FNOA: Antioxidants (2011-2012)

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

To investigate the association of use of vitamin (VS), mineral (MS) and non-vitamin non-mineral supplements (NVNMS) with common age-related eye diseases.

Inclusion Criteria:

Participants in the Beaver Dam Eye Study.

Exclusion Criteria:

Not specified.

Description of Study Protocol:

Recruitment

A private census of Beaver Dam, Wisconsin was performed in 1987 to 1988 to identify all eligible. 

Design

Population-based prospective cohort study with incidence data. Investigations included:

  • Supplement use with the incidence of eye disease 
  • Eye disease with the incidence of supplement. 

Blinding used 

Not indicated 

Intervention 

The use of vitamin, mineral and non-vitamin non-mineral supplements.

Statistical Analysis

  • To incorporate the changing usage patterns of supplements over the course of the study, incidence was investigated with logistic regression in each five-year hand (baseline to five-year follow-up, five-year follow-up to 10-year follow-up and 10-year follow-up to 15-year follow-up) updating the covariates at the start of each interval.
  • Each band was combined using generalized estimating equations (GEEs)
  • The odds of outcome did not significantly change between each interval
  • All models were adjusted for age and gender
  • The study purpose was to present possible associations rather than to determine casual effects, so there was no adjustment for multiple comparisons.

 

Data Collection Summary:

Timing of Measurements

Baseline, five years, 10 years and 15 years.

Dependent Variables

Incidence of age-related:

  • Cataracts
  • Age-related macular degeneration (AND)
  • High intraocular pressure (IOP).

Independent Variables

  • Incidence of supplement use including: 
    • Multivitamin
    • Vitamin A
    • Vitamin C
    • Vitamin D
    • Vitamin E
    • B vitamins
    • Iron
    • Calcium
    • Zinc
    • Magnesium
    • Potassium
    • Garlic
    • Lecithin
    • Glucosamine
    • Ginseng
    • Ginkgo biloba
    • ω-3 fatty acid
    • Alfalfa
    • Saw palmetto
    • Bilberry
    • Cranberry.

Control Variables

  • Age
  • Sex
  • Ethnicity
  • Height
  • Blood pressure
  • Baseline intraocular pressure
  • Baseline visual fields
  • Baseline fundus and lens photography.
Description of Actual Data Sample:
  • Initial N4,926
  • Attrition (final N):
    • 1988 to 1990: n=4,926
    • 1993 to 1995: n=3,722
    • 1998 to 2000: n=2,962
    • 2003 to 2005: n=2,375
  • Age: 43 to 86 years old
  • Ethnicity: 95% White
  • Other relevant demographics: 56% female
  • Anthropometrics:
  • LocationBeaver Dam, WI, USA.

 

Summary of Results:

Supplement Use With The Incidence of Eye Disease

No evidence of associations was found with the use of VSs, MSs or NVNMs and the incidence of nuclear cataract.

The following had decreased odds of incidence of cortical cataract. The use of:

  • Multivitamins (odds ratio [OR], 0.77; 95% confidence interval [CI], 0.62-0.95) 
  • Single supplements or combinations containing vitamins A (OR, 0.42; 95% CI, 0.24-0.73), and D (OR, 0.54; 95% CI, 0.32-0.93) and zinc (OR, 0.63; 95% CI, 0.41-0.98).

Use of bilberry was associated with increased odds of posterior subcapsular cataract (OR, 5.5; 95% CI, 1.2-24.7).

The following were associated with incident late AMD: Use of:

  • Vitamin A (OR, 3.05; 95% CI, 1.60-5.82)
  • Vitamin C (OR, 2.47; 95% CI, (1.5-4.08)
  • Vitamin E (OR, 1.78; 95% CI, 1.04-3.05) 
  • B complex (OR, 4.15; 95% CI, (1.67-10.29)
  • Zinc (OR, 2.11; 95% CI, 1.09-4.07) 
  • Garlic (OR, 3.18; 95% CI, 1.59-6.39).

Eye Disease With the Incidence of Supplement Use

Nuclear cataract was associated with decreased odds of taking a multivitamin supplement (OR, 8; 95% CI, 0.65-0.97) and decreased odds of taking ω-3 fatty acids (OR, 0.5; 95% CI, 0.3-0.8).

Cortical cataract was associated with decreased odds of taking lecithin (OR, 0.4; 95% CI, .1-1) and saw palmetto (OR, 0.4; 95% CI, 0.1-1).

Posterior subcapsular cataracts were associated with decreased use of:

  • MSs (OR, 0.6; 95% CI, 0.4-0.9)
  • Garlic (OR, 0.4; 95% CI, 0.2-0.9) 
  • Ginkgo biloba (OR, 0.1; 95% CI, 0-0.9).

Early AMD was associated with an increased risk of taking vitamin A (OR, 1.74; 95% CI (1.25-2.43) and zinc (OR, 1.41; 95% CI, 1.08-1.85).

Late AMD was associated with increased use of:

  • Vitamin A (OR, 7.55; 95% CI, 4.03-14.17) 
  • Vitamin C (OR, 4.31; 95% CI, 2.44-7.64) 
  • Vitamin E (OR, 3.3; 95% CI, 1.75-6.23) 
  • Zinc (OR, 5.20; 95% CI, 2.78-9.75).

Having a high IOP (>21 mmHg) was not associated with taking any VS, MS or NVNMS.

Glaucoma at the baseline examination was associated with decreased odds of taking vitamin C (OR, 0.2; 95% CI, 0.1-1) and calcium (OR, 0.4; 95% CI, 0.2-1) five years later.

Specific Vitamin Use and AMD 

  • Excluding multivitamin use, there was an increasing frequency of use of other preparations that contain vitamins A, C and E and zinc at each examinations (18.2% at baseline to 55.2%) for those with any AMD
  • Persons taking multivitamins had a prevalence of AMD similar to that of those not taking these supplements.
Author Conclusion:
  • The data did not support the notion that any of the supplements taken in the Beaver Dam Eye Study offered protection against incident nuclear or posterior cataract, early or late AMD or elevated IOP.
  • It must be kept in mind that ingested supplements (as well as systemic medications) may have untoward effects on the eye as well as systemically
  • Supplements are not subject to the same toxicity studies are drugs and may contain contaminants, variable dosages and non-standard analogs of the alleged preparation and may interact in known and unknown ways with other supplements and medications.
Funding Source:
Government: National Institutes of Health and Research to Prevent Blindness
Reviewer Comments:

The authors note the following limitations:

  • Lack of uniform information on dose and duration of use of any preparation
  • There may be advantages of taking some specific supplements together and there were too few people taking specific combinations to assess this
  • Dietary intake of nutrients may have a different influence on the disease process than supplements and there was not adequate information to judge this
  • There may be other environmental and genetic factors that influence the impact of these supplements on disease and there was not information to evaluate these possibilities.

Other limitations include that information about intervention detail for supplements such as amount and length of time taken was not provided. Intervening factors were not considered. Information about selection and comparison of study groups, withdrawals and blinding was not included in this study, but may have been provided in the initial Beaver Dam Eye Study.

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? No
  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? No
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? No
  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) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? ???
  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? ???
  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? 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? ???
  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? ???
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? No
  6.6. Were extra or unplanned treatments described? No
  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? 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