Disturbances in BCAA Metabolism and the Effects of Feeding and Exercise in COPD

The Effects of Exercise on the Metabolic Fate of Branched Chain Amino Acids in Relation to Aging and Chronic Disease.

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.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Dietary supplement: Caseinate; Dietary supplement: Whey protein isolate; Dietary supplement: Soy; Dietary supplement: soy+BCAA

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

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Maastricht, Netherlands
    • Maastricht UMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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)

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Caseinate protein intake; 18 mg protein/kg body weight caseinate and 46 mg maltodextrin / kg body weight per 20 min sip feeding	Dietary supplement: Caseinate; 18 mg protein/kg body weight caseinate and 46 mg maltodextrin / kg body weight per 20 min sip feeding; Other Names: casein
EXPERIMENTAL: Whey protein isolate intake; 18 mg protein/kg body weight whey protein isolate and 46 mg maltodextrin / kg body weight per 20 min sip feeding	Dietary supplement: Whey protein isolate; 18 mg protein/kg body weight whey protein isolate and 46 mg maltodextrin / kg body weight per 20 min sip feeding; Other Names: Whey
EXPERIMENTAL: Soy protein intake; 18 mg protein/kg body weight soy and 46 mg maltodextrin / kg body weight per 20 min sip feeding	Dietary supplement: Soy; 18 mg protein/kg body weight soy and 46 mg maltodextrin / kg body weight per 20 min sip feeding
EXPERIMENTAL: soy+BCAA protein intake; 18 mg protein/kg body weight soy+BCAA and 46 mg maltodextrin / kg body weight per 20 min sip feeding	Dietary supplement: soy+BCAA; 18 mg protein/kg body weight soy+BCAA and 46 mg maltodextrin / kg body weight per 20 min sip feeding

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Net whole body protein synthesis	Net whole body protein synthesis during protein feeding and the response to a 20 min cycle exercise bout	6 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in whole body protein synthesis rate	Whole body protein synthesis rate during protein feeding and the response to 20 min cycle exercise bout	6 hours
Change in Leucine turnover	Leucine turnover during protein feeding and the response to a 20 min cycle exercise bout	6 hours
Change in Isoleucine turnover	Isoleucine turnover during protein feeding and the response to a 20 min cycle exercise bout	6 hours
Change in Valine turnover	Valine turnover during protein feeding and the response to a 20 min cycle exercise bout	6 hours
Change in plasma lactate concentration	Plasma lactate during protein feeding and the response to a 20 min cycle exercise bout	6 hours
Change in NH3 concentration	Plasma NH3 during protein feeding and the response to a 20 min cycle exercise bout	6 hours
Change in plasma amino acids concentrations	Plasma amino acid concentrations during protein feeding and the response to a 20 min cycle exercise bout	6 hours
Splanchnic extraction of amino acids during protein feeding	Splanchnic extraction of amino acids during protein feeding and the response to a 20 min cycle exercise bout	6 hours
Change in whole body protein breakdown rate	Whole body protein breakdown rate during protein feeding and the response to cycle exercise	6 hours

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Collaborators: European Dairy Association (EDA), Brussels

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2002
• Primary Completion (ACTUAL): December 1, 2003
• Study Completion (ACTUAL): December 1, 2004

Study Registration Dates

• First Submitted: August 9, 2011
• First Submitted That Met QC Criteria: August 16, 2011
• First Posted (ESTIMATE): August 17, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): August 17, 2011
• Last Update Submitted That Met QC Criteria: August 16, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: exercise; COPD; protein metabolism; branched-chain amino acid metabolism; protein feeding
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: MEC 02-059.3