Supplements for Age-Related Macular Degeneration

If you are over age 75, there is a good chance that someone you know has been diagnosed with some form of age-related macular degeneration (AMD),[1], [2] a leading cause of vision loss and blindness in older adults in the U.S.

Our article in the June 2015 issue of Worst Pills, Best Pills News reviewed prescription injections that may help to prevent vision loss in patients with the most harmful type of AMD.[3]

In addition to drugs, patients with AMD are also frequently advised by their doctors to take a dietary supplement containing high doses of zinc and antioxidants.[4],[5] This advice is mainly based on two large, publicly funded clinical trials, known as Age-Related Eye Disease Studies (AREDS and AREDS2), which demonstrated that this combination of supplements can slow the progress of AMD in patients with later stages of the disease.[6],[7]

Dietary supplements bearing the name AREDS or AREDS2 are now broadly marketed to promote general eye health.[8] But these high-dose supplements are not right for everyone who wants good vision: They have proven benefits only among people with specific stages of AMD, and some of their ingredients have been linked to side effects including gastrointestinal problems and prostate and lung cancers.

Learn who can benefit from — and who should not take — these high-dose supplements, and which ingredients to look for on the label.

Stages of AMD

AMD is a disease that damages the macula, the part of the retina responsible for sharp, detailed central vision needed for “straight-ahead” activities such as reading and driving.[9]

AMD has three stages: early, intermediate and advanced. In the early stage, tiny yellow deposits called drusen appear beneath the retina.[10] For 99 percent of patients with early AMD, the disease does not progress for five years, if at all, to advanced AMD, the stage when the disease causes serious vision loss.[11]

People with intermediate AMD have larger drusen or pigment changes in the retina. About one in five of these patients will progress to advanced AMD within five years.[12] ,[13]

Most vision loss occurs in people with advanced, or late-stage, AMD, when the disease causes significant damage to the macula, either through gradual breakdown of cells in the macula and supporting tissue (geographic atrophy or "dry" AMD) or abnormal blood vessel growth (neovascular or “wet” AMD).[14]

The AREDS trials

The AREDS trials explored whether specific dietary supplements could slow the progression of AMD and prevent vision loss.[15],[16] The first AREDS trial, a large randomized, placebo-controlled trial that concluded in 2001, showed that daily use of supplements containing high doses of vitamin C, vitamin E and beta carotene, plus the minerals zinc and copper, can slow disease progression in patients at high risk for developing advanced AMD.[17] Subjects taking these supplements who had intermediate or advanced AMD in at least one eye were about 25 percent less likely to experience vision loss than those taking a placebo.[18]

But the AREDS supplement regimen did not slow the disease or prevent vision loss in patients with early-stage AMD.[19],[20] The supplements also did not protect against the risk of cataracts.[21]

After completion of the first AREDS trial, safety concerns remained about the supplements that had been used. Most importantly, results from other research showed that beta carotene taken at the dose used in the AREDS trial increased the risk of lung cancer in current smokers (the AREDS trial itself had too few smokers and lung cancer cases to evaluate this risk).[22],[23] Also, subjects in the AREDS trial taking the supplements had more gastrointestinal, urinary and genital adverse effects, which may have been caused by the high dose of zinc (80 milligrams [mg]) used.[24]

AREDS2, another large, randomized, placebo-controlled trial that concluded in 2012, tested whether the supplement formula could be made safer and more effective.[25] For this complex trial, subjects were randomly assigned to various combinations of the following supplements daily: vitamins C and E, beta carotene, zinc (25 or 80 mg) with copper, omega-3 fatty acids, and the antioxidants lutein and zeaxanthin, which occur naturally in the retina and lens and may help absorb damaging light.[26] Current smokers were excluded from the groups receiving beta carotene because of the lung cancer risk.

AREDS2 showed that removing beta carotene and lowering the zinc dose did not reduce the supplement formula’s protective effect against developing advanced AMD.[27]

While omega-3 fatty acids had no AMD benefits, lutein and zeaxanthin were more effective than beta carotene at reducing the risk of progressing to advanced AMD. The benefits were particularly strong for patients with low lutein and zeaxanthin in their diets.[28],[29]

Persistent safety concerns

The AREDS2 trial generated new knowledge to improve the supplement formula, but ongoing safety concerns remain.

Of particular note, the results from AREDS2 revealed that beta carotene increased the risk of lung cancer even among former smokers.[30], [31]

AREDS2 data also showed that the lower-dose zinc (25 mg per day), while equally effective at preventing AMD disease progression, did not result in lower rates of gastrointestinal, urinary and genital adverse effects compared with the high-dose zinc.[32]

The same high dose of vitamin E (400 international units [IU] daily) given in both the AREDS and AREDS2 trials was linked to increased risk of prostate cancer when taken as the only supplement in a large, publicly funded randomized clinical trial.[33],[34]

Finally, high-dose vitamins and minerals can sometimes interfere with medications and compete with other vital nutrients for absorption into the body, potentially causing additional problems.[35]

What You Can Do

If you have been diagnosed with intermediate or advanced AMD, talk to your doctor about taking an AREDS or AREDS2 supplement.[36]

Other patients should avoid these supplements. They offer no proven benefits for early-stage AMD, cataracts or any other eye diseases,[37] and they contain high-dose vitamins and minerals that may cause harmful side effects.

Be sure to check the product label before buying, as not all AREDS supplements contain the doses of vitamins and minerals actually tested in the AREDS trials.[38] ,[39]

The ingredients shown to be most effective and safest in the AREDS and AREDS2 trials were:

• 500 mg of vitamin C
• 400 IU of vitamin E
• 25 or 80 mg zinc
• 2 mg copper
• 10 mg lutein and 2 mg zeaxanthin

If you are a current or former smoker, avoid AREDS supplements that contain beta carotene, because they can increase your risk of lung cancer.

Tell your doctor if you are taking an AREDS or AREDS2 supplement, as the high doses of vitamins and minerals may affect other medications.

References

[1] The Eye Diseases Prevalence Research Group. Prevalence of age- related macular degeneration in the United States. Arch Ophthalmol. 2004;122:564-572.

[2] Klein R, Klein B, Linton K. Prevalence of age-related maculopathy: The Beaver Dam Eye Study. Opthalmology. 1992;99:933-943.

[3] Injections for age-related macular degeneration. Worst Pills, Best Pills News. June 2015. /newsletters/view/971. Accessed May 18, 2016.

[4] National Eye Institute. The AREDS formulation and age-related macular degeneration. Updated November 2011 https://nei.nih.gov/amd/summary.

[5] Arroyo JG, Trobe J, Schmader KE, Wilterdink JL. Age-related macular degeneration: Treatment and prevention. Topic 6912. Version 53.0. UpToDate. 2016. http://www.uptodate.com. Accessed May 18, 2016.

[6] 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.

[7] The Age-Related Eye Disease Study 2 (AREDS2) Randomized Clinical Trial. 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. http://jama.jamanetwork.com/article.aspx?articleid=1684847. Accessed May 18, 2016.

[8] American Academy of Ophthalmology. Top-selling eye vitamins found not to match scientific evidence. December 9, 2014. http://www.aao.org/newsroom/news-releases/detail/top-selling- eye-vitamins-found-not-to-match-scient. Accessed May 18, 2016.

[9] National Eye Institute (NEI). Age-related macular degeneration (AMD). https://nei.nih.gov/health/maculardegen/. Accessed May 18, 2016.

[10] National Eye Institute (NEI). Facts about age-related macular degeneration. Updated September 2015. https://nei.nih.gov/health/maculardegen/armd_facts. Accessed May 18, 2016.

[11] American Academy of Ophthalmology. AAO Retina/Vitreous PPP Panel. Age-related macular degeneration PPP – Updated 2015. January 2015. http://www.aao.org/preferred-practice-pattern/age-related-macular- degeneration-ppp-2015. Accessed May 18, 2016.

[12] National Eye Institute (NEI). Facts about age-related macular degeneration. Updated September 2015. https://nei.nih.gov/health/maculardegen/armd_facts. Accessed May 18, 2016.

[13] American Academy of Ophthalmology. AAO Retina/Vitreous PPP Panel, Age-related macular degeneration PPP – Updated 2015. January 2015. http://www.aao.org/preferred-practice-pattern/age-related- macular-degeneration-ppp-2015#references. Accessed May 18, 2016.

[14] National Eye Institute (NEI). Facts about age-related macular degeneration. Updated September 2015. https://nei.nih.gov/health/maculardegen/armd_facts. Accessed May 18, 2016.

[15] 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.

[16] Age-Related Eye Disease Study 2 (AREDS2) Research Group, Chew EY, Clemons TE, et al. Secondary analyses of the effects of lutein/zeaxanthin on age-related macular degeneration progression: AREDS2 report No. 3. JAMA Ophthalmol. 2014;132(2):142-149. doi: 10.1001/jamaophthalmol.2013.7376.

[17] 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.

[18] Ibid.

[19] AAO Retina/Vitreous PPP Panel. Age-related macular degeneration PPP – Updated 2015. January 2015. http://www.aao.org/preferred-practice-pattern/age-related-macular- degeneration-ppp-2015. Accessed May 18, 2016.

[20] 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.

[21] Age-Related Eye Disease Study Group. A randomized, placebo- controlled, clinical trial of high-dose supplementation with vitamins C and E and beta carotene for age-related cataract and vision loss. AREDS Report No. 9. Arch Ophthalmol. 2001;199 (10):1439-1452.

[22] National Eye Institute. The AREDS formulation and age-related macular degeneration. Updated November 2011. https://nei.nih.gov/amd/summary#9. Accessed May 18, 2016.

[23] National Cancer Institute. Antioxidants and cancer prevention. January 16, 2014. http://www.cancer.gov/about- cancer/causes-prevention/risk/diet/antioxidants-fact-sheet. Accessed June 22, 2016.

[24] National Institutes of Health. DailyMed. Levaquin label (updated November 2015). http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a1f01e8e-97e9-11de- b91d-553856d89593#S1.13. Accessed February 16, 2016.

[25] The Age-Related Eye Disease Study 2 (AREDS2) Randomized Clinical Trial. 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. http://jama.jamanetwork.com/article.aspx?articleid=1684847. Accessed May 18, 2016.

[26] National Eye Institute. For the public: What the AREDS means for you. May 2013. https://nei.nih.gov/areds2/PatientFAQ. Accessed May 18, 2016.

[27] Ibid.

[28] National Eye Institute. NIH study provides clarity on supplements for protection against blinding eye disease. May 5, 2013. https://nei.nih.gov/news/pressreleases/050513. Accessed May 18, 2016.

[29] The Age-Related Eye Disease Study 2 (AREDS2) Randomized Clinical Trial. 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. http://jama.jamanetwork.com/article.aspx?articleid=1684847. Accessed May 18, 2016.

[30] National Eye Institute. NIH study provides clarity on supplements for protection against blinding eye disease. May 5, 2013. https://nei.nih.gov/news/pressreleases/050513. Accessed May 18, 2016.

[31] The Age-Related Eye Disease Study 2 (AREDS2) Randomized Clinical Trial. 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. http://jama.jamanetwork.com/article.aspx?articleid=1684847. Accessed May 18, 2016.

[32] Ibid.

[33] National Cancer Institute. Selenium and vitamin E cancer prevention trial (SELECT): Questions and answers. Updated July 7, 2015. http://www.cancer.gov/types/prostate/research/select-trial-results-qa. Accessed May 19, 2016.

[34] Increased prostate cancer risk with vitamin E supplements. Worst Pills Best Pills News.February 2012. /newsletters/view/783.

[35] National Eye Institute. For the public: what the AREDS means for you. May 2013. https://nei.nih.gov/areds2/PatientFAQ. Accessed May 18, 2016.

[36] AAO Retina/Vitreous PPP Panel, Age-related macular degeneration PPP – Updated 2015. January 2015.  Accessed May 18, 2016.

[37] American Academy of Ophthalmology. Top-selling eye vitamins found not to match scientific evidence. December 9, 2014. http://www.aao.org/newsroom/news-releases/detail/top-selling-eye-vitamins-found-not-to-match-scient. Accessed May 19, 2016.

[38] Ibid.

[39] Yong JJ, Scott IU, Greenberg PB. Ocular nutritional supplements: Are their ingredients and manufacturers’ claims evidence-based? Ophthalmology. 2015;122(3):595-599.