The Landmark AREDS and AREDS2 Studies
The Age-Related Eye Disease Studies (AREDS and AREDS2) are two of the most significant clinical trials in modern ophthalmology. Sponsored by the National Eye Institute (NEI), these studies aimed to determine if specific vitamins and minerals could reduce the risk of progression for age-related macular degeneration (AMD) and cataracts. AMD is a leading cause of vision loss for people aged 50 and older, affecting the macula, the part of the retina responsible for sharp, central vision.
The initial AREDS, which concluded in 2001, established that a daily high-dose antioxidant and zinc supplement could slow the progression of AMD in individuals at high risk. This led to the widespread recommendation and availability of the original AREDS formulation.
What Was the Original AREDS Formula?
The first formulation identified by the study contained specific amounts of Vitamin C, Vitamin E, beta-carotene, zinc, and copper [1, 2].
While effective, researchers had new questions. There were concerns about the safety of high-dose beta-carotene, particularly its link to an increased risk of lung cancer in current and former smokers [1]. Additionally, scientists hypothesized that other nutrients, like the carotenoids lutein and zeaxanthin, and omega-3 fatty acids, might offer better results.
The AREDS2 Study: A Quest for Improvement
This led to the launch of the AREDS2 study in 2006. Its primary goal was to see if the original formula could be improved for safety and effectiveness. The study tested several variations of the formula [1, 2]:
- Adding Lutein and Zeaxanthin: These are carotenoids found in the retina, and it was thought they could be beneficial.
- Adding Omega-3 Fatty Acids: Specifically DHA and EPA, which are also important for retinal health.
- Removing Beta-Carotene: To test if it could be safely replaced.
- Lowering the Dose of Zinc: To see if a lower dose was equally effective with fewer side effects.
The study involved thousands of participants over five years and its results, published in 2013, fundamentally changed the recommended supplement for AMD [1, 2].
Key Findings: Why the Formula Changed
The AREDS2 study concluded with several critical findings that directly led to the new formulation [1, 2, 3]:
- Beta-Carotene Risk Confirmed: The study confirmed that beta-carotene increases the risk of lung cancer in people who smoke or have a history of smoking. Furthermore, removing it from the formula did not decrease the supplement's effectiveness.
- Lutein and Zeaxanthin are Effective Replacements: The study found that a combination of lutein and zeaxanthin was a safe and effective substitute for beta-carotene. In fact, participants who took an AREDS formula with lutein and zeaxanthin instead of beta-carotene had a lower risk of progressing to advanced AMD compared to those on the original formula with beta-carotene.
- Omega-3s Showed No Added Benefit: Adding omega-3 fatty acids to the AREDS formulation did not show any additional reduction in the risk of AMD progression.
- Lower Zinc Dose Was Effective: The study showed that a lower dose of zinc was as effective as the original higher dose, although the original higher dose was retained in the final recommendation as it was proven effective in the first study.
Comparison: AREDS vs. AREDS2 Formula
| Ingredient | Original AREDS Formula | Final AREDS2 Formula | Key Change & Reason |
|---|---|---|---|
| Vitamin C | Specific amount | Same amount | No change. [1, 2] |
| Vitamin E | Specific amount | Same amount | No change. [1, 2] |
| Beta-Carotene | Specific amount | Removed | Increased lung cancer risk in smokers/ex-smokers. Not essential for efficacy. [1, 2, 3] |
| Lutein | Not Included | Specific amount | Added as a safer and more effective replacement for beta-carotene. [1, 2, 3] |
| Zeaxanthin | Not Included | Specific amount | Added alongside lutein for improved retinal protection. [1, 2, 3] |
| Zinc | Specific amount | Same amount | No change in final recommendation, though a lower dose was also found to be effective. [1, 2, 3] |
| Copper | Specific amount | Same amount | No change; remains necessary to prevent zinc-induced copper deficiency. [1, 2, 3] |
| Omega-3s | Not Included | Not Included in final formula | Tested in the study but showed no significant additional benefit for AMD progression. [1, 2] |
Who Should Take AREDS2 Supplements?
It's crucial to understand that AREDS2 supplements are not for everyone. They are not proven to prevent the initial development of AMD. The NEI recommends these supplements for people with intermediate or advanced AMD in one eye. They are not recommended for people with early-stage AMD or for general eye health prevention in the absence of disease [1, 4]. Before starting any supplement regimen, it is essential to consult with an ophthalmologist to determine if it is appropriate for your specific condition.
Conclusion: An Evolution, Not a Discontinuation
The idea that AREDS2 was 'discontinued' is a misunderstanding of the scientific process. The AREDS2 study led to the discontinuation and replacement of the original AREDS formula. This change represents a significant advancement in evidence-based medicine, providing a safer and more effective tool for millions of people at risk of vision loss from advanced AMD. The resulting AREDS2 formulation, free of beta-carotene and enhanced with lutein and zeaxanthin, is the current standard of care recommended by eye health professionals [1, 4].
For more information directly from the source, visit the National Eye Institute's page on AREDS/AREDS2 [1].
