Toxicity and blood ammonia rise resulting from intravenous amino acid administration in man: the protective effect of l-arginine.

A study of amino acid toxicity was undertaken following the observation that a mixture of intravenously administered L-amino acids that had been nutritionally adequate in a patient became toxic when L-arginine was deleted. This toxicity was unexpected for the amino acid mixture, even without arginine, contained all of the amino acids determined by Rose (1) to be essential to man. Readdition of L-arginine, however, prevented the toxicity. Subsequent studies by Guillino, Winitz, Birnbaum, Otey, Cornfield, and Greenstein suggested that the toxicity of arginine deficient L-amino acid mixtures might be attributable to a blood ammonia rise (2, 3). Investigation of the arginine-deficient amino acid mixture in dogs (4) demonstrated a marked blood ammonia rise on intravenous administration and indicated that the toxic manifestations, convulsion and death were attributable to ammonia formation. L-arginine administration prevented the blood ammonia rise and toxicity. The present studies were undertaken to demonstrate in man the blood ammonia rise that can develop from intravenous administration of an L-amino acid mixture deficient in arginine, and to confirm the capacity of L-arginine to significantly reduce the blood ammonia changes produced by this mixture. Glycine was also used to produce an elevation of blood ammonia, and the role of L-arginine in preventing this rise was investigated.