How Antioxidants Can Help People with AMD

AMD stands for age-related macular degeneration (AMD), which is a common eye condition that causes loss of central vision in older adults. The macula is the part of the retina that allows us to see things sharply and in detail, such as reading, writing, driving, or recognizing faces. AMD damages the macula, making the vision blurry or distorted, and is the leading cause of blindness with an estimated 400 to 500 cases per year in New Zealand. 

AMD can progress from early to intermediate to late stages. In early AMD, lipid material accumulates in deposits underneath the retinal pigment epithelium. These deposits are known as drusen and can be seen as pale yellow spots on the retina. The affected person will probably be unaware that they have a problem. As the disease progresses, the drusen become larger (intermediate AMD). In the later stages of the disease, the cells in the macula gradually die and leave patches of missing retina (dry AMD), and sometimes, new and harmful blood vessels grow in the macula causing bleeding and scarring, and rapid decline in vision (wet AMD).

One in seven people over 50 years will get AMD, and the chance of having AMD gets higher as people get older with about one out of three people aged 80 years or older having early signs of the disease.

There’s no cure for AMD, but there are some treatments that can slow down its progression or improve its symptoms, including antioxidants vitamins and minerals.

Why might antioxidant vitamins and minerals be helpful?

Oxidative stress is a major factor in the development and progression of AMD. Oxidative stress occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the ability of the antioxidant defense system to neutralize them. ROS are unstable molecules that can damage cellular components such as DNA, proteins, and lipids. The retina is particularly vulnerable to oxidative stress because it has a high metabolic rate, a high oxygen consumption, a high exposure to light, and a high content of polyunsaturated fatty acids that are prone to oxidation.

The link between dietary antioxidants and AMD has been studied in many observational studies, but the results are not consistent. People who have a diet rich in antioxidants, or who choose to take supplements regularly, often adopt a more healthy lifestyle, which may also reduce their risk of AMD. Randomised controlled trials (RCT), whereby people are randomly allocated to supplements or placebo, are the best way to find out if antioxidants help with AMD.

What is the latest research on antioxidants and AMD?

A recent Cochrane systematic review (13 Sept 2023) looked at the clinical trial effects of antioxidant vitamin or mineral supplements, alone or in combination with placebo or no intervention on the progression of AMD in people with AMD. The review included 26 studies that involved 11,952 people aged 65 to 75 years from different countries.

Most of the evidence came from two major clinical trials called Age-Related Eye Disease Studies (AREDS and AREDS2) sponsored by the US National Eye Institute. The first trial AREDS involved more than 4500 participants who ranged from having no AMD to advanced AMD while the second trial had 3640 participants with different stages of AMD or cataract.

Any vitamin or mineral known to act as an antioxidant in the body, or known to be a key component of an antioxidant enzyme in the retina, were considered for the review. These included: vitamin C, vitamin E, beta-carotene, carotenoids, selenium and zinc.

While there are many carotenoids, the review focused specifically on lutein and zeaxanthin as they are the main constituents of the macular pigment. Lutein and zeaxanthin are also believed to both to mop up reactive singlet oxygen and play a role in filtering blue light to avoid damage to the sensory neurons.

Overall, people who took antioxidant vitamins and minerals were less likely to experience deterioration and develop late AMD (odds ratio (OR) 0.72, 95% confidence interval (CI) 0.58 to 0.90; 3 studies, moderate-certainty evidence) than people who did not take them. For people with early AMD, who are at low risk of progression, this would equate to approximately four fewer cases of progression to late AMD for every 1000 people taking vitamins (one fewer to six fewer cases). For people with intermediate AMD at higher risk of progression, this corresponded to approximately 78 fewer cases of progression for every 1000 people taking vitamins (26 fewer to 126 fewer).

Results for the single component supplements compared to placebo found that people taking zinc supplements alone may be less likely to progress to late AMD in a similar magnitude (OR 0.83, 95% CI 0.70 to 0.98; 3 studies, moderate-certainty) to that of antioxidant vitamin supplementation. Only one study included vitamin E alone; however, the study was underpowered and the estimate effect was judged to be very low-certainty evidence. Lastly, lutein (10 mg) with or without zeaxanthin (2 mg) was shown to have little or no effect on progression to late AMD (risk ratio, RR 0.94, 95% CI 0.87 to 1.01; 1 study)

The review had some limitations, such as the different types and doses of supplements that different studies used, the lack of data on adverse effects and the possible impact of other factors such as diet and lifestyle on AMD progression. While the results are promising, more research is needed to identify the optimal formula, dose, duration, and target population for this intervention.

What is the key message?

People with AMD may delay the progression of their condition by 20% to 25% if they take antioxidant vitamins and zinc at the levels described in this review. This may be of interest to people with AMD given the few treatment options for AMD and vision is rarely recovered.

What are the practical applications?

Antioxidant formulations are increasingly marketed for use in age-related eye diseases like AMD.

Most of the beneficial evidence came from the AREDS trials, which contained high doses that were well beyond recommended daily intakes and difficult to consume from foods as a part of a normal diet.

AREDS2 antioxidant and mineral formulation taken daily included:

• Vitamin C, 500 mg
• Vitamin E, 400 IU
• Lutein, 10 mg
• Zeaxanthin, 2 mg
• Zinc (as zinc oxide), 80 mg
• Copper (as cupric oxide), 2 mg 

We reviewed a number of over-the-counter supplements, and the following most closely matches the AREDS formulation:

Blackmores Macu-Vision

Each tablet contains vitamin C, 250 mg; vitamin E, 200 IU; zinc oxide, 50 mg; cupric oxide, 1.25 mg

90 tablets cost $49 (Blackmores) equivalent to approximately $0.54 per tablet or $1.08 per day if two tablets are taken to match the AREDS formulation albeit without lutein or zeaxanthin.

Note the review suggested little effect with lutein and zeaxanthin alone compared with placebo.

Directed use on label is one tablet once a day, with contraindications and cautions noting that zinc may be dangerous when taken in large amounts or for a long period of time.