What Is the Difference Between AREDS and AREDS2?

What Is the Difference Between AREDS and AREDS2?

AREDS and AREDS2 are related but not identical eye‑vitamin formulations. The original AREDS formula contained vitamin C, vitamin E, beta‑carotene, zinc, and copper, whereas AREDS2 replaced beta‑carotene with lutein and zeaxanthin and refined zinc dosing to improve safety while maintaining protection against progression to advanced age‑related macular degeneration (AMD).(1–4)

Key Facts at a Glance

• AREDS (original): vitamin C 500 mg, vitamin E 400 IU, beta‑carotene 15 mg, zinc 80 mg (as zinc oxide), copper 2 mg.(1,5,6)
• AREDS2 (updated): vitamin C 500 mg, vitamin E 400 IU, zinc 80 mg (or lower in some products), copper 2 mg, lutein 10 mg, zeaxanthin 2 mg, no beta‑carotene.(1,3,4)
• Both formulas reduced the 5‑year risk of progression from intermediate to advanced AMD by about 25% in high‑risk patients.(1–3,5)
• AREDS2 showed that adding lutein/zeaxanthin without beta‑carotene was at least as effective and safer for smokers and former smokers.(2–4,7)
• Omega‑3 fatty acids (DHA/EPA) were tested in AREDS2 but did not provide additional benefit in slowing AMD progression.(2,8)
• Current guidelines generally recommend AREDS2‑type formulations for eligible AMD patients rather than the original AREDS formula.(1–4)

How the Original AREDS Formula Was Designed

The Age-Related Eye Disease Study (AREDS) was a large National Eye Institute (NEI) trial that tested whether high‑dose antioxidant vitamins plus zinc could slow progression of AMD.(1,5,6) Participants were randomized to placebo, antioxidants only, zinc only, or a combination of antioxidants and zinc. The combination group received the now‑famous AREDS formulation: vitamin C 500 mg, vitamin E 400 IU, beta‑carotene 15 mg, zinc 80 mg, and copper 2 mg daily.(1,5,6,9)

In participants with intermediate AMD or advanced AMD in one eye, this combination reduced the 5‑year risk of progression to advanced AMD by about 25% and the risk of moderate vision loss by about 19% compared with placebo.(1,5,6,9) There was no meaningful benefit for participants with early or no AMD.(5,6) As a result, the AREDS formula became standard of care for high‑risk AMD patients.

Why AREDS Needed Updating

Subsequent evidence raised safety concerns about beta‑carotene, especially in smokers. Large cancer‑prevention trials (ATBC, CARET) found that high‑dose beta‑carotene increased lung cancer risk in current and former smokers.(2,3,7) In the AREDS cohort, a numerically higher—but not definitive—rate of lung cancer was seen in participants taking beta‑carotene, most of whom were former smokers.(2,3,7)

At the same time, observational and experimental data suggested that lutein and zeaxanthin, the main macular carotenoids, might provide similar or better retinal protection without increasing lung cancer risk.(2,3,7,10) Questions also arose about whether the 80‑mg zinc dose in AREDS was higher than necessary and whether adding omega‑3 fatty acids could further slow AMD progression.(2,8,10) These issues motivated the design of AREDS2.

Key Changes in the AREDS2 Formula

AREDS2 was a multicentre randomized trial that tested several modifications to the original formulation.(2,10,11) The main changes were:

• Carotenoids:
• Remove beta‑carotene.
• Add lutein 10 mg + zeaxanthin 2 mg.
• Zinc:
• Compare high‑dose zinc 80 mg vs reduced dose 25 mg, both with copper 2 mg.
• Omega‑3 fatty acids:
• Test the addition of DHA 350 mg + EPA 650 mg daily.

Across treatment arms, vitamins C (500 mg), E (400 IU), and copper (2 mg) were kept constant.(2,10,11) Importantly, all participants had intermediate AMD or advanced AMD in one eye, similar to the high‑risk groups in AREDS.(2,10,11)

Comparative Effectiveness: AREDS vs AREDS2

AREDS2 showed that adding lutein/zeaxanthin while removing beta‑carotene maintained the protective effect on AMD progression and, in some analyses, provided a modest additional benefit.(2,3,10,11) Secondary analyses reported that eyes receiving lutein/zeaxanthin had a hazard ratio (HR) for progression to late AMD of about 0.88–0.91 compared with those not receiving these carotenoids, suggesting a small but meaningful relative risk reduction.(4,10,11)

In contrast, adding omega‑3 fatty acids did not significantly reduce progression to advanced AMD compared with placebo.(2,8,10) Regarding zinc, AREDS2 found no clear difference in efficacy between 80‑mg and 25‑mg doses, although the study was not powered primarily to detect small differences in zinc effectiveness.(2,10,11)

A 10‑year follow‑up of the AREDS2 cohort confirmed that lutein/zeaxanthin remained a safe replacement for beta‑carotene and that beta‑carotene nearly doubled lung cancer risk, particularly in former smokers, whereas lutein/zeaxanthin did not increase this risk.(4) This reinforced the shift toward AREDS2‑type formulations.

Practical Differences for Patients

In practice, the main differences patients need to understand are:

• Carotenoid source
• AREDS: beta‑carotene (not recommended for smokers/former smokers).(2,3,7)
• AREDS2: lutein + zeaxanthin (macular carotenoids, safer for lung cancer risk).(2–4,10)
• Safety profile
• AREDS: associated with increased lung cancer risk in smokers due to beta‑carotene.(2–4,7)
• AREDS2: avoids beta‑carotene and is considered safer, especially for current or former smokers.(2–4)
• Zinc dose
• Labelled AREDS2 products may contain 80 mg or lower doses (for example 25–40 mg); available evidence suggests lower doses are likely just as effective with fewer gastrointestinal side effects.(2,10,11,12)
• Omega‑3s
• Not part of the core AREDS2 formula; patients may obtain omega‑3s from diet (fish, marine oils) or separate supplements if needed, but these are not required components of the evidence‑based eye vitamin regimen.(2,8,10)

For most high‑risk AMD patients today, professional societies and the NEI recommend AREDS2-based supplements, rather than the original AREDS formula, because they preserve efficacy while improving safety.(1–4,10,11)

When to Use Each Formula

Current consensus is:

• Use AREDS2 formulations for:
• Patients with intermediate AMD in one or both eyes.
• Patients with advanced AMD in one eye and less advanced disease in the fellow eye.
• Avoid AREDS (beta‑carotene–containing) formulations in:
• Current or former smokers due to increased lung cancer risk.
• Most modern practice, since AREDS2 offers a safer alternative with comparable or slightly better efficacy.(2–4,7,10,11)

People without AMD or with only early AMD (small drusen) generally do not need either formula, as trials did not show benefit for prevention at those stages.(5,6,9)

Summary

The original AREDS and the updated AREDS2 formulas share the same core goal—reducing the risk of progression from intermediate to advanced AMD—but differ in key ingredients. AREDS combined vitamins C and E, beta‑carotene, zinc, and copper; AREDS2 removed beta‑carotene, added lutein and zeaxanthin, and explored lower zinc doses and omega‑3s. Clinical trial data show that AREDS2‑type formulations maintain at least the same protective effect against AMD progression and are safer, particularly for smokers, because they avoid beta‑carotene–related lung cancer risk. As a result, AREDS2 is now the preferred evidence‑based supplement strategy for eligible AMD patients.

FAQs

Which is better: AREDS or AREDS2?
For most patients, AREDS2 is preferred because it replaces beta‑carotene with lutein and zeaxanthin, preserving or slightly enhancing protection against AMD progression while avoiding increased lung cancer risk seen with beta‑carotene.(2–4,7,10,11)

Should smokers ever use the original AREDS formula?
No. Because beta‑carotene nearly doubled lung cancer risk in current and former smokers, guidelines advise that smokers and ex‑smokers avoid beta‑carotene–containing AREDS formulations and use AREDS2 preparations instead.(2–4,7)

Do I need extra omega‑3 supplements if I am taking AREDS2?
AREDS2 found no added benefit of omega‑3 fatty acids for slowing AMD progression, so they are not required as part of the eye vitamin formula.(2,8,10) A diet rich in fatty fish is still encouraged for general health.

Does the amount of zinc matter between AREDS and AREDS2?
AREDS2 suggested that a lower zinc dose (around 25 mg) is likely as effective as 80 mg when combined with the rest of the formulation, with potentially fewer side effects.(2,10–12) Many clinicians favour moderate‑dose zinc within AREDS2 products.

If I already take an AREDS product, should I switch to AREDS2?
Patients who are current or former smokers, or who wish to minimize long‑term beta‑carotene exposure, are generally advised to switch to an AREDS2 formulation after discussing this with their eye‑care provider.(1–4,7,10,11)

This article is for educational purposes only and reflects current scientific literature at the time of writing.

References

1. National Eye Institute. AREDS/AREDS2 clinical trials: about AREDS and AREDS2. 2025. Available from: https://www.nei.nih.gov/eye-health-information/clinical-trials/age-related-eye-disease-studies-aredsareds2/about-areds-and-areds2
2. National Eye Institute. AREDS/AREDS2 frequently asked questions. 2020. Available from: https://www.nei.nih.gov/research/clinical-trials/age-related-eye-disease-studies-aredsareds2/aredsareds2-frequently-asked-questions
3. Chew EY, Clemons TE, Sangiovanni JP, et al. The Age-Related Eye Disease Study 2 (AREDS2): micronutrients in the treatment of AMD. Adv Nutr. 2017;8(1):40–53. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC5227975
4. Clemons TE, Chew EY, Klein ML, et al. Long-term outcomes of adding lutein/zeaxanthin and ω-3 fatty acids to the AREDS supplement on AMD progression and lung cancer risk. JAMA Ophthalmol. 2022;140(8):747–757. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC9164119
5. Age-Related Eye Disease Study Research Group. 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. Arch Ophthalmol. 2001;119(10):1417–1436. Available from: https://jamanetwork.com/journals/archopthalmology/fullarticle/268224
6. Macular Degeneration Foundation. Vitamins and zinc (AREDS)—a treatment for macular degeneration? 2016. Available from: https://www.macular.org/living-and-thriving-with-amd/nutrition/important-nutrients/antioxidant-vitamins-and-zinc-areds
7. American Optometric Association. Lutein, zeaxanthin reaffirmed over beta-carotene in AREDS2. 2022. Available from: https://www.aoa.org/news/clinical-eye-care/health-and-wellness/lutein-zeaxanthin-reaffirmed-over-beta-carotene-in-areds2
8. 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(19):2005–2015. Available from: https://pubmed.ncbi.nlm.nih.gov/23644932
9. BrightFocus Foundation. Vitamins for age-related macular degeneration: do you have the correct formula? 2024. Available from: https://www.brightfocus.org/resource/vitamins-for-age-related-macular-degeneration-do-you-have-the-correct-formula
10. Vision Research Center of New York. Understanding AREDS vitamins: benefits for age-related macular degeneration. 2024. Available from: https://www.vrcny.com/blog/understanding-areds-vitamins-benefits-for-age-related-macular-degeneration
11. Chew EY, Clemons TE, Agrón E, et al. Long-term follow-up of AREDS2 participants: impact of lutein/zeaxanthin vs beta-carotene on progression to late AMD. JAMA Ophthalmol. 2022;140(8):747–757. Available from: https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2792855
12. VisionDefender. AREDS vs. AREDS 2: what changed & why it matters. 2025. Available from: https://www.visiondefender.co.uk/areds-vs-areds-2-what-changed-why-it-matters