By Damon Dierker, OD, FAAO
Age-related macular degeneration (AMD) is the leading cause of adult blindness in the United States. Although there is no cure for AMD, actions such as ceasing smoking , making dietary changes , and adding nutritional supplementation with macular carotenoids have proven benefits, even in early AMD. Additionally, the AREDS2 study confirmed that risk of progression to choroidal neovascularization (CNV) can be reduced with a combination of antioxidants, carotenoids, and zinc in patients with bilateral intermediate AMD or late AMD in one eye.
Could Zinc Be Making Patients Worse?
Practitioners continue to show concern that zinc supplementation may have negative effects on AMD patients. Genetic analysis of the AREDS dataset found that a subgroup of patients receiving zinc supplements showed negative outcomes (i.e. they were more likely to progress to CNV) associated with certain polymorphisms.6,7 However, these findings could not be replicated by AREDS investigators.8 Importantly, independent analyses of the AREDS dataset by Seddon  and Vavvas  concluded that the effectiveness of AREDS supplements appears to differ by genotype.
Although not proven, high doses of dietary and supplemental zinc have been associated with prostate hypertrophy , prostate cancer [12,13], and genitourinary-caused hospitalizations. AREDS2 investigated whether a lower dose of zinc (25mg compared to 80mg) would be comparable in reducing risk of progression to advanced disease. Lowering the zinc dosage revealed no statistically significant effect. Additionally, recent genetic analysis of AREDS2 subgroups showed no difference in efficacy of low doses versus high doses of zinc  between groups.
A recently published study using an entirely new, real-world dataset found that long-term use of AREDS supplements significantly increases the risk of CNV in some patients due to their genetic makeup. Patients taking only a half-dose of AREDS supplements (40mg of zinc) for at least 5 years were included in this analysis.
When Considering Zinc
So, what is a medically minded optometrist to do when considering recommending zinc supplements in AMD patients? I see two reasonable choices:
Obtain in-office genetic testing (Macula Risk, ArcticDx) to determine if your patient may be potentially harmed by zinc supplements. If so, avoid prescribing a supplement containing zinc. I recommend MacuHealth once daily for these patients.
If you choose not to offer genetic testing, recommend an AREDS2 based supplement with 25mg dose of zinc instead of 80mg, as this appears to be equally efficacious. MacuHealth PLUS+ is an excellent choice.
Nutritional supplementation in AMD cases is critical, as is the need to be mindful of recommending any treatment that may result in a negative outcome.
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