Therapeutic benefits of glutamine: An umbrella review of meta-analyses

Abstract

Abstract. Glutamine may be an essential amino acid in patients with catabolic disease, as it has been demonstrated that circulating glutamine levels drop during critical illness and following major surgery; this may result in an increase in secondary infection risk, recovery time and mortality rates. However, there is much discrepancy in the literature with regards to randomized controlled studies, and therefore, the present study is an umbrella review of published meta-analyses, conducted to examine the effectiveness of glutamine's role as a therapeutic agent. A search using PubMed, Cochrane Library and CINAHL from January 1st, 1980 to December 31st, 2016 was conducted using the following strategy: 'Glutamine AND (meta-analysis OR systematic review)' and publications were retrieved, which provided quantitative statistical analysis of pooled treatment effects on the relative risks of infectious complications, mortality and length of stay in hospital. A total of 22 meta-analyses were entered into the current umbrella review. As displayed in Tables I, II and III, these analyses are split into three groups, based on different parameters. Of the 19 meta-analyses investigating the effects of infectious complications, 15 identified statistically significant reductions in complications, with relative risks ranging between 0.42 and 0.93. In addition, 12 of the 18 meta-analyses analyzing the length of hospital stays presented statistically significant reductions in the length of stay, with reductions ranging between 0.19 to 4.73 days. Only 4 of the 15 meta-analyses studying mortality effects identified statistically significant reductions in mortality with relative risks ranging between 0.64 and 1.28. Statistically significant heterogeneity was observed in 16 of 22 meta-analyses, and publication bias was observed in five of 11 meta-analyses. Glutamine supplementation for critically ill or surgical patients through parenteral or enteral routes appears to reduce the rate of hospital acquired infectious complications and shortening of the length of stay in hospital. Furthermore, glutamine supplementation appeared to reduce the rate of in-patient mortality, but the majority of meta-analyses did not reach statistical significance. However, researchers must appreciate the positive results with caution in light of the fact that there exists statistically significant heterogeneity for the majority of meta-analyses, and statistically significant publication bias in almost half.

ESPEN guideline on clinical nutrition in the intensive care unit

“…Of note none of the groups received the planned high dose protein resulting in a mean delivery of 0.9 g/kg/ day. Meta-analysis showed that enteral GLN reduces increased gut permeability significantly but does not reduce mortality [220,221].…”

Food and Drug Administration Approval of Glutamine for Sickle Cell Disease: Success and Precautions in Glutamine Research

“…Such studies showed the following: Parenteral gln administered in appropriate doses appears to have effects on reducing the incidence of nosocomial infection, possibly decreasing ventilation time, and maybe lowering mortality and length of intensive care unit and/or hospital stay 22 – 24 . Not all studies show the same results, but a recent umbrella analysis agrees in a qualified manner with many of these conclusions 25 Positive effects have not been observed with enteral gln feedings 26 .…”

Combined Enteral and Parenteral Glutamine Supplementation in Endotoxemic Swine: Effects on Portal and Systemic Circulation Levels

“…Second, the supramaximal dose used has already been applied clinically; intensive care unit patients were randomized to receive 0–0.86 g/kg L-GLN in order to investigate the relation of the dose to muscle concentration [22], while 0.65 g/kg was considered the maximally tolerated oral dose in children [23]. Third, contrary to existing recommendations [24, 25], GLN was provided without any concomitant nutritional support. This could be justified by the short duration of the protocol and the good nutritional status of the animals.…”