1. Broekhuizen, R
  2. Wouters, E F
  3. Creutzberg, E C
  4. Weling-Scheepers, C A
  5. Schols, A M

Article Content

Thorax. 2005;60(5):376-382.



Muscle wasting and decreased muscle oxidative capacity commonly occur in patients with chronic obstructive pulmonary disease (COPD). Polyunsaturated fatty acids (PUFA) have been shown to mediate several inflammatory and metabolic pathways which may be involved in the pathogenesis of muscle impairment in COPD. The aim of this study was to investigate the effect of PUFA modulation on systemic inflammation, reversal of muscle wasting, and functional status in COPD.



Eighty patients with COPD (57 men) with forced expiratory volume in 1 second (FEV(1)) 37.3 (13.8)% predicted received 9-g PUFA or placebo daily in a double-blind randomized fashion during an 8-week rehabilitation program. Body composition (bioelectrical impedance), functional capacity (lung function, incremental cycle ergometry test, submaximal cycle test, isokinetic quadriceps strength) and inflammatory markers (C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha) were assessed at baseline and after 8 weeks.



Both groups had similar increases in weight, fat-free mass (FFM), and muscle strength. The peak load of the incremental exercise test increased more in the PUFA group than in the placebo group (difference in increase 9.7 watts (95% CI, 2.5 to 17.0), P = .009) even after adjustment for FFM. The duration of the constant work rate test also increased more in patients receiving PUFA (difference in increase 4.3 min (95% CI, 0.6 to 7.9), P = .023). The positive effects of PUFA could not be attributed to a decrease in systemic levels of CRP, IL-6, and TNF-alpha.



This is the first study to show beneficial effects of PUFA on exercise capacity in patients with COPD.



Skeletal muscle dysfunction is an important cause of exercise limitation and functional impairment for many patients with COPD. This muscle dysfunction is believed to result from several factors, including aging, deconditioning and disuse, nutritional impairment, and systemic inflammation. Skeletal muscle dysfunction in individual persons likely results from various combinations of these, as well as other factors. Recognition of the multifactorial basis of skeletal muscle dysfunction in COPD has led to significant research focused on intervention strategies designed to improve muscle function and/or ways to enhance the benefits of exercise training and pulmonary rehabilitation. For example, several investigators have assessed the role of nutritional or anabolic hormone supplementation for patients with COPD, with variable clinical results.


In the present study, Broekhuizen and colleagues have demonstrated that supplementation of patients with severe COPD with polyunsaturated fatty acids (PUFA) during 8 weeks of exercise rehabilitation led to greater improvements in peak exercise workload and constant work load exercise duration following training than did placebo. The benefits of PUFA administration were present despite the fact that both groups of patients had comparable changes in weight, fat-free mass, and muscle strength following training. This is an interesting study, because PUFA may mediate some of the processes involved in the pathogenesis of skeletal muscle dysfunction in COPD, and therefore PUFA supplementation may improve muscle function. The mechanisms by which the PUFA supplementation improved exercise capacity were, however, unclear in this study. Of note, there was no difference noted between treatment groups in the inflammatory markers C-reactive protein, interleukin-6, or tumor necrosis factor. Further studies will be necessary to clarify the mechanisms by which PUFA may improve the exercise tolerance of patients with COPD. However, if confirmed in subsequent studies, PUFA repletion may prove more beneficial than general nutritional supplementation as a method to optimize benefits of exercise training achieved in rehabilitation programs.-CR