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AREDS 2 Ingredients for Age-Related Macular Degeneration

Research published in 2015 by the U.S. National Eye Institute showed that 6 AREDS 2 ingredients were critical in supporting the health of the eye in macular degeneration. This article explains the development and final conclusions of that research.

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In late 2001, the National Eye Institute announced the first eye vitamin formula that was successful in slowing the progress of age-related macular degeneration (AMD).  The study was known as the Age-Related Eye Disease Study, with the acronym AREDS.

Until that time, eye vitamins stocked the shelves at most pharmacies and grocery stores showed no proven benefit against an eye condition that could proceed to blindness. 

Unlike opinions, this was a powerful study with the following features:

  • It involved 3,640 of patients.
  • The study took place over 6 years.
  • The study participants were RANDOMIZED. This meant that participants did not know if they were receiving the full AREDS formula, zinc alone, or placebo.
  • The researchers did not know what formula the participants were taking. When both participant and researcher do not know what is being tested, it is known as DOUBLE BLIND, and it is considered a hallmark of a powerful scientific study.
  • The study was PROSPECTIVE, which means the researchers started the study knowing nothing rather than look at past results. When researchers do this, they strive to disprove the NULL HYPOTHESIS. In the case of AREDS, the null hypothesis would be, "These nutritional supplements will not be of benefit for people with macular degeneration." When the null hypothesis has been proven incorrect, the study now has an important finding.

Prospective, randomized, double-blind studies are the most important and powerful in scientific research.

AREDS found that 5 ingredients, taken in high doses, were effective in slowing (but not reversing or curing) age-related macular degeneration:

  • Beta-carotene: 25,000 IU (beta-carotene is a precursor form of Vitamin A)
  • Vitamin C: 500 mg
  • Vitamin E: 400 IU
  • Zinc: 80 mg
  • Copper: 2 mg (prevents a zinc-induced anemia)

And interestingly, AREDS found that zinc alone was nearly as beneficial as all five ingredients.

But as important as AREDS was, there were two problems with the study ingredients.

  1. Beta-carotene, a precursor form of Vitamin A, was found it two large population studies to unexpectedly increase the rate of lung cancer in heavy smokers. In each of the studies, the opposite was expected, due to its anti-oxidation effects. Both studies had to be halted mid-stream when the findings showed the higher risks. 
  2. Although of benefit, the high zinc caused some patients to have side effects that required medical care, including urinary tract disorders.

Why weren't lutein and zeaxanthin used in AREDS? At the time of the study, they were not yet commercially available.

In May 2013, the National Eye Institute followed up with the the AREDS 2 research to address the issues above.

Like AREDS, AREDS 2 involved thousands (4,203) of patients studied over five years. In comparing AREDS vs AREDS 2, the latter study was more complex, and attempted to look at the interplay of multiple factors. 

The AREDS 2 conclusions are below, and show differences when comparing AREDS vs AREDS 2.

  • A modified AREDS Formula with both Lutein and Zeaxanthin, but without beta-carotene, was 18% more effective than that the original AREDS research.
  • Lutein and Zeaxanthin absorption was improved when beta-carotene was removed from the formula.
  • Beta carotene was again proven to increase lung cancer in former smokers.
  • No significant decrease in benefit was found with 25 mg daily Zinc versus 80 mg daily.
  • Omega 3s were NOT found to be beneficial in Grade 3 and 4 macular degeneration patients.

Therefore, the AREDS 2 Ingredients are as follows, as a daily dose:

  1. Lutein: 10 mg
  2. Zeaxanthin: 2 mg
  3. Vitamin C: 500 mg
  4. Vitamin E: 400 IU (Natural Vitamin E contains approximately 270 mg of Vitamin E, while Synthetic Vitamin E contains approximately 180 mg of Vitamin E)
  5. Zinc: 25-80 mg
  6. Copper: 1-2 mg (Copper does not have impact on AMD. It is generally provided in a 1:40 ratio with zinc to prevent zinc-induced anemia.)

    Most AREDS 2 supplements require two tablets or capsules per day, so that the AREDS 2 ingredients listed above are half of that per capsule.

    Based upon AREDS vs AREDS 2, VisiVite AMD supplements do not contain beta-carotene. The Zinc levels in most VisiVite AMD formulas have also been reduced to 40 mg daily except for VisiVite AREDS 2 E-Free Blue Formula (because it contains one fewer ingredient with no Vitamin E) and VisiVite AREDS 2 Zinc-Free White Formula, when genetic testing of Complement Factors shows benefit for some people to remove zinc from the 6 ingredients recommended in AREDS 2. Finally, the copper level has been reduced to maintain the 40:1 zinc to copper ratio used in AREDS 2.

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