NSUP: Vitamin B12 (2008)

Citation:
 
Study Design:
Class:
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Quality Rating:
Research Purpose:

To note occurrence of food-cobalamin malabsorption within the elderly population and observe if supplementation of cobalamin is sufficient in alleviating this condition.

Inclusion Criteria:
  • Participants in an already determined prospective cohort study involving elderly participants with cobalamin deficiency
  • Subjects older than 65 years of age
  • Identified as having a confirmed cobalamin deficiency
  • Serum cobalamin level less than 160pg per ml confirmed in two samples or in association with total homocysteine level greater than 13umol
  • Diagnosis of food-cobalamin malabsorption (determined based on Carmel's criteria)
  • Normal Schillings test
  • Lack of serum antibodies to intrinsic factor
  • Daily intake of vitamin B12 or at least five mcg.
Exclusion Criteria:
  • Those not part of the cohort
  • Younger than 65 years of age
  • Diagnosis of pernicious anemia
  • Nutritional cobalamin deficiency
  • Post-surgical malabsorption
  • Cobalamin deficiency of undetermined origin
  • Folate deficiency (folate less than five mcg per L)
  • Use of medications that interfere with folate metabolism (such as colchicine, methotrexate, or salazopyrine)
  • History of malignancy
  • History of hypersensitivity to cobalamin
  • Inability to follow physician's directives
  • Inability to take oral medication.
Description of Study Protocol:

Recruitment

  • Participants were recruited in the Department of Internal Medicine and Nutrition between January 1995 and January 1999
  • 75 patients were found to have a cobalamin deficiency related to food-cobalamin malabsorption
  • 10 subjects were included within this study
  • Participants in existing cohort.

Criteria for Food Cobalamin Malabsorption (FCM)

  • Low serum vitamin B12 levels
  • Normal results of Schilling test
  • No anti-intrinsic factor antibodies
  • No dietary cobalamin deficiencies.

Associated Agents and Clinical Conditions

  • Gastric disease
  • Pancreatic insufficiency
  • Gastric or intestinal bacterial overgrowth
  • Drugs
  • Alcohol abuse
  • Sjogren syndrome, systemic sclerosis
  • Haptocorrine deficiency
  • Aging or idiopathis.

Design

Prospective cohort design.

Intervention

First six subjects were given oral crystalline cyanocobalamin at a weekly dose of 5,000mcg and the remaining four subjects were given 3,000mcg per week for at least three months.

Statistical Analysis

  • Pre-treatment and post-treatment values were compared with student's T-test for paired data
  • P-values under 0.05 were considered statistically significant
  • All data expressed as the median or mean ± standard deviation and range.
Data Collection Summary:

Timing of Measurements

  • Clinical exam: Baseline (before diagnosis of food-cobalamin malabsorption), every month during treatment period (at least three months and at six months)
  • Serum samples: Before and after oral cobalamin treatment, for CBC, serum cobalamin, folate and homocysteine levels
  • Patients were screened for response to treatment at Month Three.

Dependent Variables

CBC (Hgb, MCV).

Independent Variables

Serum cobalamin levels (greater than 160pg per ml).

Description of Actual Data Sample:
  • Initial N: 75
  • Attrition (final N): 10 (six female and four male)
  • Age: Median age was 78±11 years
  • Ethnicity: All were caucasian
  • Other relevant demographics: Patients recruited initially from the Departments of Internal Medicine and Geriatrics of the Hopitaux Universitaires de Strasbourg, France
  • Location: Strasbourg, France.
Summary of Results:
  • Mean pre-treatment cobalamin level was 103±33pg per dL
  • Mean pre-treatment homocysteine level was 20.5±8.6umol per L
  • Mean pre-treatment hemoglobin was 9.6±1.7g per dL.

Results

  • All patients were treated with oral cobalamin for a minimum of three months. The mean duration of treatment was 4.1±1.4 months. Compliance with therapy was good and no adverse events were reported.
  • After three months of treatment, serum cobalamin levels increased in eight subjects, compared to baseline (mean increase 103±33pg per dL). After treatment, all except one subject no longer met the criteria for cobalamin deficiency.
  • All 10 subjects increased hemoglobin levels (mean increase 1.9g per dL; P<0.01) and decreased mean corpuscular volumes (mean decrease 7.8fL; P<0.001)
  • Three subjects reported clinical improvement in neurological function.
Author Conclusion:

Moderate doses of crystalline cyanocobalamin, given orally, may be an effective treatment for food-cobalamin malabsorption.

Funding Source:
Reviewer Comments:
  • Small sample size
  • Short treatment duration
  • Lack of randomization.
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? Yes
  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? 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")? Yes
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? N/A
  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? 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.) ???
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? ???
  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? ???
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  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? 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? ???
  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)? ???
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? ???
  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