Antioxidants, omega-3 lack benefit in age-related macular degeneration

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1. Previous large-scale studies have demonstrated a benefit of oral vitamin and mineral antioxidants for lowering the risk of age-related macular degeneration.

2. In the present study, the authors show no additional benefit over placebo for adding oral retinal pigment proteins or long-chain fatty acids to these supplements. 

Evidence Rating Level: 1 (Excellent) 

Study Rundown: In the present study, the authors examine the role of two supplement combinations previously reported in observational studies to decrease the risk of progression to advanced age-related macular degeneration (AMD).  Though the mechanism of their effect is unknown, lutein and zeaxanthin are retinal pigment components, and docosahexanoic acid (DHA) and eicosapentanoic acid (EHA) are omega-3 fatty acids involved in retinal structure and signaling.  This investigation is built upon the Age-Related Eye Disease Study (AREDS) published by this group, which demonstrated that an oral supplement composed of vitamin C, vitamin E, beta-carotene, zinc, and copper reduced the risk of progression to advanced AMD by 25% (see link below).  In this follow-up trial, the authors did not find a clear overall benefit of other retinal pigment proteins or long-chain fatty acids for preventing the progression to advanced AMD or slowing the loss of visual acuity. Nonetheless, secondary analyses suggested the combination of lutein and zeaxanthin may be beneficial in select patient populations.

The study has key limitations, particularly in its approach to its secondary analyses.  Since the original AREDS publication, beta-carotene has been implicated in increasing lung cancer risk in smokers.  To investigate alternatives to the original AREDS supplement, the authors chose to randomize smokers and other participants to regimens without beta-carotene. Furthermore, some participants refused randomization, leading to a larger proportion of patients receiving the original AREDS supplement.  By fragmenting patient groups in this way, the study was unable to control for a major variable in treatment, and reduced the power of their results within these smaller subgroups.  That said, significant findings were still achieved with the use of lutein and zeaxanthin, which raises the need for further research regarding the use of these supplements in AMD.

Click to read the study in JAMA

Relevant Reading: Long-term effects of vitamins C and E, β-Carotene, and zinc on age-related macular degeneration: AREDS report no. 35

In-Depth [double-blinded randomized controlled trial]: The authors studied 4,203 participants at risk for advanced AMD who had participated in the AREDS trial. Participants all received the original AREDS supplement, though in a secondary randomization some received a modified version with no beta carotene, lower zinc levels, or both.  All patients were randomized to take oral combinations of lutein and zeaxanthin, DHA and EHA, both, or placebo.  After a mean 4.9 years of follow-up, no significant decrease in progression to AMD or loss of visual acuity was obtained from either supplement in the primary randomization when compared with placebo (p>0.05), though, participants receiving lutein and zeaxanthin had a significantly decreased risk (hazard ratio 0.71, p=0.05) when compared with those receiving either DHA and EHA or placebo.

By Jeff Dewey and Rif Rahman

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