Patsy Westcott explores the studies casting new light on the benefits of eye health supplements for those with the sight-stealing condition AMD.
🕒 12 min read
Age-related Macular Degeneration (AMD) is the leading cause of sight loss in developed countries, affecting hundreds of millions of people across the world, including 7% of the over-50s in Ireland.
AMD causes progressive death of cells in the macula: the part of the retina responsible for the clear, central vision we need to drive, read and recognise faces. It's not known what causes it, but age, genes, smoking, exposure to sunlight and diet can all affect risk.
There's no way to prevent AMD and no cure, although there are now some treatments. This is the remarkable story of how scientists discovered the power of dietary supplements to help delay AMD's progress.
What are the AREDS studies?
The AREDS, short for Age-related Eye Disease Studies, are a series of influential studies that have provided huge amounts of useful information about the natural course of AMD and the supplements that may help to slow its progression.
AREDS and AREDS2 were double-blind randomised controlled trials (RCTs) set up to examine the risk factors, likely progression and outlook for age-related macular degeneration and cataracts.
In particular, scientists set out to probe the effects of certain vitamins, minerals and other micronutrients on the conditions' progression and sight loss. The studies were sponsored by America's National Eye Institute (NEI).
In the years following the studies, researchers have conducted several follow-ups and refined their conclusions.
The condition begins with the development of small fatty protein deposits called drusen, which can be seen by the optometrist during an eye test. As it progresses, these may become larger or more abundant, and small areas of the macula may change colour. At this intermediate stage you may start having vision problems, such as struggling to adjust to changing light.
At a later stage abnormal blood vessels may grow into the retina and leak fluid, causing the retina to become wet. This wet AMD is called choroidal neovascularisation. Late-stage dry AMD, called geographic atrophy, affects the fovea, the centremost area of the macula, which is responsible for visual acuity. Symptoms include blind spots in the central vision as well as loss of sharpness of vision.
AREDS – the first study
What was the study?
The first AREDS – called simply AREDS or sometimes AREDS1 – examined the effects of high doses of vitamins C and E, beta-carotene, and zinc on the progression of AMD, cataracts and visual acuity (sharpness of vision).
Who took part?
Some 4,757 participants aged 55-88 years (69 years average) with AMD, cataracts, or both, were recruited from 11 specialist US eye clinics from November 1992 to January 1998. Just over half (56%) were women and nine out of ten (96%) were white.
Researchers tracked their eye health for five years. Participants fell into four categories: no AMD, intermediate, and advanced AMD.
How was it done?
Participants were randomly allocated to one of four supplement regimes.
- A daily antioxidant supplement containing 500 mg vitamin C, 400 IU vitamin E, and 15 mg beta-carotene
- A daily zinc supplement containing 80 mg zinc oxide plus 2 mg copper oxide (to avoid the anaemia that can result from high doses of zinc)
- A combination of the antioxidant supplement plus the zinc supplement (final AREDS formula)
- A dummy pill (placebo)
What did it show?
The first results published in 2001 showed that of 3,640 participants followed up for an average of just over six years, antioxidants plus zinc protected against developing advanced AMD by 28%; zinc and copper alone reduced the odds of advanced AMD by 25%; while antioxidants alone resulted in a 20% reduced risk.
Importantly when participants with more severe AMD at the outset of the study were removed from the equation, there was a 34% reduction in those taking antioxidants plus zinc, a 29% reduction in those taking zinc alone; and a 24% reduction in those taking antioxidants alone.
Participants taking antioxidants plus zinc (original AREDS formula) saw a moderate reduction in the sharpness of their eyesight (visual acuity) of around a quarter (27%).
What were the conclusions?
The researchers advised that everyone aged 55 plus should have a dilated eye test to assess their risk of advanced AMD. A dilated eye test involves dilating the eye with drops to enable the examiner to see more of the retina.
In addition, those with extensive medium-size drusen, at least one large druse, evidence of cell damage in one or both eyes, or advanced AMD or vision loss due to AMD in one eye (and without contraindications such as smoking) should consider taking an antioxidant plus zinc supplement such as the one in the study.
AREDS – ten years on
In 2014 researchers published a follow-up report looking at the progression of moderate to advanced AMD in 3,549 of the original AREDS participants, who were followed for a further five years. Perhaps unsurprisingly they discovered that the risk of progression to advanced AMD increased with age and with the severity of drusen.
Women and current smokers were at a higher risk of wet AMD, as were those with the most severe drusen at the outset of the study. The researchers conclude that 'the natural history of AMD (is) a relentless loss of vision' in those who develop advanced AMD.
AREDS2 – refining the evidence
What was the study?
Observational studies had suggested that a diet higher in lutein and zeaxanthin, two carotenoid nutrients, and the omega 3 long-chain fatty acids DHA and EPA might further lower the risk of progression to advanced AMD. In the light of these studies, scientists devised another more complicated study – AREDS2 – to explore the potential benefits of adding these nutrients to the AREDS formula.
Researchers also wanted to discover the effect of omitting beta-carotene, lowering the dose of zinc, or both in the AREDS formula, bearing in mind the higher incidence of lung cancer in smokers who take beta-carotene (see above). The study began in 2006 with results reported in 2013.
Who took part?
Some 4,203 participants aged 50 to 85 years deemed at high risk of progression to advanced AMD were enrolled in the study, which took place in 82 specialist eye clinics in the US. They included participants with intermediate AMD (large drusen in both eyes) or intermediate AMD (large drusen) in one eye and advanced AMD in the other. Almost all (96%) were white and just over half (57%) were women.
How was it done?
Participants were randomly allocated to take one of the following in addition to an AREDS supplement:
- Lutein (10 mg) + zeaxanthin (2 mg)
- DHA (350 mg) + EPA (650 mg)
- Lutein + zeaxanthin and DHA + EPA
- Placebo – as all participants in AREDS2 were at high risk of advanced AMD and were taking an AREDS supplement, in effect there was no real placebo group
Researchers also examined the effects of modifying the original AREDS supplement by taking the beta-carotene out and substituting the original 80 mg zinc with a lower 25 mg dose. This was chosen in the light of data suggesting that this is the largest amount of zinc capable of being absorbed. Specifically participants were allocated to take one of the following:
- AREDS formula
- AREDS formula without beta-carotene
- AREDS formula with lower dose of zinc (25 mg)
- AREDS formula without beta-carotene and with lower dose of zinc (25mg)
Some 3,032 participants took the modified formula. Meanwhile 1,148 chose to take the original AREDS formula and were not randomised. Only those who had never smoked or had quit the habit took the beta-carotene formula.
What did it show?
In an average follow-up of five years, 1,608 participants progressed to advanced AMD. Neither adding lutein and zeaxanthin nor DHA and EPA appeared to significantly reduce progression to advanced AMD. Nor did taking out beta-carotene or lowering the dose of zinc.
However, more lung cancers were observed in people who took beta-carotene compared with those who took the version without beta-carotene (mainly ex-smokers).
Smokers – and former smokers – are at increased risk of AMD and lung cancer. However, studies that emerged during the first AREDS also show an increased risk of lung cancer in smokers and former smokers taking beta-carotene.
For this reason, in the first AREDS researchers suggested that it might be wise for smokers to avoid beta-carotene and opt to take only some of the ingredients in the AREDS formula. This is one reason why in the second AREDS study the alternative carotenoids lutein and zeaxanthin – two yellow pigments found in the 'seeing' part of the eye – were used instead of beta-carotene.
What were the conclusions?
The researchers concluded that adding lutein and zeaxanthin, DHA and EPA or both to the AREDS formula didn't further lower the risk of progressing to advanced AMD.
In light of the possible increased risk of lung cancer in former smokers the researchers suggested substituting lutein and zeaxanthin for beta-carotene in the AREDS formula.
Although these results were somewhat disappointing in respect of the addition of lutein and zeaxanthin to the AREDS formulation, something partly attributable to the complex nature of the study design, there were enough hints of a potentially beneficial effect for researchers to suggest further studies of these two nutrients.
AREDS2 – ten years on
In 2022 a new AREDS report was published showing that the AREDS2 formula is not only safer but also more effective than the original AREDS formula at slowing AMD progression.
In this study the researchers followed up 3,883 of the original 4,203 participants in AREDS2 for another five years from the end of AREDS2 with the aim of discovering the long-term effects of the supplements on the development of lung cancer or the progression to advanced AMD.
Although all the participants had been taking the AREDS2 formula containing lutein and zeaxanthin after the end of AREDS2, the study showed that the risk of lung cancer was almost double in people who had ever smoked and who took beta-carotene. There was no increased risk of lung cancer in those who took lutein and zeaxanthin.
In addition in the ten years of follow-up the group taking lutein and zeaxanthin in AREDS2 had an extra 20% reduction in their risk of progressing to advanced AMD compared to those originally allocated to receive beta-carotene.
The researchers conclude that given the enormous number of people across the world who are anticipated to develop AMD by 2040 (288 million) even a modest treatment effect would be important.
AREDS2 – the latest
In July 2024 a new analysis of AREDS and AREDS2 data showed that taking an AREDS formula supplement slowed progression of late-stage dry AMD.
In the study researchers looked again at the retinal scans taken during the studies and found that, for those with late-stage dry AMD, taking the antioxidant supplement slowed the development of so-called geographic atrophy, the term used to describe late-stage dry AMD (see above).
Specifically, the supplements slowed the rate of expansion of geographic atrophy towards the fovea by more than half (55%). The fovea is a small depression in the centre of the macula where vision is sharpest. More than 20% of people with AMD have geographic atrophy.
Retinex Max
'Nature's sunglasses' containing lutein and zeaxanthin
- Contains 20 mg lutein and 2,000 µg zeaxanthin
- Powerful carotenoids found in high concentrations in the eye
- Supports long-term eye health
What AREDS means for you – supporting your eye health
Put a traffic light on your plate. Green and red veg – think kale, red peppers, spinach, lettuce, leeks, broccoli and peas – are all good sources of lutein. Eggs contain both lutein and zeaxanthin. Meanwhile orange and yellow fruit, and veg such as sweetcorn and yellow and orange peppers, contain zeaxanthin. Light cooking and cooking with oil and fat may aid absorption.
Reduce glare. Wear a wide-brimmed or peaked cap or hat. Use anti-glare filters on your spectacles. Reduce the brightness of your computer screen – consider yellow anti-glare spectacles. Ensure home lighting is bright and even but avoid light shining directly into your eyes. Keep car windscreens clean and get anti-reflection coated lenses for any glasses you use for driving.
Keep up with your eye tests. Regular eye tests are vital to pick up the early signs of AMD, cataracts and other conditions affecting the eyes as we get older. You should have an eye test at least every two years or more often if your optometrist advises.
Block blue light. Blue-blocking lenses protect eyes from blue light as well as reducing glare. They can also help sharpen images, as blue light tends to make things hazy. Such lenses are available from low-vision services, sensory impairment teams and resource centres for the visually impaired.
Choose sunglasses with care. Sunglasses should have a UV filter – UV400 should block 100% of UV light. Choose glasses with a European CE mark or look for BS EN ISO 12312-1:2013.
Consider a supplement. Think about taking a supplement, such as Retinex® Max: a maximum-strength formulation specifically designed to support vision and eye health long-term.
The conclusions of the AREDS cataracts studies are less clear-cut than those relating to AMD.
In the original AREDS none of the formulas had any 'apparent effect' on the seven-year risk of developing cataract(s) or their progression or loss of sharpness of vision. It's worth noting, however, that the participants were relatively well-nourished and that a limited number of antioxidants were used.
Similarly supplementing with lutein and zeaxanthin in AREDS2 had no statistically overall effect on rate of progression of cataracts, the rates of cataract surgery or vision loss.
The researchers note, however, that as in the original AREDS, AREDS2 participants tended to be better nourished than most, with higher dietary intakes of lutein and zeaxanthin and omega 3 long-chain fatty acids.
They observe, moreover, that in relatively poorly nourished Chinese people vitamin supplementation did reduce the risk of progression of clouding of the lens.
The jury is still out, but those who are relatively less well-nourished might benefit from a supplement containing lutein and zeaxanthin to slow the progression of cataracts.