NSUP: Vitamin B12 (2008)

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

To determine the relationship between vitamin B12 and folate status on macrocytosis, anemia and cognitive impairment in the elderly population.

Inclusion Criteria:
  • Participant of the 1999 to 2002 US National Health and Nutrition Examination Survey
  • 60 years old and older.
Exclusion Criteria:
  • Serum creatinine concentrations indicative of renal dysfunction
  • Recent anemia therapy
  • History of stroke
  • Heavy alcohol use
  • Diseases of the liver, kidney or coronary arteries.
Description of Study Protocol:
  • Recruitment: NHANES study participant
  • Design: Cross-sectional study
  • Blinding used: N/A
  • Intervention: N/A
  • Statistical analysis: Regression analysis.
Data Collection Summary:

Timing of Measurements

The following data was collected from NHANES data:

  • Serum folate
  • Serum creatinine
  • Serum ferritin
  • Cognitive series (Mini-Mental).

 Dependent Variables

  • Low vitamin B12 (defined as a serum vitamin B12 concentration less than 148pmol per L or a or a serum methylmalonic acid concentration greater than 210nmol per L)
  • Normal vitamin B12
  • High folate (defined as a serum folate concentration greater than 55nmol per L).

 Independent Variables 

  • Cognitive Impairement
  • Anemia
  • Macrocytosis.
Description of Actual Data Sample:

Initial N

  • Normal vitamin B12 status: 1,113 (422 males, 690 females)
  • Low vitamin B12 status: 346 (117 males, 228 females).

Attrition (Final N)

Of the 3,706 senior survey participants, 1,684 were eligible, 1,078 were ineligible and eligibility status could not be determined for 944.

Age

  • Normal vitamin B12 status: 70±0.3 years
  • Low vitamin B12 status: 72±0.39 years years.

Ethnicity

  • Non-Hispanic white
    • Normal vitamin B12 status: 81%
    • Low vitamin B12 status: 85%.
  • Non-Hispanic black
    • Normal vitamin B12 status: 8%
    • Low vitamin B12 status: 4.4%.
  • Mexican American
    • Normal vitamin B12 status: 3.1%
    • Low vitamin B12 status: 2.1%.

Anthropometrics  

Not described.

Location

US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA.

Summary of Results:
  • Low vs. normal vitamin B12 status was associated with anemia [odds ratio (OR), 2.7; 95% CI, 1.7, 4.2], macrocytosis (OR, 1.8; 95% CI, 1.01, 3.3) and cognitive impairment (OR, 2.5, 95% CI, 1.6, 3.8)
  • In the group with a low vitamin B12 status, serum folate greater than 59nmol per L (80th percentile), as opposed to under 59nmol per L, was associated with anemia (OR, 3.1; 95% CI, 1.5, 6.6) and cognitive impairment (OR, 2.6; 95% CI, 1.1, 6.1)
  • In the normal vitamin B12 group, ORs relating high vs. normal serum folate to these outcomes were less than one.
Author Conclusion:
  • In seniors with low vitamin B12 status, high serum folate was associated with anemia and cognitive impairment
  • When vitamin B12 status was normal however, high serum folate was associated with protection against cognitive impairment.
Funding Source:
Government: USDA
Reviewer Comments:

  • Lack of a gold-standard indicator of low vitamin B12
  • Population with previous health problems
  • Limited demographics
  • 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.) 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.) Yes
  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? 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.) ???
  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? Yes
  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? 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? 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