The Age-Related Eye Disease Study 1 and 2 (AREDS and AREDS2) nutritional supplements have been shown to decrease the risk of progression from intermediate to advanced age-related macular degeneration (AMD) in large randomized controlled trials.1,2 Given the increased risk of lung cancer in smokers with beta-carotene in the original AREDS formula and the possible benefit of lutein/zeaxanthin over beta-carotene in the AREDS2 formula, the AREDS2 formula has become the standard recommended formula for all patients with intermediate AMD.3 Here, we found that a significant number of supplements containing “AREDS” or “AREDS2” in their label are, in fact, not compliant with the AREDS2 clinical trials formula and are also more expensive than compliant formulas. The Dietary Supplement Health and Education Act (DSHEA) of 1994 considers a supplement misbranded if the supplement “is covered by the specifications of an official compendium” and “fails to so conform”.4 This suggests that AREDS2-labeled supplements that deviate from the AREDS2 formula may be in violation of federal law.
“AREDS” and “AREDS2” were used as search terms in Amazon and Google Shopping. The top 30 search results, excluding items marked as promoted ads, were recorded for each search, and each product was checked for compliance with the AREDS2 formula. Although the original AREDS formulation contained high-dose zinc (80 mg), the AREDS2 clinical trial found no statistically significant difference between low-dose zinc (25 mg) and high-dose zinc (80 mg).2 Therefore, we did not consider the inclusion of low-dose zinc to be a deviation from the AREDS2 formula.
A total of 120 search results were analyzed (Figure 1a) and 30.8% (37/120) of the products did not adhere to the AREDS2 formula. Compared to the AREDS2 formula, 14.2% (17/120) were missing at least one ingredient, 13.3% (16/120) contained less of at least one ingredient, 17.5% (21/120) contained more of at least one ingredient, and 15.8% (19/120) contained at least one extra ingredient when it wasn’t advertised as such on the bottle. The AREDS1 rather than AREDS2 formula was followed in 5.8% of products (7/120). Of note, the products that deviated from the AREDS2 formulation were 26.0% more expensive than those that complied ($0.63 vs. $0.50 per day, p = 0.0027) (Figure 1b).
Fig 1.
(a) Analysis of adherence to AREDS2 formula of products resulting from Google Shopping, Amazon, and pooled searches. (b) Cost analysis of adherent versus non-adherent formulas.
Of the 37 products that did not adhere to the AREDS2 formula, all but two had the term “AREDS” or “AREDS2” included in the name of the product. Several non-compliant formulations used the misleading term “AREDS2-based” in their labeling. We find it especially troubling that patients must pay more on average for nonadherent products than for adherent brands.
We considered results which contained duplicate or highly similar products to be separate entities in our analysis. The majority of the duplicate products were variations of the Bausch & Lomb PreserVision® AREDS2 supplement (65 out of the 120 total results), which is compliant with the AREDS2 formula. Treating duplicate products in this manner may have skewed our results to underrepresent the number of non-compliant formulas available on the online marketplace.
It is possible that supplements available in physical stores may have less variation in formula and pricing. However, given market shifts towards online purchases and that many clinicians may not ask patients where they obtain supplements, we believe online availability and pricing is a reasonable proxy to highlight the problem of AREDS2 formula compliance.
In summary, our analysis shows that many supplements marketed as AREDS/AREDS2 are not compliant with AREDS2. Clinicians should be specific in their recommendation of AREDS2 formulations to avoid inaccurate dosing. Examples of AREDS2-adherent brands available online are listed in the Table.
Table:
Brands adherent to AREDS2 formula
| Bausch & Lomb PreserVision® AREDS2 Formula |
| Ojoslabs Maculabs® AREDS2 Based Formula |
| Viteyes AREDS2 Based Formula Macular Support |
| NatureMade Vision with AREDS 2 Formula |
| Systane Icaps® Eye Vitamin & Mineral Supplement AREDS2 |
| Focus Select AREDES2 Based Formula Eye Vitamin & Mineral Supplement |
| Visual Advantage Macular Support |
Key Messages:
The AREDS2 formula is the standard formula that should be taken by all patients with intermediate AMD.
A significant number of supplements labeled as “AREDS” or “AREDS2” are not compliant with the AREDS2 clinical trials formula.
Clinicians should be specific in their recommendation of AREDS2 formulations to avoid inaccurate dosing.
References
- 1.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. doi: 10.1001/archopht.119.10.1417 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Age-Related Eye Disease Study 2 Research Group. 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 [DOI] [PubMed] [Google Scholar]
- 3.Chew EY, Clemons TE, Agrón E, et al. Long-term Outcomes of Adding Lutein/Zeaxanthin and ω−3 Fatty Acids to the AREDS Supplements on Age-Related Macular Degeneration Progression: AREDS2 Report 28. JAMA Ophthalmology. Published online June 2, 2022. doi: 10.1001/jamaophthalmol.2022.1640 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Office of Dietary Supplements - Dietary Supplement Health and Education Act of 1994. Accessed May 8, 2022. https://ods.od.nih.gov/About/DSHEA_Wording.aspx