Vitamin Supplements for Macular Degeneration
An evidence-based guide to AREDS2, Macutec Once Daily and Macu-Vision Plus
Should I be taking vitamin supplements for my eye health?
A common question patients ask is “Should I be taking vitamin supplements for my eyes?”
Scientific studies have shown that a specific combination of antioxidant vitamins and minerals can reduce the risk of progression to advanced AMD in selected patients. However, these supplements are not recommended for everyone, do not prevent macular degeneration from developing, and cannot restore vision that has already been lost.
Furthermore, not all commercially available eye supplements contain the same ingredients or nutrient doses. Some formulations closely resemble those evaluated in major clinical trials, whereas others differ substantially.
This information will summarise the evidence behind retinal supplements, explains who is most likely to benefit, discusses the advantages and limitations of treatment, and compares the two formulations most commonly encountered by Australian patients.
What are AREDS and AREDS2 supplements?
The evidence for vitamin supplementation in AMD comes predominantly from two large clinical studies conducted in the United States: the Age-Related Eye Disease Study (AREDS) and the subsequent AREDS2 trial.
The original AREDS results were published in 2001. In patients at sufficiently high risk for macular degeneration progression, the specific combination of antioxidant vitamins and zinc used in the study reduced the risk of developing advanced macular degeneration by approximately 25% over five years.
AREDS2 was designed to refine the original formulation. It examined the addition of lutein and zeaxanthin, the addition of omega-3 fatty acids, the removal of beta-carotene and a reduction in the zinc dose. Long-term follow-up subsequently supported replacing beta-carotene with lutein and zeaxanthin, particularly because beta-carotene was associated with an increased risk of lung cancer in former smokers. Omega-3 supplementation did not reduce the risk of AMD progression.
These studies remain the principal evidence supporting vitamin supplements for AMD. It is impotant to remember that these studies were performed two decades ago in a United States population. Dietary intake, background nutritional status, supplement use, smoking patterns and genetic composition may differ between populations. Care should be taken when extrapolating the results to an Australian population. Nevertheless, these two studies remain the best available evidence on which to base clinical recommendations on the role of vitamin supplements for macular degeneration. .
What is the composition of the AREDS 2 formulation?
The AREDS2 formulation most often referred to in ophthalmology is the National Eye Institute formulation used for patients at higher risk of progression to advanced AMD. It contains vitamin C, vitamin E, lutein, zeaxanthin, zinc and copper, and does not contain beta-carotene.
In AREDS2, beta-carotene was removed because of lung cancer concerns in current and former smokers, and lutein/zeaxanthin became the preferred carotenoid combination.
Who is most likely to benefit from vitamin supplements ?
The evidence is strongest for patients with:
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intermediate AMD in one or both eyes
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late AMD in one eye, with an at-risk fellow eye
Late AMD includes both advanced dry macular degeneration (geographic atrophy) and wet (neovascular) macular degeneration. A patient receiving eye injections for wet macular degeneration in one eye may benefit for supplementation to reduce the risk of progression in the other eye.
Intermediate and large drusen with corresponding elevations on OCT imaging in macular degeneration
Who is unlikely to benefit from vitamin supplements ?
AREDS2 supplements have not been shown to prevent macular degeneration from developing in a healthy retina. They have also not been shown to prevent early macular degeneration from progressing to intermediate macular degeneration. Vitamin supplements have not been shown to reduce the risk of macular degeneration in people with a family history of the condition.
The Royal Australian and New Zealand College of Ophthalmologists recommended in its Choosing Wisely Campaign
"AREDS-based vitamin supplements only have a proven benefit for patients with certain subtypes of age-related macular degeneration. There is no evidence to prescribe these supplements for other retinal conditions, or for patients with no retinal disease"
For patients with no AMD or only early disease, RANZCO highlights the importance of a healthy diet containing fruit, dark green leafy vegetables, fish and nuts, together with avoidance of smoking.
Healthy foods for macular degeneration including fish, leafy greens, berries and nuts
Aim of AREDS based vitamin supplements
An AREDS2-type supplement is intended to reduce the future risk of progression in a patient whose macular degeneration has reached an appropriate stage, to reduce the risk of more advanced macular damage.
The AREDS vitamins do NOT:
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remove drusen
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restore damaged photoreceptors or retinal pigment epithelium
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reverse geographic atrophy
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improve an established macular scar
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treat active wet AMD
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replace anti-VEGF injections or retinal monitoring
Why were lutein and zeaxanthin substituted for beta-carotene?
Lutein and zeaxanthin are carotenoids concentrated within the macula. In AREDS2 they were investigated as an alternative to beta-carotene.
This became clinically important because beta-carotene supplementation had previously been associated with an increased risk of lung cancer among smokers.
Long-term follow-up of AREDS2 also found a higher incidence of lung cancer among participants allocated beta-carotene, most of whom were former smokers, whereas this increased risk was not observed with lutein and zeaxanthin.
Current and former smokers should therefore avoid macular supplements containing beta-carotene. Most contemporary AREDS2-type
formulations use lutein and zeaxanthin instead.
Common formulations available in Australia
Macutec Once Daily and Blackmores Macu-Vision Plus are two of the formulations most commonly encountered by Australian patients. Both contain the main AREDS2 nutrient categories, but the doses differ.
An older formulation, Macu-Vision, is still sold in Australia based on the AREDS1 study. It contains only half the dose of vitamin C, vitamin E and copper, contains no lutein or zeaxanthin and has the maximum Australian recommended daily zinc dose.
An important point is that Macutec Once Daily provides the AREDS2 lutein, zeaxanthin, vitamin C and copper quantities, while using the lower 25 mg zinc dose investigated in AREDS2.
Macu-Vision Plus contains the same broad categories of nutrients, but at approximately half the lutein, zeaxanthin, vitamin C, vitamin E and copper doses, with a higher zinc dose of 40 mg.
An older formulation, Macu-Vision, is still sold in Australia based on the AREDS1 formulation. It contains only half the dose of vitamin C, vitamin E and copper, contains no lutein or zeaxanthin and has the maximum recommended zinc dose.
Why the zinc dose is important
AREDS2 showed that a formulation using 25 mg zinc was effective. The Australian Government's Nutrient Reference Values recommend an adult upper level of 40 mg zinc per day from all sources, including food and supplements. This is especially relevant for elderly patients, who may already be taking multivitamins or other supplements.
Excess zinc can cause nausea, stomach upset, constipation, altered taste and reduced copper absorption.
Macu-Vision Plus contains 40 mg zinc in one tablet, which already reaches the recommended maximum dose for adult. It contains only half the AREDS2 doses of lutein, zeaxanthin, vitamin C, vitamin E and copper. If two Macu-Vision Plus tablets are taken each day to reach the AREDS2 lutein and zeaxanthin doses, the zinc intake would become 80 mg per day from the supplement alone, well exceeding the recommended Australian adult upper level.
The Nutrient Reference Values (NRVs) was a joint initiative of the Australian National Health and Medical Research Council (NHMRC) and the New Zealand Ministry of Health (MoH). Further information about zinc intake is available in the linked document below
Our approach at Eye and Retina Specialists, Sydney
At Eye and Retina Specialists, our ophthalmologists may recommend retinal vitamin supplements according to the stage of macular degeneration and the findings in each eye. This assessment may include dilated retinal examination, OCT imaging, retinal photography and consideration of recognised progression-risk features.
As demonstrated by the available evidence, patients with intermediate macular degeneration or advanced macular degeneration in one eye with an at-risk fellow eye, an AREDS2-based formulation may provide a worthwhile reduction in the risk of further progression.