Clinical trial NCT01418469: Disturbances in BCAA Metabolism and the Effects of Feeding and Exercise in COPD
Official title: The Effects of Exercise on the Metabolic Fate of Branched Chain Amino Acids in Relation to Aging and Chronic Disease.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: COPD
protein metabolism
branched-chain amino acid metabolism
exercise
protein feeding
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: European Dairy Association (EDA), Brussels
First posted: 2011-08-17
Enrollment: 24
Sex: MALE
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: Studies on resting human muscle show that ingestion of the branched-chain amino acids (BCAA): leucine, valine and isoleucine have an anabolic effect on muscle protein metabolism. However, the effects of BCAA intake on protein metabolism during exercise are less clear. When BCAA were supplied as single amino acids, without other amino acids and/or carbohydrates, no effects were observed on protein kinetics. On the other hand, ingestion of BCAA during running appeared to reduce the catabolic effect of running on muscle protein metabolism. These experiments were all performed with mixtures of the BCAA with or without carbohydrates but not in the form of complete meals with food protein as a basis. Therefore, it is still unknown whether a protein meal, containing a substantial amount of BCAA is beneficial during exercise by inducing an anabolic effect.

Whey and Casein protein contain a substantial amount of BCAA in contrast to Soy protein. Therefore, it is hypothesized that milk-based proteins are a better and more physiological source of BCAA during exercise and will lead to more protein anabolism. Most of the available studies have been carried out in young and fit humans but there are hardly any data are available in the increasing population of the elderly. Therefore it is still unknown whether a BCAA rich protein meal can enhance the anabolic effect of exercise in older individuals.

Besides sarcopenia, a substantial part of the elderly is suffering from a chronic systemic disease such as chronic obstructive pulmonary disease (COPD). COPD represents an important health care problem. COPD is the fourth leading cause of death and will be the third leading cause worldwide in 2020. Besides the local impairment, COPD is a chronic wasting disease, associated with alterations in intermediary metabolism. Substantial disturbances have been found in BCAA (and related) metabolism in these patients at rest and during exercise. It might therefore be of clinical relevance to study the metabolic effects of BCAA rich protein meals in patients with COPD at rest and during exercise.

Detailed description: In this study we investigate whether milk based protein sources of BCAA (casein and whey proteins) are superior to soy protein in the stimulation of protein anabolism before, during and after cycle exercise in COPD and healthy elderly and young subjects, and whether adding BCAA to soy protein will increase protein anabolism in these subjects.

To investigate Leucine, Isoleucine and Valine metabolism during and after exercise in COPD and healthy subjects

Eligibility criteria: Inclusion Criteria:

* Irreversible chronic airflow limitation (FEV1 \<70% of predicted)
* Clinically stable condition

Exclusion Criteria:

* Oxygen supplementation
* Respiratory tract infection or exacerbation of his disease at least 4 weeks prior to the study
* Oral corticosteroids as maintenance medication
* Other concomitant metabolic disease (ie malignancy, cardiac failure, recent surgery, severe endocrine, hepatic or renal disorder)

Primary outcomes:
measure: Change in Net whole body protein synthesis
timeFrame: 6 hours
Secondary outcomes:
measure: Change in whole body protein synthesis rate
timeFrame: 6 hours
measure: Change in Leucine turnover
timeFrame: 6 hours
measure: Change in Isoleucine turnover
timeFrame: 6 hours
measure: Change in Valine turnover
timeFrame: 6 hours
measure: Change in plasma lactate concentration
timeFrame: 6 hours
measure: Change in NH3 concentration
timeFrame: 6 hours
measure: Change in plasma amino acids concentrations
timeFrame: 6 hours
measure: Splanchnic extraction of amino acids during protein feeding
timeFrame: 6 hours
measure: Change in whole body protein breakdown rate
timeFrame: 6 hours
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht UMC
Study officials:
affiliation: University of Arkansas
name: Nicolaas EP Deutz, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Engelen MP, Rutten EP, De Castro CL, Wouters EF, Schols AM, Deutz NE. Supplementation of soy protein with branched-chain amino acids alters protein metabolism in healthy elderly and even more in patients with chronic obstructive pulmonary disease. Am J Clin Nutr. 2007 Feb;85(2):431-9. doi: 10.1093/ajcn/85.2.431.
citation: Engelen MP, Rutten EP, De Castro CL, Wouters EF, Schols AM, Deutz NE. Altered interorgan response to feeding in patients with chronic obstructive pulmonary disease. Am J Clin Nutr. 2005 Aug;82(2):366-72. doi: 10.1093/ajcn.82.2.366.
citation: Engelen MP, De Castro CL, Rutten EP, Wouters EF, Schols AM, Deutz NE. Enhanced anabolic response to milk protein sip feeding in elderly subjects with COPD is associated with a reduced splanchnic extraction of multiple amino acids. Clin Nutr. 2012 Oct;31(5):616-24. doi: 10.1016/j.clnu.2012.04.006. Epub 2012 Jun 6.
citation: Engelen MP, Rutten EP, De Castro CL, Wouters EF, Schols AM, Deutz NE. Casein protein results in higher prandial and exercise induced whole body protein anabolism than whey protein in chronic obstructive pulmonary disease. Metabolism. 2012 Sep;61(9):1289-300. doi: 10.1016/j.metabol.2012.03.001. Epub 2012 Apr 17.