Cancer Causes & Control

, Volume 19, Issue 1, pp 75–87 | Cite as

Vitamin E and selenium supplementation and risk of prostate cancer in the Vitamins and lifestyle (VITAL) study cohort

  • Ulrike Peters
  • Alyson J. Littman
  • Alan R. Kristal
  • Ruth E. Patterson
  • John D. Potter
  • Emily White
Original Paper



Vitamin E and selenium are promising nutrients for the prevention of prostate cancer, and both are currently being tested in a large randomized trial for prostate cancer. However, results are not expected for at least 6 years.

We aimed to investigate the association of vitamin E and selenium supplementation with prostate cancer in the VITamins And Lifestyle (VITAL) study, a cohort study specifically designed to examine supplement use and future cancer risk.


In a prospective design, 35,242 men recruited between 2000 and 2002 from western Washington State completed a questionnaire, including detailed questions about vitamin E and selenium supplement intake during the past 10 years from brand-specific multivitamins and single supplements. Using linkage to the western Washington SEER cancer registry, we documented 830 new cases of prostate cancer from baseline through December 2004.


A 10-year average intake of supplemental vitamin E was not associated with a reduced prostate cancer risk overall [hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.65–1.1 for ≥400 IU/day vs. non-use, p for trend 0.36]; however, risk for advanced prostate cancer (regionally invasive or distant metastatic, n = 123) decreased significantly with greater intake of supplemental vitamin E (HR 0.43, 95% CI 0.19–1.0 for 10-year average intake ≥400 IU/day vs. non-use, p for trend 0.03). There was no association between selenium supplementation and prostate cancer risk (HR 0.90, 95% CI 0.62–1.3 for 10-year average intake >50 μg/day vs. non-use, p for trend 0.97).


In this prospective cohort, long-term supplemental intake of vitamin E and selenium were not associated with prostate cancer risk overall; however, risk of clinically relevant advanced disease was reduced with greater long-term vitamin E supplementation.


Prostate cancer Vitamin E Selenium Vitamin supplements Cohort 



Confidence interval


Odds ratio

VITAL cohort

Vitamins and lifestyle cohort



We thank the participants of the Vitamins and Lifestyle study for their support. All authors were responsible for the study concept and design, and participated in writing the manuscript. AJL analyzed the data and UP drafted the manuscript. None of the authors had a personal or financial conflict of interest. Grant support: Supported by grant R01 CA74846, the Career Development grant K22 CA118421 and the Cancer Prevention training grant R25T CA94880 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services.


  1. 1.
    Klein EA, Thompson IM, Lippman SM et al (2001) SELECT: the next prostate cancer prevention trial. Selenium and vitamin E cancer prevention trial. J Urol 166:1311–5PubMedCrossRefGoogle Scholar
  2. 2.
    Klein EA, Thompson IM, Lippman SM et al (2003) SELECT: the selenium and vitamin E cancer prevention trial. Urol Oncol 21:59–65PubMedGoogle Scholar
  3. 3.
    Klein EA, Thompson IM, Lippman SM et al (2001) SELECT: the next prostate cancer prevention trial. Selenium and Vitamin E cancer prevention trial. J Urol 166:1311–1315PubMedCrossRefGoogle Scholar
  4. 4.
    Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG (1973) Selenium: biochemical role as a component of glutathione peroxidase. Science 179:588–590PubMedCrossRefGoogle Scholar
  5. 5.
    Combs GF Jr, Gray WP (1998) Chemopreventive agents: selenium. Pharmacol Ther 79:179–192PubMedCrossRefGoogle Scholar
  6. 6.
    Ripple MO, Henry WF, Rago RP, Wilding G (1997) Prooxidant-antioxidant shift induced by androgen treatment of human prostate carcinoma cells. J Natl Cancer Inst 89:40–48PubMedCrossRefGoogle Scholar
  7. 7.
    Iynem AH, Alademir AZ, Obek C, Kural AR, Konukoglu D, Akcay T (2004) The effect of prostate cancer and antiandrogenic therapy on lipid peroxidation and antioxidant systems. Int Urol Nephrol 36:57–62PubMedCrossRefGoogle Scholar
  8. 8.
    Tam NN, Gao Y, Leung YK, Ho SM (2003) Androgenic regulation of oxidative stress in the rat prostate: involvement of NAD(P)H oxidases and antioxidant defense machinery during prostatic involution and regrowth. Am J Pathol 163:2513–2522PubMedGoogle Scholar
  9. 9.
    Fleshner NE, Klotz LH (1998) Diet, androgens, oxidative stress and prostate cancer susceptibility. Cancer Metastasis Rev 17:325–330PubMedCrossRefGoogle Scholar
  10. 10.
    Tapiero H, Townsend DM, Tew KD (2003) The antioxidant role of selenium and seleno-compounds. Biomed Pharmacother 57:134–44PubMedCrossRefGoogle Scholar
  11. 11.
    Loft S, Poulsen HE (1996) Cancer risk and oxidative DNA damage in man. J Mol Med 74:297–312PubMedCrossRefGoogle Scholar
  12. 12.
    Dial S, Eitenmiller RR (1995) Tocopherols and tocotrienols in key foods in the U.S. diet. In: Ong ASH, Niki E, Packer L (eds) Nutrition, lipids, health, and disease. AOCS Press, Champaign, IL, pp 327–342Google Scholar
  13. 13.
    McLaughlin PJ, Weihrauch JL (1979) Vitamin E content of foods. J Am Diet Assoc 75:647–665PubMedGoogle Scholar
  14. 14.
    Institute of Medicine I (2000) Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. Washington, DC: National Academy PressGoogle Scholar
  15. 15.
    Blatt DH, Leonard SW, Traber MG (2001) Vitamin E kinetics and the function of tocopherol regulatory proteins. Nutrition 17:799–805PubMedCrossRefGoogle Scholar
  16. 16.
    Traber MG, Kayden HJ (1989) Preferential incorporation of alpha-tocopherol vs gamma- tocopherol in human lipoproteins. Am J Clin Nutr 49:517–526PubMedGoogle Scholar
  17. 17.
    Heinonen OP, Albanes D, Virtamo J et al (1998) Prostate cancer and supplementation with alpha-tocopherol and beta- carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst 90:440–446PubMedCrossRefGoogle Scholar
  18. 18.
    Lonn E, Bosch J, Yusuf S et al (2005) Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA 293:1338–1347PubMedCrossRefGoogle Scholar
  19. 19.
    Schwarz K, Foltz C (1957) J Am Chem Soc 79, 3292Google Scholar
  20. 20.
    Grossman JN, Grosz AE, Schweitzer PN, Schruben PN (2005) The National Geochemical Survey Team . The National Geochemical Survey–Database and Documentation. U.S. Geological Survey Open-File Report 2004–1001.
  21. 21.
    Kubota J, Allaway WH, Carter DL, Cary EE, Lazar VA et al (1967) Selenium in crops in the United States in relation to selenium-responsive diseases of animals. J Agric Food Chem 15:448CrossRefGoogle Scholar
  22. 22.
    Levander OA (1985) Considerations on the assessment of selenium status. Fed Proc 44:2579–2583PubMedGoogle Scholar
  23. 23.
    Holden J, Gebhardt R, Davis C, Lurie D (1991) A nationwide study of the selenium content and variability in white bread. J Food Compost Anal 4:183–195CrossRefGoogle Scholar
  24. 24.
    Clark LC, Combs GF Jr, Turnbull BW et al (1996) Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional prevention of cancer study group. JAMA 276:1957–1963PubMedCrossRefGoogle Scholar
  25. 25.
    Duffield-Lillico AJ, Reid ME, Turnbull BW et al (2002) Baseline characteristics and the effect of selenium supplementation on cancer incidence in a randomized clinical trial: a summary report of the Nutritional Prevention of Cancer Trial. Cancer Epidemiol Biomarkers Prev 11:630–639PubMedGoogle Scholar
  26. 26.
    Clark LC, Dalkin B, Krongrad A et al (1998) Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial. Br J Urol 81:730–734PubMedGoogle Scholar
  27. 27.
    Hill KE, Xia Y, Akesson B, Boeglin ME, Burk RF (1996) Selenoprotein P concentration in plasma is an index of selenium status in selenium-deficient and selenium-supplemented Chinese subjects. J Nutr 126:138–145PubMedGoogle Scholar
  28. 28.
    Neve J (1995) Human selenium supplementation as assessed by changes in blood selenium concentration and glutathione peroxidase activity. J Trace Elem Med Biol 9:65–73PubMedGoogle Scholar
  29. 29.
    Longnecker MP, Taylor PR, Levander OA et al (1991) Selenium in diet, blood, and toenails in relation to human health in a seleniferous area. Am J Clin Nutr 53:1288–1294PubMedGoogle Scholar
  30. 30.
    Hunter DJ, Morris JS, Chute CG et al (1990) Predictors of selenium concentration in human toenails. Am J Epidemiol 132:114–122PubMedGoogle Scholar
  31. 31.
    Pennington JA, Young BE, Wilson DB (1989) Nutritional elements in U.S. diets: results from the Total diet study, 1982 to 1986. J Am Diet Assoc 89:659–664PubMedGoogle Scholar
  32. 32.
    White E, Patterson RE, Kristal AR et al (2004) VITamins And Lifestyle cohort study: study design and characteristics of supplement users. Am J Epidemiol 159:83–93PubMedCrossRefGoogle Scholar
  33. 33.
    Patterson RE, Kristal AR, Levy L, McLerran D, White E (1998) Validity of methods used to assess vitamin and mineral supplement use. Am J Epidemiol 148:643–649PubMedCrossRefGoogle Scholar
  34. 34.
    Patterson RE, Neuhouser ML, White E, Kristal AR, Potter JD (1998) Measurement error from assessing use of vitamin supplements at one point in time. Epidemiology 9:567–569PubMedCrossRefGoogle Scholar
  35. 35.
    Patterson RE, Levy L, Tinker LF, Kristal AR (1999) Evaluation of a simplified vitamin supplement inventory developed for the Women’s Health Initiative. Public Health Nutr 2:273–276PubMedCrossRefGoogle Scholar
  36. 36.
    Medical Economics Staff (2002) Physicians Desk Reference for Nonprescription Drugs and Dietary Supplements. Medical Economics, MontvaleGoogle Scholar
  37. 37.
    Satia-Abouta J, Patterson RE, King IB et al (2003) Reliability and validity of self-report of vitamin and mineral supplement use in the vitamins and lifestyle study. Am J Epidemiol 157:944–954PubMedCrossRefGoogle Scholar
  38. 38.
    Satia JA, King IB, Morris JS, Stratton K, White E (2005) Toenail and Plasma Levels as Biomarkers of Selenium Exposure. Ann EpidemiolGoogle Scholar
  39. 39.
    Kristal AR, Feng Z, Coates RJ, Oberman A, George V (1997) Associations of race/ethnicity, education, and dietary intervention with the validity and reliability of a food frequency questionnaire: the Women’s Health Trial Feasibility Study in Minority Populations. Am J Epidemiol 146:856–869PubMedGoogle Scholar
  40. 40.
    Patterson RE, Kristal AR, Tinker LF, Carter RA, Bolton MP, Agurs-Collins T (1999) Measurement characteristics of the Women’s Health Initiative food frequency questionnaire. Ann Epidemiol 9:178–187PubMedCrossRefGoogle Scholar
  41. 41.
    Schakel SF, Buzzard IM, Gebhardt SE (1997) Procedures for estimating nutrient values for food composition databases. J Food Compost Anal 10:102–114CrossRefGoogle Scholar
  42. 42.
    Korn EL, Graubard BI, Midthune D (1997) Time-to-event analysis of longitudinal follow-up of a survey: choice of the time-scale. Am J Epidemiol 145:72–80PubMedGoogle Scholar
  43. 43.
    Hosmer DW, Lemeshow S (1999) Applied survival analysis: regression modeling of time to event data. Wiley series in probability and statistics. Texts and references section. Wiley, New YorkGoogle Scholar
  44. 44.
    Church DF, Pryor WA (1985) Free-radical chemistry of cigarette smoke and its toxicological implications. Environ Health Perspect 64:111–126PubMedCrossRefGoogle Scholar
  45. 45.
    Frei B, Forte TM, Ames BN, Cross CE (1991) Gas phase oxidants of cigarette smoke induce lipid peroxidation and changes in lipoprotein properties in human blood plasma. Protective effects of ascorbic acid. Biochem J 277(Pt 1):133–138PubMedGoogle Scholar
  46. 46.
    Pryor WA, Hales BJ, Premovic PI, Church DF (1983) The radicals in cigarette tar: their nature and suggested physiological implications. Science 220:425–427PubMedCrossRefGoogle Scholar
  47. 47.
    Shibata A, Paganini-Hill A, Ross RK, Henderson BE (1992) Intake of vegetables, fruits, beta-carotene, vitamin C and vitamin supplements and cancer incidence among the elderly: a prospective study. Br J Cancer 66:673–679PubMedGoogle Scholar
  48. 48.
    Chan JM, Stampfer MJ, Ma J, Rimm EB, Willett WC, Giovannucci EL (1999) Supplemental vitamin E intake and prostate cancer risk in a large cohort of men in the United States. Cancer Epidemiol Biomarkers Prev 8:893–899PubMedGoogle Scholar
  49. 49.
    Schuurman AG, Goldbohm RA, Brants HA, Van den Brandt PA (2002) A prospective cohort study on intake of retinol, vitamins C and E, and carotenoids and prostate cancer risk (Netherlands). Cancer Causes Control 13:573–582PubMedCrossRefGoogle Scholar
  50. 50.
    Kirsh VA, Hayes RB, Mayne ST et al (2006) Supplemental and dietary vitamin E, beta-carotene, and vitamin C intakes and prostate cancer risk. J Natl Cancer Inst 98:245–254PubMedGoogle Scholar
  51. 51.
    Rodriguez C, Jacobs EJ, Mondul AM, Calle EE, McCullough ML, Thun MJ (2004) Vitamin E supplements and risk of prostate cancer in U.S. men. Cancer Epidemiol Biomarkers Prev 13:378–382PubMedGoogle Scholar
  52. 52.
    Miller ER III, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E (2005) Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 142:37–46PubMedGoogle Scholar
  53. 53.
    Gann PH, Ma J, Giovannucci E et al (1999) Lower prostate cancer risk in men with elevated plasma lycopene levels: results of a prospective analysis. Cancer Res 59:1225–1230PubMedGoogle Scholar
  54. 54.
    Hsing AW, Comstock GW, Abbey H, Polk BF (1990) Serologic precursors of cancer. Retinol, carotenoids, and tocopherol and risk of prostate cancer. J Natl Cancer Inst 82:941–946PubMedCrossRefGoogle Scholar
  55. 55.
    Nomura AM, Stemmermann GN, Lee J, Craft NE (1997) Serum micronutrients and prostate cancer in Japanese Americans in Hawaii. Cancer Epidemiol Biomarkers Prev 6:487–491PubMedGoogle Scholar
  56. 56.
    Goodman GE, Schaffer S, Omenn GS, Chen C, King I (2003) The association between lung and prostate cancer risk, and serum micronutrients: results and lessons learned from beta-carotene and retinol efficacy trial. Cancer Epidemiol Biomarkers Prev 12:518–526PubMedGoogle Scholar
  57. 57.
    Helzlsouer KJ, Huang HY, Alberg AJ et al (2000) Association between alpha-tocopherol, gamma-tocopherol, selenium, and subsequent prostate cancer. J Natl Cancer Inst 92:2018–2023PubMedCrossRefGoogle Scholar
  58. 58.
    Huang HY, Alberg AJ, Norkus EP, Hoffman SC, Comstock GW, Helzlsouer KJ (2003) Prospective study of antioxidant micronutrients in the blood and the risk of developing prostate cancer. Am J Epidemiol 157:335–344PubMedCrossRefGoogle Scholar
  59. 59.
    Weinstein SJ, Wright ME, Pietinen P et al (2005) Serum alpha-tocopherol and gamma-tocopherol in relation to prostate cancer risk in a prospective study. J Natl Cancer Inst 97:396–9PubMedGoogle Scholar
  60. 60.
    Knekt P, Aromaa A, Maatela J et al (1988) Serum vitamin E and risk of cancer among Finnish men during a 10-year follow-up. Am J of Epidemiol 127(2): 28–41Google Scholar
  61. 61.
    Hartman TJ, Albanes D, Pietinen P et al (1998) The association between baseline vitamin E, selenium, and prostate cancer in the alpha-tocopherol, beta-carotene cancer prevention study. Cancer Epidemiol Biomarkers Prev 7:335–340PubMedGoogle Scholar
  62. 62.
    Eichholzer M, Stahelin HB, Ludin E, Bernasconi F (1999) Smoking, plasma vitamins C, E, retinol, and carotene, and fatal prostate cancer: seventeen-year follow-up of the prospective basel study. Prostate 38:189–198PubMedCrossRefGoogle Scholar
  63. 63.
    Bieri JG, Corash L, Hubbard VS (1983) Medical uses of vitamin E. N Engl J Med 308(18): 1063–1071PubMedCrossRefGoogle Scholar
  64. 64.
    Burton GW, Ingold KU (1981) Autoxidation of biological molecules. 1. The antioxidant activity of vitamin E and related chain-breaking phenolic antioxidants in vitro. J Am Chem Soc 103:6472CrossRefGoogle Scholar
  65. 65.
    Ni J, Wen X, Yao J et al (2005) Tocopherol-associated protein suppresses prostate cancer cell growth by inhibition of the phosphoinositide 3-kinase pathway. Cancer Res 65:9807–9816PubMedCrossRefGoogle Scholar
  66. 66.
    Israel K, Yu W, Sanders BG, Kline K (2000) Vitamin E succinate induces apoptosis in human prostate cancer cells: role for Fas in vitamin E succinate-triggered apoptosis. Nutr Cancer 36:90–100PubMedCrossRefGoogle Scholar
  67. 67.
    Malafa MP, Fokum FD, Andoh J et al (2006) Vitamin E succinate suppresses prostate tumor growth by inducing apoptosis. Int J Cancer 118:2441–2447PubMedCrossRefGoogle Scholar
  68. 68.
    Mahoney CW, Azzi A (1988) Vitamin E inhibits protein kinase C activity. Biochem Biophys Res Commun 154:694–697PubMedCrossRefGoogle Scholar
  69. 69.
    Venkateswaran V, Fleshner NE, Klotz LH (2002) Modulation of cell proliferation and cell cycle regulators by vitamin E in human prostate carcinoma cell lines. J Urol 168:1578–1582PubMedCrossRefGoogle Scholar
  70. 70.
    Yu A, Somasundar P, Balsubramaniam A, Rose AT, Vona-Davis L, McFadden DW (2002) Vitamin E and the Y4 agonist BA-129 decrease prostate cancer growth and production of vascular endothelial growth factor. J Surg Res 105:65–8PubMedCrossRefGoogle Scholar
  71. 71.
    Zhang M, Altuwaijri S, Yeh S (2004) RRR-alpha-tocopheryl succinate inhibits human prostate cancer cell invasiveness. Oncogene 23:3080–3088PubMedCrossRefGoogle Scholar
  72. 72.
    Zhang Y, Ni J, Messing EM, Chang E, Yang CR, Yeh S (2002) Vitamin E succinate inhibits the function of androgen receptor and the expression of prostate-specific antigen in prostate cancer cells. Proc Natl Acad Sci USA 99:7408–7413PubMedCrossRefGoogle Scholar
  73. 73.
    Li H, Stampfer MJ, Giovannucci EL et al (2004) A prospective study of plasma selenium levels and prostate cancer risk. J Natl Cancer Inst 96:696–703PubMedCrossRefGoogle Scholar
  74. 74.
    Van den Brandt PA, Zeegers MP, Bode P, Goldbohm RA (2003) Toenail selenium levels and the subsequent risk of prostate cancer: a prospective cohort study. Cancer Epidemiol Biomarkers Prev 12:866–871PubMedGoogle Scholar
  75. 75.
    Nomura AM, Lee J, Stemmermann GN, Combs GF Jr (2000) Serum selenium and subsequent risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 9:883–887PubMedGoogle Scholar
  76. 76.
    Yoshizawa K, Willett WC, Morris SJ et al (1998) Study of prediagnostic selenium level in toenails and the risk of advanced prostate cancer. J Natl Cancer Inst 90:1219–1224PubMedCrossRefGoogle Scholar
  77. 77.
    Brooks JD, Metter EJ, Chan DW et al (2001) Plasma selenium level before diagnosis and the risk of prostate cancer development. J Urol 166:2034–2038PubMedCrossRefGoogle Scholar
  78. 78.
    Vogt TM, Ziegler RG, Graubard BI et al (2003) Serum selenium and risk of prostate cancer in U.S. blacks and whites. Int J Cancer 103:664–670PubMedCrossRefGoogle Scholar
  79. 79.
    Goodman GE, Schaffer S, Bankson DD, Hughes MP, Omenn GS (2001) Predictors of serum selenium in cigarette smokers and the lack of association with lung and prostate cancer risk. Cancer Epidemiol Biomarkers Prev 10:1069–1076PubMedGoogle Scholar
  80. 80.
    Knekt P, Aromaa A, Maatela J et al (1990) Serum selenium and subsequent risk of cancer among Finnish men and women. J Natl Cancer Inst 82:864–868PubMedCrossRefGoogle Scholar
  81. 81.
    Allen NE, Morris JS, Ngwenyama RA, Key TJ (2004) A case–control study of selenium in nails and prostate cancer risk in British men. Br J Cancer 90:1392–1396PubMedCrossRefGoogle Scholar
  82. 82.
    Ghadirian P, Maisonneuve P, Perret C et al (2000) A case-control study of toenail selenium and cancer of the breast, colon, and prostate. Cancer Detect Prev 24:305–3013PubMedGoogle Scholar
  83. 83.
    Peters U, Foster CB, Chatterjee N et al (2007) Serum selenium and risk of prostate cancer-a nested case-control study. Am J Clin Nutr 85:209–217PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  • Ulrike Peters
    • 1
    • 2
  • Alyson J. Littman
    • 1
    • 2
    • 3
  • Alan R. Kristal
    • 1
    • 2
  • Ruth E. Patterson
    • 4
  • John D. Potter
    • 1
    • 2
  • Emily White
    • 1
    • 2
  1. 1.Cancer Prevention ProgramFred Hutchinson Cancer Research CenterSeattleUSA
  2. 2.University of WashingtonSeattleUSA
  3. 3.Department of Veterans Affairs Epidemiologic Research and Information CenterSeattleUSA
  4. 4.Amylin Pharmaceuticals, Inc.San DiegoUSA

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