gamma-linolenic-acid and Cachexia

Topics: Cachexia; gamma-Linolenic Acid; Humans; Pancreatic Neoplasms; T-Lymphocytes; Tumor Necrosis Factor-alpha

Cachexia is common in patients with pancreatic cancer and has been associated with persistent activation of the hepatic acute phase response and increased energy expenditure. Fatty acids have been shown to have anticachectic effects in animal models and to reduce inflammatory mediators in healthy subjects and patients with chronic inflammatory disease. Eighteen patients with unresectable pancreatic cancer received dietary supplementation orally with fish oil capsules (1 g each) containing eicosapentaenoic acid 18% and docosahexaenoic acid 12%. Anthropometric measurement, body composition analysis, and measurement of resting energy expenditure and serum C-reactive protein were performed before and after supplementation with a median of 12 g/day of fish oil. Patients had a median weight loss of 2.9 kg/month (IQR 2-4.6) prior to supplementation. At a median of 3 months after commencement of fish oil supplementation, patients had a median weight gain of 0.3 kg/month (IQR 0-0.5) (p < 0.002). Changes in weight were accompanied by a temporary but significant reduction in acute phase protein production (p < 0.002) and by stabilisation of resting energy expenditure. This study suggests a component fish oil, perhaps EPA, merits further investigation in the treatment of cancer cachexia.

Topics: Acute-Phase Proteins; Cachexia; Dietary Fats, Unsaturated; Eicosapentaenoic Acid; Energy Metabolism; Fish Oils; gamma-Linolenic Acid; Humans; Pancreatic Neoplasms; Weight Gain

The effect of the polyunsaturated fatty acids eicosapentaenoic acid (EPA) and gamma-linolenic acid (GLA) on host body weight loss and tumor growth has been investigated in mice bearing a cachexia-inducing colon adenocarcinoma, the MAC16. EPA effectively inhibited both host weight loss and tumor growth rate in a dose-related manner with optimal effects being observed at a dose level of 1.25 to 2.5 g/kg. At these concentrations host body weight was effectively maintained, and there was a delay in the progression of growth of the tumor, such that overall survival was approximately doubled in EPA-treated animals, using the criteria dictated by the United Kingdom Coordinating Committee for the welfare of animals with neoplasms. Even when tumor growth resumed, weight loss did not occur. Animals bearing the MAC16 tumor showed a decreased protein synthesis and an increased degradation in skeletal muscle. Treatment with EPA significantly reduced protein degradation without an effect on protein synthesis. The effect of GLA on both host body weight loss and tumor growth was much less pronounced than that of EPA, with an effect only being seen at a dose of 5 g/kg, at which some toxicity was observed. In vitro studies showed that while EPA was effective in inhibiting tumor-induced lipolysis, GLA was ineffective in this respect. However, prostaglandin E1, which is formed from GLA in vivo, showed partial reversal of tumor-induced lipolysis and probably accounted for the anticachectic effect of GLA. These results suggest that EPA as the pure fatty acid should be considered for clinical investigation as both an anticachectic and antitumor agent, since prior work has shown that the other major component of fish oil docosahexaenoic acid is without pharmacological activity in this system.

Topics: Animals; Antineoplastic Agents; Cachexia; Eicosapentaenoic Acid; Female; gamma-Linolenic Acid; Linolenic Acids; Lipolysis; Mice; Muscles; Neoplasms, Experimental; Proteins