Nutritional status in chronic obstructive pulmonary disease: role of hypoxia

Nutrition. 2011 Feb;27(2):138-43. doi: 10.1016/j.nut.2010.07.009. Epub 2010 Dec 9.


In patients with chronic obstructive pulmonary disease (COPD), malnutrition and limited physical activity are very common and contribute to disease prognosis, whereas a balance between caloric intake and exercise allows body weight stability and muscle mass preservation. The goal of this review is to analyze the implications of chronic hypoxia on three key elements involved in energy homeostasis and its role in COPD cachexia. The first one is energy intake. Body weight loss, often observed in patients with COPD, is related to lack of appetite. Inflammatory cytokines are known to be involved in anorexia and to be correlated to arterial partial pressure of oxygen. Recent studies in animals have investigated the role of hypoxia in peptides involved in food consumption such as leptin, ghrelin, and adenosine monophosphate activated protein kinase. The second element is muscle function, which is strongly related to energy use. In COPD, muscle atrophy and muscle fiber shift to the glycolytic type might be an adaptation to chronic hypoxia to preserve the muscle from oxidative stress. Muscle atrophy could be the result of a marked activation of the ubiquitin-proteasome pathway as found in muscle of patients with COPD. Hypoxia, via hypoxia inducible factor-1, is implicated in mitochondrial biogenesis and autophagy. Third, hormonal control of energy balance seems to be affected in patients with COPD. Insulin resistance has been described in this group of patients as well as a sort of "growth hormone resistance." Hypoxia, by hypoxia inducible factor-1, accelerates the degradation of tri-iodothyronine and thyroxine, decreasing cellular oxygen consumption, suggesting an adaptive mechanism rather than a primary cause of COPD cachexia. COPD rehabilitation aimed at maintaining function and quality of life needs to address body weight stabilization and, in particular, muscle mass preservation.

Publication types

  • Review

MeSH terms

  • Anorexia / etiology
  • Appetite
  • Cachexia / complications*
  • Cytokines / metabolism
  • Energy Intake*
  • Energy Metabolism
  • Exercise
  • Ghrelin / metabolism
  • Human Growth Hormone / metabolism
  • Humans
  • Hypoxia / complications*
  • Hypoxia-Inducible Factor 1 / metabolism
  • Leptin / metabolism
  • Malnutrition / complications*
  • Muscular Atrophy / etiology
  • Nutritional Status*
  • Oxygen / metabolism
  • Pulmonary Disease, Chronic Obstructive / complications*


  • Cytokines
  • Ghrelin
  • Hypoxia-Inducible Factor 1
  • Leptin
  • Human Growth Hormone
  • Oxygen