FNOA: Antioxidants (2011-2012)

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

To investigate the association between dietary antioxidant from daily foods and supplements and the 10-year incidence of age-related macular degeneration (AMD) in an older Australian cohort. Of particular interest were intakes of combined β-carotene, zinc, and vitamins C and E.

 

Inclusion Criteria:

Aged 49 and older.

 

Exclusion Criteria:

No exclusion criteria were reported.

Description of Study Protocol:

Recruitment 

Subjects were participants in the Blue Mountain Eye Study. Recruitment methods for participants in this study were not outlined. 

Design

Population-based cohort study

Eye examinations were performed at baseline, five years, and 10 years. At each exam participants underwent a comprehensive eye examination after pupil dilation and 30 degree stereoscopic retinal photographs were taken. When lesions were identified at follow-up, side by side grading of the baseline and follow-up photographs were performed.

Patients completed a 145-item semiquantitative food frequency questionnaire at baseline that included questions on strength and frequency of dietary supplement intake.

A standardized questionnaire was administered at baseline to collect information on demographics, family history, medications taken, self-reported diagnosis of diabetes, acute myocardial infarction, angina or stroke and smoking history. Participants were asked what their main job was in their working life and were assigned an occupational prestige score based on the Daniel Occupational Prestige Scale. Fasting blood samples were drawn for clinical biochemistry assessment. 

Blinding used

Not applicable 

Intervention

Not applicable 

Statistical Analysis

Relative risks and confidence intervals were calculated using discrete linear logistic models to examine the association of baseline dietary antioxidant intake and the 10-year incidence of early, late or any AMD lesion. These models were adjusted for age, gender and smoking.

Antioxidant intakes were analyzed as continuous variables and as tertiles.

The Bonferroni correction was applied to adjust for multiple tests.

 

Data Collection Summary:

Timing of Measurements

Dietary intake and potential confounding factors were collected at baseline (1992-1994). Follow-up eye exams took place at five and 10 years. 

Dependent Variables

Age-related macular degeneration as measured by stereoscopic retinal photographs graded using the Wisconsin Grading System.

Independent Variables

  • Dietary and supplement intakes of antioxidants (β-carotene, zinc, vitamins A and C), as collected by a baseline food frequency questionnaire and analyzed using the Australian Tables of Food Composition (1990)
  • Dietary and supplement intakes of combined lutein and zeaxanthin, lycopene, β-cryptoxanthin, and α-carotene as measured by the US. Department of Agriculture Carotenoid Food Composition database.

Control Variables

  • Age
  • Gender
  • Smoking.

 

 

Description of Actual Data Sample:
  • Initial N: =2,900
    • 3,654 participants received baseline examinations
    • The Food Frequency Questionnaire was returned by 3,267 participants with 2,900 of those usable
    • The gender breakdown of participants was not provided
  • Attrition (final N): 2,335 participants in the original cohort (75.1% of survivors) were re-examined after five years and 1,952 (53.4% of survivors) of the original cohort returned for the 10-year exam 
  • Age: All participants were aged 49 and older. Mean age of the entire study group was not reported.
  • Ethnicity: Not specified, although the area of the study was described as "primarily white"
  • Other relevant demographics: Demographic data was collected, but not reported for the entire study group.
  • Anthropometrics: No anthropometric data was collected.
  • Location: West of Sydney, Australia.

 

Summary of Results:
  • Those in the top decile of total zinc intake (≥15.8mg per day) were significantly less likely to develop early AMD (RR 0.54; 95% CI, 0.30-0.97; P=0.041) or any AMD (RR, 0.56, 95% CI, 0.32-0.97; P=0.040) compared with the remaining population. Those within the top tertile of dietary lutein and zeaxanthin intake were significantly less likely to develop neovascular AMD and those above the median intake were less likely to develop indistinct soft or reticular drusen.
  • Increasing β-carotene intake, either from diet alone or from diet and supplements combined was associated with a higher risk of neovascular AMD.
  • Those in the top tertiles of intake of vegetables, compared with the remaining population, has a significantly reduced risk of developing any AMD (RR, 0.64; 95% CI, 0.41-0.98, P=0.040)
  • No significant association was shown between higher or lower intake of β-carotene, vitamin C, vitamin E, and zinc and incident AMD
  • When the Bonferroni correction was applied, most of the results were nonsignificant.

Association between Baseline Dietary Antioxidant Intake and 10-Year Incident Late Age-Related Macular Degeneration in the Blue Mountains Eye Study

Nutrient (Tertile) Late AMD
No. of Outcomes at Risk
Late AMD
Adjusted RR
(95% CI)
Late AMD
Adjusted RR
(95% CI)
Neovascular AMD
No. of Outcomes at Risk
Neovascular AMD
Adjusted RR (95% CI)
Neovascular AMD
Adjusted RR (95% CI)
β-carotene (diet)      
1  14/672  1.00 1.00  7/675 1.00  1.00
2  17/683 1.11(0.52-2.36) 0/86(0.39-1.93) 10/684 1.37(0.50-3.74) 0.94(0.30-2.88)
3  28/680 1.68(0.85-3.34) 1.65(0.83-3.28) 21/681 2.32(0.95-5.6) 2.41(0.98-5.91)
P value for trend    0.11 0.10    0.048  0.027
β-carotene (diet plus supplements)      
1  12/674  1.00  1.00  6/676  1.00  1.00
2  20/684  1.55(0.73-3.30)  1.28(0.58-2.82)  12/686  1.90(0.69-5.24)  1.47(0.49-4.38)
3  27/677  1.83(0.89-3.76)  1.86(0.90-3.84)  20/678  2.49(0.97-6.40)  2.68(1.03-6.96)
P value for trend    0.11  0.080    0.059  0.029
Lutein and zeaxanthin      
1  19/673  1.00  1.00  13/675  1.00  1.00
2  23/682  1.18(0.62-2.25)  1.11(0.58-2.13  16/684  1.19(0.56-2.54)  1.12(0.52-2.41)
3  17/680  0.76(0.38-1.56)  0.72(0.34-1.50)  9/681  0.46(0.18-1.19)  0.37(0.13-1.05)
P value for trend    0.41  0.36    0.097  0.061
Vitamin A (diet)      
1 14/679 1.00 1.00 7/682 1.00 1.00
2 15/680 0.99(0.46-2.13 0.97(0.44-2.12) 10/82 1.39(0.52-3.73) 1.42(0.51-3.91)
3 30/676 1.78(0.91-3.49) 1.66(0.84-3.30) 21/676 2.26(0.93-5.52) 2.12(0.85-5.28)
P value for trend   0.065 0.11   0.057 0.093
Vitamin A (diet plus supplements)      
1  13/677  1.00 1.00 7/681 1.00  1.00
2  18/681  1.23(0.58-2.59) 1.17(0.55-2.49) 11/682 1.50(0.57-3.94)  2.03(0.79-5.24)
3  28/677  1.71(0.85-3.44) 1.60(0.79-3.25) 20/677 2.10(0.86-5.16)  1/96(0.74-5.15)
P value for trend    0.11  0.17   0.098  0.44
Vitamin E (diet plus supplements)          
1  11/677  1.00  1.00  8/680  1.00  1.00
2  28/677  2.71(1.27-5.75)  2.83(1.28-6.23)  18/678  1.50(0.57-3.94)  2.03(0.79-5.24)
3  20/681  2.21(1.02-4.80)  2.55(1.14-5.70)  12/682  2.10(0.86-5.16)  1/96(0.74-5.15)
P value for trend     0.4  0.22    0.098  0.44

  

 

 

Author Conclusion:

The authors found that higher dietary intake of lutein and zeaxanthin may confer protection against long-term incident neovascular AMD or indistinct soft or reticular drusen and that zinc intake from diet and supplements combined may protect against early or any AMD.

A high intake of vegetables was also protective for any AMD.

The authors could not confirm the protective effect of the combined high intakes of β carotene, zinc and vitamins C and E.

Funding Source:
Government: Australian National Health and Medical Research Council
University/Hospital: University of Sydney, Sydney, Australia
Reviewer Comments:

Several details of the study, including methods and procedures, were reported elsewhere but were unavailable in this paper. Based on the information provided the reviewer was unable to determine much information about the study population.

The conclusions drawn from this study were based on one food frequency questionnaire taken at baseline. This reviewer believes that it is difficult to accurately determine nutrient intake from food and supplements based on a FFQ taken at one point in time.

There was no information provided as to the reasons for the participants who did not return for follow-up at five and 10 years.

Data on the ages of all participants was not provided. "Greater than 49 years of age" could include a wide variability in ages and ability to accurately complete a food frequency questionnaire.

It appears that participants who did not complete the food frequency questionnaire were followed up at five and 10 years with examinations. It is difficult for this reviewer to sort out exactly how many of those who originally participated in the study actually completed both the food frequency and were followed up at 10 years. As a result, this reviewer is unclear on the exact n of those who completed the 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? ???
  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? ???
  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? ???
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? No
  4.1. Were follow-up methods described and the same for all groups? ???
  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%.) No
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? No
  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? 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? N/A
  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