One of the major objections to the clinical use of mixtures of amino acids derived from hydrolysis of casein is the occurrence of nausea, vomiting, flushing, and headaches. These undesirable symptoms occur more frequently if the rate of administration is rapid. In a previous communication (1) it was shown that the elimination of many of these reactions could be accomplished by reducing the rate of infusion; it was further observed that mixtures of amino acids could be given at exceedingly rapid rates (100 ml. of a 10 per cent mixture per minute or the equivalent of 100 grams of protein could be given intravenously in less than three hours) without causing any discomfort to the patient.Earlier investigators (2,3,4) found that if amino acid preparations were given intravenously at a slow rate, usually less than 8 per cent of the administered amino acid nitrogen was lost by urinary spillage. Thus, it was desirous to learn whether the advantages gained by the rapid intravenous infusion of the well-tolerated amino acid mixtures might be offset by an increased urinary loss. This study was planned to compare the urinary amino acid nitrogen loss following the intravenous administration of amino acid mixtures at rapid rates with the loss which occurred following the intravenous injection of casein digests at rates approaching maximum tolerance. In addition, studies were designed to obtain comparable control data regarding the amount of amino acid nitrogen lost due to the "washing-out" effect following the injection of equal volumes of physiological saline.
METHODSMale patients with no detectable metabolic disorders were used as subjects for this study. All food was withheld after the previous evening meal until the four-hour study period of the following morning was completed. On the morning of the day of the study the patient emptied his bladder and the intravenous injection of the test solution was started; all voided urine was collected for the next four hours with the patient emptying his bladder at the end of the period. The same method for urine sample collection was used with each preparation studied. The interval between each test for a given patient varied from three to five days, thus providing a period for stabilization. By using a urine collection period of only four hours an important practical advantage was gained in that there was only a slight interference with the general hospital routine; the patient lost only one meal (breakfast) and was therefore more cooperative during the entire period of study.Three amino acid preparations were used: Preparation I 1, 2 consisted of a 10 per cent solution of an enzymatic hydrolysate of casein, Preparation II 3 was an acid hydrolysate of casein fortified with tryptophane, and Preparation V 4 was a "VUJN" type of mixture of amino acids prepared by the recombination and fortification of fractions of a casein hydrolysate. All amino acid solutions used were diluted with sterile water to provide a test dose which had a total nitrogen content of approximately 5.4 gms. per ...