No prostate cancer risk reduction with selenium, vitamins E and C supplementation

SELECT and The Physicians’ Health Study II demonstrate insignificant changes in cancer risk and prevention after antioxidant supplementation.

Selenium, vitamin E and vitamin C — in combination or alone — did not prevent or reduce the risk for prostate or other cancers, according to data from the SELECT and The Physician’s Health Study II trials, both published in an online early edition of the Journal of the American Medical Association.

To determine the preventive effects of selenium and vitamin E on prostate and other cancers, researchers conducted SELECT, a randomized, placebo-controlled trial. The study included 35,533 healthy men aged 50 years or older from 427 sites in the United States, Canada and Puerto Rico. Between August 2001 and June 2004, participants were randomly assigned to selenium, vitamin E, selenium plus vitamin E or placebo.

On Sept. 15, 2008 the independent data and safety monitoring committee recommended the trial be halted early due to the supplements’ inability to prevent prostate cancer. On Oct. 23, 2008, at a median follow-up of 5.46 years, participating study centers were informed of the decision and the supplements were discontinued.

According to the researchers, the rates of prostate cancer did not differ significantly between the four treatment groups: 416 cases in placebo, 432 cases in selenium, 473 cases in vitamin E and 437 cases in vitamin E plus selenium. Prostate cancer HRs were 1.13 for vitamin E alone (95% CI, 0.99-1.29), 1.05 for selenium plus vitamin E (95% CI, 0.91-1.20) and 1.04 for selenium alone (95% CI, 0.90-1.18).

Cancer stage and grade diagnosed during the trial were early and low and were similar for all groups, according to the researchers. The percentage of patients with an annual PSA examination and digital rectal exam was high for all groups. Similarly, the rate of biopsies was comparable for all four groups.

“These data underscore the prudence that is needed in considering recommendations to use agents for the prevention or control of disease in the absence of convincing clinical trial results,” the researchers wrote.

Results reiterated

In a randomized, double blind, placebo-controlled factorial trial researchers examined the efficacy of vitamins E and C in reducing the risk for prostate and total cancer. The Physicians’ Health Study II was conducted from 1997 to 2007.

The study included 14,641 male physicians in the United States aged 50 years or older; 1,307 men had a history of prior cancer at baseline. Participants were randomly assigned to 400 IU vitamin E every other day and 500 mg vitamin C daily.

At a mean follow-up of eight years, the researchers reported 1,943 confirmed cancer cases and 1,008 prostate cancer cases. According to the researchers, some men had multiple events and 1,661 men died during follow-up.

Overall prostate cancer rates were similar for vitamin E (9.1 per 1,000 person-years) and placebo (9.5 per 1,000 person-years), and vitamin E had no effect on prostate cancer incidence (HR=0.97; 95% CI, 0.85-1.09). Similarly, overall cancer rates were comparable among vitamin E groups: 17.8 per 1,000 person-years in the active group and 17.3 per 1,000 person-years in the placebo group.

According to the researchers, vitamin E did not affect prostate cancer prevention among participants without a history of prostate cancer.

Similar findings were reported in the vitamin C groups: the overall rate for total cancer was 17.6 per 1,000 person-years in the active group and 17.5 per 1,000 person-years in the placebo group. Vitamin C had no effect on total cancer (HR=1.01; 95% CI, 0.92-1.10). Prostate cancer rates were similar between the two groups: 9.4 cases per 1,000 person-years for active vitamin C and 9.2 cases per 1,000 person-years for placebo vitamin C (HR=1.02; 95% CI, 0.90-1.15).

In an accompanying editorial, Peter H. Gann, MD, ScD, in the department of pathology at the University of Illinois at Chicago, addressed the lack of benefit afforded by selenium, vitamin E and vitamin C. He also discussed the notion that previously reported benefits of selenium and vitamin E may have been due to chance and notes that future research should incorporate “a firmer basis for causal hypotheses.”

“Until then, physicians should not recommend selenium or vitamin E — or any other antioxidant supplements — to their patients for preventing prostate cancer,” he wrote. – by Stacey L. Adams

JAMA. 2008;doi: 10.1001/jama.2008.863.
JAMA. 2008;doi:10.1001/jama.2008.862.
JAMA. 2008;doi:10.1001/jama.2008.864.