Engelen MP. Alterations in whole-body arginine metabolism in chronic obstructive pulmonary disease. Am J Clin Nutr. 2016 Jun;103(6):1458-64. doi: 10.3945/ajcn.115.125187. Epub 2016 May 4.