Saturday, December 7, 2013

Nutrition to prevent Macular Degeneration: The AREDS2 Study

Macular degeneration treatment in Vancouver, BC.

AMD (age-related macular degeneration) is the leading cause of blindness in those over 50.  AMD breaks down cells in the layer of tissue called the retina in the back of the eye that provide
sharp central vision.  This is the type of vision that is necessary for tasks such as reading, driving, and recognizing faces.  Advanced AMD can lead to significant vision loss and is the leading cause of blindness in North America.

This is normal vision:

This is vision people with AMD:

Vision with macular degeneration

Optimal nutrition has been shown to be effective in slowing or preventing the advanced stages of AMD, allowing patients to keep their vision for much longer than would otherwise be the case.  The most highly regard studies are known as the AREDS studies.  There are now two studies, known as AREDS and, the latest study (published in 2013), AREDS2.

AREDS 2 formula based AMD treatment in Vancouver, BC.

The purpose of the AREDS2 study was to evaluate the efficacy and safety of particular nutrient supplementation: lutein plus zeaxanthin and/or omega-3 long-chain polyunsaturated fatty acid supplements in reducing the risk of developing AMD. The study also assessed the effect of reducing the amount of zinc and of omitting beta carotene from the original AREDS formula.

This was the original AREDS formulation:
  • 500 milligrams (mg) of vitamin C
  • 400 international units of vitamin E
  • 15 mg beta-carotene
  • 80 mg zinc as zinc oxide
  • 2 mg copper as cupric oxide

These were the modifications that were tested in AREDS2?
  • 10 mg lutein and 2 mg zeaxanthin
  • 1000 mg of omega-3 fatty acids (350 mg DHA and 650 mg EPA)
  • No beta-carotene
  • 25 mg zinc

The results of AREDS2 were summarized by Stuart P Richer OD, PhD as follows:

The AREDS2 results for the average American with a suboptimal daily intake of lutein/zeaxanthin showed a statistically significant prevention of catastrophic vision loss, primarily neovascularization. That was an incredible result, favoring a new AREDS2 formulation minus beta carotene but with lutein plus zeaxanthin. 

AREDS2 showed that there was an approximate 34% reduction overall in the risk of premanent vision loss. This means that with optimal nutrition many hundreds of thousands of people could have avoided vision disability that has made them illegal to drive and that requires them to take injections that costs hundreds of dollars each time.

Not only does optimal nutrition prevent serious eye disease, nutrients such as carotenoids have been shown to improve visual performance by providing patients with better contrast sensitivity and shortened glare recovery and better visual processing.  The carotenoids lutein and zeaxanthin have also been shown to improve cognitive function in the elderly.

NEI Press Release

Below is an excerpt from the press release issued by the National Eye Institute on the results of the AREDS 2 sudy explaining that adding lutein and zeaxanthin to the original AREDS formulation had the beneficial result of a greater reduction in the risk of developing AMD when beta-carotene is removed from the formulation because beta-carotene blocks the absorption of lutein and zeaxanthin.  Therefore the optimal formulation is the include lutein and zeaxanthin but to remove beta-caroteine.  Beta-caroteine also increases the risk of lung cancer in smokers or former smokers. This is a formulation that is good for everyone, as pointed out by one of the researchers quoted below.

In the first AREDS trial, participants with AMD who took the AREDS formulation were 25 percent less likely to progress to advanced AMD over the five-year study period, compared with participants who took a placebo. In AREDS2, there was no overall additional benefit from adding omega-3 fatty acids or a 5-to-1 mixture of lutein and zeaxanthin to the formulation. However, the investigators did find some benefits when they analyzed two subgroups of participants: those not given beta-carotene, and those who had very little lutein and zeaxanthin in their diets.

When we looked at just those participants in the study who took an AREDS formulation with lutein and zeaxanthin but no beta-carotene, their risk of developing advanced AMD over the five years of the study was reduced by about 18 percent, compared with participants who took an AREDS formulation with beta-carotene but no lutein or zeaxanthin,” said Emily Chew, M.D., deputy director of the NEI Division of Epidemiology and Clinical Applications and the NEI deputy clinical director. “Further analysis showed that participants with low dietary intake of lutein and zeaxanthin at the start of the study, but who took an AREDS formulation with lutein and zeaxanthin during the study, were about 25 percent less likely to develop advanced AMD compared with participants with similar dietary intake who did not take lutein and zeaxanthin.” 
Because carotenoids can compete with each other for absorption in the body, beta-carotene may have masked the effect of the lutein and zeaxanthin in the overall analysis, Chew said. Indeed, participants who took all three nutrients had lower levels of lutein and zeaxanthin in their blood compared to participants who took lutein and zeaxanthin without beta-carotene Removing beta-carotene from the AREDS formulation did not curb the formulation’s protective effect against developing advanced AMD, an important finding because several studies have linked taking high doses of beta-carotene with a higher risk of lung cancer in smokers. Although smokers were not given a formulation with beta-carotene in AREDS2, the study showed an
association between beta-carotene and risk of lung cancer among former smokers. About half of AREDS2 participants were former smokers. “Removing beta-carotene simplifies things,” said Wai T. Wong, M.D., Ph.D., chief of the NEI Neuron-Glia Interactions in Retinal Disease Unit and a co-author of the report. “We have identified a formulation that should be good for everyone regardless of smoking status,” he said. Adding omega-3 fatty acids or lowering zinc to the AREDS formulation also had no effect on AMD progression.

More than 4,000 people, ages 50 to 85 years, who were at risk for advanced AMD participated in AREDS2 at 82 clinical sites across the country. Eye care professionals assess risk of developing advanced AMD in part by looking for yellow deposits called drusen in the retina. The appearance of small drusen is a normal part of aging, but the presence of larger drusen indicates AMD and a risk of associated vision loss. Over time, the retina begins to break down in areas where large drusen are present during a process called geographic atrophy. AMD can also spur the growth of new blood vessels beneath the retina, which can leak blood and fluid, resulting in sudden vision loss. These two forms of AMD are often referred to as dry AMD and wet AMD respectively. 

Frequently asked quesitons

Click here for the FAQ page on AREDS2 from the National Eye Institute.

Here are two questions that we frequently get asked at our Vancouver eye clinic:
Can a daily multivitamin alone provide the same vision benefits as an AREDS formulation?
No. The vitamins and minerals tested in the AREDS and AREDS2 trials were provided in much higher doses than what is found in multivitamins. Also, it is important to remember that most of the trial participants took multivitamins. Taking an AREDS formulation clearly provided a benefit over and above multivitamins.
Can diet alone provide the same high levels of antioxidants and zinc as the AREDS formulations?
No. The high levels of vitamins and minerals are difficult to achieve from diet alone. However, previous studies have suggested that people who have diets rich in green, leafy vegetables—a good source of lutein/zeaxanthin—have a lower risk of developing AMD. In the AREDS2 trial, the people who seemed to benefit most from taking lutein/zeaxanthin were those who did not get much of these nutrients in their diet. Within this group, those who received lutein/zeaxanthin supplements had a 26 percent reduced risk of developing advanced AMD compared with those who did not receive the supplements.