DLM: Homocysteine, Folate, B6 or B12 (2007-2011)

Citation:

Yang LK, Wong KC, Wu MY, Liao SL, Kuo CS, Huang RF. Correlations between folate, B12, homocysteine levels, and radiological markers of neuropathology in elderly post-stroke patients. J Am Coll Nutr. 2007 Jun;26(3):272-8

PubMed ID: 17634173
 
Study Design:
Cross-sectional study
Class:
D - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:

To investigate serum levels of folate, B12, and total homocysteine (tHcy) in elderly post-stroke patients, and the possible correlations with radiological markers of neuropathology.

Inclusion Criteria:
  • Post-stroke
  • Elderly (patients were 58-80 y.o. in this study)
  • Department of Neuorlogy at Cardinal Tien Hospital patients
Exclusion Criteria:
  • Patients with Aphasia and/or a concurrent diagnosis of dementia were excluded
  • Patients who had not had a stroke
  • Patients who were not considered "elderly"
Description of Study Protocol:

Recruitment:  Poststroke patients were recruited from the Department of Neurology of Cardinal Tien Hospital, which has affiliations with Fu-Jen University in Taiwan.  Median time interval from occurrence of stroke was 2 years (2.3 ± 1.1 years). The study protocol was approved by both the Committee on Medical Research of the Cardinal Tien Hospital and the Ethical Review Board of Fu-Jen University. Informed consent was secured from all the participants.

 

Design: Cross-sectional study design

 

Dietary Intake/Dietary Assessment Methodology: During scheduled outpatient consultations, experienced dietitians were assigned to assist patients complete a  semiquantitative food frequency questionnaire (FFQ) covering the previous 6-month period (recent intake), and the immediately preceding 24 hours (current intake). The FFQ was developed exclusively in our laboratory for assessment of folate and B12 intakes in the Taiwanese population. It has been validated by multiple 24-hour recalls (r = 0.86, P < 0.001) and by plasma folate levels (r = 0.57, P < 0.001).Patients were asked to complete questionnaires concerning medical history, personal habits, and use of medications.  Smoking, alcohol consumption, and intake of vitamin supplements were recorded. 


Intervention: N/A

 

Statistical Analysis

  • Statistical analyses were performed using the Statistical Analysis System (SAS/STAT Version 6.12, SAS Institute, Cary, NC).
  • Chi-square test was used for categorical variables.
  • Student t-test was used for continuious variables to examine between group values.
  • Whenever P values were <0.05, the differences were considered statistically significant.
  • Correlations between clinical features, lifestyle, vitamin status, tHcy levels and brain lesions were evaluated using both tHcy and serum folate levels in teriles and as continuous variables.
  • Means recorded for each parameter across the tertiles were compared by ANOVA (analysis of covariance).
  • Logistic regression models were used to estimate the odds ratio (95% CI) for infarctions and global brain atrophy with respect to tHcy and vitamin status.
  • Non-normally distributed dependent variables were frist transformed using a logarithmic function.
Data Collection Summary:

Timing of Measurements - one-time data collection (median time from occurrence of stroke was 2 years (2.3 ± 1.1 years)

Dependent Variables:  Cerebral vascular injuries (Magnetic resonance imaging (MRI) or computed tomography (CT) was used for evaluation of brain lesions including infarction and atrophy )

Independent Variables:

Dietary folate and vitamin B12 intakes were evaluated by a 24-h recall using a semi-quantitative questionnaire.

Circulating levels of folate, B12, and tHcy were measured.

Control Variables- sex, age, diseases status, and cerebrovascular lesions 

Description of Actual Data Sample:

Initial N: 89 total (62 of whom also underwent an MRI or CT imaging)

Attrition (final N): 89 total (62 of whom also underwent an MRI or CT imaging) - one-time data collection

Age:57.9-80.5 years old

Ethnicity: Taiwanese

Other relevant demographics:None

Anthropometrics : No difference was observed between groups in relation to BMI

Location:Department of Neurology of Cardinal Tien Hospital (affiliated with Fu-Jen University), Taiwan.

 

Summary of Results:
  • Mean folate intakes of these post-stroke patients were 69% of the recommended dietary allowances (RDA).
  • Mean B12  intakes of these post-stroke patients were 261% of the recommended dietary allowances (RDA).
  • Inadequate folate levels, defined as serum folate < 6 ng/mL, was noted in 68% of these post-stroke patients.
  • Hyperhomocysteinemia levels (tHcy ≥15 μmol/L) were observed in 48%. According to tertiles of serum tHcy and folate levels, the rate of brain atrophy, but not brain infarctions, are significantly associated with elevated tHcy (P = 0.0126) and decreased folate levels (P = 0.0273).
  • After adjustments for age, sex, disease status, brain infarctions and carotid stenosis, the odds ratio of brain atrophy was 9.8 (95% CI: 1.7–56.4, P = 0.0101) in the hyperhomocysteinemia group and 9.6 (95% CI: 1.1– 81.3, P = 0.0377) in the low folate group (serum folate < 3.0 ng/mL) compared with the group with normal tHcy and folate levels.
  • Of the 62 patiens who agreed to undergo MRI or CT, the prevalence of brain atrophy & brain infarction was 39.3% and 8837% respectively.
  • No significant association was noted between vitamin B12 levels and/or folate intake and brain lesions.

 

Author Conclusion:

Data from this study show that elderly post-stroke patients are prone to folate deficiency and hyperhomocycsteinemia , which both contribute to a higher risk of brain atrophy.  Since brain atrophy is considered one of the preclinical markers of Alzheimer's disease, post-stroke paitnes should undergo periodic neurologic assessment and monitoring of folate and tHcy levels.  Whether or not folate supplementation may reduce the risk of brain atrophy in elderly post-stroke patients requires further investigation in longitudinally-designed studies.

Reviewer Comments:
  • Small sample size (89 patients total, 62 of whom agreed to undergo MRI or CT)
    • CT scans are less sensitive to spotty infarcts <1 cm in size (done in those reluctant to undergo MRI)
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) N/A
  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) 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? 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? No
3. Were study groups comparable? ???
  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.) 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? No
  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? 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? Yes
  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? Yes
  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.) Yes
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? Yes
  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? ???
  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? No
  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? Yes
  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? 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? 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? No
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
 
 

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