Glutamine: No Simple Yes or No

The amino-acid glutamin seems to play an important role in the critically ill patient by inducing cellular protection pathways, modulation of the inflammatory response and the prevention or organ injury. Glutamine depletion on ICU admission has been linked with increased mortality and clinical trials form the last 20 years demonstrated reduced mortality, infectious complications and ICU/hospital length of stay when giving glutamine. This is one of the reasons ICU’s give glutamine when total parenteral nutrition (TPN) is required. …sounds like all ICU patients should get glutamine!

In April 2013 the NEJM published a randomised trial of glutamine and antioxidants in critically ill patient by Heyland et al. Against their expectations they found a trend towards increased mortality at 28 days among patients who received early glutamine intravenously and enterally as compared to those who did not. Actually, the early provision of glutamine did not improve clinical outcome and glutamine was associated with an increase in mortality among critically ill patients with multi-organ failure.
… so should we stop giving glutamine?

In April 2014 now Heyland and his co-authors (the same guy from the NEJM paper) published a systematic review in Critical Care. In this paper they looked at 26 publications on parenteral glutamine supplementation in the ICU and could actually show that in conjunction with nutrition support glutamine was associated with a significant reduction in hospital mortality and hospital length of stay. They stated that parenteral glutamine supplementation as a component of nutrition support should continue to be considered to improve outcomes in critically ill patient.
… that all seems confusing and contradicting!

Actually all these papers aren’t conflicting at all. They offer a differentiated insight into the usage of glutamine… the answer lies in the written details of the study settings. Heylands publication in the NEJM presents a quite different setting compared to most of the previous studies where glutamine was found to be rather beneficial. 
In the NEJM’s publication patients received the highest dose of glutamine (more than in other studies before) which was given intravenously and enterally. This study specifically included critically ill patients with multi-organ failure, most of them in shock. In most previous studies this was an exclusion criteria. Also treatment with glutamine was initiated within 24h after admission to ICU, whereas other studies gave glutamine later in the course of disease together with TPN. And finally all these patients received enteral nutrition, while previous studies mostly focused on parenteral nutrition (TPN). 

And finally, Heyland (again) just now published a post hoc analysis of the NEJM publication in the Journal of Parenteral & Enteral Nutrition (JPEN) showing that early administration of high-dose glutamine separately from artificial nutrition had the greatest potential to be harmful in patients with multi-organ failure that included renal dysfunction.

For these reasons Heyland came to the conclusion that early administration of glutamine in critically ill patients with multi-organ failure was harmful. At the same time it seems beneficial when given after resolution of shock especially in the conjunction with TPN.


– Early administration of high-dose glutamine in critically ill patients with multi-organ failure may be harmful, especially in conjunction with renal dysfunction

– Supplemental glutamine (predominantly as a component of TPN) may improve clinical income when given to appropriate patients and after resolution of multi-organ failure and shock

– Supplemental glutamine should not be given in high dose (>0.5 g/kg/d)

Wischmeyer PE, Critical Care 2014,18;R76

Qi-Hong C, Critical Care 2014,18;R8

Heyland D, N Engl J Med 2013;368:1489-97

Heyland D, J Parenter Enteral Nutr, May 5 2014


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