CI: Supplemental Intravenous Glutamine (2011)


Powell-Tuck J, Jamieson CP, Bettany GE, Obeid O, Fawcett HV, Archer C, Murphy DL. A double-blind, randomized, controlled trial of glutamine supplementation in parenteral nutrition. Gut. 1999 Jul; 45 (1): 82-88.

PubMed ID: 10369709
Study Design:
Randomized Controlled Trial
A - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:

Determine if inclusion of 20g free glutamine as part of the nitrogen source in PN reduces length of hospital stay or mortality.

Inclusion Criteria:
  • Aged 18-65 years
  • Gave consent
  • Nutrition team judged that PN was clinically indicated.
Exclusion Criteria:
  • Did not give consent
  • Fluid restriction <2,000mL per 24 hours
  • Creatinine >200μmol/L
  • Liver failure (prothrombin ratio >1:8 or hepatic encephalopathy present).
Description of Study Protocol:


Some patients who met inclusion criteria not included due to undefined administrative reasons although this not determined on clinical grounds; No patient excluded after randomization


  • Double-blind RCT
  • Randomization done in pharmacist by sealed envelopes; blocks of 10 to ensure approximately equal numbers of subjects in treatment/placebo groups.

Blinding used

  • Identical labeling of PN bags to blind nutrition team and other clinical staff
  • Assignment unmasked to principal investigators after 50 subjects and again at end of study when 170 patients had been randomized.


  • Energy and N requirements determined for each patient by use of standard computer program (validated in previous study)
  • All trial patients had minimum of 11g N
    • Glutamine-containing PN had 20g glutamine (to replace 3.8g N) with remainder supplied as Eloamin
    • N source for non-glutamine PN varied between Vamin 14, Vamin 18, Intrafusin and Synthamin
  • All feedings contained full complement of vitamins and trace elements. 

 Statistical Analysis

  • Power analyses:
    • Mortality assessed as death with 180 patients (90 per group) required to show halving of mortality rate of 35% (from previous audit) (P=0.05, 1-β=0.8)
    • Morbidity assessed using LOS and power analysis using control LOS 44 days, 170 patients needed to show mean reduction of just under 10 days (P=0.05, 1-β=0.8)
  • Wilcoxon ranked pairs to assess morbidity and quality of life.
Data Collection Summary:

Timing of Measurements

Discharge or death

Dependent Variables

  • Primary:
    • Mortality (death during hospital stay)
    • Length of hospital stay (days)
  •  Secondary:
    • Septic complications (positive culture)
    • Quality of life (scored mood sleep, energy, appetite, pain and mobilization on 10-point scale with 0="perfect" and 10 "as bad as it can be".

Independent Variables

  • Glutamine in PN solution
  • Control PN (isonitrogenous without glutamine).

Control Variables

PN solutions were isonitrogenous

Description of Actual Data Sample:
  • Initial N: 170 (60% male); of that number, 25 were ICU patients
  • Attrition (Final N): 168 (decided two who had been randomized did not require TPN)
  • Age: NS difference between groups
    • Control 50±19 years
    • GLN treatment 49±34 years
  • Ethnicity: Not described
  • Other relevant demographics:
    • Hematology patients: 32/168
    • Surgery patients: 38/168
    • Gynecology patients: 0/168
    • Medicine patients: 12/168
    • Pooled ICU: 25/168 patients (illness severity not described for this group)
  • Anthropometrics: No significant differences
  • Location: London, UK.


Summary of Results:

Key Findings

Variables GLN (N not given) Control PN (N not given) Statistical Significance of Group Difference
Mortality (median, IQR days) in pooled ICU cohort  9/25 (36%)  10/17 (59%)  P>0.05
Length of hospital stay (median, IQR days) in pooled ICU cohort  37.5
45 (16-85)  P>0.05 




Author Conclusion:

Benefit of glutamine supplementation of PN was not proved.

Funding Source:
Reviewer Comments:

Not sure the treatment and control PN formulas were isonitrogenous. Patients received a minimum of 11g N per day plus trace minerals, vitamins and energy and protein as determined were needed by a standardized computer program. There was no description of what was in one liter of PN solution.

This study received a neutral quality rating due to #2: Was the selection of study subjects/patients free from bias? Of 495 patients screened, only 170 were randomized. The 325 were excluded due to "administrative reasons" that were not defined. In addition, results were given for a pooled ICU cohort, but nowhere in the article did the investigators tell how many in the ICU group were on GLN or the control PN.

Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? ???
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? Yes
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) Yes
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? Yes
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? Yes
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? Yes
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? Yes
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) Yes
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? N/A
  6.6. Were extra or unplanned treatments described? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? N/A
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? Yes
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? No
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? Yes
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes