Supplement Use is Beneficial in Age-related Macular Degeneration

Eye News: AREDS Results - Supplements Use is Beneficial in Age-related Macular Degeneration

December 2, 2001

AREDS Results: Beneficial Effects Found with Antioxidant and Zinc Supplements in those at High Risk for Age-Related Macular Degeneration.

(From the Age-Related Disease Study Research Group. Arch Ophthal 2001;119:1417-1436.)


Macular degeneration is the leading cause of irreversible severe visual loss in Caucasians age 50 or older in the United States. It has been estimated that this 2.2% of those older than age 65 have worse than 20/200 vision (legally blind) due to this condition. For more information about the condition known as age-related macular degeneration, or AMD, go to Age-related Macular Degeneration.

Many studies have been done attempting to determine if vitamin supplementation helps to prevent the risk of vision loss from macular degeneration. Most have been fairly non-conclusive. However, the results in study cited above appear to indicate a protective effect of certain high dose supplements in individuals at high or moderate risk for macular degeneration.

The Study Design

The Age-Related Eye Disease Study (AREDS) is an 11 center double-masked clinical trial looking at the possible beneficial effects of antioxidant and zinc supplementation in reducing the risk of vision loss from age-related macular degeneration (AMD). In a "double-masked trial", neither the study participants (patients) nor the observers (physicians) know who is actually taking the supplements being studied, and who is taking a placebo. This helps to reduce bias in evaluating the study results. In this study, 3640 participants were enrolled between the age of 55 and 80. Participants were enrolled in the study as follows:

  • One or both eyes had evidence of macular degeneration, such as:
    Extensive small drusen (yellow deposits in the retina seen in AMD)
    Intermediate sized drusen
    Large drusen
    Non-central "geographic atrophy" of the retina
    Retinal pigmentary abnormalities
  • One eye, but not both, could have advanced AMD or advanced vision loss from AMD.
  • At least one eye had best-corrected (with glasses) vision 20/30 or better.
  • Participants were randomly assigned to groups receiving daily oral tablets containing either:
    Antioxidants (500mg vitamin C, 400 IU vitamin E, 15 mg beta carotene)
    80 mg zinc, as zinc oxide, and 2mg copper, as cupric oxide
    Both antioxidants plus zinc together
    or Placebo
  • Participants did not have other eye diseases which would interfere with the assessment of AMD, worsening cataract at the time of beginning the study, no other prior eye surgery except cataract extraction, and no other disorders which would cause a loss of vision such as optic atrophy or uveitis.

Average follow-up time for the study participants was 6.3 years, and only 2.4% was lost to follow-up. Eye examinations were given at the beginning of the study, and then annually thereafter, including retinal photographs. Participants were also given the opportunity to take a general multivitamin (Centrum) if desired, and these were provided by the study. A bottle containing a specific number of supplements, placebo, or Centrum was given to the participants, and unused pills were counted to determine compliance with the regimen.

Participants were divided into 4 categories based on their baseline ocular characteristics:

  • Category 1 - both eyes were essentially free of macular degeneration, and vision was 20/30 or better in both eyes.
  • Category 2 - one or both eyes had mild or borderline macular degeneration, and vision was 20/30 or better in both eyes.
  • Category 3 - neither eye had advanced macular degeneration, but at least one eye had more severe drusen in size or number. One eye had at least 20/30 vision.
  • Category 4 - one eye had 20/30 or better vision and did not have advanced AMD, while the other eye either had advanced AMD or vision loss from AMD.


A total of 4757 were enrolled in AREDS. Of the 1117 in Category 1 (little or no evidence of AMD), only 5 developed advanced AMD during the study time, thus preventing statistical analysis of any benefit of receiving supplements in this group. Therefore, the report primarily focuses on the 3640 participants in Categories 2-4.
96% of these participants were Caucasian, 56% women, and the median age was 69. Only 8% were cigarette smokers at baseline, and 67% chose to take Centrum in addition to the study supplement or placebo.

Risk of Progression to Advanced Macular Degeneration, by study category:

  • Category 2 participants (mild AMD) had only a 1.3% probability of progressing to advanced AMD over 5 years.
  • Category 3 participants (moderate AMD) had an 18% probability of progressing to advanced AMD in 5 years.
  • Category 4 participants (advanced AMD in one eye) had a 43% probability of progressing to advanced AMD in the other eye in 5 years.

Risk of Progression to Advanced Macular Degeneration, by study treatment:

  • In Category 2 participants, only 15 progressed to advanced AMD by year 5, and 316 progressed to Categories 3 or 4. There was no evidence of any treatment benefit delaying the progression of AMD in Category 2 (mild AMD) participants.
  • In Category 3 and Category 4, there was a beneficial effect of antioxidant use alone (vitamins C, E, and beta carotene), in zinc use alone, and a combination of antioxidants and zinc, when compared to placebo.
    The risk of significant worsening of vision by year 5 was 29% in the placebo group (categories 3 and 4).
    The risk of visual loss was 10% lower in those taking antioxidants only, at 26% by year 5.
    The risk of visual loss was 14% lower in those taking zinc only, at 25% by year 5.
    The risk of visual loss was 21% lower in those taking antioxidants AND zinc, at 23% by year 5.
    The trend of decreasing risk with the use of antioxidants and zinc alone or in combination continues to increase with increasing time in the study, being even lower at 7 years.

It was also found that individuals assigned to the antioxidant group had higher blood levels of vitamins C and E and beta carotene at year 1. Those in the zinc group were also found to have higher blood levels of zinc by year 1. There is some risk of having decreased copper absorption during zinc supplementation, which is why copper supplements were included with the zinc. Copper blood levels were not found to significantly decrease during the study.

There were minimal complications from the supplement use. There was an increased reporting of skin yellowing in the beta carotene group. There was an increased rate of hospitalizations for genitourinary problems in men and women in the zinc group. Known possible complications of supplement use include:

  • Vitamin C - increased risk of kidney stones
  • Vitamin E - increased risk of fatigue, muscle weakness, decreased thyroid function, increased hemorrhagic stroke risk
  • Beta-carotene - yellow skin, increased risk of lung cancer in smokers (beta carotene was not given in tobacco users.)
  • Zinc - anemia, decreased HDL cholesterol, upset stomach


By the results of this well designed study, it appears that individuals at high risk for macular degeneration will benefit by taking the supplement regimen detailed in this study. Those with little or no evidence of macular degeneration did not indicate any treatment benefit by taking supplements, but the overall rate of developing advanced AMD was low in these groups. Recommended steps based on this study include:

  • Have a comprehensive eye examination by an ophthalmologist to determine the risk of developing AMD.
  • If there is found to be high risk for AMD, consider taking the supplement regimen used in this study. Note that the amounts of vitamins C, E, beta carotene, and zinc are much higher than typically found in multivitamin preparations. Prior to starting supplementation use, one's primary care physician should be consulted to determine if there are any medical problems, contraindications, or interactions which would make supplementation dangerous (such as beta carotene use in smokers leading to an increased risk of lung cancer).
  • Consider other precautions which may be beneficial in reducing the risk of vision loss from AMD, including:
    Stopping smoking.
    Wearing ultraviolet protecting sunglasses.
    Eating foods high in carotenoids lutein and zeaxanthin, such as kale, turnip greens, collard greens, and spinach (leafy green vegetables).
    Having regular eye examinations and monitoring vision using an Amsler Grid.
    Report any change in vision immediately.


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