JRSM >
Volume 97, Number 9 >
Pp. 425-427
Department of Human Nutrition, Queen Mary's School of Medicine and Dentistry, Barts and The London NHS Trust, London, UK
Correspondence to: Raymond D'Souza, Digestive Disease Research Centre, Queen Mary's School of Medicine and Dentistry, Barts and The London NHS Trust, Whitechapel, London E1 1BB, UK E-mail: raymonddsou{at}yahoo.com
 | INTRODUCTION |
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 TOP INTRODUCTION CONSEQUENCES OF GLUTAMINE...LIMITATIONS TO USE OF...CLINICAL STUDIESCONCLUSIONSREFERENCES |
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Glutamine has numerous functions in normal physiology—for example, it acts as a precursor for protein synthesis; it provides the nitrogen for synthesis of arginine, purines, pyrimidines, nucleotides, glutathione and taurine (the last two being important antioxidants); and it transports amino-nitrogen to intestine, liver and kidney.1–3 With its involvement in renal ammoniagenesis it plays a key role in acid–base homoeostasis.2 Particularly reliant on glutamine as a fuel are the rapidly dividing cells of the gastrointestinal tract (enterocytes, colonocytes) and the immune system (lymphocytes, macrophages).3,4 Glutamine may affect stress-induced accumulation of extracellular fluid by changing the cellular hydration state.4 An increase in cellular hydration acts as an anabolic proliferative signal, whereas cell shrinkage is catabolic and anti-proliferative.
Under normal circumstances glutamine is readily synthesized and stored in skeletal muscle whilst lesser amounts are produced in the liver, lungs and brain.1 Since it can be produced by the body it is regarded as a nonessential aminoacid. However, this does not apply to conditions of excessive organ/tissue demand such as sepsis and other states of catabolic stress declines greatly.4 In these circumstances, production of glutamine in the body is insufficient to meet the increased requirement by the gut, immune system, liver and kidneys.4 The demands are then met in part by protein breakdown in skeletal muscle, with release of large amounts of glutamine and glutamine becomes a conditionally essential aminoacid.
| CONSEQUENCES OF GLUTAMINE DEPLETION |
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TOPINTRODUCTIONCONSEQUENCES OF GLUTAMINE...LIMITATIONS TO USE OF...CLINICAL STUDIESCONCLUSIONSREFERENCES |
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| LIMITATIONS TO USE OF FREE GLUTAMINE |
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TOPINTRODUCTIONCONSEQUENCES OF GLUTAMINE...LIMITATIONS TO USE OF...CLINICAL STUDIESCONCLUSIONSREFERENCES |
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The drawback of glutamine instability can, however, be overcome by use of synthetic dipeptides.6,7 Dipeptides with glutamine residues at the C-terminal position are highly soluble in water and are reasonably stable during heat sterilization and storage.6,7 Two preparations now available for addition to parenteral nutrition are L-alanyl-L-glutamine (Ala-Gln) and glycyl-L-glutamine. These intravenous preparations seem free from side-effects and the infused peptide is quickly hydrolysed.6,7 Supplementation with glutamine or glutamine-containing dipeptides improves nitrogen balance and maintains the intracellular glutamine pool, though the doses required are much higher than the standard daily oral intake of around 5 g.6
| CLINICAL STUDIES |
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TOPINTRODUCTIONCONSEQUENCES OF GLUTAMINE...LIMITATIONS TO USE OF...CLINICAL STUDIESCONCLUSIONSREFERENCES |
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Glutamine-supplemented enteral feeding
Where there is a choice, enteral feeding is preferable to parenteral. In
the critically ill patient on the intensive-care unit, parenteral nutrition is
used only when enteral feeding is unsuccessful or impractical. Conventional
enteral feeds provide some glutamine (protein-based enteral products 6–8
g/day, and peptide-based products 1–5 g/day), but this is insufficient
for the critically ill patient and some workers argue for supplements of
10–20
g/day.10
50–80% of free glutamine is absorbed by the gut during routine enteral
feeding and plasma glutamine can be seen to rise with supplementation.
Supplemented enteral feeds can reverse the changes in intestinal permeability
associated with parenteral feeds, possibly by yielding a high glutamine
concentration (>2.5 mmol/L) in the gut
lumen.11–13
Some researchers find that addition of glutamine to enteral nutrition formulas
in critically ill patients reduces rates of pneumonia, sepsis and bacteraemia,
with shortened hospital stays and lower hospital
costs,11–14
but others report no
benefit.15 In a
systematic review of work on enteral glutamine, Novak et
al.16 reach
negative conclusions—no reduction in mortality, complications or
hospital stay.
Perhaps one reason for this disappointing result is that high doses of enteral glutamine are difficult to give, particularly during the early course of the illness. In the work on parenteral glutamine, high doses were seen to be more effective than low doses. One way to provide high concentrations would be to give the glutamine intravenously, separately from the enteral feed.17 In low-birthweight babies the evidence on enteral glutamine is more secure: it reduces morbidity, lessening the incidence of sepsis.18
Glutamine-supplemented parenteral feeding
The first clinical study with a synthetic dipeptide was performed in 1989
in patients undergoing elective resection of the colon or
rectum.19 An
improvement in net nitrogen balance in the glutamine-replacement TPN subgroup
was associated with maintenance of the intracellular glutamine
pool.17 In surgical
patients, TPN supplemented with Gly-Gln improved nitrogen economy, had an
immunostimulatory effect on lymphocytes, maintained plasma glutamine
concentration and shortened hospital
stay.19,20
| Box 1 Patient groups that may benefit from glutamine
supplementation (modified from Ref.
25) Severe catabolic illness Burns, multiple trauma Bone marrow transplantation Acute/chronic infection Other critical illness Intestinal dysfunction Inflammatory bowel disease Infectious enteritis Necrotizing enterocolitis or intestinal immaturity Short-bowel syndrome Mucosal damage following chemotherapy, radiation, or critical disease Surgical gastrointestinal patients Immunodeficiency syndromes Immune system dysfunction associated with critical illness or bone marrow transplantation Acquired immunodeficiency syndrome Advanced malignant disease Glutamine-depleted patients with cancer cachexia Low-birthweight babies
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Since then, glutamine-enriched TPN has been found beneficial in several conditions.19–25 It can help to maintain the structure and function of the small bowel in inflammatory bowel disease or neoplastic disease and thus reduce bacterial translocation,3 and improves weight gain, reduces hospital stay and lessens the risk of nosocomial infections in patients undergoing bone marrow transplantation.22 After bone marrow transplantation the treatment has been associated with increased percentages of lymphocytes and improved markers of T-cell function together with a degree of hepatic protection, possibly due to its effects on tissue glutathione concentrations;22 moreover, glutamine-supplemented patients showed advantages in psychosocial wellbeing, whether through some direct action in the brain or through its effects on protein status. Intravenous glutamine supplementation in severely burned patients reduced Gram-negative bacteraemia, with a trend towards lower mortality.23 In meta-analysis, Novak et al.16 combined two large studies of critically ill patients21,23 who had gastrointestinal failure. Their conclusion was that, after six days of infusion, glutamine-supplemented patients had a moderately (but significantly) lower mortality rate than the non-supplemented. They also concluded that a glutamine dose higher than 0.20 g/kg per day has a greater effect than a lower dose.16 Like enteral glutamine, parenteral supplementation is beneficial in low-birthweight babies, in whom it reduces sepsis, lessens time on the ventilator and speeds the change to enteral feeds.24
| CONCLUSIONS |
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TOPINTRODUCTIONCONSEQUENCES OF GLUTAMINE...LIMITATIONS TO USE OF...CLINICAL STUDIESCONCLUSIONSREFERENCES |
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With parenteral glutamine, the patients most likely to benefit are the critically ill and those at high risk of gut dysfunction. In such patients, a dose of 15–25 g per day may be sufficient. Like enteral glutamine it is beneficial in low-birthweight babies, reducing sepsis and time on the ventilator. The availability of stable preparations of glutamine dipeptide opens the way to better management of the subgroups of patients most at risk.
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TOPINTRODUCTIONCONSEQUENCES OF GLUTAMINE...LIMITATIONS TO USE OF...CLINICAL STUDIESCONCLUSIONSREFERENCES |
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