COMMENTARY

Vitamins for Age-Related Macular Degeneration

Ronald C. Gentile, MD; John M. Aljian, MD

Disclosures

January 16, 2018

A Multibillion-Dollar Industry

John M. Aljian, MD: Hello, my name is Dr John Aljian. I'm an ophthalmologist practicing in New York City. I am here with Dr Ronald Gentile, a retina specialist and clinical professor of ophthalmology at New York Eye and Ear Infirmary of Mount Sinai. We're here today to discuss vitamin therapy for the most common cause of vision loss in US adults: macular degeneration.

There seems to be confusion and uncertainty among our patients [about] whether or not they should be taking vitamins and supplements, how much they should be taking, and why they should be taking them, along with compliance issues. We have patients who have no problem taking prenatal vitamins when they are pregnant. We have young people who take supplements for exercise and building muscle. I would like to take something to grow some more hair on my head; I would be compliant with that. But when it comes to vitamin therapy and vision, there seems to be some reluctance.

Ronald C. Gentile, MD: Vitamin supplements are very common, and the vitamin and supplement industry is huge—$37 billion [a year].[1] An online survey[2] done by the Council for Responsible Nutrition sampled [2001] adults in the United States, and found that [1528] of them (76%) reported using dietary supplements. I find this interesting, because vitamin supplementation is on the rise. When you compare the data from this year with [those from] last year, you can see there is a large percentage increase.

What was the main reason they were using supplements [as determined by this survey]? Of those who responded, [46%] said it was for overall health and wellness, 30% to fill nutritional gaps, and 28% used them for energy. The other reasons people are using vitamin supplementation [are] immune health; bone health; heart health; and, in some, just for healthy aging.

Now, what are the most common vitamin supplements being used? Over 50% of the people who responded were taking a multivitamin. Then the next ones were vitamin D, vitamin C, calcium, and vitamin B or B complex.

I want to remind everyone that vitamin supplements are treated differently by the US Food and Drug Administration (FDA). The FDA is not authorized to review dietary supplement products for safety and effectiveness before they are marketed. The manufacturers and distributors of dietary supplements are responsible for making sure their products are safe before they go to the market. You see this all the time—warnings going out on different vitamins after the fact, after the vitamin has already been used.

I also want to remind the listeners that vitamins are put into two different classifications: water-soluble and fat-soluble. Water-soluble vitamins are eliminated in the body via the urine. If you take a lot of water-soluble vitamins, you are going to have very expensive urine. The problem is, when it comes to toxicity, those are the fat-soluble vitamins, because they are mostly stored in the liver. Which ones do you have to worry about in terms of the fat-soluble [vitamins]? Those are vitamin A, vitamin K, vitamin E, and vitamin D.

Vitamins and Macular Degeneration

Dr Gentile: I want to talk about vitamins and macular degeneration, because this is a topic that a lot of our listeners want to know about, and they want to see the data behind it. There are very few things out in the literature that are as strong as vitamins for age-related macular degeneration (AMD). I want to go through with you what is recommended in terms of vitamins.

In the United States, there are 15 million people with macular degeneration[3]; the majority of them have dry macular degeneration, and a smaller percentage has wet macular degeneration. Every year, there are 2 million new cases of AMD.[4] It is the leading cause of legal blindness in patients over 65 years of age.[5,6] This is why this is so important.

If you look at the disease burden projection of AMD worldwide from a study by Wong and colleagues,[3] they projected that the number of people in 2020 who will have AMD is 196 million and by 2040, 288 million.

Dr Aljian: It is tremendous.

Dr Gentile: The Age-Related Eye Disease Study (AREDS)[7] looked at vitamin supplementation for AMD, and they also looked at cataracts. The study started in 1992, and it was a 10-year study. They were looking at antioxidants and minerals; the antioxidants were vitamin C, vitamin E, and beta-carotene, and the minerals were zinc as zinc oxide and copper as cupric oxide. They wanted to determine whether [antioxidants and minerals] had any effect on the progression of vision loss.

They divided macular degeneration into three stages: early, intermediate, and advanced. What is early macular degeneration? Those patients are usually asymptomatic and may have a few small drusen, a few medium-sized drusen. What is intermediate [macular degeneration]? Those with intermediate have many medium-sized drusen or one or larger drusen. Those with advanced [macular degeneration] will have either central geographic atrophy or wet AMD in one eye.

[The AREDS] had almost 5000 participants. AMD is a disease of the elderly, so the age range was 55-80 years, and [the study] was performed in 11 clinical centers. They had four treatment groups: zinc alone, antioxidants alone, a combination of antioxidants and zinc, and placebo. They found the benefits were in patients with intermediate AMD or advanced AMD; they did not find [an apparent benefit] in patients with early AMD.

The antioxidants plus zinc had the lowest risk of developing advanced stages of macular degeneration and vision loss. Zinc alone and antioxidants alone also reduced the risk. What was the reduction? If you look at [the antioxidants plus zinc], there was a 25% reduction in the progression and a 19% reduction in vision loss. This is pretty substantial when you think about the number of people who are developing AMD. If you look at the group taking zinc alone, it decreased the development of advanced AMD by 21% and decreased vision loss by 11%. Those with antioxidants alone decreased AMD progression by 17% and vision loss by 10%.

I also wanted to bring up beta-carotene, vitamin A, and the risk for cancer. The Beta-Carotene and Retinol Efficacy Trial (CARET)[8] found that beta-carotene actually increased the risk for lung cancer. The Alpha-Tocopherol, Beta-Carotene (ATBC) Lung Cancer Prevention Study[9] also had similar findings. This was concerning about the AREDS formula, because it did have beta-carotene. When you look at AREDS2,[10] they did have lung cancer in 2% of participants who got the AREDS formula with beta-carotene compared with 0.9% of participants who took the AREDS formula without beta-carotene.

Dr Aljian: This is concerning, especially considering that the only controllable risk factor for macular degeneration is smoking—and then we were giving patients vitamins and perhaps increasing their risk for lung cancer.

Dr Gentile: That is how we go to the AREDS2 formula: They wanted to eliminate the beta-carotene and added lutein and zeaxanthin instead of the beta-carotene. AREDS2, which was started in 2006, also looked at omega-3 fatty acids. They wanted to also lower the zinc content. What they found is that replacing beta-carotene with lutein and zeaxanthin was effective. There was no difference with the addition of omega-3 fatty acids.

What is in the AREDS2 formula? We have vitamin C, 500 mg; vitamin E, 400 IU; zinc, 80 mg; copper, 2 mg (the 2 mg of copper are meant to prevent the anemia associated with high doses of zinc); lutein, 10 mg; and zeaxanthin, 2 mg.

In a nutshell: The AREDS and AREDS2 formulas are helpful in preventing this devastating disease to as many patients as possible who are candidates for this vitamin supplementation.

Dr Aljian: I tell my patients, if they are smoking, that they have to stop smoking.

The constituents you just went over—what is in the AREDS2 vitiamin—it is not an exotic, proprietery molecule from a research lab. It is vitamin C, zinc, copper, lutein, and zeaxanthin; all have been around forever. I also believe that there is a reason that vegetables have brilliant color, so we pick them up and eat them as part of a healthy diet. We encourage that too.

Ron, that was a great discussion—very informative. I am certain that you straightened out all the misconceptions that doctors have about vitamin therapy for macular degeneration.

Dr Gentile: Thank you, John; my pleasure.

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