Researchers found no extra benefit to adding lutein and zeaxanthin, omega 3 fatty acids EPA and DHA, or both to the Age-Related Eye Disease Study (AREDS) formulation, which already included antioxidant vitamins C and E, beta-carotene and zinc, according to a study published in the Journal of the American Medical Association (JAMA).
The AREDS2 formulation did not further reduce risk of progression to advanced age-related macular degeneration (AMD), researchers concluded. However, because of potential increased incidence of lung cancer in former smokers, lutein + zeaxanthin could be an appropriate carotenoid substitute for beta-carotene.
The original AREDS formulation has been shown to reduce the risk of progression to advanced AMD. Researchers sought to determine whether adding lutein + zeaxanthin, DHA + EPA, or both to the AREDS formulation further 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.
AREDS2, a multicenter, randomized, double-masked, placebo-controlled phase 3 study with a 2 × 2 factorial design, was conducted 2006-2012 and enrolled 4,203 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.
Participants were randomized to receive FloraGLO lutein (10 mg) + OPTISHARP 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.
Median follow-up was 5 years, with 1,940 study eyes (1,608 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.
A separate study published in JAMA Ophthalmology indicated that nutritional intake of lutein, zeaxanthin and omega 3 fatty acids EPA and DHA may be beneficial for patients affected by AMD.
The LUTEGA study demonstrates that supplementation with a combination of these nutrients can result in increased concentrations of lutein, zeaxanthin and fatty acids in plasma and a significant improvement in the optical density of the macular pigment.
Carried out over a 12-month period, the randomized, double-blind, placebo-controlled, parallel clinical trial took place at Friedrich Schiller University Jena, Germany. A total of 172 individuals with nonexudative (dry form) AMD were recruited to evaluate the effects of the administration of either a capsule containing 10+1 mg of lutein and zeaxanthin (from FloraGLO lutein) and 100 mg DHA + 30 mg EPA or twice these dosages (20/2/200/60) on the plasma xanthophyll concentrations and fatty acid profiles, antioxidant capacity in plasma, and optical density of the macular pigment. The results demonstrate that the study supplementation significantly improved the plasma antioxidant capacity, circulating macular xanthophyll levels, and the optical density of the macular pigment. These are important factors that could help reducing the risk of progression to wet AMD, what would be particularly relevant in the studied population.
“AMD is a progressive disease that causes the degeneration of the macula, a yellow pigmented spot in the retina that is responsible for high acuity vision, leading to irreversible and dramatic impact upon vision and patient quality of life” said Samanta Maci, senior manager, Scientific Affairs and Technical Services, Kemin. “Most commonly affecting people aged 50 and over, AMD is a growing concern amongst aging populations around the globe and the number of people diagnosed with early AMD is projected to double by 2020. Often referred to as the macular pigment, lutein and zeaxanthin are the only two dietary carotenoids that physiologically accumulate in the macula. By filtering out the high-energy blue light and reducing damage from free radicals, higher levels of lutein and zeaxanthin are associated with a decreased risk of AMD and improved visual function.”
AREDS2 Study Results Released