Craig Blackwell, MD

Santa Cruz, CA
Diplomate: American Board of Ophthalmology
Fellow: American Academy of Ophthalmology

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An Ophthalmology Practice in Santa Cruz, CA

Vitamin A and AREDS

Vitamin A in AREDS

After AREDS was underway a surprise development caused investigators to reconsider inclusion of Vitamin A in the original formulation. Contemporaneous studies found that smokers who took a Vitamin A supplement (Beta-Carotene) had increased risk of lung cancer and mortality. Following is a review of those studies which will affect those of you who smoke and have Macular Degeneration.


The Beta-Carotene and Retinol Efficacy Trial, aptly abbreviated as CARET.

This study was begun in the early 1980’s when it was thought that supplementing Vitamin A, because of its antioxidant properties, would be protective against development of cancer.

  • Participants. There were 18,314 participants, chosen because they were at increased risk of lung cancer either from smoking or significant exposure to asbestos.
  • Treatment. They were given Beta-Carotene (30mg) and Retinyl Palmitate (25,000 IU) per day.
  • End Points. The study was specifically looking at development of lung cancer, cardiovascular mortality and all cause mortality.
  • Result. The study was stopped before the scheduled completion date because those receiving supplements were found to be at significantly increased risk. ┬áCompared with placebo, the supplement group had:
  • Lung Cancer: 28% increase incidence
  • Cardiovascular Disease Mortality: increased
  • All Cause Mortality: 17% increase

Is this result a fluke? First, in a study involving more than 18,000 people it is unlikely that such a large percentage difference would be a random occurrence. Second, there were other similar studies with the same result

ATBC, Alpha-Tocopherol, Beta-Carotene Cancer Prevention Trial

  • Participants: Finland. 29,000 male smokers.
  • Supplement: Vitamin E and Beta-Carotene (20mg per day).
  • Followed for 6 years.

Physician’s Health Study

  • Participants: 11,000 male physicians. Half were current or former smokers.
  • Supplement: Beta-Carotene (50mg on alternate days).
  • Followed for 12 years

Women’s Health Study

  • Participants: 40,000 health professionals
  • Supplement: Beta-Carotene (50mg on alternate days)
  • Followed for 2 years.

Four Studies Combined

Tanvetyanon combined the data from all four of the above studies and analyzed risk. Published in the journal Cancer in July 2008. Reference (2).

  • Participants: Combined total 110,000 (approx.)
  • Half received Beta-Carotene Supplement, Half as Control.

Risk of Lung Cancer

With Beta-Carotene

Odds Ratio

(95% CI)

Current Smoker




Previous Smoker

No Increase



Never Smoked

No Increase



Table. Risk of Lung Cancer with Beta-Carotene supplement versus no supplement, divided according to smoking status. (Reference 2)


  1. The risk of lung cancer in current smokers increases 24% with supplemental Beta-Carotene.
  2. In former smokers, if there is an increased risk it does not rise to statistical significance.
  3. The increased risk of lung cancer returned to baseline after stopping the Beta-Carotene supplement.
  4. Beta-Carotene seems to be the culprit, not the Retinyl Palmitate.

Vitamin Supplements

Because of the Vitamin A question participants in AREDS who smoked were offered a formulation without Beta-Carotene.

Today, in any drug store there are a multitude of vitamin supplements available. The ones emulating the AREDS formula come with antioxidant vitamins, Zinc, Copper and either Beta-Carotene or Lutein as a substitute; for example, PreserVision Lutein and Ocuvite Lutein.

AREDS 2 is currently underway with an expanded package of supplements. The primary formula includes Lutein and Zeaxanthan, Omega-3-Fatty Acids or a combination of both. A second arm includes the AREDS vitamins. Complete information at


(1) The CARET study with six year follow-up (available on line):

Goodman G, et al.,The Beta-Carotene and Retinol Efficacy Trial: Incidence of Lung Cancer and Cardiovascular Disease Mortality During 6-Year Follow-up. Journal of the National Cancer Institute, 2004; 96: 1743-50.

(2) The combined analysis of the four studies (also available on line).

Tanvetyanon T, Bepler G, Beta-Carotene in Multivitamins and the Possible Risk of Lung Cancer. Cancer 2008;113:150-7

CBlackwell. Feb.2009