Should Lutein and Other Nutritional Supplements Be Given
for the Therapy of Age-Related Macular Degeneration?
Y. Chew, MD
National Eye Institute,
National Institutes of Health, Bethesda, MD
Our colleagues and patients often question the role of lutein in the treatment of age-related macular degeneration (AMD). According to observational data, individuals with a high dietary intake of lutein/zeaxanthin have a lower risk of advanced AMD than those with a low intake of lutein/zeaxanthin.1,2,3 Although this finding was not consistent among other studies, especially the population-based studies,4,5 pharmaceutical companies have marketed a number of formulations which contain lutein and other antioxidant vitamins and minerals. Patients often experience confusion when they are confronted with a number of such products labeled for eye health on the store shelf. The media has also played a role in promoting the unproven benefits of lutein for AMD.
Currently, there are supporting data mainly from observational studies, in which patients with disease are compared with those without the disease. Such studies are important in generating hypotheses to test, but may not provide data to support treatment recommendations. There are no conclusive results based on limited data from a randomized controlled trial of lutein for the therapy of AMD.6
The proven treatment for prevention of advanced AMD is the formulation tested in the Age-Related Eye Disease Study (AREDS) which contains vitamins C (500 mg), E (400 International Units [IU]), beta carotene (15 mg), zinc oxide (80 mg) and copper (as cupric oxide 2 mg). The AREDS formulation reduced the risk of advanced AMD, defined as neovascular AMD or geographic atrophy involving the center of the macula, by 25% compared with the placebo group at five years follow-up.7 Similarly, the risk of moderate visual loss (decrease of 15 or more letters of vision) was reduced by 19%. This formulation is recommended to persons with intermediate AMD (those with large drusen) in both eyes or those with advanced AMD in one eye and NOT for individuals with early AMD.
The National Eye Institute/National Institutes of Health is conducting a new controlled, randomized trial, the Age-Related Eye Disease Study 2 (AREDS2), to assess the roles of lutein (10 mg)/zeaxanthin (2 mg) and omega-3 long chain polyunsaturated fatty acids or LCPUFAs (docosahexanoic acid [DHA] and eicosapentanoic acid [EPA], total of 1 gm).8 Observational data have shown a decreased risk of advanced AMD in those participants with higher fish consumption or higher intake of omega-3 fatty acids compared to those with lower intake or fish or omega-3 fatty acids.9 Of the 4,000 participants to be randomly enrolled into AREDS2, 1000 will be in the control group, 1000 in the lutein/zeaxanthin group, 1000 in the LCPUFA group, and 1000 in the group with combination of both supplements.
The secondary randomization in AREDS2 will test the following changes to the AREDS formulation in those participants who will consent to it (otherwise, the original AREDS formulation will be provided for them). Because beta-carotene has been associated with an increased risk of lung cancer when given to cigarette smokers,10,11 the AREDS formulation will be evaluated as to the merits of eliminating beta-carotene from the formulation. The dose of zinc tested in AREDS was the dose supported in the past by a small clinical trial.12 Current data suggest that only 25 mg of zinc may be maximally absorbed13. AREDS2 will evaluate the lowering of the zinc oxide to 25 mg.
All participants of AREDS2 will also be offered the opportunity to take a multivitamin. This study will follow all enrolled participants through five years. Enrollment has started in over 80 clinic sites in the US, in both academic institutions and private practices. To find the participating site nearest you, please visit
http://www.nei.nih.gov/AREDS2. Working together, we hope to provide our colleagues and patients answers to questions regarding the role of these nutritional supplements for the therapy of AMD, a disease of significant public health importance.
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