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 crystalline cobalamin, in the form of milk product or by a capsule, on the cobalamin status of elderly Dutch people with a mild cobalamin deficiency.

Inclusion Criteria:

Mild cobalamin deficiency, defined as a serum cobalamin concentration ranging from 100pmol to 300pmol per L and plasma MMA concentrations were at least 0.30micromol per L
70 years old or older
Residence of shelter housing.

Exclusion Criteria:

History of cobalamin deficiency
High cobalamin (over 50mcg per day)
High folate (over 200mcg per day)
Use of supplementation or injections
Gastrointestinal surgery
Renal dysfunction (serum creatinine over 120micromol per L)
Anemia
Cancer.

Description of Study Protocol:

Recruitment

Netherlands sheltered housing, direct mailings.

Design

Randomized, parallel, double-blind placebo-controlled trial
81 men and women aged 70 and older with Mild cobalamin deficiency received either a cobalamin fortified supplement (milk or capsule) or placebo for 12 weeks while consuming their usual diet.

Blinding Used

Yes.

Intervention

Subjects were randomly assigned to consume either a cobalamin fortified supplement (milk or capsule) or placebo for 12 weeks while consuming their usual diet
Journals were kept for compliance
A list of products rich in cobalamin, mainly liver products, was provided to participants of the milk trial.

Statistical Analysis

ANOVA
Chi-square
Levene’s test
Kruskal-Wallis test
Student’s T-test
Wilcoxon’s signed-rank test
Mann-Whitney U-test
Bonferroni corrections.

Data Collection Summary:

Timing of Measurements

The following data was collected at baseline and 12 weeks

Plasma methylmalonic acid
Homocysteine concentrations
Serum cobalamin concentrations
Plasma homocysteine
Red blood cell (RBC) folate
Hemoglobin
Hematocrit.

Dependent Variables

Plasma methylmalonic acid
Homocysteine concentrations
Serum cobalamin concentrations
Plasma homocysteine
Red blood cell (RBC) folate.

Independent Variables

Cobalamin fortified mi lk
Cobalamin fortified ca psule.

Description of Actual Data Sample:

Initial N

113
Cobalamin capsules: N=48 (23 capsule, 25 placebo)
Milk capsules: N=41 (19 milk, 19 placebo).

Attrition (Final N)

81
Cobalamin capsules: N=19 (24 placebo)
Milk capsules: N=19 (19 placebo).

Age

Cobalamin capsules: 82±5.4 years (placebo, 82±4.7 years)
Cobalamin milk: 81±5.6 years (placebo, 82±3.7 years).

Ethnicity

Not described.

Anthropometrics

Weight for cobalamin capsules: 70.3±11.2kg (placebo, 74.2±10.3kg)
Weight for cobalamin milk: 74.4±11.8kg (placebo, 70.5±11.4kg).

Location

Wageningen University, The Netherlands.

Summary of Results:

Fortified Milk Group
- The mean (±SD) increase in serum cobalamin was 250±96pmol per L
- The median (fifth and 95th percentiles) decreased in plasma
- MMA was 0.19pmol per L (-0.76, 0.04).
The median decrease in plasma homocysteine was 4.0pmol per L (0.3, 3.0)
Cobalamin Capsule Group
- The mean increase in serum cobalamin was 281±136pmol per L
- The median decrease in plasma MMA was 0.18pmol per L (-2.95, 0.14)
- The median decrease in plasma homocysteine was 1.8pmol per L (-10.6, 2.4).
All changes were significantly different from those in the Placebo Capsule Group (P<0.01).

Author Conclusion:

Overall crystalline cobalamin, in the form of fortified milk or capsules, can improve cobalamin status
The improvement in cobalamin status in our study was not different between carriers, although the content of cobalamin in milk was somewhat lower (60mcg) than that in the capsules.

Funding Source:

Industry:

Dutch Dairy Association

Commodity Group:

Reviewer Comments:

Data set from a parallel study used in results
Holo-transcobalamin not used as an indicator of cobalamin deficiency
Content of cobalamin in capsules vs. milk was different
Small sample size
Limited presentation of demographic data
No power calculation presented
No description of diet composition.

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?	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")?	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?	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?	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?	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?	N/A
	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?		N/A
	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?	N/A
	7.7.	Were the measurements conducted consistently across groups?	N/A
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