Antioxidants and Cancer Prevention (Fact Sheet)

Alpha-Tocopherol/Beta-Carotene Cancer Prevention Study (ATBC): This trial investigated whether the use of alpha-tocopherol and/or beta-carotene supplements for 5 to 8 years could help reduce the incidence of lung and other cancers in middle-aged male smokers in Finland. Initial results of the trial, reported in 1994, showed an increase in the incidence of lung cancer among the participants who took beta-carotene supplements (20 mg per day); in contrast, alpha-tocopherol supplementation (50 mg per day) had no effect on lung cancer incidence (8). Later results showed no effect of beta-carotene or alpha-tocopherol supplementation on the incidence of urothelial (bladder, ureter, or renal pelvis), pancreatic, colorectal, renal cell (kidney), or upper aerodigestive tract (oral/pharyngeal, esophageal, or laryngeal) cancers (9,10,11,12).

Carotene and Retinol Efficacy Trial (CARET): This U.S. trial examined the effects of daily supplementation with beta-carotene and retinol (vitamin A) on the incidence of lung cancer, other cancers, and death among people who were at high risk of lung cancer because of a history of smoking or exposure to asbestos. The trial began in 1983 and ended in late 1995, 2 years earlier than originally planned. Results reported in 1996 showed that daily supplementation with both 15 mg beta-carotene and 25,000 International Units (IU) retinol was associated with increased lung cancer and increased death from all causes (all-cause mortality) (13). A 2004 report showed that these adverse effects persisted up to 6 years after supplementation ended, although the elevated risks of lung cancer and all-cause mortality were no longer statistically significant (14). Additional results, reported in 2009, showed that beta-carotene and retinol supplementation had no effect on the incidence of prostate cancer (15).

Physicians’ Health Study I (PHS I): This trial examined the effects of long-term beta-carotene supplementation on cancer incidence, cancer mortality, and all-cause mortality among U.S. male physicians. The results of the study, reported in 1996, showed that beta-carotene supplementation (50 mg every other day for 12 years) had no effect on any of these outcomes in smokers or nonsmokers (16).

Women’s Health Study (WHS): This trial investigated the effects of beta-carotene supplementation (50 mg every other day), vitamin E supplementation (600 IU every other day), and aspirin (100 mg every other day) on the incidence of cancer and cardiovascular disease in U.S. women ages 45 and older. The results, reported in 1999, showed no benefit or harm associated with 2 years of beta-carotene supplementation (17). In 2005, similar results were reported for vitamin E supplementation (18).

Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) Study: This trial investigated the effects of daily supplementation with a combination of antioxidants and minerals on the incidence of cancer and cardiovascular disease in French men and women. The initial results of the study, reported in 2004, showed that daily supplementation with vitamin C (120 mg), vitamin E (30 mg), beta-carotene (6 mg), and the minerals selenium (100 μg) and zinc (20 mg) for a median of 7.5 years had no effect on the incidence of cancer or cardiovascular disease or on all-cause mortality (19). However, when the data for men and women were analyzed separately, antioxidant and mineral supplementation was associated with lower total cancer incidence and all-cause mortality among men but not among women, and with an increase in skin cancer incidence, including melanoma, among women but not among men (19,20). The beneficial effects of the supplements for men disappeared within 5 years of ending supplementation, as did the increased risk of skin cancer among women (21,22). 

Heart Outcomes Prevention Evaluation–The Ongoing Outcomes (HOPE–TOO) Study: This international trial examined the effects of alpha-tocopherol supplementation on cancer incidence, death from cancer, and the incidence of major cardiovascular events (heart attack, stroke, or death from heart disease) in people diagnosed with cardiovascular disease or diabetes. The results, reported in 2005, showed no effect of daily supplementation with alpha-tocopherol (400 IU) for a median of 7 years on any of the outcomes (23).

Selenium and Vitamin E Cancer Prevention Trial (SELECT): This U.S. trial investigated whether daily supplementation with selenium (200 μg), vitamin E (400 IU), or both would reduce the incidence of prostate cancer in men ages 50 and older. The study began in 2001 and was stopped in 2008, approximately 5 years earlier than originally planned. Results reported in late 2008 showed that the use of these supplements for a median duration of 5.5 years did not reduce the incidence of prostate or other cancers (24). Updated findings from the study, reported in 2011, showed that, after an average of 7 years (5.5 years on supplements and 1.5 years off supplements), there were 17 percent more cases of prostate cancer among men taking vitamin E alone than among men taking a placebo (25). No increase in prostate risk was observed for men assigned to take selenium alone or vitamin E plus selenium compared with men assigned to take a placebo (24).

Physicians’ Health Study II (PHS II): This trial examined whether supplementation with vitamin E, vitamin C, or both would reduce the incidence of cancer in male U.S. physicians ages 50 years and older. The results, reported in 2009, showed that the use of these supplements (400 IU vitamin E every other day, 500 mg vitamin C every day, or a combination of the two) for a median of 7.6 years did not reduce the incidence of prostate cancer or other cancers, including lymphoma, leukemia, melanoma, and cancers of the lung, bladder, pancreas, and colon and rectum (26).

Overall, these nine randomized controlled clinical trials did not provide evidence that dietary antioxidant supplements are beneficial in primary cancer prevention. In addition, a systematic review of the available evidence regarding the use of vitamin and mineral supplements for the prevention of chronic diseases, including cancer, conducted for the United States Preventive Services Task Force (USPSTF) likewise found no clear evidence of benefit in preventing cancer (27).