What is AREDS2?
AREDS2 is a specific oral supplement formulation containing lutein (10 mg) and zeaxanthin (2 mg), vitamin C (500 mg), vitamin E (400 IU), zinc (25 or 80 mg), and copper (2 mg), designed to reduce the risk of progression to advanced age-related macular degeneration in patients with intermediate AMD or advanced AMD in one eye 1.
Background and Development
AREDS2 was developed as a refinement of the original AREDS formulation, specifically replacing beta-carotene with lutein/zeaxanthin due to the demonstrated increased risk of lung cancer in smokers and former smokers taking beta-carotene 2. The study evaluated whether adding lutein/zeaxanthin and omega-3 fatty acids would further reduce AMD progression risk, and also assessed whether zinc could be reduced from 80 mg to 25 mg 1.
Specific Formulation Components
The AREDS2 supplement contains:
- Lutein 10 mg + Zeaxanthin 2 mg (replacing beta-carotene from original AREDS)
- Vitamin C: 500 mg
- Vitamin E: 400 IU
- Zinc: 25 mg or 80 mg (both doses showed no significant difference in AMD progression)
- Copper: 2 mg (necessary to prevent copper-deficiency anemia when taking zinc)
Evidence for Efficacy
The long-term data strongly support lutein/zeaxanthin as superior to beta-carotene. At 10-year follow-up, lutein/zeaxanthin showed a hazard ratio of 0.91 for progression to late AMD (95% CI, 0.84-0.99; P = .02), while beta-carotene nearly doubled the risk of lung cancer (OR 1.82,95% CI 1.06-3.12; P = .02) 3. When directly comparing lutein/zeaxanthin versus beta-carotene, the hazard ratio for late AMD was 0.85 (95% CI, 0.73-0.98; P = .02), demonstrating both better safety and efficacy 3.
Who Should Take AREDS2
Patients with bilateral intermediate AMD (bilateral large drusen with or without pigment changes) or advanced AMD in one eye are the appropriate candidates 4, 1. The formulation can reduce the risk of progression to advanced AMD by as much as 36% over a 10-year period 4.
Important Safety Considerations
- Zinc at 80 mg increases genitourinary hospitalizations (7.5% vs 4.9% without zinc; P=0.001), including urinary tract infections, prostatic hyperplasia in men, and stress incontinence in women 4
- Beta-carotene should be avoided entirely given the lung cancer risk, particularly in current or former smokers 3
- Patients should have their primary care physician review the supplements before starting long-term supplementation due to potential adverse effects 4
Critical Pitfall
Many over-the-counter products marketed as "AREDS2" contain substantially lower doses than the evidence-based formulation - averaging 52.3% less vitamin C, 61.2% less vitamin E, and 40.1% less zinc than recommended 5. Clinicians should verify that patients are taking supplements with the actual AREDS2 dosages, not underdosed commercial variants.