Loss of muscle protein is generally a central component of weight loss in Chronic Obstructive Pulmonary Disease (COPD) patients. 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. The investigators recently observed that in order to enhance protein anabolism, manipulation of the composition of proteins and amino acids in nutrition is required in normal-weight COPD. Intake of casein protein resulted into significant protein anabolism in these patients. The anabolic response to casein protein was even higher than after whey protein intake. A substantial number of COPD patients, underweight as well as normal weight to obese, is characterized by an increased inflammatory response. This group failed to respond to nutritional therapy. Previous experimental research and clinical studies in cachectic conditions (mostly malignancy) indicate that polyunsaturated fatty acids (PUFA) are able to attenuate protein degradation by improving the anabolic response to feeding and by decreasing the acute phase response. Eicosapentaenoic acid (EPA) (in combination with docosahexaenoic acid (DHA)) has been shown to effectively inhibit weight loss in several disease states, however weight and muscle mass gain was not present or minimal. Until now, limited research has been done examining muscle protein metabolism and the response to EPA and DHA supplementation in patients with COPD. It is the investigator's hypothesis that supplementation of 2g/day EPA+DHA in COPD patients during 4 consecutive weeks will increase the muscle anabolic response to a high quality protein supplement as compared to a placebo, and supplementation of 3.5g/day EPA+DHA will increase the anabolic response even further. In the present study both the acute and chronic effects of EPA+DHA versus a placebo on muscle and whole body protein metabolism will be examined. The principal endpoint will be the extent of stimulation of net fractional muscle protein synthesis as this is the principal mechanism by which the effect of EPA+DHA on muscle anabolism can be measured. The endpoint will be assessed by isotope methodology which is thought to be the reference method.
Specific aim 1: To test the hypothesis that supplementation of 3.5g EPA+DHA will increase the acute net fractional muscle protein synthesis more in COPD patients as compared to healthy controls in response to a high quality protein supplement. Specific aim 2: To test the hypothesis that 3.5g/day EPA+DHA for 4 consecutive weeks induces a higher increase in net fractional muscle protein synthesis in response to a high quality protein supplement as compared to 2g/day EPA+DHA in COPD patients. Therefore, to answer the specific aims in this study only the COPD subjects will undergo a 4-week intervention period.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
DOUBLE
Enrollment
64
Dose: 7.0 g/day (= 7 capsules/day).
Dose: 7.0 g/day (= 7 capsules/day = 3.5g EPA+DHA/day).
Dose: 7.0 g/day (= 4 capsules/day fish oil = 2.0g EPA+DHA/day and 3 capsules/day olive oil).
Texas A&M University
College Station, Texas, United States
Fractional muscle protein synthesis and breakdown rate (FSR and FBR) of mixed muscle protein (%/h) and net fractional muscle protein synthesis (nFSR = FSR - FBR)
On the study days the primary outcome measure is determined acutely before and after 4 hours of feeding and after intake of either the 3.5 g EPA+DHA, a placebo or 2.0 g EPA+DHA (last category only applicable to COPD group). After study day 1 COPD patients undergo a 4-week intervention period of daily EPA+DHA or placebo supplementation and on their return visit (2nd study day) the primary outcome measure is determined again.
Time frame: Acutely before and after 4 hours of feeding and the change after 4 weeks of EPA+DHA or placebo supplementation
Net whole body protein synthesis (whole body protein synthesis and breakdown rate)
On the study days the primary outcome measure is determined acutely before and after 4 hours of feeding and after intake of either the 3.5 g EPA+DHA, a placebo or 2.0 g EPA+DHA (last category only applicable to COPD group). After study day 1 COPD patients undergo a 4-week intervention period of daily EPA+DHA or placebo supplementation and on their return visit (2nd study day) the primary outcome measure is determined again.
Time frame: Acutely before and after 4 hours of feeding and the change after 4 weeks of EPA+DHA or placebo supplementation
Whole body myofibrillar protein breakdown rate
On the study days the primary outcome measure is determined acutely before and after 4 hours of feeding and after intake of either the 3.5 g EPA+DHA, a placebo or 2.0 g EPA+DHA (last category only applicable to COPD group). After study day 1 COPD patients undergo a 4-week intervention period of daily EPA+DHA or placebo supplementation and on their return visit (2nd study day) the primary outcome measure is determined again.
Time frame: Acutely before and after 4 hours of feeding and the change after 4 weeks of EPA+DHA or placebo supplementation
Glutathione turnover
On the study days the primary outcome measure is determined acutely before and after 4 hours of feeding and after intake of either the 3.5 g EPA+DHA, a placebo or 2.0 g EPA+DHA (last category only applicable to COPD group). After study day 1 COPD patients undergo a 4-week intervention period of daily EPA+DHA or placebo supplementation and on their return visit (2nd study day) the primary outcome measure is determined again.
Time frame: Acutely before and after 4 hours of feeding and the change after 4 weeks of EPA+DHA or placebo supplementation
Body composition
Body composition as measured by Dual-Energy X-ray Absorptiometry. Determined on study day 1 and after 4 weeks on study day 2 for COPD patients.
Time frame: On study day 1 and the change from study day 1 on study day 2
Skeletal and respiratory muscle strength and fatigue
Determined on study day 1 and after 4 weeks on study day 2 for COPD patients.
Time frame: On study day 1 and the change from study day 1 on study day 2
Inflammatory profile (CRP, IL6, IL1b, TNFα, IL8 and IL10)
Determined on study day 1 and after 4 weeks on study day 2 for COPD patients.
Time frame: On study day 1 and the change from study day 1 on study day 2
Other plasma products
Insulin, glucose, urea, cortisol, lactate, blood fatty acid profile (EPA, DHA, arachidonic acid, protectins and resolvins). Some of the parameters are measured on a single occasion and others are measured repeatedly during 10 hours on each study day (e.g. insulin and glucose). Determined on study day 1 and after 4 weeks on study day 2 for COPD patients.
Time frame: On study day 1 and the change from study day 1 on study day 2
Oxidative capacity
Oxidative capacity, including peroxisome proliferator-activated receptor (PPAR) and muscle fiber typing. Determined before and after 4 hours of feeding.
Time frame: On study day 1 and 2
Molecular markers (mTOR) of muscle wasting
Time frame: On study day 1 and the change from study day 1 on study day 2
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