NSUP: Vitamin B12 (2008)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

To examine the relationship between cognitive malfunction and high-dose vitamins on blood vitamin concentrations in healthy non-vitamin deficient elderly.

Inclusion Criteria:
  • Good health
  • Ability to see, hear, read and write
  • Ability to comprehend language and directions
  • Diagnosis of therapeutically controlled hypertension, cardiac disease, orthopedic problems and diabetes
  • Mini-Mental State Examination (MMSE) score less than 24
  • Currently taking a daily multi-vitamin.
Exclusion Criteria:
  • Evidence of dementia, schizophrenia, Parkinson's disease, Alzheimer's disease, confusional problems, mental retardation, neurologic, organic or pharmacological mental syndromes
  • Initial hypovitaminemia
  • Psychotropic drugs
  • Occasional intake of barbiturates or tranquilizers or their derivatives was prohibited for at least seven days before undertaking an MMSE to test cognitive function.
Description of Study Protocol:
  • Recruitment: New Jersey Center for the Aged
  • Design: Randomized controlled trial
  • Blinding used: No
  • Intervention: Half of the subjects were given a high-dose multi-vitamin supplement with three meals each day for a year. The other half did not receive a high-dose multi-vitamin supplement.
  • Statistical analysis: Percentage change.
Data Collection Summary:

Timing of Measurements

Baseline and one year blood vitamin concentrations were obtained including

  • Folic acid
  • Vitamin B6
  • Vitamin B12
  • Vitamin C
  • Vitamin A
  • Vitamin E
  • Riboflavin
  • Nicotinates
  • Pantothenate
  • Thiamin
  • Biotin.

Dependent Variables

High-dose vitamin supplementation.

Independent Variables

  • MMSE
  • Folic acid
  • Vitamin B6
  • Vitamin B12
  • Vitamin C
  • Vitamin A
  • Vitamin E
  • Riboflavin
  • Nicotinates
  • Pantothenate
  • Thiamin
  • Biotin.
Description of Actual Data Sample:
  • Initial N: 20 (10 multi-vitamin, 10 non-multivitamin)
  • Attrition (final N): 20 (10 multi-vitamin, 10 non-multivitamin)
  • Age: 79 to 90 years old
  • Ethnicity: Not described
  • Anthropometrics: Not described
  • Location: Department of Preventative Medicine and Community Health: New Jersey Medical School, Newark, New Jersey.
Summary of Results:

Non-Vitamin Supplemented Group Over One Year

  • Nine experienced a drop in riboflavin
  • Eight experienced a drop in vitamin B6
  • Seven experienced a drop in folate and vitamin A
  • Six experienced a drop in vitamin B12 and pantothenate
  • Five experienced a drop in vitamin C
  • Three experienced a drop in vitamin E and nicotinates
  • No change in MMSE
  • No signs of developing organic dementia.

Vitamin Supplemented Group Over One Year

  • Hypervitaminosis, as evidenced by percentage change of 0% to 1,549%
  • No evidence of vitamin toxicity
  • No change in MMSE
  • No signs of developing organic dementia.
Author Conclusion:
  • Massive hypervitaminosis did not reverse cognitive malfunctions status 
  • Vitamin B12 blood concentrations increased by 14% to 189% in non-vitamin B12 deficient elderly and increased folate deficiency by 108% to 1,549% in non-folate deficient elderly, yet no cognitive improvement was seen
  • Depression of blood vitamins may be unrelated to worsening cognitive malfunction.

 

Funding Source:
Reviewer Comments:
  • Small sample size
  • No description of diet
  • No description of demographics
  • No description of anthropometrics
  • No placebo used
  • Unclear if control group continued multivitamin supplement as ordered before the start of the study
  • No diary used of compliance
  • Limited examination of cognitive function.
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? ???
  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? ???
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
3. Were study groups comparable? No
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) ???
  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.) 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? N/A
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? ???
  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.) ???
  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? 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? 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? No
  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? No
  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? No
  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