AREDS2 Formula — Research Profile

AREDS2 is recommended for people diagnosed with intermediate AMD in one or both eyes, or advanced AMD in one eye. It is NOT proven to prevent AMD from starting or to help early-stage AMD. Ask your ophthalmologist to stage your AMD before starting. The formula is not recommended for people without AMD. ^[1]

The main change was replacing beta-carotene (15 mg) with lutein (10 mg) and zeaxanthin (2 mg). Beta-carotene was linked to increased lung cancer risk in smokers. The AREDS2 10-year follow-up confirmed that lutein/zeaxanthin was actually more effective than beta-carotene for AMD prevention, making it the preferred formulation for all patients.

AREDS2 was specifically designed and tested for intermediate-to-advanced AMD. For general eye health without AMD, the high zinc dose (80 mg) may be unnecessary and could cause side effects. A simpler lutein/zeaxanthin supplement (10 mg/2 mg) may be more appropriate for general macular support.

The AREDS2 formula contains vitamin C 500 mg, vitamin E 400 IU, zinc 80 mg, copper 2 mg, lutein 10 mg, and zeaxanthin 2 mg daily. Copper is included specifically to prevent zinc-induced copper deficiency caused by the high 80 mg zinc dose. The formula is typically taken as 2 capsules per day.

Copper (2 mg) is included to prevent zinc-induced copper deficiency. The AREDS2 formula contains 80 mg of zinc — well above the 40 mg upper tolerable intake level — which can block copper absorption over time. Without supplemental copper, long-term high-dose zinc could lead to copper deficiency anemia.

The AREDS2 trial demonstrated approximately 25% reduction in progression to advanced AMD over 5 years compared to placebo. A 10-year follow-up confirmed these sustained protective effects, with the lutein/zeaxanthin formulation performing better than the original beta-carotene version.

The 80 mg zinc dose exceeds the formal upper tolerable intake level of 40 mg, yet it was well-tolerated in the 4,203-participant AREDS2 trial over 5 years. Gastrointestinal upset is the most common side effect. The copper included in the formula helps prevent zinc-induced copper deficiency.

The AREDS2 formula replaced beta-carotene with lutein and zeaxanthin specifically to eliminate the lung cancer risk that beta-carotene posed to smokers. The updated formula is considered safe for smokers and former smokers. Always confirm the product label does not contain beta-carotene.

The AREDS2 formula should be divided into two doses daily — morning and evening — taken with meals. The lutein and zeaxanthin components are fat-soluble and require dietary fat for absorption. Taking it with food also reduces the gastrointestinal side effects associated with the high-dose zinc.

The 80 mg zinc in AREDS2 may interfere with certain antibiotics including tetracyclines and quinolones by reducing their absorption. These medications should be taken at least 2 hours apart from AREDS2. Proton pump inhibitors may also reduce zinc absorption from the formula.

The 10-year follow-up (Chew et al., 2022) confirmed that the lutein/zeaxanthin formulation outperformed beta-carotene for AMD prevention over the long term. This landmark finding established that the AREDS2 modification was not just safer but actually more effective, making lutein/zeaxanthin the definitive choice for all patients.

AREDS2 has not been proven to prevent AMD from developing in people who do not already have the condition. The trial enrolled participants aged 50-85 who already had intermediate AMD or advanced AMD in one eye. For people without AMD, a simpler lutein/zeaxanthin supplement is more appropriate.

Some AREDS2 products add omega-3s, meso-zeaxanthin, or astaxanthin beyond the core formula. The AREDS2 trial itself found that added omega-3 fatty acids did not provide additional AMD benefit. However, the CREST trials suggest adding meso-zeaxanthin may enhance macular pigment density beyond what lutein and zeaxanthin alone achieve.

The AREDS2 trial enrolled 4,203 participants aged 50-85 across multiple clinical centers in the United States. Sponsored by the NIH National Eye Institute, it remains the largest and most definitive clinical trial on nutritional supplementation for age-related macular degeneration, with a primary 5-year follow-up and subsequent 10-year data.