Skip to main content
Thorax logoLink to Thorax
. 2005 May;60(5):376–382. doi: 10.1136/thx.2004.030858

Polyunsaturated fatty acids improve exercise capacity in chronic obstructive pulmonary disease

R Broekhuizen 1, E Wouters 1, E Creutzberg 1, C Weling-Scheepers 1, A Schols 1
PMCID: PMC1758900  PMID: 15860712

Abstract

Background: 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.

Methods: Eighty patients with COPD (57 men) with forced expiratory volume in 1 second (FEV1) 37.3 (13.8)% predicted received 9 g PUFA or placebo daily in a double blind randomised fashion during an 8 week rehabilitation programme. 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 tumour necrosis factor (TNF)-α) were assessed at baseline and after 8 weeks.

Results: 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 W (95% CI 2.5 to 17.0), p = 0.009) 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 = 0.023). The positive effects of PUFA could not be attributed to a decrease in systemic levels of CRP, IL-6 and TNF-α.

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

Full Text

The Full Text of this article is available as a PDF (145.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aguilaniu B., Flore P., Perrault H., Page J. E., Payan E., Lacour J. R. Exercise-induced hypoxaemia in master athletes: effects of a polyunsaturated fatty acid diet. Eur J Appl Physiol Occup Physiol. 1995;72(1-2):44–50. doi: 10.1007/BF00964113. [DOI] [PubMed] [Google Scholar]
  2. Agustí A., Morlá M., Sauleda J., Saus C., Busquets X. NF-kappaB activation and iNOS upregulation in skeletal muscle of patients with COPD and low body weight. Thorax. 2004 Jun;59(6):483–487. doi: 10.1136/thx.2003.017640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Asada Kazuhiro, Sasaki Shigekazu, Suda Takafumi, Chida Kingo, Nakamura Hirotoshi. Antiinflammatory roles of peroxisome proliferator-activated receptor gamma in human alveolar macrophages. Am J Respir Crit Care Med. 2003 Oct 16;169(2):195–200. doi: 10.1164/rccm.200207-740OC. [DOI] [PubMed] [Google Scholar]
  4. Baarends E. M., Schols A. M., Akkermans M. A., Wouters E. F. Decreased mechanical efficiency in clinically stable patients with COPD. Thorax. 1997 Nov;52(11):981–986. doi: 10.1136/thx.52.11.981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Baarends E. M., Schols A. M., Mostert R., Wouters E. F. Peak exercise response in relation to tissue depletion in patients with chronic obstructive pulmonary disease. Eur Respir J. 1997 Dec;10(12):2807–2813. doi: 10.1183/09031936.97.10122807. [DOI] [PubMed] [Google Scholar]
  6. Barber M. D., Ross J. A., Voss A. C., Tisdale M. J., Fearon K. C. The effect of an oral nutritional supplement enriched with fish oil on weight-loss in patients with pancreatic cancer. Br J Cancer. 1999 Sep;81(1):80–86. doi: 10.1038/sj.bjc.6690654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Black L. F., Hyatt R. E. Maximal respiratory pressures: normal values and relationship to age and sex. Am Rev Respir Dis. 1969 May;99(5):696–702. doi: 10.1164/arrd.1969.99.5.696. [DOI] [PubMed] [Google Scholar]
  8. Creutzberg E. C., Schols A. M., Weling-Scheepers C. A., Buurman W. A., Wouters E. F. Characterization of nonresponse to high caloric oral nutritional therapy in depleted patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2000 Mar;161(3 Pt 1):745–752. doi: 10.1164/ajrccm.161.3.9808075. [DOI] [PubMed] [Google Scholar]
  9. Creutzberg Eva C., Wouters Emiel F. M., Mostert Rob, Weling-Scheepers Clarie A. P. M., Schols Annemie M. W. J. Efficacy of nutritional supplementation therapy in depleted patients with chronic obstructive pulmonary disease. Nutrition. 2003 Feb;19(2):120–127. doi: 10.1016/s0899-9007(02)00841-9. [DOI] [PubMed] [Google Scholar]
  10. Di Francia M., Barbier D., Mege J. L., Orehek J. Tumor necrosis factor-alpha levels and weight loss in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1994 Nov;150(5 Pt 1):1453–1455. doi: 10.1164/ajrccm.150.5.7952575. [DOI] [PubMed] [Google Scholar]
  11. Engelen M. P., Schols A. M., Does J. D., Gosker H. R., Deutz N. E., Wouters E. F. Exercise-induced lactate increase in relation to muscle substrates in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2000 Nov;162(5):1697–1704. doi: 10.1164/ajrccm.162.5.9910066. [DOI] [PubMed] [Google Scholar]
  12. Fearon K. C. H., Von Meyenfeldt M. F., Moses A. G. W., Van Geenen R., Roy A., Gouma D. J., Giacosa A., Van Gossum A., Bauer J., Barber M. D. Effect of a protein and energy dense N-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial. Gut. 2003 Oct;52(10):1479–1486. doi: 10.1136/gut.52.10.1479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gautrin D., Newman-Taylor A. J., Nordman H., Malo J. L. Controversies in epidemiology of occupational asthma. Eur Respir J. 2003 Sep;22(3):551–559. doi: 10.1183/09031936.03.00047803. [DOI] [PubMed] [Google Scholar]
  14. Gosker H. R., van Mameren H., van Dijk P. J., Engelen M. P. K. J., van der Vusse G. J., Wouters E. F. M., Schols A. M. W. J. Skeletal muscle fibre-type shifting and metabolic profile in patients with chronic obstructive pulmonary disease. Eur Respir J. 2002 Apr;19(4):617–625. doi: 10.1183/09031936.02.00762001. [DOI] [PubMed] [Google Scholar]
  15. Gosker Harry R., Lencer Nicole H. M. K., Franssen Frits M. E., van der Vusse Ger J., Wouters Emiel F. M., Schols Annemie M. W. J. Striking similarities in systemic factors contributing to decreased exercise capacity in patients with severe chronic heart failure or COPD. Chest. 2003 May;123(5):1416–1424. doi: 10.1378/chest.123.5.1416. [DOI] [PubMed] [Google Scholar]
  16. Grimble Robert F., Howell W. Martin, O'Reilly Gillian, Turner Stephen J., Markovic Olivera, Hirrell Sharon, East J. Malcolm, Calder Philip C. The ability of fish oil to suppress tumor necrosis factor alpha production by peripheral blood mononuclear cells in healthy men is associated with polymorphisms in genes that influence tumor necrosis factor alpha production. Am J Clin Nutr. 2002 Aug;76(2):454–459. doi: 10.1093/ajcn/76.2.454. [DOI] [PubMed] [Google Scholar]
  17. Gulick T., Cresci S., Caira T., Moore D. D., Kelly D. P. The peroxisome proliferator-activated receptor regulates mitochondrial fatty acid oxidative enzyme gene expression. Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11012–11016. doi: 10.1073/pnas.91.23.11012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hamilton A. L., Killian K. J., Summers E., Jones N. L. Muscle strength, symptom intensity, and exercise capacity in patients with cardiorespiratory disorders. Am J Respir Crit Care Med. 1995 Dec;152(6 Pt 1):2021–2031. doi: 10.1164/ajrccm.152.6.8520771. [DOI] [PubMed] [Google Scholar]
  19. Jakobsson P., Jorfeldt L. Long-term oxygen therapy may improve skeletal muscle metabolism in advanced chronic obstructive pulmonary disease patients with chronic hypoxaemia. Respir Med. 1995 Aug;89(7):471–476. doi: 10.1016/0954-6111(95)90122-1. [DOI] [PubMed] [Google Scholar]
  20. Jones N. L., Summers E., Killian K. J. Influence of age and stature on exercise capacity during incremental cycle ergometry in men and women. Am Rev Respir Dis. 1989 Nov;140(5):1373–1380. doi: 10.1164/ajrccm/140.5.1373. [DOI] [PubMed] [Google Scholar]
  21. Keller H., Dreyer C., Medin J., Mahfoudi A., Ozato K., Wahli W. Fatty acids and retinoids control lipid metabolism through activation of peroxisome proliferator-activated receptor-retinoid X receptor heterodimers. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2160–2164. doi: 10.1073/pnas.90.6.2160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Komatsu Wataru, Ishihara Kenji, Murata Masakazu, Saito Hiroaki, Shinohara Kazuki. Docosahexaenoic acid suppresses nitric oxide production and inducible nitric oxide synthase expression in interferon-gamma plus lipopolysaccharide-stimulated murine macrophages by inhibiting the oxidative stress. Free Radic Biol Med. 2003 Apr 15;34(8):1006–1016. doi: 10.1016/s0891-5849(03)00027-3. [DOI] [PubMed] [Google Scholar]
  23. Maltais F., LeBlanc P., Simard C., Jobin J., Bérubé C., Bruneau J., Carrier L., Belleau R. Skeletal muscle adaptation to endurance training in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1996 Aug;154(2 Pt 1):442–447. doi: 10.1164/ajrccm.154.2.8756820. [DOI] [PubMed] [Google Scholar]
  24. Maltais F., LeBlanc P., Whittom F., Simard C., Marquis K., Bélanger M., Breton M. J., Jobin J. Oxidative enzyme activities of the vastus lateralis muscle and the functional status in patients with COPD. Thorax. 2000 Oct;55(10):848–853. doi: 10.1136/thorax.55.10.848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Maltais F., Simard A. A., Simard C., Jobin J., Desgagnés P., LeBlanc P. Oxidative capacity of the skeletal muscle and lactic acid kinetics during exercise in normal subjects and in patients with COPD. Am J Respir Crit Care Med. 1996 Jan;153(1):288–293. doi: 10.1164/ajrccm.153.1.8542131. [DOI] [PubMed] [Google Scholar]
  26. Martel Marie-Josée, Rey Evelyne, Beauchesne Marie-France, Perreault Sylvie, Lefebvre Geneviève, Forget Amélie, Blais Lucie. Use of inhaled corticosteroids during pregnancy and risk of pregnancy induced hypertension: nested case-control study. BMJ. 2005 Jan 19;330(7485):230–230. doi: 10.1136/bmj.38313.624352.8F. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Moses A. W. G., Slater C., Preston T., Barber M. D., Fearon K. C. H. Reduced total energy expenditure and physical activity in cachectic patients with pancreatic cancer can be modulated by an energy and protein dense oral supplement enriched with n-3 fatty acids. Br J Cancer. 2004 Mar 8;90(5):996–1002. doi: 10.1038/sj.bjc.6601620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ortega Francisco, Toral Javier, Cejudo Pilar, Villagomez Rafael, Sánchez Hildegard, Castillo José, Montemayor Teodoro. Comparison of effects of strength and endurance training in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2002 Sep 1;166(5):669–674. doi: 10.1164/rccm.2107081. [DOI] [PubMed] [Google Scholar]
  29. Sala E., Roca J., Marrades R. M., Alonso J., Gonzalez De Suso J. M., Moreno A., Barberá J. A., Nadal J., de Jover L., Rodriguez-Roisin R. Effects of endurance training on skeletal muscle bioenergetics in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999 Jun;159(6):1726–1734. doi: 10.1164/ajrccm.159.6.9804136. [DOI] [PubMed] [Google Scholar]
  30. Schols A. M., Soeters P. B., Mostert R., Pluymers R. J., Wouters E. F. Physiologic effects of nutritional support and anabolic steroids in patients with chronic obstructive pulmonary disease. A placebo-controlled randomized trial. Am J Respir Crit Care Med. 1995 Oct;152(4 Pt 1):1268–1274. doi: 10.1164/ajrccm.152.4.7551381. [DOI] [PubMed] [Google Scholar]
  31. Schoonjans K., Peinado-Onsurbe J., Lefebvre A. M., Heyman R. A., Briggs M., Deeb S., Staels B., Auwerx J. PPARalpha and PPARgamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. EMBO J. 1996 Oct 1;15(19):5336–5348. [PMC free article] [PubMed] [Google Scholar]
  32. Schoonjans K., Staels B., Auwerx J. The peroxisome proliferator activated receptors (PPARS) and their effects on lipid metabolism and adipocyte differentiation. Biochim Biophys Acta. 1996 Jul 26;1302(2):93–109. doi: 10.1016/0005-2760(96)00066-5. [DOI] [PubMed] [Google Scholar]
  33. Shahar E., Folsom A. R., Melnick S. L., Tockman M. S., Comstock G. W., Gennaro V., Higgins M. W., Sorlie P. D., Ko W. J., Szklo M. Dietary n-3 polyunsaturated fatty acids and smoking-related chronic obstructive pulmonary disease. Atherosclerosis Risk in Communities Study Investigators. N Engl J Med. 1994 Jul 28;331(4):228–233. doi: 10.1056/NEJM199407283310403. [DOI] [PubMed] [Google Scholar]
  34. Steiner M. C., Barton R. L., Singh S. J., Morgan M. D. L. Bedside methods versus dual energy X-ray absorptiometry for body composition measurement in COPD. Eur Respir J. 2002 Apr;19(4):626–631. doi: 10.1183/09031936.02.00279602. [DOI] [PubMed] [Google Scholar]
  35. Wigmore S. J., Fearon K. C., Maingay J. P., Ross J. A. Down-regulation of the acute-phase response in patients with pancreatic cancer cachexia receiving oral eicosapentaenoic acid is mediated via suppression of interleukin-6. Clin Sci (Lond) 1997 Feb;92(2):215–221. doi: 10.1042/cs0920215. [DOI] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES