SUPPLEMENTAL NUTRITION WITH ORNITHINE ALPHA-KETOGLUTARATE IN RATS WITH CANCER-ASSOCIATED CACHEXIA - SURGICAL-TREATMENT OF THE TUMOR IMPROVES EFFICACY OF NUTRITIONAL SUPPORT

We investigated the use of ornithine alpha-ketoglutarate in treatment of rats bearing Morris hepatoma 7777. Rats received diets containing e ither ornithine alpha-ketoglutarate, which has been used in other cata bolic states (i.e., injury, sepsis), or an isonitrogenous, isocaloric diet containing glycine. Untreated tumors grew to a mass of 11 g/100 g body weight over the 3-wk period after implantation and induced progr essive anorexia, negative nitrogen balance, and body and tissue wastin g. Compared with glycine, ornithine alpha-ketoglutarate had no effect on tumor growth, but also did not alter the catabolic effects of the t umor on its host. We hypothesized that capture of amino acids by the t umor limited the efficacy of supplemental nutrition here and in publis hed reports in which tumor burden comprised 4-30% of body weight. This is supported by our observation that at 3 wk of implantation the rate of protein deposition plus amino acid oxidation by the tumor was equi valent to similar to 70% of the host's daily protein intake. To parall el the clinical situation in which tumor burden is small at diagnosis and initiation of treatment, the same diets were tested in rats treate d by excision of the tumor at a limited stage of the disease. Rats rec eived 3 d preoperative nutrition with ornithine alpha-ketoglutarate or glycine, and continued on the same diets for 3 or 6 d postoperatively . Compared with glycine-fed rats, ornithine alpha-ketoglutarate-fed ra ts showed a more positive nitrogen balance, higher concentrations of g lutamine and branched-chain amino acids in muscle, and accelerated pro tein deposition in small intestine (P < 0.05). Our results explain the lack of success of nutritional support in untreated cancer and underl ine the need for clinically relevant animal models for further studies .