here to read the full text of the AREDS clinical trial on the Archives
of Opthalmology website
The Age-Related Eye Disease Study (AREDS) was a major study sponsored
by the National Eye Institute and conducted at 11 medical research
centers around the country. This large-scale clinical trial was
undertaken because age-related macular degeneration (AMD) is the
leading cause of vision impairment among people 65 and older, and
because the treatments for preventing its advanced forms are very
limited. Started in 1992, the results of this study were reported
in October, 2001.
Over 3,600 older
participants were followed for about six years during the trial. Patients were
initially assigned to different categories based on the extent and type of their
disease €“ from early to intermediate, and more advanced stages of AMD. They then
received one of four supplements: a placebo, high-dose
copper and antioxidants (vitamins C, E and
beta-carotene), or a combination of
copper plus the antioxidants.
Both the antioxidants and
the mineral supplements each appeared to offer protection. But the benefits were
greatest for those who received the antioxidant and
zinc combination, and who were in the highest-risk categories (patients with
intermediate and advanced forms). Supplementation with antioxidants and
zinc significantly reduced the risk of progressing to more advanced AMD in
these groups by 25%, and reduced their risk of vision loss by 27%.
The study was not able to
show that supplements could prevent AMD, or restore vision already lost. But
supplements can play a key role in helping people at risk for advanced AMD curb
its advancement and preserve their vision. With the caveats that high dose
beta-carotene should be avoided by smokers and ex-smokers, and that
supplement takers need to be routinely monitored, the study confirmed the
general safety and benefit of these high-potency supplements in maintaining
While the researchers
lutein along with vitamins
E, this carotenoid was not available when the study started. Instead they
beta-carotene, which was being studied at the time in heart disease.
Findings from this multicenter, NEI and NIH sponsored study were reported in the October 2001 issue of Archives of Ophthalmology. The study followed 3,640 participants, aged 55-80, for an average of 6.3 years. Patients were initially enrolled in four AMD categories based on the size and extent of retinal drusen and level of visual acuity decline (Table 1), and were randomly assigned to one of four treatment arms:
While the investigators acknowledged the importance of lutein and zeaxanthin for macular health, these carotenoids were not available for use in supplements when the study began. Instead, the investigators chose beta-carotene, which was then being studied for heart disease and cancer.
AMD Categories In AREDS
Category 1: few small or no drusen
Category 2: several small drusen or a few medium-sized drusen in one or both eyes, or pigment abnormalities
Category 3: many medium-sized drusen or one or more large drusen in one or both eyes
Category 4: advanced AMD in one eye, or vision loss due to AMD in one eye only
Although the antioxidant and zinc supplements each appeared to offer some protection, the benefits of supplementation were greatest for those patients who received the antioxidant and zinc combination, and who were in the highest-risk category groups.
Supplementation with combined antioxidants and zinc significantly reduced the risk of progression to advanced AMD in these groups by 25%. A significant risk reduction in vision loss was also seen in the higher-risk groups taking both zinc and antioxidants, with an odds reduction of 27% (Table 2).
Very few patients with less severe AMD went on to develop advanced cases. Therefore the study was unable to detect whether the zinc and antioxidant combination might delay or prevent progression in subjects at an earlier stage. However, when the researchers included the less severe category (category 2) with the more advanced categories (3 and 4), the combined supplements showed an odds reduction in the visual acuity outcome that approached statistical significance (Table 2).
Most of the participants experienced few side effects. People in the zinc groups had more frequent urinary-tract related problems than placebo-takers (7.5% vs. 5%), although it's not clear whether zinc played a role in their occurrence. Another caveat is that high dose beta-carotene is contra-indicated for smokers and recent ex-smokers. The AREDS trial confirmed the general safety and benefit of these high-potency nutrients in preserving vision among well-nourished, older people with intermediate to more advanced AMD.
Effect of Treatment on Risk of Visual Acuity Loss Score Greater or Equal to 15 Letters from baseline
Participants in AMD Categories 2, 3 & 4 (n=3597)
Participants in AMD Categories 3 and 4 (n=2549)
OR (99% CL)
Antioxidants vs. placebo
zinc vs. placebo
Antioxidant + zinc - Combination vs. Placebo
*Significant at p≤.01
Click here to read the full text of the AREDS clinical trial on the Archives of Opthalmology website.
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