AREDS2 Formulation Dosing for AMD
The recommended AREDS2 formulation for adults with intermediate AMD or advanced AMD in one eye consists of: vitamin C 500mg, vitamin E 400 IU, zinc 25mg, copper 2mg, lutein 10mg, and zeaxanthin 2mg, taken once daily. 1
Who Should Receive AREDS2 Supplementation
Patients with intermediate or advanced AMD in one eye should be prescribed AREDS2 supplements immediately, as this reduces the risk of progression to advanced AMD by up to 36% over 10 years. 1, 2
High-Risk Features Requiring Supplementation:
- Bilateral large drusen (≥125 μm) 1, 3
- Confluent drusen with RPE clumping or atrophy 1, 3
- Advanced AMD in one eye with large drusen in the fellow eye 1, 2
- Family history of AMD 3
Early AMD with only small drusen does NOT require AREDS2 supplementation, as the absolute risk reduction is minimal (approximately 4 fewer cases per 1000 people). 4
Specific Formulation Components and Rationale
The AREDS2 formulation represents critical modifications from the original AREDS formula based on safety data: 1
Key Component Changes:
- Beta-carotene was eliminated due to an 18% increased cumulative incidence of lung cancer in current and former smokers (23 lung cancers vs 11 in the no beta-carotene group, RR 1.28). 1, 5
- Lutein 10mg and zeaxanthin 2mg replaced beta-carotene as safer carotenoid alternatives, with exploratory analyses showing HR 0.82 (95% CI 0.69-0.96) for progression to late AMD when substituted. 1, 6
- Zinc dose reduced from 80mg to 25mg because the lower dose shows equivalent efficacy while reducing genitourinary hospitalizations. 1
- Copper 2mg is mandatory to prevent copper-deficiency anemia from zinc supplementation. 1
Critical Safety Considerations Before Prescribing
Coordinate with the patient's primary care physician before initiating long-term AREDS2 supplementation due to documented adverse effects. 1
Specific Safety Concerns:
- Never prescribe beta-carotene-containing formulations to current or former smokers due to documented lung cancer risk. 1, 5
- Zinc supplementation at 80mg was associated with increased genitourinary hospitalizations in the original AREDS trial. 1, 4
- Monitor for gastrointestinal symptoms, the most common adverse effect. 4
What AREDS2 Does NOT Do
AREDS2 supplements are NOT a substitute for anti-VEGF therapy in wet (neovascular) AMD - patients with wet AMD require immediate intravitreal anti-VEGF injections regardless of supplementation status. 1
Evidence of Benefit:
- Reduces progression to late AMD (OR 0.72,95% CI 0.58-0.90) 4
- Reduces progression to neovascular AMD (OR 0.62,95% CI 0.47-0.82) 1
- Reduces visual acuity loss of 3+ lines (OR 0.77,95% CI 0.62-0.96) 1
For patients with intermediate AMD at higher risk, this translates to approximately 78 fewer cases of progression per 1000 people taking vitamins over 5 years. 4
Essential Patient Counseling
Provide an Amsler grid for daily home monitoring and instruct patients to return immediately for any new visual symptoms, particularly metamorphopsia (wavy or distorted lines). 1, 3
Mandatory smoking cessation counseling at every visit - smoking is the single most critical modifiable risk factor, with current smokers facing 2-3 times higher AMD progression risk. 2, 3