Objective: Patients with cancer are characterized by decreased muscle protein synthesis and glutamine availability that contribute to an impaired immune response. These abnormalities worsen after surgical stress. We tested the hypothesis that pharmacologic doses of branched-chain amino acids would improve the early metabolic response after major cancer surgery.
Methods: By using a crossover experimental design, we compared the metabolic effects of isonitrogenous solutions of balanced and branched-chain-enriched amino acid mixtures infused at the rate of 82 mg x h(-1) x kg(-1) for 3 h in patients with colorectal or cervical cancer on the first and second days after radical surgery combined with intraoperative radiation therapy. The ratios of leucine to total amino acid (grams) in the two mixtures were 0.09 and 0.22, respectively. Muscle protein and glutamine kinetics were determined by using stable isotope of amino acids and the leg arteriovenous balance technique. Glucose and insulin were continuously infused throughout the 2-d study to maintain near euglycemia.
Results: Rates of muscle protein synthesis and degradation were not significantly affected by the balanced amino acid infusion. In contrast, the isonitrogenous, branched-chain-enriched amino acid mixture accelerated muscle protein turnover by stimulating (P <or= 0.05) protein synthesis. The rate of muscle glutamine de novo synthesis did not significantly change after infusion of the balanced amino acid mixture but increased (P <or= 0.05) by 263 +/- 69% during infusion of the branched-chain-enriched amino acid mixture.
Conclusions: An excess of branched-chain amino acids in the presence of an optimal profile of other essential amino acids acutely increased muscle protein synthesis and glutamine flux from skeletal muscle in cancer patients after surgery.