NSA: Serum Proteins (2009)


Smith G, Robinson PH, Fleck A. Serum albumin distribution in early treated anorexia nervosa. Nutrition. 1996 Oct; 12 (10): 677-684.

PubMed ID: 8936490
Study Design:
B - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:
  • To investigate how distribution of albumin changes in malnourished humans who do NOT have any acute phase response
  • Specifically, the goal was to study the kinetics of albumin distribution and catabolism in a group of patients with anorexia nervosa (AN).
Inclusion Criteria:
  • Actual inclusion criteria are not specifically defined, other than to state the subjects were suffering from AN and had been admitted to the local Eating Disorders Unit     
  • Eight female patients were recruited, of whom six consented  
  • Six controls were selected who were female members of staff from Charing Cross Hospital with normal BMI, not on any dietary restrictions. No other criteria were listed.
Exclusion Criteria:

None stated.

Description of Study Protocol:


  • If admitted to the local Eating Disorder Unit, participants were then recruited in compliance with the Hospital Ethics Committee and 1983 Declaration of Helsinki    
  • Six controls were recruited from the staff at Charing Cross Hospital. These controls had normal BMI and were not undertaking any dietary restriction. 


  • Six participants with AN were enrolled to complete the study of albumin metabolism. In addition, six "matched" controls were selected form staff at Charing Cross Hospital.    
  • Autologous albumin was prepared using the labelled iodine. This labeled autologous albumin was injected into a vein. Ten minutes following injection, a 3ml sample was taken from a venous cannula in the opposite arm. Eight samples were taken from this cannula over the first hour to determine transcapillary escape rate. Following this, that cannula was removed and further blood samples were then taken at three hours, six hours and daily intervals for six days, then every other day up to day 14.   

Statistical Analysis

  • Three-compartment model of the distribution of albumin and assuming that catabolism occurs close to the plasma pool  
  • Transcapillary Escape Rate (TER) was measured  using linear regression of the log10 albumin corrected plasma activity against time   
  • Non-linear regression was also used to check study technique 
  • Statistical analysis of the study data was performed using the Mann-Whitney rank sum test to compare values betweeen groups   
  • BMDP statistical software package (3R and 3S) were used for all of the analysis.  
Data Collection Summary:

Timing of Measurements    

The average length of time between the admission and the protein turnover study was 9.5 days (range 6-15 days). Autologous albumin was prepared using the labelled iodine. The measurements were then taken as follows:

  • This labeled autologous albumin was injected into a vein 
  • At 10 minutes following injection, a 3ml sample was taken from a venous cannula in the opposite arm
  • Eight samples were then taken from this cannula over the first hour to determine TER 
  • Following this, the cannula was removed and further blood samples were then taken at three hours, six hours, and daily intervals for six days, then every other day up to day 14.   

Dependent Variables

The variables below were calculated at the intervals described above with respect to total values, as well as amount per kg body weight, amount per kg of non-muscle lean mass,

  • Albumin
  • Extravascular albumin in pool B
  • Extravascular albumin in pool C
  • Plasma albumin
  • Urine creatinine excretion
  • Transcapillary escape rate
  • Fractional catabolic rate (FCR)
  • Numerous other plasma measurements including total protein, WBC, RBC, HCT, Total lymph, TSH, antithyroglobulin.

Independent Variables    


 Control Variables

  • All study participants received the autologous albumin infusion as described above in design  
  • Dietary intake was also measured, but not strictly controlled. The AN subjects were in the refeeding phase of their treatment program and the control subjects were allowed to eat per usual 
  • Diet food records were recorded for the AN subjects once per week, and for the control subjects once in the study.  
Description of Actual Data Sample:
  • Initial N: 6 controls, 6  AN
  • Attrition (final N): 6 controls, 6 AN
  • Mean age: Controls: 23.8 years; AN  27.2 years
  • Ethnicity: Not disclosed
  • Other relevant demographics: None noted
  • Location: Charing Cross Hospital, United Kingdom.


Summary of Results:


  Control Anorexia Nervosa P

Transcapillary escape rate (% x h -1)


7.0 (1.49) 


6.9 (0.54)



Fractional catabolic rate 0.109 (0.006) 0.099 (0.006) NS

Actual  catabolic rate (g x d -1)

8.08 (0.812)

10.14 (0.770)


Total EV albumin mass (g/kg) Visually displayed with a column graph, but specific numbers not provided. Visually displayed with a column graph, but specific numbers not provided. 36% higher in AN subjects, P<0.05
Extravascular albumin/total intravascular albumin mass

Visually displayed with a column graph, but specific numbers not provided.

Visually displayed with a column graph, but specific numbers not provided.

Higher in AN subjects

Pool A albumin g/kg of nonmuscle lean weight Visually displayed with a column graph, but specific numbers not provided. Visually displayed with a column graph, but specific numbers not provided.

Higher in C


Total Pool A albumin (g/kg muscle weight) Visually displayed with a column graph, but specific numbers not provided. Visually displayed with a column graph, but specific numbers not provided. Higher in AN P<0.01
Total Pool C albumin  (g/kg muscle weight) Visually displayed with a column graph, but specific numbers not provided. Visually displayed with a column graph, but specific numbers not provided.

Higher in AN 


Total albumin Visually displayed with a column graph, but specific numbers not provided. Visually displayed with a column graph, but specific numbers not provided.

Higher in AN 


Other Findings 

  • Mean plasma albumin concentrations in the AN group did not differ from that of the reference range
  • Significantly lower values for urine creatinine excretion and urine nitrogen excretion were found in the AN group, when compared to the controls.  
Author Conclusion:
  • The concentration of albumin in serum or plasma cannot be used as a reliable indicator of nutritional status
  • It has been shown, however, to be a useful index of prognosis in situations when the acute-phase response is induced such as in injury, surgery, infections and other. 
Funding Source:
University/Hospital: Charing Cross and Westminister Medical School, London, UK
Reviewer Comments:
  • The study is small, but seems to be meticulously done in an effort to describe the kinetics of albumin in the body in the malnourished subject who is not experiencing an acute phase response. However, numerous details are left out about recruitment, subject inclusion criteria, control criteria and how the study was funded. It is unclear whether this affects the quality of the results, but unfortunately, it would be difficult to reproduce the study unless numerous assumptions are made about the health and well-being of the subjects, both the AN and the control.
  • The paper is not well written, but the conclusions made are well-founded. Essentially, in the end, the paper ties together data from other studies that show that plasma albumin concentration is determined to a large extent by variables other than its rates of synthesis and catabolism, such as fluid volume shifts, changes in vascular permeability and abnormal losses. It is pointed out that in a subject with an acute-phase response you will usually see a lowering of plasma albumin concentration due to an increase in the transcapillary escape rate (TER), and not due to a change of synthesis rate of albumin. Also, they note that the TER will increase with the onset of the acute phase respnse. It is shown that the albumin levels are sustained at an equal or higher level in AN subjects when adjusted for body weight. 


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) N/A
  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) N/A
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? ???
  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? No
  2.2. Were criteria applied equally to all study groups? ???
  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? N/A
3. Were study groups comparable? N/A
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) ???
  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.) Yes
  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? N/A
  4.1. Were follow-up methods described and the same for all groups? N/A
  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%.) N/A
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? ???
  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? N/A
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  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.) N/A
  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? N/A
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? N/A
  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? N/A
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? N/A
  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? N/A
  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? ???
  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? N/A
  8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
9. Are conclusions supported by results with biases and limitations taken into consideration? No
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? N/A
10. Is bias due to study's funding or sponsorship unlikely? ???
  10.1. Were sources of funding and investigators' affiliations described? No
  10.2. Was the study free from apparent conflict of interest? ???