Nutritional aspects of cancer

Abstract

Various aspects of the complex metabolic syndrome known as cancer cachexia were studied. The MAC 16 adenocarcinoma of the colon passaged in NMR I mice was found to be a suitable model for the study of cachexia, since it produces a significant weight loss when tumour mass is less than 1% of host body weight without a reduction in food intake. The effect of the presence of the MAC 16 adenocarcinoma on blood metabolite levels and body composition were also studied. Both the fat and the non-fat mass were reduced in tumour-bearing animals, but despite the loss of adipose tissue there was no evidence of ketosisas might be expected in simple starvation. Both blood glucose and plasma insulin levels were reduced. The ability of the MAC 16 tumour and other non-involved tissues from NMR I mice to use ketone bodies as an energy source was assessed by measuring levels of the three enzymes required for ketone body utilisation. Low levels of activity of 3-oxo acid-CoA transferase were found in the MAC 16 tumour suggesting that the capacity of the tumour to use ketone bodies as an energy source may be limited.An attempt was made to reverse cachexia by selectively depriving the tumour of metabolic substrates for energy production by feeding aketogenic regime, since ketone bodies are thought to maintain homeostasis during starvation. Diets with up to 80% of the energy supplied from medium chain triglycerides, with or without the inclusion of arginine 3-hydroxybutyrate, were fed to NMR I mice. There was a reduction of both host weight loss and tumour size by increasing the lipid contribution of the diet. Under the normal dietary regime the MAC 16 tumour is poorly vascularised and centrally necrotic. After treatment with the ketogenic diets the areas of necrosis were greatly reduced and the degree of vascularisation increased, changes which may make the tumour more vulnerable to chemotherapy and radiotherapy.