Effect of selenium and vitamin E on risk of PC and other cancers: The Selenium and Vitamin E Cancer Prevention Trial (SELECT)

Division of Cancer Medicine, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 01/2009; 301(1):39-51. DOI: 10.1001/jama.2008.864
Source: PubMed


Secondary analyses of 2 randomized controlled trials and supportive epidemiologic and preclinical data indicated the potential of selenium and vitamin E for preventing prostate cancer.
To determine whether selenium, vitamin E, or both could prevent prostate cancer and other diseases with little or no toxicity in relatively healthy men.
A randomized, placebo-controlled trial (Selenium and Vitamin E Cancer Prevention Trial [SELECT]) of 35,533 men from 427 participating sites in the United States, Canada, and Puerto Rico randomly assigned to 4 groups (selenium, vitamin E, selenium + vitamin E, and placebo) in a double-blind fashion between August 22, 2001, and June 24, 2004. Baseline eligibility included age 50 years or older (African American men) or 55 years or older (all other men), a serum prostate-specific antigen level of 4 ng/mL or less, and a digital rectal examination not suspicious for prostate cancer.
Oral selenium (200 microg/d from L-selenomethionine) and matched vitamin E placebo, vitamin E (400 IU/d of all rac-alpha-tocopheryl acetate) and matched selenium placebo, selenium + vitamin E, or placebo + placebo for a planned follow-up of minimum of 7 years and a maximum of 12 years.
Prostate cancer and prespecified secondary outcomes, including lung, colorectal, and overall primary cancer.
As of October 23, 2008, median overall follow-up was 5.46 years (range, 4.17-7.33 years). Hazard ratios (99% confidence intervals [CIs]) for prostate cancer were 1.13 (99% CI, 0.95-1.35; n = 473) for vitamin E, 1.04 (99% CI, 0.87-1.24; n = 432) for selenium, and 1.05 (99% CI, 0.88-1.25; n = 437) for selenium + vitamin E vs 1.00 (n = 416) for placebo. There were no significant differences (all P>.15) in any other prespecified cancer end points. There were statistically nonsignificant increased risks of prostate cancer in the vitamin E group (P = .06) and type 2 diabetes mellitus in the selenium group (relative risk, 1.07; 99% CI, 0.94-1.22; P = .16) but not in the selenium + vitamin E group.
Selenium or vitamin E, alone or in combination at the doses and formulations used, did not prevent prostate cancer in this population of relatively healthy men.
clinicaltrials.gov identifier: NCT00006392.

Download full-text


Available from: Jaime Claudio,
  • Source
    • "In general, there have been disappointing findings from several costly clinical trials of antioxidant supplements showing not only no health benefits but potential harms. The Selenium and Vitamin E Cancer Prevention Trial (SELECT), conducted among 35,533 North American men aged 50 and older, was prematurely stopped because of lack of efficacy of vitamin E and Se supplementation (200 mg/d) in cancer prevention and because of a small, though non-statistically significant increase in the number of cases of adult onset diabetes in participants taking only Se [41] [42]. Thus, for ethical reasons it would be difficult to justify the initiation of additional RCTs of micronutrient supplements; moreover, it is highly unlikely that adequately powered trials of Se and cardiovascular outcomes will be initiated in the near future. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Mounting evidence supports the hypothesis that functional foods containing physiologically-active components may be healthful. Longitudinal cohort studies have shown that some food classes and dietary patterns are beneficial in primary prevention, and this has led to the identification of putative functional foods. This field, however, is at its very beginning, and additional research is necessary to substantiate the potential health benefit of foods for which the diet–health relationships are not yet scientifically validated. It appears essential, however, that before health claims are made for particular foods, in vivo randomized, double-blind, placebo-controlled trials of clinical end-points are necessary to establish clinical efficacy. Since there is need for research work aimed at devising personalized diet based on genetic make-up, it seems more than reasonable the latter be modeled, at present, on the Mediterranean diet, given the large body of evidence of its healthful effects.
    Nutrition Metabolism and Cardiovascular Diseases 10/2014; 24(12). DOI:10.1016/j.numecd.2014.10.010 · 3.32 Impact Factor
  • Source
    • "Although vitamin E looks like a promising treatment for NASH, there are concerns about the long-term effects of vitamin E with a meta-analysis showing a small overall increase in all-cause mortality at doses >400 IU/day.47 It has also been reported that there might be an increased risk of haemorrhagic stroke48 and prostate cancer49 with high dose treatment. Vitamin E has not been evaluated in patients with cirrhosis or diabetes and NASH. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) affects up to a third of the population in many developed countries. Between 10% and 30% of patients with NAFLD have non-alcoholic steatohepatitis (NASH) that can progress to cirrhosis. There are metabolic risk factors common to both NAFLD and cardiovascular disease, so patients with NASH have an increased risk of liver-related and cardiovascular death. Management of patients with NAFLD depends largely on the stage of disease, emphasising the importance of careful risk stratification. There are four main areas to focus on when thinking about management strategies in NAFLD: lifestyle modification, targeting the components of the metabolic syndrome, liver-directed pharmacotherapy for high risk patients and managing the complications of cirrhosis.
    10/2014; 5(4):277-286. DOI:10.1136/flgastro-2013-100404
  • Source
    • "Results from geographic, animal and clinical studies strongly point to a positive association between selenium and chemoprevention [1]–[3]. Nonetheless, supranutritional intake of dietary selenium in the form of selenomethionine does not prevent prostate cancer [4]. Among the many selenium compounds, methylseleninic acid (MSeA) has been demonstrated to be exceptionally effective in counteracting prostate, pancreatic and breast cancers in mice [5]–[8]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Ovarian cancer, the deadliest of gynecologic cancers, is usually not diagnosed until advanced stages. Although carboplatin has been popular for treating ovarian cancer for decades, patients eventually develop resistance to this platinum-containing drug. Expression of neurogenic locus notch homolog 3 (Notch3) is associated with chemoresistance and poor overall survival in ovarian cancer patients. Overexpression of NICD3 (the constitutively active form of Notch3) in OVCA429 ovarian cancer cells (OVCA429/NICD3) renders them resistance to carboplatin treatment compared to OVCA429/pCEG cells expressing an empty vector. We have previously shown that methylseleninic acid (MSeA) induces oxidative stress and activates ataxia-telangiectasia mutated and DNA-dependent protein kinase in cancer cells. Here we tested the hypothesis that MSeA and carboplatin exerted a synthetic lethal effect on OVCA429/NICD3 cells. Co-treatment with MSeA synergistically sensitized OVCA429/NICD3 but not OVCA429/pCEG cells to the killing by carboplatin. This synergism was associated with a cell cycle exit at the G2/M phase and the induction of NICD3 target gene HES1. Treatment of N-acetyl cysteine or inhibitors of the above two kinases did not directly impact on the synergism in OVCA429/NICD3 cells. Taken together, these results suggest that the efficacy of carboplatin in the treatment of high grade ovarian carcinoma can be enhanced by a combinational therapy with MSeA.
    PLoS ONE 07/2014; 9(7):e101664. DOI:10.1371/journal.pone.0101664 · 3.23 Impact Factor
Show more