EAL

NSUP: Vitamin B12 (2008)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To test whether a very-low-dose of oral vitamin B₁₂can increase serum vitamin B₁₂ levels in subjects with sub-clinical deficiency and whether there is a dose response
The final objective was to obtain quantitative data for determining the optimal level for vitamin B₁₂ flour fortification.

Inclusion Criteria:

Low serum vitamin B₁₂ levels (less than 162pmol per L)
More than 70 years of age
Absence of fatal disease and life expectancy greater than one month
Planned hospitalization duration greater than one month
Lack of relevant signs of vitamin B₁₂ deficiency (i.e., absence of severe cognitive impairment with a Mini-Mental Status Examination (MMSE) greater than or equal to 23 of 30 points (25); hemoglobin greater than 100g per L; absence of clinical peripheral neuropathy; absence of clinical signs of subacute combined degeneration of the spinal cord)
Absence of known vitamin B₁₂ hypersensitivity
Willingness to give a written consent to participate in this study
Food-bound vitamin B₁₂ malabsorption according to Carmel's criteria, excluding the Schilling test.

Exclusion Criteria:

None given.

Description of Study Protocol:

Recruitment: Between June 2003 and March 2004 every patient entering Emile Roux Hospital was screened for vitamin B₁₂status
Design: Patients were randomly assigned to one of six groups of vitamin B₁₂ (2.5mcg, 5.0mcg, 10mcg, 20mcg, 40mcg or 80mcg per day) oral dose supplementation daily for 30 days
Blinding used: Not disclosed
Intervention: Varying doses of oral vitamin B₁₂ (2.5mcg, 5.0mcg, 10mcg, 20mcg, 40mcg or 80mcg per day).

Statistical Analysis

A dose-response model was used to calculate the number of patients to be included in this study
The analysis of the dose response for each biological variable was performed using a mixed model
P<0.05 was considered significant.

Data Collection Summary:

Timing of measurements: Serum samples obtained at Days One, 15 and 30
Dependent variables: Serum vitamin B₁₂ levels
Independent variables: Oral doses of vitamin B₁₂ supplements.

Description of Actual Data Sample:

Initial N: N=89
Attrition (final N): N=67
Age: 83.3±7.4
Ethnicity: Undisclosed.

Anthropometrics

Baseline characteristics

Gender: 43.3 % male
Serum vitamin B₁₂: 120±49pmol per L
Total vitamin B₁₂ intake: 3.1±0.9mcg per day

Location

Limeil-Brevannes, France.

Summary of Results:

	Vitamin B₁₂ (mcg per Day)
	2.5	5	10	20	40	80
Subjects, N	8	12	12	12	11	12
Serum B₁₂, pmol per L (Baseline)	111±38	124±44	128±44	103±54	126±40	127±6
Day 15	17.8±7.2	17.4±5.4	17.1±7.1	16.7±4.9	14.7±5.0	14.2±3.8
Day 30	163±44	142±33	182±67	171±67	205±56	206±67

Author Conclusion:

Very low doses of crystalline cyanocobalamin can normalize serum vitamin B₁₂ levels in the studied population but with substantial variability among subjects at low doses
Results from this study can be used in the design of a public health program for safe flour fortification with folic acid plus vitamin B₁₂.

Funding Source:

Reviewer Comments:

Study lasted only 30 days
22 out of the 89 study participants did not complete the study
Vitamin B₁₂ assays performed for the screening were not used for analysis
Some of the patients included in this study, on the basis of a low-screening dosage, had a normal serum vitamin B₁₂concentrations at the second determination several days later, using a more precise method. Therefore, the study population should be described as older patients with low to low-normal serum vitamin B₁₂ concentrations.

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?	???
	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%.)	???
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	???
	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?	Yes
	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?	Yes
	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?	???
	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?	???
	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)?	Yes
	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?	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