The Age-Related Eye Disease Study (AREDS) was a clinical trial sponsored by the National Eye Institute that ran from 1992 to 2001.[1] The study was designed to:
- investigate the natural history and risk factors of age-related macular degeneration (AMD) and cataracts, and
- evaluate the effects of high doses of antioxidants and zinc on the progression of the two conditions in those with AMD.
The results were reported in the October 2001 issue of Archives of Ophthalmology.[1] The study followed 3640 individuals for an average of 6.3 years between 1992 and 2001. The researchers concluded that high levels of antioxidants and zinc can reduce some people's risk of developing advanced AMD by about 25 percent.[1] Advanced AMD is defined as either choroidal neovascularization (wet macular degeneration) or atrophic age-related macular degeneration (geographic atrophy). The anti-oxidants and zinc supplements only reduced the risk of progression to wet macular degeneration. Those that benefited from the dietary supplements included those with intermediate-stage AMD and those with advanced AMD in one eye only. The supplements had no significant effect on the development or progression of cataracts. "High levels" in this case were defined to be:
- 500 milligrams of vitamin C;
- 400 international units of vitamin E;
- 15 milligrams of beta-carotene (or 25,000 international units of vitamin A);
- 80 milligrams of the dietary mineral zinc, in the form of zinc oxide; and
- two milligrams of copper as cupric oxide, added to prevent copper deficiency anemia, a condition associated with high levels of zinc intake.
Bausch & Lomb was a collaborator in the study.[2] They and other suppliers provide supplements pre-packaged with formulations based on this study.
Studies in 2016[3] and 2018[4] later showed that this average 25 percent reduction in risk from the combination of anti-oxidants and zinc varies by genotype.
AREDS2
edit| Ingredient | AREDS | AREDS2 |
|---|---|---|
| Vitamin C | 500mg | 500mg |
| Vitamin E | 400IU | 400IU |
| Beta-carotene | 15mg |  Removed
|
| Cupric oxide | 2mg | 2mg |
| Lutein | 10mg | |
| Zeaxanthin | 2mg | |
| Zinc | 80mg | 80mg |
The original AREDS study was followed by AREDS2, a five-year study that started in 2006 to test whether the original AREDS formulation would be improved by adding omega-3 fatty acids; adding lutein and zeaxanthin; removing beta-carotene; or reducing zinc.[6][7][8] In AREDS2, participants took one of four AREDS formulations: the original AREDS formulation, AREDS formulation with no beta-carotene, AREDS with low zinc, AREDS with no beta-carotene and low zinc. In addition, they took one of four additional supplement or combinations including lutein and zeaxanthin (10 mg and 2 mg), omega-3 fatty acids (1,000 mg), lutein/zeaxanthin and omega-3 fatty acids, or placebo.[6][8]
The study reported that there was no overall additional benefit from adding omega-3 fatty acids or lutein and zeaxanthin to the formulation. However, the study did find benefits in two subgroups of participants: those not given beta-carotene, and those who had very little lutein and zeaxanthin in their diets. Removing beta-carotene did not curb the formulation's protective effect against developing advanced AMD,[6] which is important given that high doses of beta-carotene have been linked to higher risk of lung cancers in smokers.[9] According to Dr. Emily Chew, "Because carotenoids can compete with each other for absorption in the body, beta-carotene may have masked the effect of the lutein and zeaxanthin in the overall analysis."[6]
The AREDS2 trial did not find a difference in the effects of 80mg versus 25mg zinc. The UK National Health Service suggests that people may take the lower dose if the higher dose upsets their stomach.[10] The 25mg zinc level has not been compared to a placebo, as of 2020[update], and 80mg remains the standard.[5]
Packaging
editThe AREDS2 formulation is often sold with all the ingredients packaged together in one pill, for convenience. These formulations may be labelled as "AREDS2", the pharmaceutical generic name, or they may be labelled with trademarked brand names, or they may be labelled with both. Some preparations not explicitly labelled as AREDS2 may not contain the correct ingredients in the correct quantities, and may contain additional, non-AREDS2 ingredients, which have no proven benefit.[10]
The AREDS2 formulation can also be taken as a set of pills which contain the individual components in the correct quantities.[10]
References
edit- ^ a b c Age-Related Eye Disease Study Research Group (October 2001). "AREDS Report No. 8: 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". Archives of Ophthalmology. 119 (10): 1417–1436. doi:10.1001/archopht.119.10.1417. PMC 1462955. PMID 11594942.
- ^ The Age-Related Eye Disease Study Research Group (June 2006). "The Age-Related Eye Disease Study (AREDS): Design Implications AREDS Report No. 1". Controlled Clinical Trials. 20 (6): 573–600. doi:10.1016/S0197-2456(99)00031-8. PMC 1473211. PMID 10588299.
- ^ Seddon, Johanna M.; Silver, Rachel E.; Rosner, Bernard (July 2016). "Response to AREDS supplements according to genetic factors: survival analysis approach using the eye as the unit of analysis". British Journal of Ophthalmology. 100 (12): 1731–1737. doi:10.1136/bjophthalmol-2016-308624. PMC 6570490. PMID 27471039.
- ^ Vavvas, Demetrios G.; Small, Kent W.; Awh, Carl C.; Zanke, Brent W.; Tibshirani, Robert J.; Kustra, Rafal (January 2018). "CFH and ARMS2 genetic risk determines progression to neovascular age-related macular degeneration after antioxidant and zinc supplementation". Proceedings of the National Academy of Sciences. 115 (4): E696–E704. Bibcode:2018PNAS..115E.696V. doi:10.1073/pnas.1718059115. PMC 5789949. PMID 29311295.
- ^ a b "AREDS/AREDS2 Frequently Asked Questions | National Eye Institute". www.nei.nih.gov. National Eye Institute/National Institutes of Health. Retrieved 14 July 2024.
- ^ a b c d "NIH study provides clarity on supplements for protection against blinding eye disease". May 2013. Archived from the original on 2013-06-07. Retrieved 2024-02-21.
- ^ Age-Related Eye Disease Study 2 Research Group (May 5, 2013). "Lutein/Zeaxanthin and Omega-3 Fatty Acids for Age-Related Macular Degeneration. The Age-Related Eye Disease Study 2 (AREDS2) Controlled Randomized Clinical Trial". JAMA. 309 (19): 2005–2015. doi:10.1001/jama.2013.4997. PMID 23644932.
- ^ a b "Age-Related Eye Disease Study 2 (AREDS2) - Full Text View". clinicaltrials.gov.
- ^ Omenn, Gilbert S.; et al. (1996). "Effects of a Combination of Beta Carotene and Vitamin A on Lung Cancer and Cardiovascular Disease" (PDF). New England Journal of Medicine. 334 (18): 1150–155. doi:10.1056/NEJM199605023341802. PMID 8602180.
- ^ a b c "AREDS 2 trial of vitamins and minerals for macular degeneration". Milton Keynes University Hospital. UK National Health Service. Retrieved 14 July 2024.
External links
edit
- NEI's website about the AREDS study
- NEI's website about the AREDS2 study