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Branched-Chain Amino Acids: Metabolism, Physiological Function, and Application: Session IV

Branched-Chain Amino Acid-Enriched Nutritional Support in Surgical and Cancer Patients^1,2

Department of Surgery, The Pennsylvania State University, College of Medicine, The Milton S. Hershey Medical Center, Hershey, PA

³ To whom correspondence should be addressed. E-mail: wsouba{at}psu.edu.

ABSTRACT

Prolonged surgical stress and advanced malignant disease lead to systemic catabolism characterized by depletion of muscle protein and oxidation of skeletal muscle BCAA. BCAA oxidation provides energy for muscle and other organs and is the precursor for amino acid synthesis to replenish alanine and glutamine depleted in catabolic states. Persistent excessive catabolism leads to skeletal muscle wasting, negative nitrogen balance, and immune compromise. BCAAs, especially leucine, stimulate protein synthesis, inhibit proteolysis (in cell culture models and in animals), and promote glutamine synthesis. A number of small and diverse clinical trials studied the effects of BCAA-enriched nutritional support in moderately to severely stressed surgical and cancer patients. The findings of these clinical trials have been inconsistent; some show improved nitrogen balance, increased skeletal muscle protein synthesis, and reduced skeletal muscle catabolism whereas others show no significant improvement. The value of these trials is compromised by small sample size, heterogeneous patients, poor study design, varying degrees of metabolic stress, and inappropriate endpoints. More recent trials that evaluate clinical outcomes in hepatocellular carcinoma patients show promising results; in addition to improving metabolic parameters, BCAA-enriched oral supplementation improved morbidity and quality of life in patients undergoing major liver resection and chemo-embolization. In summary, the role of BCAAs in the nutritional support of stressed surgical and cancer patients remains to be clearly defined, despite their potential beneficial biological properties.

KEY WORDS: • branched-chain amino acids • total parenteral nutrition • TPN • enteral nutrition • catabolism • cancer • surgical stress

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