TL;DR  

The original AREDS trial found that high-dose antioxidants plus zinc reduced the risk of advanced AMD by about 25% in people with intermediate disease. Newer research confirms the benefit but recommends replacing beta-carotene with lutein and zeaxanthin—especially for smokers—based on updated AREDS2 findings. These supplements don’t prevent AMD but can slow progression in people already at high risk.

Early Research on Antioxidants and AMD

According to a nationwide clinical trial sponsored by the National Eye Institute (NEI), and reported in the October 2001 issue of Archives of Ophthalmology, supplementation with antioxidants and zinc reduces the risk of AMD (age-related macular degeneration) [1]. Antioxidants are nutrients that protect from free radicals. Free radicals are like chemical “bullets” that damage tissue. Antioxidants are like chemical “bullet-proof vests”. Researchers found that for patients at risk for developing advanced AMD, taking vitamin C (500 mg/day), vitamin E (400 IU/day), beta-carotene (15 mg/day), and zinc (80 mg/day) lowered the risk by about 25%. “This is an exciting discovery because, for people at high risk for developing advanced AMD, these dietary supplements are the first effective treatment to slow the progression of the disease,” said Paul A. Sieving, M.D., Ph.D., director of the NEI.

Earlier studies have shown that people eating diets high in green leafy vegetables have a lower risk of developing AMD. This Study involved 4,757 participants, 55-80 years of age. Participants in the study were given one of four treatments: 1) zinc alone; 2) antioxidants alone; 3) a combination of antioxidants and zinc; or 4) a placebo. The groups taking zinc alone or the antioxidants alone (vitamins C, E, and beta-carotene), experienced some benefit, but not as much as the group taking the combination.

Dr. Sanjay Sharma is the founding director of Queen’s University’s Cost-Effective Ocular Health Policy Unit. Queen’s University is in Kingston Ontario. According to Dr. Sharma, “We project that this strategy [high-dose vitamin supplementation (Vitamins C and E, plus beta carotene and zinc)], if applied to those with the advanced ‘dry’ form of AMD over the coming decade could potentially save the North American health care system more than $1.5 billion.”

Newer AMD Research

Newer research has refined, but not overturned, these findings. The original Age-Related Eye Disease Study (AREDS) confirmed that a high-dose combination of vitamin C, vitamin E, beta-carotene, and zinc reduced the risk of progression to advanced AMD by about 25% in people with intermediate AMD or advanced AMD in one eye [1]. Later, the AREDS2 trial tested adding lutein, zeaxanthin, and omega-3 fats to the original formula and found no additional overall benefit for slowing AMD progression, but it did show that replacing beta-carotene with lutein and zeaxanthin is safer for current and former smokers because beta-carotene was linked with a higher risk of lung cancer in that group [2-4].

Systematic reviews from the Cochrane Collaboration now conclude that AREDS-type antioxidant and zinc supplements can modestly slow progression in people who already have intermediate or advanced AMD, but they do not prevent AMD from developing in people without the disease [5-7] In other words, these supplements are best viewed as a disease-modifying option for specific higher-risk patients, not a general preventive for everyone.

FAQ

What is the difference between AREDS and AREDS2?

The biggest change is that AREDS2 replaces beta-carotene with lutein and zeaxanthin. This avoids the increased lung cancer risk linked to beta-carotene in current and former smokers. AREDS2 also tested omega-3s, but they didn’t improve outcomes.

Who benefits most from AREDS-type supplements?

People with intermediate AMD, or those with advanced AMD in one eye, benefit the most. People with mild or early disease showed little to no benefit in the trials.

Are lutein and zeaxanthin better than beta-carotene?

For smokers and former smokers, absolutely yes. For everyone else, AREDS2 shows lutein and zeaxanthin provide protection without the safety concerns of beta-carotene.

Do AREDS supplements restore lost vision?

No. These supplements help slow progression, but they don’t cure AMD or reverse existing vision loss.

References:

  1. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Archives of Ophthalmology. 2001;119(10):1417–1436.
  2. Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA. 2013;309(19):2005–2015. doi:10.1001/jama.2013.4997.
  3. The Age-Related Eye Disease Study 2 (AREDS2): rationale, design, and methods. Ophthalmology. 2012;119(11):2280–2287. doi:10.1016/j.ophtha.2012.05.027
  4. Long-term outcomes of adding lutein/zeaxanthin and ω-3 fatty acids to the AREDS supplements on age-related macular degeneration progression and lung cancer risk: extended follow-up of the AREDS2 trial. JAMA Ophthalmology. 2022;140(7):692–701. doi:10.1001/jamaophthalmol.2022.1427.
  5. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration. Cochrane Database of Systematic Reviews. 2023;CD000254 (update).
  6. Antioxidant vitamin and mineral supplements to prevent the development of age-related macular degeneration. Cochrane Database of Systematic Reviews. 2017;CD000253
  7. Antioxidant vitamin and mineral supplements for age-related macular degeneration.
    Cochrane Database of Systematic Reviews. 2002;CD000254.