Our foregoing investigations have demonstrated that infusion of isotonic amino acid solutions (A3W) containing no dextrose are much more effective in preserving the Body Cell Mass of hospitalized patients than routine therapy with isotonic dextrose (D5W). The effectiveness of this therapy is surprising in view of established concepts on the regulation of protein metabolism, but it can be explained by recognizing the importance of rapid fat mobilization of endogenous stores, including the development of starvation ketosis, during periods of negative caloric balance and disease. We have developed a model describing the interplay between different substrates and the metabolic leverage of different nutrients in the overall regulation of energy and protein metabolism. This model accounts for hitherto unexplainable metabolic behaviors and suggests new hypotheses which will be investigated in experimental animals. In general, this concept of metabolic regulation has major and novel implications for the design of intravenous and oral nutritional therapy. The immediate goals of the project are: to further develop protein sparing therapy with A3W; to design improved amino acid compositions for this therapy; to compare the value of this therapy against routine therapy with D5W, particularly with respect to their effects on protein synthesis in the viscera, cellular immune response and water distribution in the body; and to evaluate the possibly unfavorable effects of treatment with D5W in leading to a state of "visceral attrition". In addition, the usefulness of "Cyclic hyperalimentation" will be evaluated. This is a modified form of total parenteral nutrition (TPN) in which amino acids are provided continuously but concentrated dextrose during part of the day only, so as to reduce the risk of fat accumulation in the liver during TPN.