Abstract | IMPORTANCE: OBJECTIVES: To determine whether adding lutein + zeaxanthin, DHA + EPA, or both to the AREDS formulation decreases the risk of developing advanced AMD and to evaluate the effect of eliminating beta carotene, lowering zinc doses, or both in the AREDS formulation. DESIGN, SETTING, AND PARTICIPANTS: The Age-Related Eye Disease Study 2 (AREDS2), a multicenter, randomized, double-masked, placebo-controlled phase 3 study with a 2 × 2 factorial design, conducted in 2006-2012 and enrolling 4203 participants aged 50 to 85 years at risk for progression to advanced AMD with bilateral large drusen or large drusen in 1 eye and advanced AMD in the fellow eye. INTERVENTIONS: Participants were randomized to receive lutein (10 mg) + zeaxanthin (2 mg), DHA (350 mg) + EPA (650 mg), lutein + zeaxanthin and DHA + EPA, or placebo. All participants were also asked to take the original AREDS formulation or accept a secondary randomization to 4 variations of the AREDS formulation, including elimination of beta carotene, lowering of zinc dose, or both. MAIN OUTCOMES AND MEASURES: Development of advanced AMD. The unit of analyses used was by eye. RESULTS: Median follow-up was 5 years, with 1940 study eyes (1608 participants) progressing to advanced AMD. Kaplan-Meier probabilities of progression to advanced AMD by 5 years were 31% (493 eyes [406 participants]) for placebo, 29% (468 eyes [399 participants]) for lutein + zeaxanthin, 31% (507 eyes [416 participants]) for DHA + EPA, and 30% (472 eyes [387 participants]) for lutein + zeaxanthin and DHA + EPA. Comparison with placebo in the primary analyses demonstrated no statistically significant reduction in progression to advanced AMD (hazard ratio [HR], 0.90 [98.7% CI, 0.76-1.07]; P = .12 for lutein + zeaxanthin; 0.97 [98.7% CI, 0.82-1.16]; P = .70 for DHA + EPA; 0.89 [98.7% CI, 0.75-1.06]; P = .10 for lutein + zeaxanthin and DHA + EPA). There was no apparent effect of beta carotene elimination or lower-dose zinc on progression to advanced AMD. More lung cancers were noted in the beta carotene vs no beta carotene group (23 [2.0%] vs 11 [0.9%], nominal P = .04), mostly in former smokers. CONCLUSIONS AND RELEVANCE: Addition of lutein + zeaxanthin, DHA + EPA, or both to the AREDS formulation in primary analyses did not further reduce risk of progression to advanced AMD. However, because of potential increased incidence of lung cancer in former smokers, lutein + zeaxanthin could be an appropriate carotenoid substitute in the AREDS formulation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00345176.
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Authors | Age-Related Eye Disease Study 2 Research Group |
Journal | JAMA
(JAMA)
Vol. 309
Issue 19
Pg. 2005-15
(May 15 2013)
ISSN: 1538-3598 [Electronic] United States |
PMID | 23644932
(Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
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Chemical References |
- Vitamins
- Xanthophylls
- Zeaxanthins
- beta Carotene
- Docosahexaenoic Acids
- Eicosapentaenoic Acid
- Zinc
- Lutein
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Topics |
- Aged
- Dietary Supplements
- Disease Progression
- Docosahexaenoic Acids
(therapeutic use)
- Double-Blind Method
- Drug Therapy, Combination
- Eicosapentaenoic Acid
(therapeutic use)
- Female
- Humans
- Incidence
- Lung Neoplasms
(epidemiology)
- Lutein
(therapeutic use)
- Macular Degeneration
(drug therapy)
- Male
- Middle Aged
- Risk
- Treatment Outcome
- Vitamins
(therapeutic use)
- Xanthophylls
(therapeutic use)
- Zeaxanthins
- Zinc
(administration & dosage)
- beta Carotene
(administration & dosage, adverse effects)
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