EE: Thermic Effect of Feeding (2013)


Cankayali I, Demiraq K, Kocabas S, Moral AR. The effects of standard and branched chain amino acid enriched solutions on thermogenesis and energy expenditure in unconscious intensive care patients. Clin Nutr. 2004; 23(2): 257-263.

PubMed ID: 15030966
Study Design:
Randomized Controlled Trial
A - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:

To compare the effects of standard and branched chain amino acid enriched solutions on thermogenesis and energy expenditure in unconscious and mechanically ventilated intensive care patients.

Inclusion Criteria:
  • Provided written informed consent
  • Patients within three to five days of their admission to the ICU
  • Unconscious according to the Glasgow Coma Score between four and eight
  • Mechanically ventilated and clinically stable patients.
Exclusion Criteria:
  • Thyroid or metabolic disorders
  • Hypo- or hyperthermia (35° or less, 38° or more Celsius)
  • Known infection source
  • Sepsis or septic shock
  • Brain death
  • Hemodynamic instability
  • Renal function disorders
  • Hepatic function disorders
  • Diabetes mellitus
  • Malnutrition
  • Pregnancy
  • Acute trauma (within first 48 hours after trauma).
Description of Study Protocol:


Patients were recruited from Ege University School of Medicine.


Randomized controlled trial. 

Blinding Used

Implied with measurements.


  • Patients were randomly assigned to receive a four-hour infusion of 0.4g per kg protein as amino acid solution
  • Group I (N=10) received standard amino acid solution FreAmine 8.5% and group II (N=10) received branched chain amino acid solution

Statistical Analysis

  • Results are presented as mean ±SD
  • Statistical analysis of the data within groups was performed by one-way analysis of variance with repeated measures and Wilcoxon test was used for post-hoc analysis to compare the data obtained from the two groups
  • P<0.05 was accepted as statistically significant.


Data Collection Summary:

Timing of Measurements

  • Hemodynamic and arterial blood gas stabilization was performed before the start of the study period
  • Basal metabolic data (REE, VO2, VCO2 and RQ) were measured during 20 minutes before the start of amino acid solution infusion
  • Indirect calorimetry was used to measure energy expenditure, oxygen consumption and carbon dioxide production every 30 minutes during the four-hour infusion period and three hours thereafter
  • Metabolic data were recorded every 30 minutes during the four-hour infusion period and at 30, 60, 120 and 180 minutes after the infusion ended.

Dependent Variables

  • Deltatrac II metabolic monitor was used to measure the resting energy expenditure (REE), oxygen consumption (VO2) and carbon dioxide production (VCO2)
    • Before the measurements, the O2 and CO2 analyzers were calibrated with a precise mixture containing 95% oxygen and 5% CO2 (Deltatrac High-Accuracy Calibration Gas, Datex Instrumentation, Helsinki, Finland), according to the manufacturer’s guidelines
    • Steady state was not described.
  • Systolic, diastolic and mean arterial pressure, heart rate and rectal temperature were recorded concomitantly with the metabolic measurements throughout the study.

Independent Variables 

  • Patients were randomly assigned to receive a four-hour infusion of 0.4g per kg protein as amino acid solution
  • Group I received standard amino acid solution FreAmine 8.5% and group II received branched chain amino acid solution.
Description of Actual Data Sample:
  • Initial N: 20 (11 women, nine men)
  • Attrition (final N): 20 (11 women, nine men)
  • Age: Range 18 to 65 years
  • Location: Izmir, Turkey.
Summary of Results:

Key Findings

  • In group I, there was a statistically significant increase in body temperature during the infusion of amino acid solution between 30 and 210 minutes
  • In group II, a statistically significant increase in body temperature during the infusion of amino acid solution occurred between 30 and 120 minutes
  • There was a significant increase in energy expenditure at 30, 150, 180 and 210 minutes in group I and at 30 to 240 minutes in group II (P<0.05)
  • Increases were as large as 153kcal in group I (from 1841±614kcal to 1994±623kcal per day at 150 minutes) and 212kcal in group II (from 1842±611kcal to 2054±716kcal per day at 120 minutes)
  • There were no differences between the two groups in terms of thermogenesis or energy expenditure values during the study (P>0.05).


Author Conclusion:

Thermogenesis and energy expenditure values were increased during the parenteral infusion of both standard amino acid- and branched chain amino acid-enriched solutions in unconscious intensive care patients without any significance in between.

Funding Source:
University/Hospital: Ege University, Izmir, Turkey
Reviewer Comments:

Small number of subjects in groups.

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? No
  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? N/A
  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? No
  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? Yes
  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? Yes
  6.6. Were extra or unplanned treatments described? Yes
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  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)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? N/A
  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? No
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