Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers

Abstract

Context Secondary analyses of two randomized controlled trials (RCTs) and supportive epidemiologic and preclinical indicated the potential of selenium and vitamin E for preventing prostate cancer. Objective To determine whether selenium or vitamin E or both could prevent prostate cancer with little or no toxicity in relatively healthy men. Design, Setting, and Participants Randomization of a planned 32,400 men to selenium, vitamin E, selenium plus vitamin E, and placebo in a double-blinded fashion. Participants were recruited and followed in community practices, local hospitals and HMOs, and tertiary cancer centers in the United States, Canada and Puerto Rico. Baseline eligibility included 50 years or older (African American) or 55 years or older (all others), a serum prostate-specific antigen (PSA) ≤ 4 ng/mL, and a digital rectal examination (DRE) not suspicious for prostate cancer. Between 2001 and 2004, 35,533 men (10% more than planned because of a faster-than-expected accrual rate) were randomly assigned to the four study arms, which were well balanced with respect to all potentially important risk factors. Interventions Oral selenium (200 µg/day from L-selenomethionine) and matched vitamin E placebo, vitamin E (400 IU/day of all rac-α-tocopheryl acetate) and matched selenium placebo, or the two combined or placebo plus placebo for a planned minimum of 7 and maximum of 12 years. Main Outcome Measures Prostate cancer (as determined by routine community diagnostic standards) and prespecified secondary outcomes including lung, colorectal and overall cancer. Results Study supplements were discontinued at the recommendation of the Data and Safety Monitoring Committee at a planned 7-year interim analysis because the evidence convincingly demonstrated no benefit from either study agent (p < 0.0001) and no possibility of a benefit to the planned degree with additional follow-up. As of October 23, 2008, median overall follow-up was 5.46 years (range, 4.17 and 7.33). Hazard ratios (number of prostate cancers, 99% confidence intervals [CIs]) for prostate cancer were 1.13 for vitamin E (n=473; CI, 0.91–1.41), 1.04 for selenium (n=432; CI, 0.83–1.30), and 1.05 for the combination (n=437; CI, 0.83–1.31) compared with placebo (n=416). There were no significant differences (all p-values > 0.15) in any prespecified cancer endpoints. There were nonsignificant increased risks of prostate cancer in the vitamin E arm (p=0.06; relative risk [RR]=1.13; 99% CI, 0l95–1.35) and of Type 2 diabetes mellitus in the selenium arm (p=0.16; RR=1.07; 99% CI, 0.94–1.22), but they were not observed in the combination arm. Conclusion Selenium or vitamin E, alone or in combination, did not prevent prostate cancer in this population at the doses and formulations used.

Inhibition of Nox4‐dependent ROS signaling attenuates prostate fibroblast activation and abrogates stromal‐mediated protumorigenic interactions

“…Several prominent clinical trials however employing dietary antioxidants yielded disappointing anticancer results 42, 43, 44. Thus, current consensus is that rather than attempting to neutralize ROS, treatment strategies aimed at reducing ROS production might represent an effective alternative approach 45.…”

Complementary medicine use by men with prostate cancer: a systematic review of prevalence studies

“…Some supplements have been investigated for prostate cancer prevention, 15,65,66 but clinical studies on their therapeutic use in prostate cancer are rare. 67 It will be interesting to see whether supplement use declines in this population, or if new supplements are sought out, as a result of major trials, such as SELECT.…”

“…67 It will be interesting to see whether supplement use declines in this population, or if new supplements are sought out, as a result of major trials, such as SELECT. 15 At present, further research on the efficacy and safety of such approaches seems warranted given that patients are initiating and/or continuing to use supplements after cancer diagnosis and possibly alongside conventional treatments. Indeed, some of these CAMs have the potential to interact with conventional medical treatments in both beneficial and detrimental ways; 68 consequently oncologists need to encourage open dialogue about these interventions to understand whether and what kinds of CAM their individual patients are using.…”

“…Since the withdrawal of PC-SPES, large-scale studies have been carried out on other biologically based practices for prostate health, notably the SELECT trial of vitamin E and selenium for cancer prevention. 15 Surveys on CAM use in prostate cancer have not recently been subjected to a rigorous systematic review incorporating quality assessment. Previous reviews on the subject need up-dating and do not provide detailed information focused on CAM use in prostate cancer.…”

Speciation of selenium dietary supplements; formation of S-(methylseleno)cysteine and other selenium compounds

“…There is now considerable debate regarding both the planning and the results of these studies. Most dramatically the SELECT trial that utilized l-selenomethionine as the active supplement, was terminated in 2008 following a conclusion that there had been no demonstrable beneficial effect on prevention of prostate cancer and there was a possible indication of increased incidence of diabetes [50]. Since selenized yeast, as employed by Clark et al and in most supplements, was not tested in the SELECT study, it is conceivable that this difference proved important and that other selenium species observed in the 'Clark' yeast were germane to those results [51,52].…”