A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8.

This was a multicenter randomized, placebo-controlled trial in 11 retinal specialty clinics in the United States. Adults aged 55 to 80 years with age-related macular degeneration changes and best-corrected visual acuity of 20/32 or better in at least one eye were enrolled, with analyses reported for active intervention arms of antioxidants (n=936), zinc (n=897), and antioxidants plus zinc (n=882).

Participants were randomized to high-dose oral antioxidant supplementation with vitamin C 500 mg, vitamin E 400 IU, and beta carotene 15 mg twice daily, zinc 80 mg daily as zinc oxide with copper 2 mg as cupric oxide, or the combination of antioxidants plus zinc. Treatment was given as two tablets twice daily for up to 8 years, compared with placebo.

The combination of antioxidants plus zinc provided the clearest benefit in higher-risk AMD (Categories 3 and 4), reducing progression to advanced AMD and visual acuity loss. At 5 years, progression to advanced AMD was 20% with antioxidants plus zinc versus 28% with placebo, with OR 0.66 (0.47-0.91) and P=.001; ≥15-letter visual acuity loss was 23% versus 29%, with OR 0.73 (0.54-0.99) and P=.008. The combination also reduced development of neovascular AMD, OR 0.62 (0.43-0.90), P=.001. Zinc alone showed a smaller benefit and antioxidants alone were weaker and often not statistically significant.

Benefits were concentrated in higher-risk AMD, so findings are less informative for lower-risk participants. Effects for antioxidants alone and zinc alone were smaller and sometimes not statistically significant, and the trial reported treatment-related adverse events such as yellow skin with antioxidants and anemia with zinc. Smoking-related beta carotene considerations also limit generalizability for some patients.