The Age-Related Eye Disease Study (AREDS) and its follow-up, AREDS2, have been instrumental in shaping our understanding of how certain nutritional supplements can support macular health. Sponsored by the National Eye Institute, these landmark studies have influenced the formulation of many popular eye supplements available today.
While the AREDS2 formula has gained widespread popularity and is often recommended by eye care professionals, it’s important to recognize that it’s not without its potential risks and limitations—an aspect that doesn’t always get the attention it deserves. The general acceptance of AREDS2 highlights its perceived benefits, but many consumers and even some professionals are not fully aware of the possible side effects and shortcomings associated with it. This gap in knowledge is something that needs to be addressed.
In this blog post, we’ll revisit the origins of AREDS and AREDS2, shedding light on some of the potential pitfalls that are often overlooked. Understanding these nuances is key to making informed decisions about your eye health.
The Original AREDS Formula
The original AREDS study was a groundbreaking moment in eye health research. It explored a specific combination of vitamins and minerals that showed considerable promise in reducing the risk of progression to advanced macular degeneration (AMD) for those already in the intermediate stages of the disease.
The formula included vitamin A or beta-carotene, vitamin C, vitamin E, zinc, and copper—each chosen for their potential to support macular health.
However, as the research evolved, so did our understanding of the risks associated with this formula.
Notably, subsequent studies uncovered a significant risk of lung cancer linked to beta-carotene, particularly in smokers. Separate trials funded by the National Cancer Institute found that beta-carotene supplementation actually increased the risk of lung cancer, raising serious concerns about its inclusion in the original AREDS formula. This discovery necessitated a revision, leading to the development of the AREDS2 formula, which aimed to retain the benefits while mitigating the risks.
Evolution to the AREDS2 Formula
In light of the concerning findings about beta-carotene, the AREDS2 study sought to refine the original formulation, aiming to maintain its protective benefits while eliminating potential risks.
This led to the replacement of beta-carotene with the macular carotenoids lutein and zeaxanthin—nutrients known for their powerful antioxidant properties and their role in supporting macular health. The updated AREDS2 formula now includes lutein, zeaxanthin, vitamin C, vitamin E, zinc, and copper.
This revised formula was a significant step forward. It successfully reduced the risk of intermediate AMD progressing to more advanced stages, all without the increased lung cancer risk associated with beta-carotene.
However, it’s important to recognize that the AREDS2 formula isn’t a catch-all solution. The study did not demonstrate any preventative effect for those with early AMD, nor did it show significant benefits for individuals who take it purely as a preventative measure.
This is a key limitation that often goes overlooked, as many people use AREDS2 supplements with the assumption that they will prevent the onset of AMD, despite a lack of supporting evidence for this use.
AREDS2 Side Effects and Risks
The AREDS2 vitamins have become a go-to choice for many people seeking to support their macular health, but it’s important to acknowledge that their popularity doesn’t mean they’re without risks or limitations.
These potential concerns are often underplayed or overlooked, even by eye care professionals and doctors, who may not be fully aware of the side effects associated with some of the ingredients in the AREDS2 formula.
Specifically, the high levels of vitamin C, vitamin E, and zinc present in this formulation can pose issues for certain individuals.
Vitamin C
Vitamin C is widely celebrated for its antioxidant properties, but there’s a side to this nutrient that’s less commonly discussed. At high doses—500 mg or more daily—vitamin C can actually have a pro-oxidant effect on the lens of the eye, potentially increasing the risk of cataract development. Research has shown that among women aged 65 and above, the use of vitamin C supplements may increase the risk of cataracts by up to 38%.
Given this, it’s advisable to take a more cautious approach. A small-to-moderate daily dose of vitamin C, preferably less than 100 mg, is recommended. Ideally, this should come from a healthy and balanced diet rather than from high-dose supplements.
Vitamin E
Vitamin E is another nutrient that, while beneficial in many ways, comes with its own set of risks when taken in high doses. Some studies have found that supplemental vitamin E at the AREDS2 dose of 400 IU or more daily is associated with a small but significant increase in the risk of death from all causes.
Additionally, there’s evidence to suggest a link between high-dose vitamin E supplementation and an increased risk of prostate cancer. The 2011 Selenium and Vitamin E Cancer Prevention Trial found a 17% increase in prostate cancer risk among men who took 400 IU of vitamin E daily over a period of seven years.
Zinc
Zinc, an essential mineral, is present in the AREDS2 formula at a dose of 80 mg, which is double the tolerable upper intake level recommended by most health authorities (40 mg daily for adults). This high dose raises several concerns. For example, a study published in the Journal of Urology found that individuals taking the AREDS formula with 80 mg of zinc were more likely to be hospitalized for urinary complications compared to those taking a placebo.
Of potentially greater consequence are findings from the Health Professionals Follow-up Study, which reported that long-term zinc supplementation—more than 75 mg daily over 15 years—could nearly double the risk of lethal and aggressive prostate cancer.
Furthermore, the presence of zinc in the AREDS2 formula could accelerate the progression to advanced AMD in individuals with certain genetic variations, specifically in the CFH and ARMS2 genes, which make the macula particularly sensitive to zinc.
In my practice, I educate all my patients that the standard AREDS 2 formulation with zinc and copper does more harm than good for 15% of people.
Dr. Paul Krawitz, Ophthalmologist, New York
For those who are sensitive to zinc, as indicated by genetic testing, a much lower intake of 8–11 mg daily is recommended. At this lower dose, no adverse effects were observed across any genetic variations.
Limited Efficacy for Prevention
One of the most important considerations when it comes to the AREDS2 formula is its limited efficacy in prevention.
Despite its widespread use, the AREDS2 formula does not offer benefits for individuals with early AMD, nor does it prevent the onset of the condition. Many people take AREDS2 supplements with the hope that it will act as a preventive measure, but the evidence simply doesn’t support this use.
Alternative Nutrients for Macular Health
The AREDS2 study has made it clear that lutein and zeaxanthin are fundamental when it comes to supporting macular health. These carotenoids play a crucial role in protecting the eyes from oxidative stress and harmful blue light, making them indispensable for maintaining healthy vision as we age.
However, given the potential risks associated with other components of the AREDS2 formula—such as high doses of vitamin C, vitamin E, and zinc—it’s worth considering alternative nutrient combinations that may offer a safer and more holistic approach to macular health.
Vitamin B12 and Folate
Compelling evidence from the Women’s Antioxidant and Folic Acid Cardiovascular Study sheds new light on the role of B vitamins in eye health, particularly in preventing age-related macular degeneration (AMD). This randomized trial found that long-term daily supplementation with vitamin B12, folate, and vitamin B6—over an average of 7.3 years—significantly reduced the risk of developing AMD by an impressive 35-40%.
What’s particularly striking about these findings is that the beneficial effects of this nutrient combination began to emerge after just two years of follow-up and continued to provide protection throughout the duration of the study.
This makes a compelling case for the preventive power of B vitamins, offering a level of protection against AMD that the AREDS2 study did not achieve.
These findings apply to the early stages of AMD development in persons without a prior diagnosis of AMD, and appear to represent the first identified means, other than avoidance of cigarette smoking, of reducing risks of AMD in persons at usual risk.
Dr. William Christen, Archives of Internal Medicine, 2009
Ginkgo Biloba
Ginkgo biloba is a fascinating plant extract with a long history of use in traditional medicine, and modern research is beginning to uncover its potential benefits for eye health. Its leaf extract is rich in over 60 bioactive compounds, including a high concentration of flavonoids and terpenoids.
These compounds are known for their ability to reduce blood viscosity, inhibit platelet aggregation, and improve overall blood circulation—factors that are particularly important for eye health.
While there has been some concern about a potential bleeding risk associated with ginkgo biloba, it’s important to note that this has not been supported by evidence from randomised clinical trials and meta-analyses. These studies have not found a significant link between ginkgo biloba and increased bleeding risk, suggesting that it can be a safe and effective option for those looking to support their eye health naturally.
Grape Seed
Grape seed extract stands out as one of the most potent sources of procyanidins—natural antioxidants that offer powerful protection for your eyes. These procyanidins are particularly effective at safeguarding the retinal ganglion cells, which are crucial for maintaining healthy vision, especially in the face of oxidative damage.
What’s truly remarkable about procyanidins is their antioxidant potency. Research has shown that the antioxidant activity of procyanidins is significantly greater than that of traditional antioxidants like vitamins C and E—50 times more powerful than vitamin C and 20 times more effective than vitamin E.
This makes procyanidins a compelling alternative to the antioxidants typically found in the AREDS2 formula, offering potentially superior protection for your eyes.
Saffron
Saffron, the vibrant spice derived from the Crocus sativus flower, is gaining recognition for its remarkable potential in supporting eye health, particularly in the treatment of age-related macular degeneration (AMD).
Saffron is rich in carotenoids, such as crocin and crocetin, which have been shown to offer significant benefits for retinal health. Studies suggest that saffron can improve retinal function, enhance visual acuity, and increase visual sensitivity in individuals with mild to moderate AMD, potentially slowing the progression of this common eye condition.
But the benefits of saffron don’t stop there. This powerful spice has also shown promise in improving visual function in individuals with diabetic maculopathy, offering a natural and holistic approach to managing these challenging conditions.
The Way Forward for Macular Health
While the AREDS and AREDS2 formulations have made significant strides in nutritional support for macular health, it’s important to recognize their potential side effects and limitations.
By focusing on essential nutrients like lutein and zeaxanthin and enhancing the formula with additional supportive ingredients—such as ginkgo biloba, grape seed extract, methylcobalamin (active vitamin B12), and L-methylfolate (active folate)—we can address these concerns. This combination not only helps preserve the benefits of the original formulations but also provides a more well-rounded approach to supporting macular health across all stages of AMD.
This is the cornerstone of the Nutravision formula. Nutravision is meticulously designed to promote long-term retinal health and optic nerve function while avoiding the potential adverse effects associated with the AREDS2 formulation.
If you’re seeking for a safe, modern way to maintain your eyesight and macular health, try Nutravision today. Support your eyes with confidence, knowing that you’ve made a decision that promotes both effectiveness and safety.
