EAL

FNOA: Antioxidants (2011-2012)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To develop a composite scoring system to summarize the combined effect of multiple dietary nutrients on age-related macular degeneration (AMD) risk because foods provide many nutrients that may interact to modify risk for multifactorial diseases such as AMD.

Inclusion Criteria:

Detailed inclusion criteria have been described extensively in the AREDS report series. A total of 4,757 participants, aged 55 to 80 years at recruitment, were enrolled.

Exclusion Criteria:

Of the original 4757 AREDS participants at baseline, excluded were:

398 persons with diabetes
108 persons with invalid calorie intake (valid intake ranging from 400kcal to 3,000kcal per day for females and 600kcal to 3,500kcal per day for males)
248 persons with missing nutritional, non-nutritional and ophthalmologic covariates.

Description of Study Protocol:

Recruitment: Detailed recruitment criteria have been described extensively in the AREDS report series. A total of 4,757 participants, aged 55 to 80 years at recruitment, were enrolled from November 1992 to January 1998. The remaining 4,003 persons contributed 7,934 eligible eyes in this study.
Design: Cross-sectional study
Blinding used: Implied with measurements.

Statistical Analysis

To evaluate the effect of a specific dietary pattern of interest, a scoring system was developed based on the percentile ranks of nutrient intakes
First three composite scores were calculated: (a) DP1 diet; (b) DP2 diet; (c) DP3 diet by specifying the dietary intakes of (a) vitamin C, vitamin E and zinc; (b) DHA, EPA and Lz; (c) dGI, respectively
The three dietary patterns were defined to represent diets rich in the AREDS trial nutrients, AREDS2 trial nutrients and low-GI foods, respectively. The composite score was defined to be the linear combination of the intake scores from individual nutrients.
Using eye as the unit of analysis, the association between the compound score and risk of prevalent AMD was evaluated
Validation, fitness and performance of the model were evaluated using bootstrapping techniques, adjusted quasi-likelihood under the independence model criterion, and the c-index, respectively.

Data Collection Summary:

Timing of measurements: Stereoscopic fundus photographs of the macula were taken and graded at baseline
Dependent variables: Risk of AMD. Stereoscopic fundus photographs of the macula were taken and graded using the AREDS protocol and AMD Classification System
Independent variables: Dietary compound score, based on dietary intakes of vitamins C and E, zinc, lutein/zeaxanthin, docosahexaenoic acid, eicosapentaenoic acid and low-dietary glycemic index (dGI).

Control Variables

Age
Gender
Education level
Race
BMI
Smoking status
Alcohol drinking
Sunlight exposure
Hypertension history
Baseline AMD classification
Presence of lens opacity
Refractive error
Total calorie intake
Energy-adjusted dietary variables.

Description of Actual Data Sample:

Initial N: 4,757 participants
Attrition (final N): 4,003 participants included in the analysis, contributing 7,934 eyes
Age: 55 to 80 at recruitment
Anthropometrics: Published elsewhere
Location: Multi-center study in the United States.

Summary of Results:

Key Findings

The results showed that higher compound scores were associated with lower risk for early AMD, indicated by drusen and advanced AMD
Validation analyses indicated that these relationships are robust (the average 50-time bootstrapping per quartile odds ratios 0.727, 0.827 and 0.753, respectively, for drusen and 0.616, 0.536 and 0.572, respectively, for advanced AMD).

Other Findings

Model selection analyses suggested that the compound score should be included, but that measures of dietary carotene should not be included.

Author Conclusion:

We found that consuming diets that provide low dGI and higher intakes of these nutrients were associated with the greatest reduction in risk for prevalent drusen and advanced AMD, whereas dietary carotene did not affect these relationships
These findings warrant further prospective studies.

Funding Source:

Government:

USDA, NIH

Not-for-profit

Johnson and Johnson Focused Giving Program, American Health Assistance Foundation

Foundation associated with industry:

Other non-profit:

Other:

Ross Aging Initiative

Reviewer Comments:

Recruitment methods, inclusion and exclusion criteria and demographic information published elsewhere.
Authors note the following limitations:
- Three aspects of this study merit further discussion: The AREDS data set, the methods used in the development of the composite scoring system and the composite scoring system, per se
- Until the results of this cross-sectional study are confirmed by randomized trials or population-based, prospective studies, it would be inappropriate to make dietary recommendations based on the present findings.

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?		???
	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?	???
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	???
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
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?	Yes
	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?	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?	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?	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?	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?	N/A
	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?	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?		???
	7.1.	Were primary and secondary endpoints described and relevant to the question?	N/A
	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?	???
	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