By David Kiefer, MD
SYNOPSIS: Several combinations of lutein, zeaxanthin, and omega-3 fatty acids did not prevent the development of
age-related macular degeneration when compared to placebo after 5 years.
SOURCE: Age-Related Eye Disease Study 2 Research Group. Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: The Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA 2013;309:2005-2015.
Addressing age-related macular degeneration (AMD), a serious public health problem
with minimal to no treatment options, these researchers explored the possibility that a higher dietary intake of lutein, zeaxanthin, and/or omega-3 fatty acids could prevent the development of AMD. This study extends the work of the Age-Related Eye Disease Study (AREDS), which showed a preventive benefit of supplementation with antioxidant vitamins and minerals. The AREDS2 nutrients have a mechanistic basis for benefiting AMD, and so were a logical next step. This was a double-blind, placebo-controlled, randomized trial in which the treatment group was supplemented with 10 mg of lutein plus 2 mg of zeaxanthin, or 350 mg of docosahexaenoic acid (DHA) plus 650 mg of eicosapentaenoic acid (EPA), or both, and followed for 5 years. A total of 4203 people were randomized; the subsequent randomization to the original AREDS supplement and details about number of participants lost to follow-up, as well as measures of adherence, are described at length in the accompanying tables. When compared with the placebo groups, there was no statistically significant reduction in the progression to AMD across any of the groups (P = 0.10-0.70). Subgroup analyses based on quintiles of dietary intake of lutein, zeaxanthin, and omega-3 fatty acids found there was a benefit of lutein plus zeaxanthin supplementation for the lowest dietary lutein and zeaxathin intake (hazard ratio = 0.74, P = 0.01). There was no effect in any of the treatment groups on mortality or visual acuity, and side effect profiles were comparable. The authors mention several possible explanations for the lack of effects, above a true negative finding, such as the need for different doses, forms, or duration of treatment for the nutrients involved.