EAL

NSUP: Vitamin B12 (2008)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To determine whether a multi-vitamin or mineral supplement formulated at 100% DV will further lower homocysteine concentrations and improve B-vitamin status in healthy older adults already consuming a diet fortified with folic acid.

Inclusion Criteria:

Total plasma homocysteine concentrations of greater than 8.0mmol per L
Healthy
Free-living
Over 50 years old.

Exclusion Criteria:

Smoker
Used dietary supplements regularly for three months before study
Taking medications known to interfere with folate metabolism
Established diseases of the gastrointestinal tract, liver or kidney
Any disability that would impede full participation in the study.

Description of Study Protocol:

Recruitment

Boston area newspaper advertisements
Direct mailings
Clinic postings.

Design

Randomized, double-blind placebo-controlled trial
80 free-living men and women aged 50 to 87 years with total plasma homocysteine concentrations of more than 8.0mmol per L received either a multi-vitamin or mineral supplement or placebo for 56 days, while consuming their usual diet.

Blinding Used

Yes.

Intervention

Subjects were randomly assigned to consume either a multivitamin or mineral supplement or placebo for 56 days while consuming their usual diet.

Statistical Analysis

Wilcoxon-Mann-Whitney test
Student T-test.

Data Collection Summary:

Timing of Measurements

The following data was collected at zero, 49 and 56 days of the intervention:

Folate, nmol per L
Pyridoxal phosphate, nmol per L
Vitamin B₆, AC
Vitamin B₁₂, nmol per L
25-OH-vitamin D
A-tocopherol
G-tocopherol
Vitamin C
Glutathione peroxidase
Vitamin A.

Dependent Variables

Dependent variables were a multi-vitamin and mineral prep.

Independent Variables

Glutathione peroxidase: Plasma (U per L), RBC (U per g HGB)
ORAC (mmol Trolox equivalent)
IL-2 receptor (pg per ml)
IL-6 (pg per ml)
IL-10 stimulated (pg per ml)
PGE2 stimulated (pg per ml).

Description of Actual Data Sample:

Initial N: 39
- Placebo: 26 males, 13 females
- Supplemented: 41 (28 male, 13 female).
Attrition (final N): 39
Age
- Placebo: 66.5±8.1 years
- Supplemented: 66.6±9.1 years.
Ethnicity: Not described.

Anthropometrics

Placebo: BMI=27.1±3.8
Supplemented: BMI=27.9±4.7.

Location

Boston, Massachusetts.

Summary of Results:

Subjects taking the supplement had significantly higher B-vitamin status and lower homocysteine concentration than controls (P=0.01)
Plasma folate, pyridoxal phosphate (PLP) and vitamin B₁₂ concentrations were increased 41.6%, 36.5% and 13.8%, respectively, in the supplemented group, whereas no changes were observed in the placebo group
The mean homocysteine concentration decreased 9.6% in the supplemented group (P=0.001) and was unaffected in the placebo group
There were no significant changes in dietary intake during the intervention.

Author Conclusion:

Small sample size
Limited presentation of demographic data
No power calculation presented
No description of randomization scheme.

Funding Source:

Government:

USDA

Industry:

Pharmative Corp.

Food Company:

Reviewer Comments:

Supplementation with a multivitamin formulated at about 100% Daily Value can decrease the prevalence of sub-optimal vitamin status in older adults and improve their micro-nutrient status to levels associated with reduced risk for several chronic diseases.

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?		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?	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?	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?		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?	N/A
	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?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes