Eicosapentaenoic Acid and Protein Modulation to Induce Anabolism in Chronic Obstructive Pulmonary Disease (COPD): Aim 2

Detailed Summary

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.

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