Introduction:
Age-related macular degeneration (AMD) definition:
AMD is an irreversible central vision loss occurring in the macula. The macula is the central part of the retina responsible for a sharp, clear, and straight visual field. Symptoms consist of central visual field haziness, distortion or wavelike images which reduce visual detail. In general, AMD is caused by fatty yellow colored deposits called drusen, atrophy, and choroidal neovascularization (abnormal formation of new blood vessels of the macula). The condition may occur as early as age 50 and incidence increases with age. AMD is divided into dry and wet types: Dry AMD is much more common and is characterized by fatty yellow colored deposits called drusen. Wet AMD occurs with abnormal blood vessel formation. AMD may be graded as early, intermediate, or advanced. It also may be staged by category 1, (low severity) with a small amount of drusen then higher categories are used to describe increasing amounts of drusen in categories 2 and 3. Category 4 (most severe) consisting of new abnormal blood vessel formation and retinal atrophy.
Preventive data on age-related macular degeneration (AMD):
Antioxidants and age related macular degeneration (AMD):
Antioxidants have been shown to reduce the progression of AMD once it occurs. The antioxidants taken as part of the Age-Related Eye Disease Study (AREDS) included vitamin C, 500 mg; vitamin E, 400 IU; beta carotene, 15 mg; and zinc, 80 mg as zinc oxide with 2 mg of cupric oxide. Copper was added to prevent copper deficiency which can occur with high dose zinc intake. Subjects were followed for almost 7 years. A beneficial reduction of AMD progression was observed among subjects with Categories 3 and 4 AMD. There was no significant change seen in mild AMD subjects (Category 1 or 2) compared to placebo. The highest protective effect was seen the supplement treatment groups taking zinc plus antioxidants. OR=0.63 (99% CI; 0.44-0.92). The antioxidants have not yet been shown to prevent the development of AMD nor did they have any benefit in development of cataracts. (1)
A systematic review on antioxidants and age related macular degeneration (AMD):
A systematic review by Kansagara D et al evaluated seven randomized controlled trials which studied nutritional supplements in patients with AMD. The authors believed that studies with the longest duration and largest group of subjects were able to better identify benefit of the antioxidants because AMD occurs slowly. The smaller studies might have been of insufficient duration or power to detect a treatment effect. The author reinforced that antioxidants prevented functional vision loss in the Age Related Eye Disease Study (AREDS) and that lutein, zeaxanthin, B vitamins, and omega-3 fatty acids have been reported to decrease AMD progression, while vitamin E and β-carotene where found to increase the risk of late AMD. (2)
Vitamin C and eye disease:
Those individuals with a high intake of vitamin C have been shown in general, to have a decreased incidence of eye diseases (3).
The Age-Related Eye Disease Study (AREDS) and mortality:
This study also found that subjects with AMD had an increase in mortality risk. After following patients for 6.5 years, 11% or 534 participants had died. This marked an increased mortality risk among participants with advanced AMD. However, participants randomly assigned to receive 80 mg zinc with 2 mg cupric oxide, whether alone or combined with antioxidants, had lower mortality than those not taking the mineral. In these AMD patients, they reported a 27% lower relative risk of mortality for zinc alone, and a 12% lower relative risk for those who took zinc combined with beta-carotene, vitamin C and vitamin E. The beneficial effect of zinc on mortality was associated with less death from respiratory causes. (4)
Lutein plus zeaxanthin and the AREDS study:
Currently, the Age-Related Eye Disease Study 2 (AREDS2) results on lutein plus zeaxanthin were pending. This study is evaluating lutein plus zeaxanthin with or without polyunsaturated fatty acid in reduction of advanced AMD. This study will also look at the results of removing beta carotene and reducing zinc used in the previous AREDS study. Beta-carotene may increase risk of late AMD and is also currently being investigated. (5)
Lowering progression of age related macular degeneration (AMD):
Diets including higher DHA, EPA, and a lower glycemic index showed a lower rate of advanced AMD progression in patients which are part of the AREDS. DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) are the major constituents of omega-3 fatty acids in fish oil and algae oil. (6)
The National Eye Institute (NEI) recommendations:
NEI recommendations are published online and which are based on the Age Related Eye Disease Study (AREDS). The NEI recommends that the eye care professional evaluate your eyes for signs of AMD using a dilated eye exam and ask your physician whether you would benefit from these antioxidants. The NEI does not recommend a particular age to start surveillance for AMD. The NEI reviewed The Selenium and Vitamin E Cancer Prevention Trial (SELECT) published in The Journal of the American Medical Association back in October of 2011. The NEI states that men should be aware that vitamin E of 400 IU per day was associated with an increased risk of prostate cancer, but those who took selenium with vitamin E did not show increased risk. Additionally, the NEI reviewed the Alpha-Tocopherol, Beta Carotene Trial (ATBC) and The Physicians Health Study II (PHS II) which showed that lower doses of vitamin E did not affect prostate cancer incidence. The NEI also reveiwed large clinical trials sponsored by the National Cancer Institute which showed that beta-carotene supplements increase risk of lung cancer in smokers. The NEI concludes that after review of the studies, beta-carotene use not only increases risk of lung cancer, but also may slightly increase risk of lung cancer for at least a period of several years after quitting smoking. (7)
Assessment and Plan: Age-Related Macular Degeneration:
- Upon any sign of new or worsening vision problems: As recommended by the National Eye Institute, have an eye care professional evaluate your eyes for signs of Age-related Macular Degeneration (AMD) using a dilated eye exam. If you are high risk for AMD or have signs of AMD, ask your physician whether or not if you would benefit from the antioxidants taken as part of the Age-Related Eye Disease Study (AREDS) including vitamin C, 500 mg; vitamin E, 400 IU; beta carotene, 15 mg; and zinc, 80 mg as zinc oxide with 2 mg of cupric oxide. Contraindications to beta-carotene supplements include smoking or previous smoker, and possible contraindications to vitamin E supplements include prostate cancer of increased risk of prostate cancer. Of note, beta-carotene may increase risk of late AMD and is currently being investigated.
- If any prior diagnosis of AMD, consider enhancement of dietary intake of vitamin C, vitamin E, beta carotene, zinc, copper, omega 3 fatty acids, lutein, and zeaxanthin from foods. A reference which shows foods containing high amounts of these nutrients is available at: Nutritive Value of Foods, United States Department of Agriculture, Agricultural Research Service, Home and Garden Bulletin Number 72. May be accessed at: https://www.ars.usda.gov/SP2UserFiles/Place/12354500/Data/SR25/nutrlist/sr25w421.pdf and http://www.nal.usda.gov/fnic/foodcomp/Data/HG72/hg72_2002.pdf
- For any previous diagnosis of AMD, consider a zinc supplement after discussing it with your primary physician or eye physician for possible reduced risk of mortality from respiratory causes. In the AREDS study, 80 mg of zinc oxide was taken. Cupric oxide, 2 mg oral once per day should be taken to prevent copper deficiency which can occur with high dose zinc.
- Please see “longevity” section for research in reduction of mortality as AMD may be associated with other diseases.
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 Oct. http://www.ncbi.nlm.nih.gov/pubmed/11594942 and http://www.nei.nih.gov/news/pressreleases/101201.asp
2.Kansagara D, Gleitsmann K, Gillingham M, Freeman M, Quiñones A. Nutritional Supplements for Age-related Macular Degeneration: A Systematic Review. VA-ESP Project #05-225; 2011. http://www.ncbi.nlm.nih.gov/books/NBK84269/
3.Jacob RA, Sotoudeh G. Vitamin C function and status in chronic disease. Nutr Clin Care. 2002 Mar-Apr;5(2):66-74. http://www.ncbi.nlm.nih.gov/pubmed/12134712?dopt=Abstract
4.AREDS Research Group. Associations of mortality with ocular disorders and an intervention of high-dose antioxidants and zinc in the Age-Related Eye Disease Study. AREDS Report No. 13. Arch Ophthalmol. 122:716-726, 2004. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1473208/?report=abstract
5.AREDS2 Research Group, Chew EY, Clemons T, SanGiovanni JP, Danis R, Domalpally A, McBee W, Sperduto R, Ferris FL. The Age-Related Eye Disease Study 2 (AREDS2): study design and baseline characteristics (AREDS2 report number 1). Ophthalmology. 2012 Nov;119(11):2282-9. http://www.ncbi.nlm.nih.gov/pubmed/22840421
6.Chiu CJ, Klein R, Milton RC, Gensler G, Taylor A. Does eating particular diets alter the risk of age-related macular degeneration in users of the Age-Related Eye Disease Study supplements? Br J Ophthalmol. 2009 Sep;93(9):1241-6. http://www.ncbi.nlm.nih.gov/pubmed/19508997
7.National Institutes of Health, National Eye Institute. The AREDS Formulation and Age-Related Macular Degeneration. Are These High Levels of Antioxidants and Zinc Right For You? Revised November of 2011. Accessed March 17, 2011. http://www.nei.nih.gov/amd/summary.asp