Do antioxidant supplements protect against cancer? It seems like a simple question, but some scientists say yes and others say no—and each side can point to evidence.

Many trials have suggested that dietary antioxidants (particularly vitamins C and E), carotenoids like beta-carotene and lycopene, and flavonoids like catechin and genistein contribute substantially to the reduction of cancer risk. These nutrients appear to inhibit oxidative damage to DNA, reduce cell proliferation, prevent blood vessels from forming in tumors, enhance immune responses against cancer cells, and/or act in other ways to block stages of cancer development.

Studies of large populations reveal that people consuming foods rich in antioxidants, including those found in traditional Mediterranean and Asian diets, are at a reduced risk for many forms of cancer. Some randomized clinical trials confirm these results. One of the earliest of these found a daily supplement containing 50 micrograms selenium, 30 mg vitamin E, and 15 mg beta-carotene administered longer than five years reduced overall cancer mortality by 13 percent. Finnish researchers gave smokers a supplement of 50 mg vitamin E for more than six years and achieved a 36 percent lower risk of prostate cancer. In 1996, in the United States, the Nutritional Prevention of Cancer Trial found 200 micrograms selenium taken daily for five years reduced the risk of prostate cancer by 63 percent.

The results of several more recent trials, however, suggest that antioxidant supplements do not reduce the risk for prostate or other cancers. For example, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) tested daily supplements of 200 micrograms selenium and/or 400 IU vitamin E but the study halted early because there was no indication that prostate cancer incidence was being reduced. It’s worth noting that participants were offered multivitamins (without selenium and vitamin E) and were allowed to take finasteride, a chemopreventive drug treatment for benign prostatic hyperplasia (BPH). Although drug intervention could have affected trial results, no data regarding subjects’ finasteride use was provided.

Nonetheless, these results are consistent with the Physicians’ Health Study II in which men received 400 IU vitamin E every other day or 500 mg vitamin C daily for eight years and showed no reduction in prostate or total cancer. (A major challenge to both studies is that the widespread use of prostate-specific antigen [PSA] tests substantially limits our ability to interpret these results. Screening enabled researchers to exclude men with elevated PSA levels, leading the study population to have unusually low prostate cancer risk.)

Finally, after almost nine years, the Women’s Antioxidant Cardiovascular Study reported no overall benefit of 500 mg vitamin C daily and/or 600 IU vitamin E or 50 mg beta-carotene every other day on total cancer incidence or mortality. Though they didn’t reach statistical significance, potential benefits were noted in the relative risk of colorectal, uterine, and ovarian cancers.

Negative outcomes should not be considered the “final word” on this topic, as the subjects will be followed for several more years and researchers are already beginning to investigate additional factors not analyzed in the first reports. For example, antioxidant concentrations in blood, smoking status, or genetic factors may be able to distinguish between people who are “responders” and “non-responders” to antioxidant supplements. Indeed, this approach reflects the new paradigm of personalized nutrition—one that understands the benefit of a supplement to an individual, not the average response of a large and diverse population.
—Jeffrey Blumberg, PhD, FACN, CNS