Beta-Carotene for Macular Degeneration

The original AREDS formula contained beta-carotene, but AREDS2 removed it after trials showed it increased lung cancer in smokers — and lutein with zeaxanthin performed at least as well without that risk. There is no reason to choose beta-carotene for macular degeneration today.

Beta-carotene was included in AREDS on the theory that antioxidant carotenoids would protect retinal tissue from oxidative damage. The flaw is that beta-carotene is not concentrated in the macula. Lutein and zeaxanthin are the carotenoids that actually accumulate there, forming the macular pigment that filters blue light and quenches singlet oxygen locally — beta-carotene is essentially absent from that tissue.

The original AREDS trial found that a formulation of vitamin C, vitamin E, beta-carotene, zinc and copper reduced progression to advanced age-related macular degeneration by about 25% over five years in people with intermediate disease. Attribution to beta-carotene specifically was never established, since the formula was tested as a package. Separately, the ATBC trial in Finnish male smokers found 18% more lung cancer with beta-carotene supplementation, and CARET was terminated early with 28% more lung cancer and 17% higher all-cause mortality in smokers and asbestos-exposed workers. AREDS2 was designed partly to resolve this: it substituted lutein 10 mg and zeaxanthin 2 mg for beta-carotene and found the substitution performed at least as well for AMD progression, with secondary analyses favouring the lutein arm in participants with low dietary carotenoid intake. AREDS2 also confirmed increased lung cancer in the beta-carotene arm, almost entirely in former smokers. The conclusion is unambiguous and has been adopted in ophthalmological practice: beta-carotene has no remaining role in AMD supplementation.

Everyone with macular degeneration is better served by the AREDS2 formulation. People with early AMD or no AMD derive no proven benefit from either formula.