EAL

FNOA: Antioxidants (2011-2012)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To examine the effect of daily supplementation with 11 vitamins and five minerals on cognitive function in older adults to assess the possibility that this could help prevent cognitive decline.

Inclusion Criteria:

Men and women aged 65 years and older living in the community
Had not taken vitamin, mineral or fish oil supplements within three months of recruitment (one month for supplements of water-soluble vitamins other than vitamin B₁₂)
All were considered by their family doctor to be suitable for the study.

Exclusion Criteria:

No participants were excluded on the basis of impaired cognitive function, but those with dementia were unlikely to volunteer or would have been excluded by their doctor.

Description of Study Protocol:

Recruitment

Subjects for the MAVIS (Mineral and Vitamin Intervention Study) were recruited from six primary health care centers in North East Scotland between February and December 2002.

Design

Randomized placebo-controlled trial.

Blinding Used

Double-blind.

Intervention

Active treatment consisted of a single tablet containing 11 vitamins and five minerals in amounts ranging from 50% to 210% of the UK Reference Nutrient Intake or matching placebo tablet taken daily for 12 months
Supplement contained 800μg vitamin A, 60mg vitamin C, 5μg vitamin D, 10mg vitamin E, 1.4mg thiamin, 1.6mg riboflavin, 18mg niacin, 6mg pantothenic acid, 2mg pyridoxine, 1μg vitamin B₁₂, 200μg folic acid, 14mg iron, 150μg iodine, 0.75mg copper, 15mg zinc and 1mg manganese.

Statistical Analysis

Intention-to-treat analyses were conducted for trial group comparisons
Statistical significance was based upon the 95% confidence interval
For the two pre-planned trial sub-group analyses (those aged 75 years and over and those at increased risk of deficiency assessed by the nutrition risk questionnaire), the 99% confidence interval was used to give the correct width of the 95% confidence interval.

Data Collection Summary:

Timing of Measurements

Risk of micronutrient deficiency assessed at baseline. Cognitive function measured face-to-face at baseline and over the telephone at 12 months.

Dependent Variables

Cognitive function measured through digit span forward and verbal fluency tests.

Independent Variables

Active treatment consisted of a single tablet containing 11 vitamins and five minerals in amounts ranging from 50% to 210% of the UK Reference Nutrient Intake or matching placebo tablet taken daily for 12 months
Compliance checked by reported consumption at monthly intervals
10% random sample provided tablets for tablet counting
Risk of micronutrient deficiency assessed by simple 17-item risk questionnaire.

Control Variables

Baseline values
Health center
Age
Gender
Place of residence (living in the community or in care).

Description of Actual Data Sample:

Initial N: 910 subjects randomized, 456 to active treatment (48% women), 454 to placebo (47% women)
Attrition (final N): 777 subjects completed the trial (85%). During the trial, 12 participants died, 77 stopped taking their tablets and 44 were lost to follow-up.
Age: Mean age (range 68 to 76 years for both):
- Supplemented group: 72 years
- Placebo group: 71 years
Anthropometrics: Both groups were well-matched in terms of baseline characteristics
Location: Northeast Scotland.

Summary of Results:

Key Findings

Compliance with taking the tablets for all participants for the whole 12-month period was over 78% in both supplemented and placebo groups
For digit span forward, there was no evidence of an effect of supplements in all participants or in subgroups defined by age or risk of deficiency
For verbal fluency, there was no evidence of a beneficial effect in the whole study population, but there was weak evidence for a beneficial effect of supplementation in the two pre-specified sub-groups of those aged 75 years and over [N=290, mean difference between supplemented and placebo groups =2.8 units (95% CI: -0.6, 6.2) and those at increased risk of micronutrient deficiency assessed by the risk questionnaire (N=260, mean difference between supplemented and placebo groups =2.5 units (95% CI: -1.0, 6.1)].

Cognitive Test Scores in the Supplemented and Placebo Groups

Participants	Difference in Digit Span Forward Scores Mean (95% CI)	Difference in Verbal Fluency Scores Mean (95% CI)
All participants	-0.1 (-0.3, 0.2)	0.8 (-0.3, 2.0)
Participants aged 75 years or over	-0.1 (-0.8, 0.6)	2.8 (-0.6, 6.2)
Participants at increased risk of deficiency	0.4 (-0.3, 1.1)	2.5 (-1.0, 5.1)

Author Conclusion:

There was no evidence for a beneficial effect of multivitamin and multimineral supplementation on two tests of cognitive function in tests in the total sample of participants, but the possibility of beneficial effects in those at higher risk of nutritional deficiency cannot be excluded. In view of the high social and economic costs of cognitive decline and the low cost of nutritional supplementation, further intervention studies in older people, particularly those at increased risk of nutritional deficiency, are still warranted.

Funding Source:

Not-for-profit

The Health Foundation (formerly PPP Healthcare Medical Trust)

Other non-profit:

Reviewer Comments:

Authors note the following limitation: Participants were classified as being at increased risk of nutritional deficiency using a simple risk questionnaire rather than by measuring their actual nutritional status from blood samples.

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")?	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?	???
	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?	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?	???
	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?	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?	???
	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)?	Yes
	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