Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration.

Systematic review/meta-analysis of randomized trials in people with age-related macular degeneration in one or both eyes, generally older adults. Studies were conducted across the USA, Europe, China, and Australia; active intervention arms ranged from very small pilot groups to large arms such as lutein plus zeaxanthin in AREDS2 2013 (N=2123) and vitamin E in VECAT 2002 (N=587).

This review evaluated antioxidant vitamin and mineral supplementation for age-related macular degeneration, including AREDS-like multivitamin formulations, vitamin E alone, zinc alone, and lutein plus zeaxanthin. Active regimens reported in the packet included zinc sulfate 200 mg, lutein 20 mg then 10 mg, lutein 10 mg, and lutein plus zeaxanthin; most comparisons were against placebo or usual care.

Overall, antioxidant vitamin and mineral supplementation probably delays progression of age-related macular degeneration, with the strongest evidence from AREDS 2001 showing a modest reduction in progression to late AMD. Zinc has moderate-certainty evidence for reducing progression to late AMD and neovascular AMD, while vitamin E alone showed little evidence of benefit. In the VECAT 2002 vitamin E arm, progression to late AMD was not reduced (RR 1.36, 95% CI 0.31 to 6.05), and no serious adverse effects were reported. AREDS 2001 reported more yellow skin in the antioxidant arm than placebo (8.3% vs 6.0%, P = 0.008), and lutein plus zeaxanthin in AREDS2 showed only modest or no risk reduction with limited, indirect evidence because participants also received the AREDS formula.

The evidence base is dominated by AREDS/AREDS2 formulations, while many smaller and shorter trials were inconsistent or underpowered. Lutein and zeaxanthin findings are exploratory and indirect because AREDS2 participants also took the AREDS formula, and exact per-arm effect sizes were not always available. Generalizability outside the studied populations, especially non-US settings, remains uncertain, and safety concerns include beta-carotene-associated lung cancer risk in former smokers.