Age-related macular degeneration (AMD) is a major cause of vision loss in older adults, affecting essential activities like reading and driving. The Age-Related Eye Disease Study 2 (AREDS2) formula showed that a specific nutrient combination—vitamin C, vitamin E, zinc, copper, lutein, and zeaxanthin benefits—can significantly slow AMD progression in intermediate stages. Recent NIH research indicates this formulation may also limit the progression of advanced “dry” AMD characterized by geographic atrophy in certain patients. These findings underscore the importance of clinical trial support nutraceuticals and evidence-based research for managing AMD through targeted nutritional strategies and dietary supplement development.
AREDS2 Nutritional Formula Shows Continued Impact on Late-Stage Age-Related Macular Degeneration
Age-related macular degeneration (AMD) is a major cause of vision loss in older adults, affecting essential activities like reading and driving. The Age-Related Eye Disease Study 2 (AREDS2) formula showed that a specific nutrient combination—vitamin C, vitamin E, zinc, copper, lutein, and zeaxanthin benefits—can significantly slow AMD progression in intermediate stages. Recent NIH research indicates this formulation may also limit the progression of advanced “dry” AMD characterized by geographic atrophy in certain patients. These findings underscore the importance of clinical trial support nutraceuticals and evidence-based research for managing AMD through targeted nutritional strategies and dietary supplement development.
Table 1: AREDS2 Nutrients and Their Role in Supporting Eye Health supplement in Older Adults
The table below summarizes key vitamins for macular degeneration and nutrients included in the AREDS2 formulation, highlighting their roles in older adults and their specific benefits in managing age-related macular degeneration (AMD). These nutrients work synergistically to support eye health supplement and preventing AMD progression with nutrients forming a strong scientific foundation for nutraceuticals product development backed by clinical trial support nutraceuticals. [1]
Vitamin / Nutrient | Purpose / Role in Late-Aged Individuals | Reason / Benefit for AMD |
Vitamin C | Antioxidant; supports overall eye health | Protects retinal cells from oxidative stress |
Vitamin E | Antioxidant; maintains healthy vision | Reduces free radical damage in retinal tissue |
Zinc | Essential mineral for eye metabolism | Supports retinal cell function and delays AMD progression |
Copper | Works with zinc to prevent deficiency | Prevents anaemia from high zinc supplementation; supports cellular function |
Lutein | Carotenoid concentrated in the retina | Filters harmful blue light; protects macula from oxidative damage |
Zeaxanthin | Carotenoid concentrated in macula | Supports macular pigment; reduces risk of advanced AMD |
Age-Related Macular Degeneration (AMD)
The eye condition known as age-related macular degeneration (AMD) or macular degeneration causes central vision loss through macula damage in the retina. The condition mainly affects people who are 60 years old or older and produces vision problems that include central vision loss and reading difficulties and colour perception issues. The two forms of late – stage AMD exist as dry and wet types with wet AMD causing more severe and rapid vision deterioration.[2]
Study Objective:
The study aims to evaluate the effectiveness of the nutritional AREDS2 formulation in slowing the progression of late-stage age-related macular degeneration (AMD), focusing on subgroups with intermediate AMD and advanced disease like geographic atrophy. It highlights the updated nutritional composition, where the benefits of lutein and zeaxanthin replace beta-carotene, to enhance safety and macular pigment support. By assessing disease progression and retinal outcomes, the research seeks to clarify the role of targeted nutritional interventions in managing advanced AMD and support evidence-based clinical recommendations. This study strengthens the role of clinical trial support nutraceuticals in validating advanced nutraceuticals product development strategies for AMD management [3] [4]
ODS Update related to AREDS and AREDS2:
The NIH funded the Age-Related Eye Disease Studies (AREDS and AREDS2) to investigate the efficacy of dietary supplement development in preventing age-related macular degeneration (AMD). The original AREDS formula, which included vitamins C and E, beta-carotene, and zinc, did not prevent AMD but reduced the risk of progression by 25%. AREDS2 in clinical study replaced beta-carotene with benefits of lutein and zeaxanthin due to increased lung cancer risks in smokers. Results from a decade-long study indicated that AREDS2 formula supplements aided in slowing foveal central vision loss, particularly in participants with geographic atrophy. Further research is required to confirm the treatment’s effectiveness in late-stage dry AMD patients.
Study | Participants / Eyes with GA | Key Comparison Groups | Progression Rate (μm/year) | Statistical Significance | Main Findings |
AREDS | 318 participants / 392 eyes | Noncentral GA with antioxidants vs. without antioxidants | 50.7 (95% CI: 38.0–63.4) vs. 72.9 (95% CI: 61.3–84.5) | P = 0.012 | Antioxidant supplementation significantly slowed GA progression toward the central macula. |
AREDS2 | 891 participants / 1210 eyes | Noncentral GA with lutein + zeaxanthin vs. without | 80.1 (95% CI: 60.9–99.3) vs. 114.4 (95% CI: 96.2–132.7) | P = 0.011 | Lutein/zeaxanthin supplementation slowed GA progression, supporting foveal sparing. |
AREDS & AREDS2 (Any GA) | Combined data | Area-based progression (all lesions) | — | AREDS: P = 0.63AREDS2: P = 0.64 | No significant effect on overall GA area growth. |
Major findings of AREDS and AREDS2:
- The National Eye Institute (NEI) conducted the Age-Related Eye Disease Studies (AREDS and AREDS2).
- The studies aimed to evaluate the impact of nutraceutical supplements on cataract and age-related macular degeneration (AMD).
- Findings indicated that developments of dietary supplements reduce the risk of AMD progression from intermediate to advanced stages by 25%.
- However, they do not prevent the initial development of AMD or influence cataract formation.
- Omega-3 fatty acids were found to have no beneficial effects on AMD or cataract prevention.
- The AREDS2 formula without beta-carotene is recommended for smokers and former smokers due to the increased lung cancer risk associated with beta-carotene.[5] [6]
Comparison of AREDS and AREDS2 Formulas:
The table below compares the original AREDS and updated AREDS2 formulations, highlighting key differences in nutrient composition. It explains the rationale behind each modification and its relevance to retinal health and age-related macular degeneration management.
Nutrient | AREDS Formula | AREDS2 Formula | Reason / Insights |
Vitamin C | 500 mg | 500 mg | Maintains antioxidant protection for retinal cells; no change needed. |
Vitamin E | 400 IU | 400 IU | Supports retinal health; antioxidant effect maintained. |
Beta-Carotene | 15 mg | – | Removed to reduce lung cancer risk in smokers. |
Copper (as cupric oxide) | 2 mg | 2 mg | Prevents copper deficiency caused by high zinc intake; supports cellular function. |
Lutein | – | 10 mg | Added to filter harmful blue light and protect macula; replaces beta-carotene. |
Zeaxanthin | – | 2 mg | Added alongside lutein to enhance macular pigment density; supports visual function. |
Zinc | 80 mg | 80 mg | Maintains retinal cell metabolism; dose unchanged. |
Result and discussion:
- In patients with foveal-sparing geographic atrophy (GA), AREDS2 dietary supplement developed the users showed about 55% slower disease progression toward the central vision area over three years compared to non-users.
- No benefit was observed in patients whose fovea was already affected at the start of the study.
- These findings suggest that AREDS2 formula may still be beneficial in late-stage dry AMD, as long as central vision remains unaffected.
- The results challenge the earlier belief that nutraceuticals product development is ineffective in advanced GA.
- A likely explanation is that antioxidants and carotenoids reduce oxidative stress, helping preserve remaining healthy retinal tissue.
- Study limitations include its retrospective design, potential confounding factors, and short follow-up duration.
- Further prospective, randomized clinical trials are needed to confirm these findings.
Regulatory Considerations and Compliance Framework for AREDS2-Based Nutritional Supplements:
This table summarizes the key regulatory domains governing AREDS2 formula supplements, highlighting safety, labelling, manufacturing quality, and policy considerations relevant to supplement of eye-health nutrition guidance.
Regulatory Domain | Guidance Focus | Regulatory Implications |
Safety & Dosage | Upper intake limits, older adult safety | Reinforce tolerable upper intake levels; recommend healthcare supervision |
Labelling & Claims | Permitted claims and disclosures | Allow structure–function claims only; require nutrient quantities and risk warnings |
Target Population | Evidence-supported use | Define eligible AMD stages; exclude unsupported populations |
Manufacturing Quality | Product integrity | Enforce GMP compliance; encourage third-party certification |
Post-Market Monitoring | Long-term safety | Mandate adverse event reporting and safety reviews |
Policy Integration | Public health relevance | Support inclusion in eye-health supplement guidelines |
Overview of Regulatory Requirements for AREDS2 Supplements Across the U.S., EU, and India:
- AREDS2 formula products in the U.S. can state “supports eye health” and must follow FDA regulations, including listing all ingredients and adhering to 21 CFR Part 111 GMP standards. Adverse event reporting is mandatory for these products.
- In the EU, EFSA permits nutraceutical product developments that meet nutrient safety limits and have approved health claims, requiring clear labelling and safety surveillance.
- Indian regulations by FSSAI mandate compliance with nutraceutical standards, approval of ingredients, functional claims, GMP adherence, and transparent labelling.[7]
Clinical implication:
- The AREDS2 formula provides visual preservation advantages to specific patients who have late-stage dry AMD.
- The treatment produces its best results for patients who develop GA outside the foveal area so doctors need to perform early detection and imaging procedures.
- Ophthalmologists need to explain to their patients that this treatment method will not eliminate their condition but it will help prevent central vision deterioration.
- Researchers need to conduct studies about the best treatment amounts and when patients should start taking the medication and how their condition will change after three years.
Product example:
Product Name: Bausch & Lomb, Preservision, AREDS 2 Formula, Eye Vitamin & Mineral Supplement
Form: Capsule form
Use: For curing the Age- related macular degeneration
Conclusion:
The NIH conducted a post-hoc study which showed that patients with late-stage dry AMD who have foveal-sparing GA can benefit from daily AREDS2 formulation supplementation because it slows down foveal progression. The research results validate the use of this formulation for suitable patients while demonstrating the requirement for upcoming clinical trials. Food Research Lab provides formulation services for nutrient-based products and interested parties can reach out to them for nutraceutical product development assistance.
Reference:
- Chew, E. Y., et al. (2021). Vitamin E in the AREDS2 formulation: Safety and efficacy for age-related macular degeneration. Redox Biology, 40, Article 101853. https://www.sciencedirect.com/science/article/pii/S2352304221000295nih
- National Eye Institute. (n.d.). AREDS/AREDS2 frequently asked questions. https://www.nei.nih.gov/research/clinical-trials/age-related-eye-disease-studies-aredsareds2/aredsareds2-frequently-asked-questionsnih
- National Institutes of Health, Office of Dietary Supplements. (2023, October 10). Vitamin E fact sheet for health professionals. https://content.govdelivery.com/accounts/USNIHODS/bulletins/3b620c2nih
- Kim, Y. N., & Cho, Y. H. (2025). Long-term efficacy of AREDS2 formula in late-stage AMD patients. Journal of Retina, 3(2), 121-130. https://www.sciencedirect.com/science/article/pii/S2666914525002519areds
- National Eye Institute. (n.d.). About AREDS and AREDS2. https://www.nei.nih.gov/research/clinical-trials/age-related-eye-disease-studies-aredsareds2/about-areds-and-areds2ncbi.nlm.nih
- Nutraceuticals World. (2023, August 15). AREDS2 formula continues benefitting AMD in certain late-stage patients: NIH analysis. https://www.nutraceuticalsworld.com/breaking-news/areds2-formula-continues-benefitting-amd-in-certain-late-stage-patients-nih-analysis/nih
- Lee, S. H., et al. (2022). Clinical outcomes of AREDS2 supplementation in Korean AMD patients. Journal of Retina, 7(2), 121-128. https://www.e-retina.or.kr/journal/view.html?doi=10.21561/jor.2022.7.2.121nih
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