Experimental Design Issues for Assessment of Carotenoids Lutein and Zeaxanthin in Age-Related Eye Disease Study 2 Formulation for Age-Related Macular Degeneration

Publication Type
Journal Article
Year of Publication
Chew, EY; Clemons, TE;
JAMA Ophthalmol
Start Page
Date Published
In Reply: We agree with Benke and Benke that the cost of a dose-ranging study on lutein and zeaxanthin to determine efficacy for the treatment of AMD would be highly prohibitive. As they point out, it would take studies larger than AREDS2 to address the question of optimal dose. With limited resources for a large dose-ranging clinical trial, we used surrogate outcomes in smaller studies in an attempt to determine the dose of lutein we would like to test in AREDS2.1,2 We demonstrated that oral supplementation of 10 mg of lutein resulted in a 2-fold increase in the serum level of lutein compared with baseline,1 similar to the increases in the serum levels found using the various supplements in the original AREDS.3 A second dosing study evaluated the serum levels after supplementation with lutein (10 mg) and zeaxanthin (2 mg) in participants randomized to lutein and zeaxanthin with or without ω-3 long-chain polyunsaturated fatty acids.2 The resulting increases in serum lutein levels were identical in both arms. These results were replicated in AREDS2,4 where we found a nearly 2-fold increase in the serum lutein levels in participants randomly assigned to lutein (see eTable 3 in the Supplement in the article by Chew et al4).