L-alanyl-L-glutamine dipeptide-supplemented total parenteral nutrition reduces infectious complications and glucose intolerance in critically ill patients: the French controlled, randomized, double-blind, multicenter study

Crit Care Med. 2006 Mar;34(3):598-604. doi: 10.1097/01.CCM.0000201004.30750.D1.


Objective: Glutamine (Gln)-supplemented total parenteral nutrition (TPN) improves clinical outcome after planned surgery, but the benefits of Gln-TPN for critically ill (intensive care unit; ICU) patients are still debated.

Design: Prospective, double-blind, controlled, randomized trial.

Setting: ICUs in 16 hospitals in France.

Patients: One-hundred fourteen ICU patients admitted for multiple trauma (38), complicated surgery (65), or pancreatitis (11).

Interventions: Patients were randomized to receive isocaloric isonitrogenous TPN via a central venous catheter providing 37.5 kcal and 1.5 g amino acids.kg-1.day-1 supplemented with either L-alanyl-L-glutamine dipeptide (0.5 g.kg-1.day-1; Ala-Gln group, n=58) or L-alanine+L-proline (control group, n=56) over at least 5 days.

Measurements and main results: Complicated clinical outcome was defined a priori by the occurrence of infectious complications (according to the criteria of the Centers for Disease Control and Prevention), wound complication, or death. The two groups were compared by chi-square test on an intention-to-treat basis. The two groups did not differ at inclusion for type and severity of injury (mean simplified acute physiology score II, 30 vs. 30.5; mean injury severity score, 44.9 vs. 42.3). Similar volumes of TPN were administered in both groups. Ala-Gln-supplemented TPN was associated with a lower incidence of complicated outcome (41% vs. 61%; p<.05), which was mainly due to a reduced infection rate per patient (mean, 0.45 vs. 0.71; p<.05) and incidence of pneumonia (10 vs. 19; p<.05). Early death rate during treatment and 6-month survival were not different. Hyperglycemia was less frequent (20 vs. 30 patients; p<.05) and there were fewer insulin-requiring patients (14 vs. 22; p<.05) in the Ala-Gln group.

Conclusions: TPN supplemented with Ala-Gln dipeptide in ICU patients is associated with a reduced rate of infectious complications and better metabolic tolerance.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Critical Care
  • Cross Infection / etiology
  • Cross Infection / prevention & control*
  • Dietary Supplements
  • Dipeptides / therapeutic use*
  • Double-Blind Method
  • Female
  • France / epidemiology
  • Glucose Intolerance / etiology
  • Glucose Intolerance / prevention & control*
  • Glutamine / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Parenteral Nutrition, Total / adverse effects
  • Parenteral Nutrition, Total / methods*
  • Prospective Studies
  • Survival Rate


  • Dipeptides
  • Glutamine
  • alanylglutamine