EAL

NSUP: Vitamin B12 (2008)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To determine the effect of small doses of oral cyanocobalamin supplements in older patients with low or borderline serum vitamin B₁₂ concentrations, but no other evidence of pernicious anemia (PA).

Inclusion Criteria:

Inpatients at MECRS and Greenvale Geriatric Center (two geriatric hospitals in the North West Health Care Network, Melbourne, Australia)
Serum B₁₂ concentration ranged between 100pmol and 150pmol per L.

Exclusion Criteria:

Out-patients
Non-elderly patients
Normal serum vitamin B₁₂ levels
Previous history of GI surgery
Previous history of malabsorption
No neoplasm or life-threatening or terminal illness
History of PA or other anemia
Prior vitamin B₁₂ treatment
Neurological disorder other than stroke.

Description of Study Protocol:

Recruitment

Patients were recruited from two area geriatric hospitals. Initial serum vitamin B₁₂ levels were drawn and if these levels were low (between 100pmol and 150pmol per L), patients were eligible to participate in the study. Informed consent was provided and medical and drug history was taken, along with a clinical exam.

Design

Complete blood examinations were conducted on all subjects. Tests collected included: Serum vitamin B₁₂, serum folate and red cell folate assays; serum creatinine; fasting homocysteine (Hcy); fasting serum gastrin; tests for the detection of gastric parietal cell and intrinsic factor antibodies. A thorough clinical assessment was also conducted, including a Mini-Mental State Examination to screen cognitive assessment regarding test orientation, memory and other cognitive abilities.
A dietitian estimated vitamin B₁₂ intake based on a reported dietary history
Patients were randomized in double-blind manner to receive either placebo or vitamin B₁₂ (either 10mcg or 50mcg) daily for four weeks
At the end of the four weeks, another clinical assessment and a repeated blood testing were conducted.

Blinding Used

Both subjects and clinicians were blinded as to intervention.

Intervention

Placebo
Vitamin B₁₂ supplement;10mcg per day
Vitamin B₁₂ supplement; 50mcg per day.

Statistical Analysis

Mean, standard deviation and range were calculated for all baseline data from each group
Results after treatment were normalized by calculating a percentage change from baseline
Differences in changes between groups were determined using one-way ANOVA
Chi-square testing was performed to detect differences in the number of responders, as defined by a 20% increase in vitamin B₁₂
Baseline correlations were calculated using linear correlation coefficient Perason R.

Data Collection Summary:

Timing of Measurements

Measurements were done at baseline and four weeks post-treatment.

Dependent Variables

Blood indices
MMSE (cognitive tests).

Independent Variables

Placebo
Vitamin B₁₂: 10mcg per day
Vitamin B₁₂: 50mcg per day.

Control Variables

Geriatric patients
Baseline serum B₁₂ levels between 100pmol and 150 pmol per L.

Description of Actual Data Sample:

Initial N

31 patients were recruited
11 patients in placebo group: Five male, six female
10 patients in the 10mcg B₁₂ group: Four males and six females
10 patients in the 50mcg B₁₂ group: Five males and five females.

Attrition (Final N)

All subjects completed the study.

Age

Placebo group: 77.6 years
10mcg B₁₂: 82.0 years
50mcg B₁₂: 84.9 years
Overall mean: 81.4 years.

Ethnicity

Unavailable. However, patients were recruited from geriatric hospitals in Melbourne, Australia.

Other Relevant Demographics

Most patients living in community prior to hospital admission
Two of placebo group, two in 10mcg B₁₂ group and three in 50mcg B₁₂ group were admitted from specialized nursing facilities.

Anthropometrics

Not available.

Location

MECRS and Greenvale Geriatric Centre in North West Health Care Netwrok, Melbourne, Australia.

Summary of Results:

No significant differences between baseline data in different groups, with the exception of mean cell volume (higher in the B₁₂ treatment groups (P=0.024)
The percentage change from baseline in serum vitamin B₁₂ concentration was the only result to reach statistical significance (P=0.046). Post-hoc Tukey HSD showed a significant difference between placebo and 50-mcg treatment (P=0.044), but not for placebo or 10-mcg treatment (P=0.886).
There was a tendency for improvement in Hcy with cyanocobalamin treatment, although it was not statistically significant. Hcy levels were not correlated with serum vitamin B₁₂ levels (P=0.886).
Vitamin B₁₂ concentrations were greater than 150pmol per L in eight, eight and four subjects in the 10-mcg and 50-mcg cyanocobalamin and placebo groups, respectively.

Author Conclusion:

A daily supplement of 50mcg, but not 10mcg, per day of vitamin B₁₂ will significantly raise mean serum vitamin B₁₂ concentration in older patients
However, even with the 50-mcg supplement, serum vitamin B₁₂ did not rise significantly in all patients tested
This suggests that a daily supplement greater than 50mcg would be necessary to protect against vitamin B₁₂ deficiency, however a supplement period of greater than one month may also suffice to raise levels significantly in all subjects
These results also suggest that supplements aim to supply more than a 50mcg amount of daily vitamin B₁₂, which could be in addition to foods fortified with the vitamin.

Funding Source:

Not-for-profit

Foundation associated with industry:

Reviewer Comments:

Small numbers in each group
Perhaps a longer supplement period may be necessary.

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)	Yes
	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.)	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?	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?	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?		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.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	Yes
	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?	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?	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?	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)?	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?	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?		No
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes