ω-3 PUFAs and Cachexia

Abstract

Patients with cancer, especially of the lung and gastrointestinal tract, exhibit a wasting syndrome called cachexia, in which there is extensive loss of both adipose tissue and skeletal muscle mass, leading to weakness and death. Although anorexia is invariably present, nutritional supplementation is unable to reverse the changes in body composition, especially the loss of lean body mass. ω-3 polyunsaturated fatty acids (PUFAs), in particular eicosapentaenoic acid (EPA), have been shown to attenuate the development of cachexia in murine models with retention of both fat and muscle protein. EPA has been shown to attenuate both the action and production of a lipolytic factor, zinc-α2-glycoprotein (ZAG), involved in loss of adipose tissue in cachexia. EPA preserves skeletal muscle in cachexia by attenuating the increased protein degradation, although it has no effect on the depression of protein synthesis. The effect on protein degradation is due to downregulation of the increased expression and activity of the ubiquitin-proteasome proteolytic pathway by preventing nuclear binding of the transcription factor nuclear factor-κB (NF-κB). Clinical studies confirm the ability of EPA to attenuate weight loss in cachectic cancer patients with resulting weight stabilisation. However, when used in combination with a high calorie, high protein nutritional supplement weight gain was seen, although there have been problems with compliance in large-scale placebo-controlled trials. Further clinical studies are warranted to confirm activity and whether it is equally effective in the treatment of cachexia in different cancer types.