NSA: Serum Proteins (2009)


Scalfi L, Laviano A, Reed LA, Borrelli R, Contaldo F. Albumin and labile-protein serum concentrations during very-low-calorie diets with different compositions. Am J Clin Nutr. 1990 Mar; 51(3): 338-342.

PubMed ID: 2309640
Study Design:
Case Study or Case Series
D - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:

To evaluate labile protein and albumin concentrations during different Very Low Calorie Diets (VLCD) containing either different amounts of protein or small amounts of carbohydrate added to protein, compared to a less restrictive hypocaloric dietary treatment.

Inclusion Criteria:

34 otherwise healthy, morbidly obese patients admitted to the Metabolic Unit, Institute of Internal Medicine and Metabolic Diseases for the period of this study (20 days).

Exclusion Criteria:

None specified.

Description of Study Protocol:


Participants were admitted patients on the medical unit who consented to participate in the study.


  • All subjects consumed a baseline diet for at least one week
  • Subjects divided into one of five treatment diets for remainder of study
  • Fasting blood samples taken on the first day of treatment diet and after (days zero, five, 10, 20)
  • Daily urine collection for use in nitrogen balance assessment.


Treatment diets were as follows.

Diet Energy (kcal) Protein (g) Carbohydrate (g) Fat (g)
1 180 40 Trace Trace
2 240 34 26 Trace
3 270 60 Trace 3
4 500 60 54 5
5 1,200 77 48 45

Statistical Analysis

  • Two- and three-way analysis of variance (ANOVA) for repeated measures
  • Tukey's test for significance of pairwise comparisons
  • Non-parametric statistics (Kruskal-Wallis test)
  • Simple and stepwise multiple regression analysis.
Data Collection Summary:

Timing of Measurements

  • Baseline was considered the first day of treatment diet after at least one week baseline maintenance diet
  • Fasting blood samples collected on day zero, five, 10 and 20
  • Daily urine collection for nitrogen balance calculation
  • Weight measurement not specified.

Dependent Variables

  • Weight loss
  • Nitrogen balance
  • Serum albumin
  • Serum prealbumin
  • Serum retinol binding protein.

Independent Variables

Treatment diets one to five as described previously.


Description of Actual Data Sample:
  • Initial N: 34 (nine males, 25 females)
  • Attrition (final N): All participants completed study
  • Location: Napoli, Italy.
Diet Sex (F:M) Age (Years) Weight (kg) Height (cm) Body Mass Index (kg/m2) Weight Loss (kg) Nitrogen Balance (mmol per Day)
1 3:2 32.4±10.1 142.8±14.0 162.8±14.1 51.7±7.7 10.4±2.2 -383±150
2 5:2 39.8±15.1 127.8±23.1 165.3±9.0 53.3±13.6 10.6±2.5 -317±183
3 6:0 35.4±19.9 133.4±29.8 159.2±8.5 46.8±8.2 9.9±2.1 -125+25
4 6:4 37.4±14.9 116.6±32.6 162.0±10.1 43.1±10.2 8.3±2.7 not available
5 5:1 41.0±11.6 123.0±16.3 159.3±10.2 49.5±9.2 3.6±1.5 83±158


Summary of Results:

Key Findings: 

  • Decreased serum prealbumin (PA) and retinol binding protein (RBP) during use of Very Low Calorie Diets (VLCD) does not depend on differences in energy content or protein intake, nor on the addition of carbohydrate-to-protein in the diet
  • PA and RBP concentrations decrease during VLCD, predominantly in the first five days, but serum albumin concentration does not change significantly. 

The Table below represents the serum concentrations (± standard deviation) of albumin (Alb, g per L), prealbumin (PA, mg per L) and retinol binding protein (RBP, mmol per L) during the 20-day study of five hypocaloric diets. Significance of P<0.05 indicated with an *  and P<0.01 with ** when applicable.

Diet Baseline
(Alb, PA, RBP)
Day 5
(Alb, PA, RBP)
Day 10
(Alb, PA, RBP)
Day 20
(Alb, PA, RBP)
1 41±2,
2 45±2,
3 47±3,
4 39±2,
5 43±3,



Author Conclusion:

Labile proteins seem to be an unreliable index for assessing overall protein status during VLCDs.

Funding Source:
University/Hospital: Institute of Internal Medicine and Metabolic Diseases, 2nd Medical School, Napoli, Italy
Other: not specified
Reviewer Comments:
  • Strengths: Controlled intake and measurements in hospital setting
  • Weaknesses: Small sample size, treatment assignment not randomized or blinded, nitrogen balance information missing for one study group.
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? Yes
  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? Yes
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) No
  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? Yes
  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")? No
4. Was method of handling withdrawals described? N/A
  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%.) N/A
  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? Yes
5. Was blinding used to prevent introduction of bias? No
  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? Yes
  5.5. In diagnostic study, were test results blinded to patient history and other test results? No
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? No
  6.6. Were extra or unplanned treatments described? No
  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? Yes
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? No
  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)? Yes
  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? N/A
  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? ???
  10.2. Was the study free from apparent conflict of interest? Yes