NSUP: Vitamin B12 (2008)

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

To determine whether there is an associaton between serum vitamin B12, vitamin C and folate levels and cognitive and affective functions in elderly Hispanics and non-Hispanic whites.

Inclusion Criteria:
  • On the Health Care Financing Administration (Medicare) registrant list for Bernalilo County, New Mexico
  • 65 years of age or older
  • Residing in Bernalilo County, New Mexico
  • Hispanic or non-Hispanic white
  • Informed consent from participant or legal guardian.
Exclusion Criteria:

None.

Description of Study Protocol:
  • Recruitment: Participants were randomly selected from the Health Care Financing Administration (Medicare) registrant list for Bernalillo County, New Mexico
  • Design: Participants were paid for a home interview followed by a paid comprehensive interview/examination covering health and health-related issues.

Statistical Analysis

  • Continuous variables were tested for normality in distribution.
  • A logarithmic transformation was applied to skewed variables (e.g., vitamin intake from food, to normalize distributions before statistical analysis)
  • Group comparisons were conducted using general linear models for continuous variables adjusting for the effects of sex, ethnicity, vitamin supplement usage, age (five-year intervals), education (high school graduate vs. non graduate) and household income (less than $15,000 vs. $15,000 or more)
  • For categorical variables, (e.g., serum vitamin concentrations above and below certain cutoff levels and use or non-use of multi-vitamin supplements), multivariate logistic regression models were fitted for each of the primary outcomes (cognitive and affective tests) adjusting for sex, ethnicity, age (years), education (years) and household income (less than $15,000 vs. $15,000 or more).
Data Collection Summary:

Timing of Measurements

During a four-hour interview and examination by a nurse practitioner, nurse and nutritionist:

  • Serum vitamin B12, vitamin C and folate were measured
  • Cognitive testing included
    1. The Mini-Mental State Exam (orientation, recall, attention, language and visual graphic ability)
    2. WAIS-R Digits Forward (attention and immediate memory)
    3. Fuld Object Memory Evaluation (learning and secondary memory)
    4. Clock drawing (visuoconstruction)
    5. Two Color Trail Making Tests (psychomotor speed and cognitive flexibility).
  • Three indicators of depression were obtained
    1. A self-report of past history of depression
    2. A list of all current medications
    3. The 15-question short version of the Yesavage Geriatric Depression Scale.
  • Dietary information was collected
    1. Dietary intakes for vitamin B12, vitamin C and folate from the Health Habits and History Questionnaire and food frequency questionnaire
    2. Information about vitamin supplementation.

Dependent Variables

  • Cognitive function
  • Affective function.
Description of Actual Data Sample:
  • Initial N: 883
  • Attrition (final N): From 751 to 816 were included in the four separate tables analyses (participants with any component of the necessary database missing were excluded from that analysis)
  • Age: 65 years of age and older (mean age, 74.1 years)
  • Ethnicity: Hispanic and non-Hispanic white
  • Location: Bernalillo County, New Mexico.
Summary of Results:
  Serum Vitamin B12 Serum Folate Serum Vitamin C

Mean±SD
<221pmol/L

Mean±SD
≥221pmol/L

P-Value

Mean±SD
<11.1nmol/L

Mean±SD
≥11.1nmol/L

P-Value

Mean±SD
<57umol/L

Mean±SD
≥57umol/L

P-Value
Number of Participants (%)
166 (21.1)
619 (78.9)
 
142 (18.1)
641 (81.9)
 
257 (32.8)
526 (67.2)
 
Age, Years
73.6±6.3
73.4±5.8
0.30
73.4±6.0
73.6±5.9
0.64
73.9±6.2
73.2±5.7
0.20
Education, Years
11.5±4.5
12.2±4.1
0.63
10.6±4.2
12.4±4.1
0.007
10.7±4.1
12.8±4.0
<0.001
Cognitive Testing Mini Mental State Exam (30)
26.7±2.4
27.0±2.7
0.37
25.9±2.8
27.1±2.5
0.002
26.4±2.9
27.2±2.4
0.90
Fuld Object Memory Evaluation Number Retrieved (10)
6.73±1.5
6.83±1.5
0.77
6.55±1.69
6.86±1.50
0.05
6.60±1.58
6.92±1.51
0.21
Total Recalled (10)
7.46±1.5
7.50±1.7
0.34
7.16±1.82
7.56±1.58
0.02
7.19±1.66
7.66±1.59
0.06
Number of Names
15.7±4.9
16.2±5.4
0.60
14.4±4.8
16.5±5.3
0.005
14.5±4.6
16.8±5.4
0.17
Digits Forward (10)
5.92±2.17
6.37±2.33
0.92
5.50±2.31
6.44±2.27
0.07
5.62±2.17
6.60±2.28
0.09
Clock Score (8)
6.22±1.6
6.21±1.6
0.31
5.98±1.73
6.26±1.55
0.94
6.12±1.67
6.28±1.52
0.48
Color Trails 1 (25)
20.9±5.0
21.5±4.8
0.84
20.2±5.3
21.6±4.7
0.14
12.1±4.6
13.8±4.8
0.18
Color Trails 2 (25)
12.9±4.6
13.3±4.8
0.60
11.8±5.1
13.5±4.6
0.04
12.1±4.6
13.8±4.8
0.18
Affective Training Geriatric Depression Scale (15)
2.07±2.46
2.03±2.51
0.27
2.42±2.69
1.96±2.44
0.55
2.34±2.51
1.88±2.46
0.28
GDS (%>6)
10.4
9.1
0.93
12.7
8.7
0.45
9.8
9.0
0.59
History of Depression (% Positive)
19.9
24.1
0.08
31.0
21.6
0.10
28.8
20.2
0.04
Currently on Antidepressants (% Positive)
5.4
4.9
0.48
5.0
5.0
0.61
4.7
5.1
0.59
Author Conclusion:
  • In recognition of absorption problems, the elderly are recommended to obtain the RDA for vitamin B12 from supplements or fortified foods. However, the combined evidence does not support the routine use of higher supplement doses of vitamin B12 or of folate or vitamin C supplements to protect against cognitive loss or mood disorders (depression).
  • Individual choices and public policy decisions should await the results of large trials, which will provide more information on the efficacy and safety of these vitamins.
Funding Source:
University/Hospital: UNM GCRC
Reviewer Comments:

Important topic, further research is warranted.

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? N/A
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) N/A
 
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? N/A
  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? N/A
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) N/A
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? N/A
  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? 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? No
  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? N/A
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  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.) N/A
  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? N/A
  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? N/A
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? N/A
  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? N/A
  7.2. Were nutrition measures appropriate to question and outcomes of concern? N/A
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? N/A
  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? 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