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Letter to the Editor |
Department of Surgery Vrije University Medical Center De Boelelaan 1117 1081 HV Amsterdam Netherlands E-mail:
pg.boelens{at}vumc.nl
Dear Sir:
We read with special interest the article titled "Glutamine: commercially essential or conditionally essential? A critical appraisal of the human data" in a recent issue of the Journal (1). In this article, Buchman attempted to analyze all the available human data on the effect of a glutamine-enriched diet on morbidity and length of hospital stay. Although his research seemed to be thorough at first glance, we were surprised to find that his conclusions were superficially and sometimes incorrectly drawn. In our comment, we confine ourselves first to the way glutamine is proposed to exert its effect on the mucosa and second to the way the study of Houdijk et al (2) was presented and discussed by Buchman.
First, no data available in the literature provide evidence that atrophy of the villi results in bacterial or endotoxin translocation. Therefore, we do not understand the rationale of the study done by Buchman et al (3) in healthy volunteers as presented on page 26 of Buchman's article (1). If the theory that glutamine deficiency is solely responsible for the changes in intestinal morphology and function is true, it would have been more appropriate to measure the glutamine content of mucosal biopsy samples instead of measuring plasma glutamine.
We also do not understand why the author focused solely on the hypothesis that glutamine exerts its effect on intestinal morphology; other theories have been proposed and may be more valuable. For instance, glutamine can increase arginine synthesis in the kidney (4). Arginine is important for wound healing, plays a role in the immune system, and is the precursor for nitric oxide. Nitric oxide is important for regulating blood flow through vital organs, such as the gut, the liver, the kidney, and the heart, especially during stress (5, 6). Arginine plasma concentrations can be rate limiting under certain circumstances. Prins et al (7) showed in a rat model that if arginine concentrations are reduced by 50%, resembling aortic surgery, a mild endotoxin challenge significantly reduces blood flow through the gut. Thus, glutamine may be important in regulating blood flow by serving as a precursor for arginine synthesis.
Furthermore, glutamine might also exert its effect by increasing plasma concentrations of taurine. Taurine is an important intracellular osmolyte that can regulate cell volume and that therefore has a major impact on the body's fluid homeostasis (8). Because Scheltinga et al (9) showed that glutamine restores body fluid distribution, it is conceivable that part of the beneficial effect of glutamine is because of its enhancement of taurine availability.
Buchman discussed the study of Houdijk et al (2) within the section on critical care (page 28). In describing this study, Buchman mentioned a significant reduction in infectious complications. He also pointed out that Houdijk et al suggested that the lesser occurrence of gram-negative infections in the glutamine group might be explained by reduced bacterial translocations. Houdijk et al stressed in their discussion that this was merely a suggested explanation of the results showing fewer gram-negative infections in the glutamine group.
In his conclusion, Buchman stated that "glutamine supplementation did not appear to be associated with a decreased incidence of infection in the studies reviewed herein." However, earlier in his article, Buchman described the significant reduction in infectious complications that were seen in the study of Houdijk et al (2). Therefore, his conclusion seems to be unfounded.
The positive effect of glutamine on infectious morbidity is also substantiated by a recent report by Novak et al (10). In this report, 14 randomized trials of 737 adult patients (surgical and critically ill) were reviewed. The authors concluded that glutamine supplementation was associated with a reduction in infectious complication rates and a shorter hospital stay without any adverse effect on mortality.
REFERENCES
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