A prospective randomized crossover trial was conducted to determine the effect of a branched chain amino acid (BCAA)-enriched solution on whole body leucine kinetics and fractional rates of albumin synthesis in patients with intra-abdominal metastatic adenocarcinoma. Ten malnourished cancer patients were provided isonitrogenous amounts of both a conventional total parenteral nutrition (TPN) formula containing 19% BCAA and a BCAA-enriched TPN formula containing 50% of the amino acids as BCAA in a random order. Whole body protein turnover was determined by a 10 hour continuous infusion of leucine 14C. Increased whole body leucine flux (68 +/- 5 mumols/kg BW/hr versus 145 +/- 11; mean +/- SEM; P less than 0.001) and oxidation (13 +/- 2 mumols/kg BW/hr to 46 +/- 5; P less than 0.001) were determined on the BCAA-enriched TPN. Increased whole body protein synthesis (2.2 +/- 0.2 g protein/kg BW/day versus 3.9 +/- 0.3; P less than 0.005) and leucine balance (2.5 +/- 0.4 g leucine/d versus 6.5 +/- 0.6; P less than 0.001) were also observed in patients receiving the BCAA-enriched TPN solution. Leucine release from protein breakdown was not statistically elevated (1.65 +/- 0.18 g protein/kg BW/d versus 2.48 +/- 0.40; P greater than 0.05) but, incorporation of leucine 14C into plasma albumin was significantly elevated (2.37 +/- 0.23 mumols/g/hr to 4.21 +/- 0.33; P less than 0.001) when the patients received BCAA-enriched TPN. Despite the better leucine balance, the improvement in the 24-hour urinary nitrogen balance was not statistically significant (6.6 +/- 3.9 g protein/d versus 11.4 +/- 2.9; control versus BCAA-enriched; P = 0.15). BCAA-enriched formulas improve whole body leucine kinetics, fractional rates of albumin synthesis, and leucine balance, and thus may favorably influence protein metabolism in cancer cachexia.