Nitrogen excretion in cancer cachexia and its modification by a high fat diet in mice

Animals transplanted with the MAC16 colon adenocarcinoma showed a loss of body weight as the tumor weight increased, without a reduction in food intake. Both adipose tissue and muscle mass decreased in tumor-bearing animals, although loss of body fat exceeded that of muscle mass for given tumor weight. Urinary nitrogen excretion was significantly elevated when the weight loss did not exceed 3 to 4 g, but above this weight loss there was a conservation of nitrogen and the excretion level fell to or below that found in non-tumor-bearing animals. The presence of a tumor alone was not sufficient to account for the elevated nitrogen excretion, since animals bearing a related colon adenocarcinoma (MAC13) that did not induce weight loss had a nitrogen excretion pattern similar to that of non-tumor-bearing controls. Feeding an isocaloric isonitrogenous diet in which 80% of the calories were supplied as medium chain triglycerides, which significantly elevated plasma levels of ketone bodies, reduced both tumor weight and host weight loss and restored both the nitrogen balance and urea excretion to that of non-tumor-bearing animals. The plasma levels of amino acids, which were reduced in the cachectic state, were also restored to control values in animals fed the medium chain triglyceride diet. These results suggest that excessive nitrogen catabolism in the cachectic state can be prevented by suitable dietary modification.