EAL

NSUP: Vitamin B12 (2008)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To determine the lowest treatment dose of oral cobalamin to normalize the elevated serum MMA levels in cobalamin-deficient older adults (65 years of age or older).

Inclusion Criteria:

Over the age of 65
Previously enrolled in a cobalamin deficiency-screening study
Plasma Cbl concentrations of under 221pmol per L and methylmalonic acid (MMA) greater than 271nmol per L.

Exclusion Criteria:

History of pernicous anemia, cobalamin deficiency, renal insufficiency or gastric or ileal surgery
Presence of life-threatening illness
Hematocrit of less than 30%.

Description of Study Protocol:

Recruitment: Enrolled in a cobalamin deficiency-screening study at one of two senior care clinics
Design: Non-randomized intervention study
Blinding used: Yes.

Intervention

22 elderly subjects with low plasma cobalamin concentrations were studied
Subjects underwent daily treatment for six weeks of 25mcg oral cobalamin, followed by six weeks of 100mcg cobalamin, followed by six weeks of 1,000mcg cobalamin for a total of 18 weeks.

Statistical Analysis

Means test
Regression models.

Data Collection Summary:

Timing of Measurements

The following data was collected at zero, six, 12 and 18 weeks:

MMA
tHcy
Complete blood count, serum cobalamin, creatinine and folate; cystathiononine and 2-methylcitric acid.

Dependent Variables

MMA
tHcy.

Independent Variables

Dose of cyanocobalamin.

Description of Actual Data Sample:

Initial N: 22 completed the entire 18 weeks; one subject completed 12 weeks
Attrition: Not described
Compliance: 94% for 25-mcg and 100-mcg doses and 92% for 1,000mcg dose (pill count)
Age: At least 65 years
Ethnicity: 17 white (non-Hispanic); one Hispanic; two African-American; one Native American; two Asian or Pacific Inslander
Anthropometrics: Not described
Location: Seattle, Washington.

Summary of Results:

The increasing dose of cobalamin supplements caused a statistically significant reduction in mean serum MMA (P<0.0001)
Treatment with 25mcg cobalamin resulted in statistically significant reductions in serum MMA concentrations from pre-treatment levels (P<0.001)
Reduction in serum MMA after treatment with 1,000mcg was statistically significant, compared with 25mcg and 100mcg (P<0.001), but treatment with 100mcg did not result in a significantly lower mean serum MMA than treatment with 25mcg cobalamin (P=0.86)
Mean tHcy was not significantly different for the five time-points for the whole study group
Most subjects did not normalize their elevated serum MMA levels until after the 1,000-mcg dose.

Author Conclusion:

Most cobalamin-deficient older people require more than 100mcg of oral cobalamin to normalize serum MMA, which is a larger dose than what is in most standard multi-vitamins and cobalamin supplements.

Funding Source:

Government:

NIH

Not-for-profit

Foundation associated with industry:

Reviewer Comments:

Small sample size
Limited presentation of demographic data

No description of dosing tolerance

No description of diet
Limited knowledge of cobalamin deficiency.

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.)	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%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	Yes
	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?		???
	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?		No
	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?	???
	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?	Yes
	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?	???
	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?	???
	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)?	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?	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