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NSUP: Vitamin B12 (2008)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

To study whether short-course (one month) oral cobalamin therapy is an effective treatment for cobalamin deficiency related to food cobalamin malabsorption.

Inclusion Criteria:

Cobalamin deficiency: serum cobalamin level less than 200pg per ml on two samples or serum cobalamin level less than 200pg per ml with total homocysteine level greater than 13umol per L.

Exclusion Criteria:
  • Pernicious anemia: Evidence of antibodies to intrinsic factor or against parietal gastric cells or abnormal Schilling's test reversed with intrinsic factor administration
  • Malabsoprtion: History of intestinal resection or recent weight loss (greater than three kg)
  • Concomitant folate defiiciency: Serum folate level less than 3.5mcg per L
  • Inability to take oral medication
  • Inability to follow physician's directive
  • Hypersensitivity to cobalamin
  • Concomitant life-threatening conditions.
Description of Study Protocol:

Recruitment

Between January 1995 and March 2002, 52 patients who were diagnosed with cobalamin deficiency related to food cobalamin malabsorption were taken from a prospective cohort study of cobalamin deficiency.

22 patients were excluded for at least one of the following reasons:

  • Concomitant folate deficiency (N=7)
  • Refusal to participate (N=6)
  • Residence outside the geographic area of Strasbourg impeding adequate follow-up (N=4)
  • Concomitant life-threatening conditions (N=3)
  • Evidence of antibodies to intrinsic factor (in a second sample. N=2).

Design

First 16 patients received a daily dose of 1,000mcg of oral crystalline cyanocobalamin for one month (group A) and the remaining 14 patients were given either 500mcg per day (N=8; Group B) or 250mcg per day (N=6; Group C) of oral crystalline cyanocobalamin for one month.

Intervention

Administration of oral crystalline cyanocobalamin.

Statistical Analysis

  • Pre-treatment and post-treatment values were compared using Student's T-test for paired data
  • P-values less than 0.05 were considered statistically significant.
Data Collection Summary:

Timing of Measurements

At end of the first month of cyanocobalamin therapy these endpoints were measured:

  • Normalization of the serum B12 level (more than 200pg per ml)
  • Reversal of blood count abnormalities
  • Hemoglobin level (greater than 12g per dL)
  • Mean erythrocyte corpuscular volume (less than 100fL)
  • Normalization of the serum total homocysteine (less than 13umol per L)
  • Evidence of medullalry regeneration (reticulocytes count over 80x106 per L).

Dependent Variables

  • Normalization of the serum B12 level (greater than 200pg per ml)
  • Reversal of blood count abnormalities
  • Hemoglobin level (greater than 12g per dL)
  • Mean erythrocyte corpuscular volume (less than 100fL)
  • Normalization of the serum total homocysteine (less than 13umol per L)
  • Evidence of medullalry regeneration (reticulocytes count over 80 X106 per L).

Independent Variables

Oral crystalling cyancobalamin 1,000ug per day, 500ug per day and 250ug per day.

Description of Actual Data Sample:
  • Initial N: 30 (20 women, 10 men)
  • Attrition (final N): 30
  • Age: 72±13 years
  • Ethnicity: Caucasians.

Other Relevant Demographics

  • Alteration of cognitive functions (impaired concentration, memory loss, disorientation; N=9)
  • Sensitive peripheral neuropathy (with impaired vibration sense or hypoactive tendon reflexes; N=7)
  • Ischemic stroke (N=2).

Anthropometrics

Causative conditions included metformin treatment for diabetes mellitus (N=5), long-term omeprazole or rantidine therapy for esophageal reflux (N=3) and alcohol abuse (N=2).

Location

Hopitaux Universitaires de Strasbourg, France.

Summary of Results:
  Pre-Post Treatment
Mean delivery dose of oral cyanocobalamin therapy (ug per day) Serum cobalamin level (pg per ml) Hemoglobin level (g per dL) Mean erythrocyte corpuscular volume (fL) Reticulocyte count (106 per L)
All the Patients N=30
716±320
135±32
11.6±2.3
95.1±7.2
32±11
 
286±88*
12.5±1.8*
92.1±5.2*
67±25*

Group A
N=16
1,000
128±24
12±2.1
94.5±6.3
34±14
 
310±93.4*
12.6± 2.1
92.6±3.9
48±21

Group B
N=8
500
133±36
10.2±3.2
86±9.7
31±15
 
262±38*
12.2±1.8
84.2±3.7

72±17
Group C
N=6
250
139±52
11±1
102.4±6.7
ND
 
242±40*
12.4±0.7
94±5.6
 
Group Without Schilling's Test Procedure
N=20
 
132±27
11.9±2.0
94.8±6.7
 
 
289±88.7*
12.4±1.9*
92.2±4.1*
 

*Statistically significant (P<0.05).

Author Conclusion:
  • For patients with food cobalamin malabsorption not related to pernicious anemia, the present findings support the view that oral crystalline cyanocobalamin is effective in treating cobalamin deficiency related to food cobalamin malabsorption and that a therapeutic respone is obtained rapidly
  • Further studies are warranted with larger sample sizes and different cyanocobalamin doses and duration.
Funding Source:
University/Hospital: Hospitaux University de Strabourg
Reviewer Comments:
  • Study lasted only one month
  • Only 30 study participants
  • Was not an RCT and had no control group
  • 10 patients received 1,000mcg of vitamin B12 as part of a Schilling test.
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? ???
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) N/A
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? ???
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) N/A
  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%.) 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? N/A
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.) No
  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? 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? 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? 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)? No
  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? N/A
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