AREDS2: Insights Into Optimal Supplements for AMD

Charles C. Wykoff, MD, PhD


May 20, 2013

In This Article

The Findings of AREDS2

In the primary analysis, adding omega-3 fatty acids (DHA and EPA) or carotenoids (lutein and zeaxanthin), or both, to the AREDS1 formulation did not significantly reduced the risk for progression to advanced AMD. After 5 years of follow-up, all 4 study groups had a 29%-31% risk for advanced AMD.

Exploratory secondary analyses of the isolated effects of DHA and EPA or lutein and zeaxanthin provided additional insight. No benefit in terms of risk reduction was seen with the addition of DHA and EPA. Therefore, at this time, there is insufficient evidence to support the use of these omega-3 fatty acids for reducing the risk for progression to advanced AMD in high-risk patients.

A significant protective effect, however, was identified for the carotenoids lutein and zeaxanthin. Specifically, consumption of lutein and zeaxanthin provided 10% additional risk reduction against progression to advanced AMD beyond the benefits of the original AREDS1 formulation (P=.05). This effect was strongest (26%) in participants with the lowest dietary intake of lutein and zeaxanthin (P=.01). When the effect of the carotenoid beta-carotene was compared with that of lutein and zeaxanthin, the latter provided 18% additional risk reduction over beta-carotene consumption (P=.02).

Analysis of the second-tier randomization of alternative AREDS1 formulations showed that lowering the zinc dose from 80 mg to 25 mg had no significant effect on progression to advanced AMD. In AREDS1, gastrointestinal conditions and hospitalizations for genitourinary diseases were significantly more common in patients receiving 80 mg of zinc than in those taking placebo. If zinc was causing these effects, it might be expected that a lower dose of zinc (25 mg vs 80 mg) would translate into a lower incidence of adverse events; but, in fact, there were no significant differences in the rate of adverse events between AREDS1 and AREDS2. Therefore, although the official recommendation is to preserve the 80-mg zinc dose, there may be a role for a lower concentration of zinc in specific patients, an issue that requires further analysis and may be a distinguishing feature among commercial products.

The other major alteration to the AREDS1 formulation studied in the second-tier randomization was elimination of beta-carotene, which had a significant effect on progression to advanced AMD in secondary analyses. In smokers, beta-carotene supplementation is not recommended because of a potentially increased risk for lung cancer.[10] Therefore, in AREDS2, all current smokers and those who had smoked within 1 year of study enrollment were assigned to groups that did not receive beta-carotene. Analyses excluding these participants revealed a significantly higher rate of lung cancer in participants who took beta-carotene than in those not who did not take beta-carotene: 2% (n = 23) vs 0.9% (n = 11; P = .4). Most (91%) of the patients who developed lung cancer were former smokers who quit smoking more than 1 year before the trial.