It was just what the doctor didn't order.
A Utah woman in her 60s had glaucoma and hoped to protect her eye health through better nutrition. So she took a daily 20-mg supplement of lutein, a carotenoid found in produce that's been shown to help prevent progression of age-related macular degeneration (AMD).
So far, so good. But why did she develop crystal deposits within her retina that are known as "foveal sparkles"? Blame her very healthy diet.
As a 2016 case report revealed, the woman had "an unusually high dietary consumption of lutein, which included a broccoli, kale, spinach, and avocado smoothie every morning."
After the medical staff stepped in, she cut out the supplement, but not the shakes. The crystals resolved in one eye -- but not the other -- at 7 months.
It turns out that anti-AMD supplements aren't always an uncomplicated therapy.
Too much can be a problem, as the Utah woman discovered. On the other hand, too little is a risk when supplement products are counterfeit or fail to contain the claimed compounds.
Here's a look at five things to know about supplements and AMD.
Evidence Is Strong for Preventing AMD Progression
A pair of studies support the use of so-called AREDS2 supplements in patients with intermediate or advanced AMD in one or both eyes. The supplements -- which contain high doses of vitamins C and E, zinc, lutein, and zeaxanthin along with copper -- appear to reduce disease progression by about 25%.
The supplements are "particularly helpful in decreasing progression to neovascular (wet) AMD, the form of advanced disease that most rapidly threatens sight," said Tiarnán Keenan, MD, PhD, of the National Eye Institute in Bethesda, Maryland, in an interview.
The initial Age-Related Eye Disease Study (AREDS), published in 2001, first showed benefit from vitamin C and E, zinc, copper, and beta-carotene.
In 2013, the AREDS2 trial showed that a new formulation continued to provide benefit. Beta-carotene was removed following reports that it boosted the risk of lung cancer, and the amount of zinc was lowered. Lutein and zeaxanthin were added.
Why do AREDS formulations work? Keenan said vitamins C and E "have strong antioxidant properties, and oxidative stress is known to be an important factor in AMD pathophysiology."
Lutein and zeaxanthin are also antioxidants and linked to reductions in inflammation and sun damage from ultraviolet rays. And, they're both "specifically concentrated in the eye," said Paul S. Bernstein, MD, PhD, of the University of Utah School of Medicine in Salt Lake City. "If the eye goes out of its way to actually concentrate a nutrient in its eye, that's a sign it's likely to be very important for function."
It's unclear why zinc is beneficial, Kennan said. As for copper, the National Eye Institute says it's added to fend off zinc-related copper deficiency.
New Data Suggest Another Benefit
Recent research has revealed additional benefits of AREDS2 for geographic atrophy, an advanced form of dry AMD.
In a report published this year, Keenan's team analyzed the AREDS and AREDS2 trials and found signs that the AREDS2 supplements slow geographic atrophy toward the central macula by about 60%.
This suggests the supplements may help preserve central vision by protecting the fovea, the most critical area for detailed sight, Keenan said.
"Given their excellent safety profile, clinicians should consider whether their patients with non-central geographic atrophy may benefit from these supplements," he said. "However, given these were post-hoc analyses, we need to perform a new dedicated clinical trial to test this. We are hoping to begin a trial like this in the coming 1 to 2 years."
Supplements May Not Protect Patients Who Don't Have AMD
There's no evidence that the AREDS2 supplements are beneficial in patients at risk of AMD who haven't developed it yet.
As Keenan explained, the AREDS studies were specifically designed to examine disease progression, not prevention of initial onset.
Studying that form of prevention would be extremely challenging, he said, since "it would require an extremely large and long clinical trial."
Anti-AMD Supplements Aren't for Everyone
The zinc component of AREDS2 formulations may pose special risks for people with certain metabolic diseases, as they may not metabolize it the same way as others, said Sheldon Rowan, PhD, of Tufts University School of Medicine and Friedman School of Nutrition Science and Policy in Boston, in an interview.
The original AREDS study used 80 mg of zinc, but AREDS2 also tested 25 mg of zinc and found that dropping it down to that dosage seemed to work "just as well and with less stomach upset," Bernstein said.
Also, some people tolerate the supplements less well, Keenan noted. "In these cases, some suggestions include taking them with food, keeping well-hydrated, splitting the dose rather between morning and evening, or trying a different brand with the same formulation."
ConsumerLab.com, which independently tests health and nutrition products, warns patients to "be aware of unnecessarily high doses of zinc in some vision formulas, which can potentially cause adverse effects, including anemia."
Drug interactions could also spell trouble, especially since AREDS combinations include higher doses of vitamins and minerals than provided in regular supplements, Rowan said.
And, as the health-obsessed Utah woman discovered, overdoing the AREDS components isn't a good idea. "More is not always better," said Bernstein, who wrote up the case with colleagues.
Supplement Manufacturers May Mislead Customers
The AREDS2 formula contains 500 mg of vitamin C, 400 IU of vitamin E, 2 mg of copper (cupric oxide), 10 mg of lutein, 2 mg of zeaxanthin, and 80 mg of zinc. But manufacturers may mislead consumers.
A 2015 study reported that only four of 11 top-selling AREDS supplement products contained the recommended levels of the ingredients.
As the report noted, "under the Dietary Supplement Health and Education Act of 1994, dietary supplements are not evaluated or regulated for efficacy or safety. Approval from the Food and Drug Administration is not required for manufacturers to market dietary supplements."
Counterfeit products are also a risk. According to ConsumerLab.com, a 2023 report said counterfeits of Bausch + Lomb's PreserVision AREDS2 supplement had been sold on Amazon. And the MacuHealth supplement company has warned of counterfeits of its products.
ConsumerLab.com offers guidance for consumers about safely buying supplements.
Disclosures
Keenan and Rowan disclosed no relevant relationships with industry. Bernstein disclosed relationships with Kemin, Bausch + Lomb, Heidelberg, DSM-Firmenich, and OmniActive.
