EAL

NSUP: Vitamin B12 (2008)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To determine whether use of an enriched drink including moderate doses of micro-nutrients can improve cognitive function in frail elderly persons.

Inclusion Criteria:

Persons aged 65 or older
BMI less than 25kg per m²
Resided in a home for elderly persons or sheltered housing residence
Enrolled between May 1999 and March 2001.

Exclusion Criteria:

Persons younger than age 65
Persons with a BMI greater than 25kg per m²
Persons not residing in a home for elderly persons or sheltered housing
Residents with cancer, GI disease, need for a therapeutic diet incompatible with supplementation or mental inability to respond to the study questions or inability in remembering to take supplement.

Description of Study Protocol:

Recruitment

Participants recruited between may 1999 and March 2001 from resident facilities.

Design

Participants randomly assigned to one of two groups (supplement and control)
Participants were matched for BMI
Enriched drink or placebo of 125ml consumed twice per day
Enriched drink contained 30% to 150% of US RDA for vitamins and minerals with enhanced amounts of antioxidants AND containing 250kcal in a daily dose
Placebo was non-caloric
The following tests were conducted initially and after six months of treatment
- Three-day diet record
- Plasma homocysteine
- Serum B₁₂
- Anthropometric measurements
- Mini-Mental State Examination (MMSE)
- Geriatric Depression Scale
- Neuro-psychological tests
- Word learning test (WLT)
- Category fluency (CF)
- Recognition memory test for words (RMTW) [Note: Serum B₁₂ was only analyzed for a selected group of 26 participants, for whom leftover serum samples were available.].

Blinding Used

Double-blind.

Intervention

Enriched drink contained 30% to 150% of US RDA for vitamins and minerals with enhanced amounts of antioxidants AND containing 250kcal in a daily dose.
Control group received placebo. The placebo contained no energy, vitamins or minerals.

Statistical Analysis

Values mentioned are means ± standard deviations for descriptives and means ± standard error of the mean for changes
Characteristics and baseline neuro-psychological test scores were compared using two-sided T-tests, chi-squared and the Wilcoxon signed rank test
Changes in neuro-psychologicals scores in both groups were analyzed using one-sided Student T-test.

Data Collection Summary:

Timing of Measurements

Prior to initiation of the intervention (baseline) and after six months of supplementation.

Dependent Variables

Biochemical indices
Neuro-psychological tests.

Independent Variables

Supplementation of vitamins, minerals, antioxidants and calories in enriched drink.

Control Variables

All tests administered by the same trained investigator at baseline and post-treatment
Compliance assessed recording consumption of supplement.

Description of Actual Data Sample:

Initial N: 101 participants; 34 did not complete study
Attrition (final N): 77 completed study; 33 placebo (53% female) and 34 treatment (62% female).

Age

Placebo: 81±7
Treatment: 84±6.

Ethnicity

NA, however the study was conducted within the Netherlands.

Other Relevant Demographics

Study conducted within the Netherlands.

Anthropometrics

BMI for Placebo Group: 24.1±2.3
BMI for Treatment Group: 23.5±2.4.

Location

Persons residing in a home for elderly persons or sheltered housing residence within the Netherlands.

Summary of Results:

Variables	Treatment Group Measures and confidence intervals	Control Group Measures and confidence intervals	Statistical Significance of Group Difference
Neuro-Psychological Tests	4.4±2.1 baseline	6.1±2.2 baseline	P<0.01
WLT	0.9±0.3 change	-0.1±0.3 change	P<0.01
Category Fluency	10.1±4.3 baseline	11.9±3.4 baseline	P=0.017
Category Fluency	1.2±0.7 change	-0.6±0.5 change	P=0.017
Biochemical Indices	18.4±7.9 baseline	17.6±5.0 baseline	P=0.000
Homocysteine	-6.3±5.9 change	-0.3±2.9 change	P=0.000
Plasma Vitamin B₁₂	304±118 baseline	290±99 baseline	P=0.003
Plasma Vitamin B₁₂	105±50	-8±16	P=0.003

Other Findings

WLT and CF professions improved significantly in treatment group compared to placebo
No significant differences for changes between groups in WKT delayed, RMTW and CF animals
Significant increase in vitamin B₁₂ concentration and decreases in homocysteine in the supplement group.

Author Conclusion:

This study adds to the growing body of evidence that nutritional supplementation may improve neuro-psychological performance in the frail elderly population
Based on this study, the effects are clinically relevant.

Funding Source:

Industry:

Numico Research Neatherland

Food Company:

Reviewer Comments:

Difficult to assess some of the cognition tests, however the study utilized proven methods
Study was placebo-controlled, however the placebo was non-caloric vs. 250 extra nutritive calories in the intervention.

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.)	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?	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")?	Yes
4.	Was method of handling withdrawals described?		???
	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%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	???
	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?	Yes
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	Yes
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?	???
	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?	???
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?	???