Effects of Low Dose of Fish Oil (EPA+DHA) vs. Combined EPA+DHA and HMB Supplementation on Protein Metabolism, Muscle Mass and Functional Capacity in Moderate to Severe COPD

Weight loss commonly occurs in patients with Chronic Obstructive Pulmonary Disease (COPD), negatively influencing their quality of life, treatment response and survival. Furthermore, limb muscle dysfunction (weakness and/or enhanced fatigue) is a major systemic comorbidity in patients with Chronic Obstructive Pulmonary Disease (COPD), negatively affecting their exercise performance, physical activity, quality of life, and mortality. As nutritional abnormalities are main contributors to muscle loss and dysfunction in COPD, nutritional support is viewed as an essential component of integrated care in these patients.

Although nutritional support is effective in the treatment of weight loss in COPD, attempts to increase muscle mass and function in COPD by supplying large amounts of protein or calories to these patients have been small. This suggests that gains in muscle mass and function are difficult to achieve in COPD unless specific metabolic abnormalities are targeted. The investigators and other researchers found that low muscle mass in COPD was strongly associated with elevated whole body protein turnover and increased myofibrillar protein breakdown rates indicative of muscle contractile protein loss. The investigators have extended this finding recently to normal weight COPD patients characterized by muscle weakness using a more precise and accurate pulse method of tau-methylhistidine tracer.

A substantial number of COPD patients, underweight as well as normal weight to obese, are characterized by an increased inflammatory response as evidenced by elevated levels of the pro-inflammatory cytokines (Tumor Necrosis Factor (TNF)-α, Interleukin (IL) 6 and 8, and the soluble TNF-α receptors (55 and 75). Furthermore, CRP levels are elevated in COPD and associated with reduced quadriceps strength, lower maximal and submaximal exercise capacity and increased morbidity.

One of the few agents capable to suppress the generation of pro-inflammatory cytokines are eicosapentanoic acid (EPA) and docosahexanoic acid (DHA), primary ω-3 fatty acids found in fish oils.

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 weight and muscle mass and function increase was not present or minimal. Also in healthy older adults, fish oil can slow the decline in muscle mass and function. A randomized clinical trial in COPD patients showed that extra nutritional supplementation with PUFAs daily of 1000 mg EPA+DHA as adjunct to exercise training during 8 weeks enhanced exercise capacity but did not lead to muscle mass gain. The patients who did not respond adequately (< 2% gain in weight), had a higher TNF-α level than those who did gain sufficient weight, which is in line with previous data in COPD showing an association between an increased systemic inflammation with non-response to nutritional therapy.