Antioxidants and Cancer Prevention

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• What are antioxidants?
• Can antioxidants prevent cancer?
• What was shown in previously published large-scale clinical trials?
• Are antioxidants under investigation in current large-scale clinical trials?
• Will NCI continue to investigate the effect of beta-carotene on cancer?
• How might antioxidants prevent cancer?
• Which foods are rich in antioxidants?

What are antioxidants?

Antioxidants are substances that may protect cells from the damage caused by unstable molecules known as free radicals. Free radical damage may lead to cancer. Antioxidants interact with and stabilize free radicals and may prevent some of the damage free radicals otherwise might cause. Examples of antioxidants include beta-carotene, lycopene, vitamins C, E, and A, and other substances.

Can antioxidants prevent cancer?

Considerable laboratory evidence from chemical, cell culture, and animal studies indicates that antioxidants may slow or possibly prevent the development of cancer. However, information from recent clinical trials is less clear. In recent years, large-scale, randomized clinical trials reached inconsistent conclusions.

What was shown in previously published large-scale clinical trials?

Five large-scale clinical trials published in the 1990s reached differing conclusions about the effect of antioxidants on cancer. The studies examined the effect of beta-carotene and other antioxidants on cancer in different patient groups. However, beta-carotene appeared to have different effects depending upon the patient population. The conclusions of each study are summarized below.

• The first large randomized trial on antioxidants and cancer risk was the Chinese Cancer Prevention Study, published in 1993. This trial investigated the effect of a combination of beta-carotene, vitamin E, and selenium on cancer in healthy Chinese men and women at high risk for gastric cancer. The study showed a combination of beta-carotene, vitamin E, and selenium significantly reduced incidence of both gastric cancer and cancer overall. (1)
• A 1994 cancer prevention study entitled the Alpha-Tocopherol (vitmain E)/Beta-Carotene Cancer Prevention Study (ATBC) demonstrated that lung cancer rates of Finnish male smokers increased significantly with beta-carotene and were not affected by vitamin E. (2)
• Another 1994 study, the Beta-Carotene and Retinol (vitamin A) Efficacy Trial (CARET), also demonstrated a possible increase in lung cancer associated with antioxidants. (3)
• The 1996 Physicians' Health Study I (PHS) found no change in cancer rates associated with beta-carotene and aspirin taken by U.S. male physicians. (4)
• The 1999 Women's Health Study (WHS) tested effects of vitamin E and beta-carotene in the prevention of cancer and cardiovascular disease among women age 45 years or older. Among apparently healthy women, there was no benefit or harm from beta-carotene supplementation. Investigation of the effect of vitamin E is ongoing. (5)

Are antioxidants under investigation in current large-scale clinical trials?

Three large-scale clinical trials continue to investigate the effect of antioxidants on cancer. The objective of each of these studies is described below. More information about clinical trails can be obtained using cancer.gov/clinicaltrials, www.clinicaltrials.gov, or the CRISP database at www.nih.gov.

• The Women's Health Study (WHS) is currently evaluating the effect of vitamin E in the primary prevention of cancer among U.S. female health professionals age 45 and older. The WHS is expected to conclude in August 2004.
• The Selenium and Vitamin E Cancer Prevention Trial (SELECT) is taking place in the United States, Puerto Rico, and Canada. SELECT is trying to find out if taking selenium and/or vitamin E supplements can prevent prostate cancer in men age 50 or older. The SELECT trial is expected to stop recruiting patients in May 2006.
• The Physicians' Health Study II (PHS II) is a follow up to the earlier clinical trial by the same name. The study is investigating the effects of vitamin E, C, and multivitamins on prostate cancer and total cancer incidence. The PHS II is expected to conclude in August 2007.

Will NCI continue to investigate the effect of beta-carotene on cancer?

Given the unexpected results of ATBC and CARET, and the finding of no effect of beta-carotene in the PHS and WHS, NCI will follow the people who participated in these studies and will examine the long-term health effects of beta-carotene supplements. Post-trial follow-up has already been funded by NCI for CARET, ATBC, the Chinese Cancer Prevention Study, and the two smaller trials of skin cancer and colon polyps. Post-trial follow-up results have been published for ATBC, and as of July 2004 are in press for CARET and are in progress for the Chinese Cancer Prevention Study.