AREDS and AREDS2 are two large clinical trials run by the National Eye Institute (NEI). AREDS, published in 2001, found that high doses of antioxidants (including vitamins C and E) plus zinc and copper lowered the chance of progressing to advanced age-related macular degeneration (AMD) in people already at higher risk. AREDS2, which ran from 2006 to 2012, tested adding lutein and zeaxanthin (which later replaced the original carotenoid), omega-3s, and a lower zinc dose. Neither trial showed that supplements prevent AMD.
If your eye doctor has mentioned "AREDS2 vitamins," those letters point back to these two studies. This article explains how each trial was set up, who took part, what the researchers found, and how to read the numbers you will see quoted. If your question is whether the formula is meant for you, our companion article What Is AREDS2 and Who Needs It? covers that.
Why these trials mattered
AMD is common. A study in JAMA Ophthalmology estimated that in 2019, about 18.34 million US adults age 40 and older had early AMD and about 1.49 million had late AMD. NEI notes that AMD and cataract are leading causes of visual impairment and blindness in the United States, and that risk rises sharply after age 65.
Observational studies, which follow what people eat and who develops disease, have linked higher zinc intake with lower AMD risk, according to the NIH Office of Dietary Supplements (ODS). But a link is not proof. To test whether a supplement itself makes a difference, researchers give some people the supplement and others a placebo (a look-alike pill with no active ingredient), then compare what happens.
How AREDS was designed
According to NEI, AREDS enrolled 4,757 people aged 55 to 80 at 11 clinics between 1992 and 1998. The median age was 69, and 56% were women. The main AMD report (AREDS Report No. 8) analyzed 3,640 of these participants, followed for an average of 6.3 years.
Participants were placed in one of four groups: antioxidants alone, zinc with copper, the full combination, or placebo. The daily doses were vitamin C 500 mg, vitamin E 400 IU, zinc 80 mg (as zinc oxide) and copper 2 mg (as cupric oxide), and the antioxidant groups also received the original formula's carotenoid.
People were also grouped by how much AMD they had. Eye doctors judge this partly by drusen, the small yellowish deposits under the retina described in our article on dry vs. wet AMD. People in the lowest-risk group had only a 1.3% chance of reaching advanced AMD over 5 years, so there was little room for a supplement to make a measurable difference.
What AREDS found
Compared with placebo, the full combination lowered the odds of progressing to advanced AMD, with an odds ratio of 0.72.
What is an odds ratio? It compares how likely something is in one group versus another. An odds ratio of 1 means no difference. A number below 1 means the outcome happened less often in the supplement group, and the further below 1, the bigger the difference. NEI describes the AREDS result as about a 25 percent lower risk of moving from intermediate to advanced AMD.
The benefit showed up in people at higher risk, meaning those with intermediate AMD or advanced AMD in one eye. In that group, the odds ratio was 0.66. Other results from Report No. 8:
- Zinc alone: odds ratio 0.75. Antioxidants alone: odds ratio 0.80. Neither was statistically significant in the full group.
- Moderate vision loss was less common with the full combination (odds ratio 0.73).
- No statistically significant serious side effect was found.
NEI summarizes the AREDS results as 25% lower progression with the full formula, 21% with zinc plus copper, and 17% with antioxidants alone. No formula reduced cataract surgery. In NEI's 10-year follow-up, 34% of the highest-risk group taking the formula progressed, compared with 44% on placebo.
How AREDS2 was designed
AREDS2 asked whether the formula could be improved. It enrolled 4,203 people aged 50 to 85 at 82 sites, and only people with intermediate AMD in both eyes, or intermediate AMD in one eye and advanced AMD in the other (NEI). Median follow-up was 5 years.
The main question, reported in JAMA in 2013, was whether adding lutein (10 mg) and zeaxanthin (2 mg), or omega-3 fatty acids (DHA 350 mg plus EPA 650 mg), would lower risk further. A second question tested versions of the AREDS formula without the original carotenoid, and with 25 mg of zinc instead of 80 mg. NEI notes that current smokers, and people who had quit less than a year before joining, did not receive the original carotenoid.
What AREDS2 found
In the main analysis, neither addition lowered risk further. The hazard ratio was 0.90 for lutein and zeaxanthin and 0.97 for omega-3s.
What is a hazard ratio? It compares how quickly an event, such as reaching late AMD, happens in two groups over the whole study. Like an odds ratio, 1 means no difference and a number below 1 means the event happened more slowly in the supplement group. A value close to 1, such as 0.97, means essentially no difference.
Over 5 years, the estimated chance of progressing to advanced AMD was 31% with placebo and 29% with lutein and zeaxanthin, a difference that was not statistically significant. The 25 mg zinc dose showed no difference from 80 mg.
The swap still mattered. AREDS2 found more lung cancers in people taking the original formula's carotenoid (23 cases vs 11), mostly in former smokers, which is one reason it was replaced with lutein and zeaxanthin. NEI reports that about 91% of the people who developed lung cancer were former smokers.
Some findings came from secondary analyses, meaning follow-up looks beyond the main question. ODS reports that people with the lowest lutein and zeaxanthin in their diets had a 26% lower risk of advanced AMD when they took them, and that the lutein version of the formula had an 18% lower risk than the version with the original carotenoid. For cataracts, AREDS2 Report No. 4 found no overall effect of lutein and zeaxanthin on cataract surgery (hazard ratio 0.96).
The 10-year follow-up and the 2023 review
A 10-year follow-up published in 2022 looked at 3,882 AREDS2 participants. Lutein and zeaxanthin were linked to a lower risk of late AMD than no lutein and zeaxanthin (hazard ratio 0.91, range 0.84 to 0.99), and to a lower risk than the original carotenoid (hazard ratio 0.85). Zinc dose made no meaningful difference (hazard ratio 1.04).
In 2023, a Cochrane review pooled 26 trials with 11,952 people. It found moderate-certainty evidence that AREDS-type supplements probably slow progression to late AMD (odds ratio 0.72). "Moderate certainty" means the true effect is probably close to this estimate, but further research could change it.
Reading the numbers: a quick guide
| Term | Plain meaning | Example from the trials |
|---|---|---|
| Odds ratio | Compares how likely an outcome is in two groups. 1 means no difference. | AREDS full formula: 0.72 |
| Hazard ratio | Compares how fast an outcome happens over time. 1 means no difference. | Zinc 25 mg vs 80 mg at 10 years: 1.04 |
| Range (confidence interval) | The span of results the data support. If it includes 1, "no difference" cannot be ruled out. | 0.84 to 0.99 for lutein and zeaxanthin at 10 years |
| Relative vs absolute | "25% lower" is relative. How many people it helps depends on their starting risk. | Cochrane: about 78 fewer cases per 1,000 with intermediate AMD, about 4 per 1,000 with early AMD |
| Main vs secondary analysis | The main analysis answers the planned question. Secondary analyses are useful but less certain. | Main: 0.90 for lutein. Secondary: lowest dietary intake group |
What the trials did not show
NEI states that AREDS and AREDS2 supplements "do not prevent AMD onset" and do not affect cataracts, and that omega-3 supplements had no effect on AMD or cataract. In its FAQ, NEI adds that there was no benefit for people with early AMD or without AMD. We cover prevention in Can AREDS2 Prevent Macular Degeneration?
Keep in mind: These trials enrolled people with specific stages of AMD. If you smoke or used to smoke, take blood thinners or other medicines, or have kidney or liver disease, talk with your eye doctor before starting any high-dose formula.
Frequently asked questions
Why do formulas still use 80 mg of zinc if 25 mg worked the same?
AREDS2 had no placebo group for the zinc comparison, so NEI still treats the placebo-controlled 80 mg AREDS results as the gold standard. Our article on zinc and copper explains the tradeoffs.
Is "AREDS3" a new NEI trial?
No. PreserVision AREDS3 is a Bausch + Lomb brand name launched in February 2026, not a National Eye Institute trial. See AREDS2 supplements compared by label.
Were the supplements safe in the trials?
AREDS found no statistically significant serious side effect, and Cochrane lists stomach and gut symptoms as the main side effect. There are specific cautions, which we cover in Are AREDS2 Vitamins Safe?
If you are comparing formulas, our science page lists the doses used in the trials.
Related reading
- Nutrition and Eye Health: What the Research Actually Shows
- What Is AREDS2 and Who Needs It?
- Lutein and Zeaxanthin: The Yellow Pigment That Shields Your Macula
- 5 Vitamins and Nutrients That Matter for Your Eyes
References
- Age-Related Eye Disease Study Research Group. AREDS Report No. 8. Arch Ophthalmol. 2001;119:1417. doi:10.1001/archopht.119.10.1417
- Age-Related Eye Disease Study 2 Research Group. Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the AREDS2 randomized clinical trial. JAMA. 2013;309:2005. doi:10.1001/jama.2013.4997
- AREDS2 Research Group. AREDS2 Report No. 4 (cataract). JAMA Ophthalmol. 2013;131:843. doi:10.1001/jamaophthalmol.2013.4412
- Chew EY, et al. AREDS2 Report No. 28 (10-year outcomes). JAMA Ophthalmol. 2022;140:692. doi:10.1001/jamaophthalmol.2022.1640
- Evans JR, Lawrenson JG. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration. Cochrane Database Syst Rev. 2023;9:CD000254. doi:10.1002/14651858.CD000254.pub5
- Rein DB, et al. Prevalence of AMD in the US in 2019. JAMA Ophthalmol. 2022;140:1202. doi:10.1001/jamaophthalmol.2022.4401
- National Eye Institute. About AREDS and AREDS2 (updated October 22, 2025) and AREDS/AREDS2 Frequently Asked Questions (updated November 19, 2020). nei.nih.gov
- NIH Office of Dietary Supplements. Zinc and Vitamin A and Carotenoids fact sheets for health professionals. ods.od.nih.gov
This article is for general education and is not medical advice. Talk with your eye doctor before starting any supplement, especially if you smoke, take other medicines, or have a health condition. These statements have not been evaluated by the Food and Drug Administration. TruVista products are not intended to diagnose, treat, cure, or prevent any disease.
