Safety and Metabolic Effects of L‐Glutamine Administration in Humans

Abstract

A series of dose-response studies was conducted to evaluate the clinical safety, pharmacokinetics, and metabolic effects of L-glutamine administered to humans. Initial studies in normal individuals evaluated the short-term response to oral loads of glutamine at doses of 0, 0.1, and 0.3 g/kg. A dose-related increase in blood glutamine occurred after oral loading and elevation of amino acids known to be end products of glutamine metabolism occurred (including alanine, citrulline, and arginine). No evidence of clinical toxicity or generation of toxic metabolites (ammonia and glutamate) was observed. Glutamine was infused intravenously in normal subjects over 4 hr at doses of 0.0125 and 0.025 g/kg/hr. In addition, glutamine was evaluated as a component of parenteral nutrition solutions (0.285 and 0.570 g/kg/day) administered for 5 days to normal subjects. Intravenous administration of glutamine was well tolerated without untoward clinical or biochemical effects. Subsequent studies in patients receiving glutamine-enriched parenteral nutrition for several weeks confirmed the clinical safety of this approach in a catabolic patient population. In addition, nitrogen retention appeared to be enhanced when glutamine was administered at a dose of 0.570 g/kg/day in a balanced nutritional solution providing adequate calories (145% of basal) and protein (1.5 g/kg/day). Nitrogen balance in patients receiving lower doses of glutamine (0.285 g/kg/day) was similar to that in patients receiving standard formulations. Further controlled clinical trials of the metabolic efficacy, tolerance, and dose response of glutamine in other patient groups are necessary to determine the appropriate use of glutamine enrichment of nutrient solutions.

Oral glutamine in paediatric oncology patients: a dose finding study

“…The glutamine was well tolerated at the 0.35, 0.5 and the 0.65 g=kg with the plasma glutamine and ammonia comparing favourably with other studies of the safety and metabolic effects of glutamine (Ziegler et al, 1990(Ziegler et al, , 1992. The subject who received the highest dose of 0.75 g=kg found the consistency unacceptable and he vomited at the time of the peak ammonia level.…”

“…This was prolonged compared with other studies of lower-dose glutamine in which the plasma glutamine level generally peaked at 30 -45 min post administration of the oral test Oral glutamine dose E Ward et al dose and then declined steadily to normal range within 90 -120 min (Ziegler et al, 1990). The peak level of ammonia was also much higher than previously seen (Ziegler et al, 1990). It was not feasible to prove the dose-limiting toxicity in more patients because only one patient was recruited at the highest dose.…”

Effect of low-dose oral glutamine on painful stomatitis during bone marrow transplantation

“…Given the current morbidity associated with marrow transplantation, the wide safety margin of oral glutamine, 15,34,35 and the known physiologic production of glutamine by muscle and adipose tissue, 36 the risk/benefit of oral glutamine as administered in this study appears highly favorable.…”

Preoperative glutamine infusion improves glycemia in heart surgery patients

“…In this study the amino acid was administered by continuous infusion. The dose used (11.2g/h) was 37% lower than that reported by Ziegler 17 . No adverse effects were observed.…”

“…In various clinical studies, the use of glutamine (50-60g/day) for periods ranging from 4 hours to 30 days did not result in any deleterious effect 16 . Volunteers treated with high doses of glutamine (0.3 g/kg) orally in a single dose (bolus) and observed for 4 hours exhibited no signs of adverse effects 17 . In this study the amino acid was administered by continuous infusion.…”