Vitamin E and prostate cancer: Where do we stand?

Only a decade has elapsed since the peak of the antioxidant vitamin boom. It began with the observation that people who eat foods rich in antioxidants (fruits, vegetables, and whole grains) enjoy substantial protection from cancer and heart disease.  One reason for this is that antioxidants protect DNA from damage by oxygen-free radicals, potentially reducing genetic errors that cause cancer. Antioxidants also protect against atherosclerosis in the walls of arteries, by reducing oxidative damage to LDL cholesterol inside atherosclerotic plaques.

Unfortunately, it didn't take long for the antioxidant boom to go bust. A series of large randomized clinical trials found that antioxidant supplements do not reduce the risk of cardiovascular disease - and they may even interfere with some cholesterol-lowering medications; they do not reduce overall deaths from cancer; and one antioxidant, beta carotene, actually increases the risk of lung cancer in male smokers.

After reviewing all the information, the U.S. Preventive Services Task Force recommended against routine vitamin use to prevent cancer and cardiovascular disease. It's a sound recommendation, but a study published just a few weeks later reminds us that the issue is not fully resolved, at least as far as vitamin E and prostate cancer is concerned.

The ATBC study: Beta carotene

The Alpha-Tocopherol, Beta Carotene Cancer Prevention trial (ATBC) was one of the first investigations to cast doubt on the value of antioxidants. ATBC was designed to test the belief that antioxidants would protect men from lung cancer. The subjects were Finnish male smokers between the ages of 50 and 69. Starting in 1985, the men were randomly assigned to receive one of four regimens: (1) 50 mg of alpha-tocopherol, the most common form of vitamin E, (2) 20 mg of beta carotene, (3) both antioxidant vitamins, or (4) a placebo. The trial concluded in 1993. When the results were announced, they sounded an alarm: Beta carotene produced an 18% increase in the risk of lung cancer and a less significant increase in the risk of prostate cancer.

After several other studies, it didn't take long for beta carotene supplements to move from the good column to the bad, at least for men who smoke. But vitamin E has also changed columns. When it comes to heart disease, that shift is justified, but a possible benefit against prostate cancer has not been ruled out.

The ATBC follow-up studies on vitamin E

When ATBC ended in 1993, the scientists continued to monitor the men. Their second report provides information on an additional six to eight years of data. Beta carotene's adverse effect on lung cancer diminished rapidly; within four years of stopping the supplement, men who had used beta carotene were no worse off than men who had never taken it.

Using new information, the follow-up study reported a reduction in the risk of prostate cancer of 34%. The apparent benefit of alpha-tocopherol diminished rapidly when supplementation was discontinued, but after six years, a 12% trend toward possible benefit was still evident. The scientists speculate that alpha-tocopheral may act on a late stage in the long, slow process that leads to prostate cancer, and that the possible benefit wanes rapidly once the supplement is discontinued.

The ATBC study issued a third report in 2005. This time the scientists analyzed blood tocopherol levels and the risk of prostate cancer in a subset of the men. Men with the highest blood levels of alpha-tocopherol enjoyed a 51% lower risk of prostate cancer than men with the lowest levels. The ATBC research provides some support for vitamin E (alpha-tocopherol), but it's not conclusive. Although it was a well-conducted randomized clinical trial, its primary goal was to evaluate lung cancer, not prostate cancer. To epidemiologists, this takes a bit of the luster off the prostate cancer findings. More important, all the subjects were smokers. When the Harvard Health Professionals Follow-Up Study looked into the matter, it found that although vitamin E supplements were linked to a reduced risk of prostate cancer in smokers, they had no effect in nonsmokers.

The last word

Should you take antioxidants to reduce your risk of prostate cancer? It's an open question. Despite the ATBC re­sults, there is not enough evidence at present to warrant widespread use of alpha-tocopherol or other forms of vitamin E. More research is needed, and several major clinical trials are already under way. In the meantime, what should we do about antioxidants? Getting lots of antioxidants from foods seems very wise. A good diet is the best way to get the nutrients we need to stay well.

March 2006 update

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