Proinflammatory cytokines, nutritional support, and the cachexia syndrome

We enjoyed the article by Moldawer and Copeland1 describing the problems with nutritional support in cachectic patients and the role of proinflammatory cytokines in promoting many of the metabolic abnormalities observed in these patients. However, we were somewhat concerned to see omega-3 fatty acids described merely as a nonprotein calorie source. We have been investigating the omega-3 fatty acid eicosapentaenoic acid (EPA) in cachectic patients with advanced pancreatic carcinoma. In a study of 18 such patients given 12 g/day of the fish oil preparation MaxEPA (Seven Seas, Hull, UK) (equivalent to 2.2 g/day EPA), we were able to show a significant attenuation of cachexia.2 Before administration of MaxEPA, study patients were losing a median of 2.9 kg/month. After 1 month patients had no median weight change. At 3 months, patients had a median weight gain of 0.2 kg/month. We recently were able to confirm this effect in a study of 27 additional cachectic pancreatic carcinoma patients given 6 g/day high purity EPA.3 Patients had a prestudy weight loss of 2.0 kg/month. At 1 month, patients had a median weight gain of 0.75 kg and at 3 months patients showed a median weight gain of 0.25 kg/month. Further investigation of such patients who received high purity EPA revealed a significant decrease in serum C-reactive protein levels and peripheral blood mononuclear cell interleukin-6 production after 1 month.4 There were minimal side effects in these studies. Although randomized trials are required, EPA would appear to be a well tolerated anticachectic agent. EPA appears to act at least in part by down-regulating proinflammatory cytokine release and the acute phase protein response. Alternatively, EPA has been shown to have inhibitory effects on the growth of human pancreatic carcinoma cells in vitro5 and also will slow the growth of experimental tumors in mice.6 We recently characterized a proteolytic factor associated with weight loss in cancer patients7 and it appears that EPA also inhibits the end-organ effects of this factor.8 We would agree with Moldawer and Copeland that anticytokine therapy has substantial potential in patients with cachexia and would suggest that EPA represents such an agent. Matthew D. Barber FRCS*, Stephen J. Wigmore FRCS*, James A. Ross Ph.D.*, Kenneth C. H. Fearon FRCS*, Michael J. Tisdale Ph.D.