This article is more than 5 years old. Information may no longer be current.
BLOG: AREDS2 results and reaction
Click Here to Manage Email Alerts
Read more blog posts from Jeffrey Anshel, OD.
The long-awaited results of the AREDS2 study were released recently. This multicenter trial was conducted in 82 clinical sites in the U.S., in both academic and community-based centers with retinal specialists from 2006 to 2012. The 4,203 participants were between 50 and 85 years of age.
Three nutritional supplements were added to the Age-Related Eye Disease Study (AREDS) formulation consisting of vitamins C, E, beta-carotene, zinc and copper: lutein, zeaxanthin and EPA/DHA from fish oil. The AREDS2 participants consented to either take the original AREDS formulation or a randomly assigned variation of the AREDS formulation.
Participants had comprehensive ocular exams at annual study visits, which included best-corrected visual acuity testing and ocular photography. The main outcome measurement was progression to advanced AMD, neovascular or central geographic atrophy determined by centralized fundus photographic grading with a standardized protocol and by history of treatment. Progression to cataract surgery and progression of lens opacity, determined by centralized ocular photography using red reflex photos with a standardized protocol and obtained at annual study visits, was a secondary outcome.
Lutein and zeaxanthin (L/Z) plus AREDS (original formula) reduced advanced AMD 10% over AREDS alone in the total cohort and reduced progression to neovascular AMD by 11% over AREDS in the total cohort and by 26% in subjects with the lowest dietary intake of L/Z (all P < 0.05). L/Z also reduced risk of progression to both advanced AMD and legal blindness by 18% when substituted for beta carotene and the risk of neovascular AMD by 22% when substituted for beta carotene. L/Z had no effect on cataract surgery or progression overall but lowered risk of progression by 30% in the group with the lowest dietary intake. EPA/DHA (fish oil) had no effect on progression. Zinc at 80 mg vs. 25 mg showed no increase in adverse events but a trend toward less progression (P < 0.05).
Beta carotene doubled lung cancer risk in past smokers (2% vs. 0.9% incidence with and without beta carotene). Current smokers were not in the beta carotene arms.
Emily Y. Chew, MD, the study lead author, stated, "Adding a 10% relative risk reduction to a formula that already has a robust effect (AREDS 1) has significant public health implications and supports addition of L/Z to the AREDS formula."
Compliance was high (by pill counts and serum markers) and subjects were better educated and had better baseline nutritional status (by Harvard Food Intake survey) than the general population. No data was presented on dietary glycemic index, body mass index (obesity) or genetic analysis. It seems rather shocking that Dr. Chew would make the statement, "We were told that more than 10 mg of lutein may be toxic to the retina.”
Really? One must wonder where she heard that. It is also important to note her statement that AREDS2 subjects had better baseline nutritional status than subjects in AREDS, so the benefits of L/Z (and potentially the null effect of omega-3 fatty acids) may be understated (as they assumed a 25% risk reduction for the original AREDS formula, and all hazard ratios for additive effects of L/Z were based on that assumption).
Limitations of the study include competitive absorption of carotenoids that limited the impact of lutein and zeaxanthin in the presence of beta carotene (which Dr. Chew acknowledged); limited generalizability to less well educated and well-nourished populations; and that almost all patients elected to take the over-the-counter supplement Centrum Silver, which contains a small amount of lutein and other carotenes and antioxidants. In other words, it seems that the jury is still out on the role of these nutrients in advanced AMD, and this study did not address early AMD or prevention of the disease. Can’t wait for AREDS3!