This article originally appeared in the August 2004 Harvard Health Letter and is provided courtesy of Harvard Health Publications.

Pills may prevent blindness, but at what cost?

Beta carotene, maybe zinc, could be risky for some.

Macular degeneration affects the center (macula) of the retina, and the condition robs older Americans of their sight more than any other single cause or condition. The Age-Related Eye Disease Study (AREDS) tested whether nutrient supplements might prevent the disease. About 4,700 people were randomly sorted into four groups. One received three nutrients with antioxidant properties (beta carotene and vitamins C and E). A second took zinc and the antioxidant nutrients combined. A third took zinc alone, and the fourth, a placebo. A little bit of copper (as cupric oxide) was added to the formulations containing zinc because extra zinc can lead to a copper deficiency.

The researchers reported the results in October 2001. The disappointing news: No effect was seen on cataracts, or on macular degeneration in its early stages (the study didn’t directly address prevention of the disease in the first place). But for people at an intermediate stage of the disease and for those with advanced-stage macular degeneration in only one eye, the supplements did make a difference. The antioxidant-zinc combination wasn’t a cure, but reduced the risk of developing a more advanced case of macular degeneration by 25%.

AREDS supplements and multivitamins: Safe together?
So many of the AREDS volunteers were taking a multivitamin that to standardize the results, researchers supplied a Centrum brand multivitamin to anyone who wanted it. About two-thirds of the study participants took them up on the offer. There wasn’t any evidence from the study that the combination caused harm. In fact, it’s possible that the AREDS supplements and the multivitamins work together.

The smoker’s formula
At one time, researchers hoped that the beta carotene would be a cheap ticket to cancer prevention. Then two important randomized trials in the ‘90s showed that at high doses, the nutrient increased lung cancer risk for smokers. In large amounts, beta carotene may change from being an antioxidant that squelches the reactive molecules that damage DNA to being a pro-oxidant that produces them.

“Smoker’s formula” versions of the AREDS supplements that don’t have beta carotene are being sold. A brand that’s advertised on the Internet substitutes lutein, another antioxidant nutrient, for beta carotene. That’s a logical switch: AREDS investigators say that they might have done the same if lutein had been available when the study started.

But the usual “buyer beware” warning may be especially relevant here. Dr. Frederick Ferris, an AREDS investigator and a top official at the National Eye Institute, told the Health Letter that the AREDS study investigators had different brands of the AREDS supplement tested. Several of them did not contain the levels of nutrients stated on the label. Dr. Ferris declined to name which ones, citing the need for further testing. The two products that lived up to their labels were Bausch and Lomb’s Ocuvite PreserVision and Alcon’s ICaps AREDS’ Formula, but neither company sells a beta carotene–free version for smokers right now. Bausch and Lomb says it may start selling a beta carotene–free product soon.

Some people have been worried about beta carotene in the AREDS supplements because of studies showing a link between high vitamin A consumption and hip fractures. Some beta carotene gets changed into vitamin A by the body, but the conversion is tightly regulated, so large doses of beta carotene don’t lead to the high vitamin A levels that have been connected to a greater fracture risk.

Zinc’s split personality
Researchers from Harvard and the National Cancer Institute published a study in 2003 that found that high zinc intake (100 milligrams or more daily) doubles a man’s chances of getting prostate cancer. Other research hints that a high intake of the mineral could be a factor in the development of Alzheimer’s disease and diabetes. But other studies suggest just the opposite — that extra zinc might have benefits. For example, a follow-up study of the AREDS participants found that those taking high doses of the mineral were less likely to have died during the six-year study than those who didn’t. The implication: Zinc might have some overall mortality benefit.

The bottom line
First, the AREDS supplements are a treatment, not an all-purpose preventive. The study showed a benefit only for people in the intermediate or later stages of the disease. Second, if you’re a current or former smoker, you need to think twice about taking the extra beta carotene in the standard AREDS supplements. Brands without beta carotene are available, but the main ones don’t offer a smoker’s version. Finally, a study linking high daily doses of zinc to prostate cancer might cause some concern, but it’s too soon to say whether the extra zinc in the AREDS supplements is a health risk.