Skip to main content

Advertisement

SpringerLink
Log in

Vitamin E Supplementation and Mortality in Healthy People: A Meta-Analysis of Randomised Controlled Trials

  • ORIGINAL ARTICLE
  • Published:
Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

Abstract

Purpose

To evaluate the effect of oral vitamin E supplementation on all-cause mortality in apparently healthy people.

Methods

A systematic review and meta-analysis was conducted on randomised controlled trials (RCTs) with ≥6 months of follow up investigating the effect of vitamin E supplementation on healthy adults in developed countries. Electronic databases (MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials) and reference lists of trial reports were searched for RCTs published between 1966 and June 2012. Three investigators assessed eligibility of identified trials. Disagreements were resolved by consensus. Two investigators independently extracted data according to the criteria.

Results

There were 18 RCTs identified with 142,219 apparently healthy participants (71,116 in vitamin E intervention groups and 71,103 in control groups) that were included in the final analysis. Fixed effect and random effects analysis of the 18 trials revealed that supplementation with vitamin E was not associated with all-cause mortality (relative risk 1.01, 95 % confidence interval 0.97 – 1.05, p = 0.65). Subgroup analyses by type of vitamin E (natural or synthetic), dose or duration of exposure, study design or quality, and pre-specified mortality outcome showed no association with all-cause mortality.

Conclusions

The evidence from pooled analysis of 18 randomised controlled trials undertaken in apparently healthy people shows no effect of vitamin E supplementation at a dose of 23–800 IU/day on all-cause mortality.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig 2

Similar content being viewed by others

References

  1. Dutta A, Dutta SK. Vitamin E and its role in the prevention of atherosclerosis and carcinogenesis: a review. J Am Coll Nutr. 2003;22(4):258–68.

    Article  CAS  PubMed  Google Scholar 

  2. Stampfer MJ, Hennekens CH, Manson JE, et al. Vitamin E consumption and the risk of coronary disease in women. N Engl J Med. 1993;328(20):1444–9.

    Article  CAS  PubMed  Google Scholar 

  3. Rimm EB, Stampfer MJ, Ascherio A, et al. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med. 1993;328(20):1450–6.

    Article  CAS  PubMed  Google Scholar 

  4. Vivekananthan DP, Penn MS, Sapp SK, et al. Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet. 2003;361(9374):2017–23.

    Article  CAS  PubMed  Google Scholar 

  5. Eidelman RS, Hollar D, Hebert PR, et al. Randomized trials of vitamin E in the treatment and prevention of cardiovascular disease. Arch Intern Med. 2004;164(14):1552–6.

    Article  CAS  PubMed  Google Scholar 

  6. Myung SK, Ju W, Cho B, et al. Efficacy of vitamin and antioxidant supplements in prevention of cardiovascular disease: systematic review and meta-analysis of randomised controlled trials. BMJ (Clinical research ed). 2013;346:f10.

    Google Scholar 

  7. Jiang L, Yang KH, Tian JH, et al. Efficacy of antioxidant vitamins and selenium supplement in prostate cancer prevention: a meta-analysis of randomized controlled trials. Nutr Cancer. 2010;62(6):719–27.

    Article  CAS  PubMed  Google Scholar 

  8. Bjelakovic G, Nikolova D, Simonetti RG, et al. Systematic review: primary and secondary prevention of gastrointestinal cancers with antioxidant supplements. Aliment Pharmacol Ther. 2008;28(6):689–703.

    Article  CAS  PubMed  Google Scholar 

  9. Cortes-Jofre M, Rueda JR, Corsini-Munoz G, et al. Drugs for preventing lung cancer in healthy people. The Cochrane database of systematic reviews. 2012;10:CD002141.

    PubMed  Google Scholar 

  10. Farina N, Isaac MG, Clark AR, et al. Vitamin E for Alzheimer’s dementia and mild cognitive impairment. The Cochrane database of systematic reviews. 2012;11:CD002854.

    PubMed  Google Scholar 

  11. Schurks M, Glynn RJ, Rist PM, et al. Effects of vitamin E on stroke subtypes: meta-analysis of randomised controlled trials. BMJ (Clinical research ed). 2010;341:c5702.

    Article  Google Scholar 

  12. Miller 3rd ER, Pastor-Barriuso R, Dalal D, et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005;142(1):37–46.

    Article  CAS  PubMed  Google Scholar 

  13. Bjelakovic G, Nikolova D, Gluud LL, et al. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA :J Am Med Assoc. 2007;297(8):842–57.

    Article  CAS  Google Scholar 

  14. Bjelakovic G, Nikolova D, Gluud LL, et al. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. The Cochrane database of systematic reviews. 2012;3:CD007176.

    PubMed  Google Scholar 

  15. Bjelakovic G, Nikolova D, Gluud C. Meta-regression analyses, meta-analyses, and trial sequential analyses of the effects of supplementation with Beta-carotene, vitamin a, and vitamin e singly or in different combinations on all-cause mortality: do we have evidence for lack of harm? PLoS One. 2013;8(9):e74558.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Chun OK, Floegel A, Chung SJ, et al. Estimation of antioxidant intakes from diet and supplements in U.S. adults. J nutri. 2010;140(2):317–24.

    Article  CAS  Google Scholar 

  17. Yang M, Chung SJ, Chung CE, et al. Estimation of total antioxidant capacity from diet and supplements in US adults. British J nutri. 2011;106(2):254–63.

    Article  CAS  Google Scholar 

  18. Tilburt JC, Emanuel EJ, Miller FG. Does the evidence make a difference in consumer behavior? Sales of supplements before and after publication of negative research results. J Gen Intern Med. 2008;23(9):1495–8.

    Article  PubMed Central  PubMed  Google Scholar 

  19. Bailey RL, Gahche JJ, Miller PE, et al. Why US adults use dietary supplements. JAMA internal medicine. 2013;173(5):355–61.

    Article  CAS  PubMed  Google Scholar 

  20. MacLennan AH, Wilson DH, Taylor AW. Prevalence and cost of alternative medicine in Australia. Lancet. 1996;347(9001):569–73.

    Article  CAS  PubMed  Google Scholar 

  21. MacLennan AH, Wilson DH, Taylor AW. The escalating cost and prevalence of alternative medicine. Prev Med. 2002;35(2):166–73.

    Article  PubMed  Google Scholar 

  22. MacLennan AH, Myers SP, Taylor AW. The continuing use of complementary and alternative medicine in South Australia: costs and beliefs in 2004. Med J Aust. 2006;184(1):27–31.

    PubMed  Google Scholar 

  23. Xue CC, Zhang AL, Lin V, et al. Complementary and alternative medicine use in Australia: a national population-based survey. J altern comp med(New York, NY). 2007;13(6):643–50.

    Article  Google Scholar 

  24. Williamson M, Tudball J, Toms M, et al. Information Use and Needs of Complementary Medicines Users. In: National Prescribing Service S, ed., 2008.

  25. Morgan TK, Williamson M, Pirotta M, et al. A national census of medicines use: a 24-hour snapshot of Australians aged 50 years and older. Med J Aust. 2012;196(1):50–3.

    Article  PubMed  Google Scholar 

  26. Brownie S. Predictors of dietary and health supplement use in older Australians. The Australian journal of advanced nursing : a quarterly publication of the Royal Australian Nursing Federation. 2006;23(3):26–32.

    Google Scholar 

  27. 27. Australian Bureau of Statistics. Australian Health Survey: Health service usage and health related actions, 2011–12, cat. no. 4364.0.55.002. Canberra: ABS; 2013.

    Google Scholar 

  28. Druesne-Pecollo N, Latino-Martel P, Norat T, et al. Beta-carotene supplementation and cancer risk: a systematic review and metaanalysis of randomized controlled trials. Int j canc J intern du canc. 2010;127(1):172–84.

    Article  CAS  Google Scholar 

  29. Gee PT. Unleashing the untold and misunderstood observations on vitamin E. Genes nutri. 2011;6(1):5–16.

    Article  CAS  Google Scholar 

  30. Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ (Clinical research ed). 2009;339:b2535.

    Article  Google Scholar 

  31. Human Development Report – The Rise of the South: Human Progress in a Diverse World. 2013

  32. The Cochrane Collaboration, editor. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 ed: Cochrane Collaboration 2011

  33. Borenstein M, Hedges L, Higgins J, et al. Comprehensive Meta-analysis Version 2. Englewood NJ: Biostat; 2005.

    Google Scholar 

  34. Collins EG, Edwin Langbein W, Orebaugh C, et al. PoleStriding exercise and vitamin E for management of peripheral vascular disease. Med Sci Sports Exerc. 2003;35(3):384–93.

    Article  CAS  PubMed  Google Scholar 

  35. Manning PJ, Sutherland WH, Williams SM, et al. The effect of lipoic acid and vitamin E therapies in individuals with the metabolic syndrome. Nutr Metab Cardiovasc Dis. 2013;23(6):543–9.

    Article  CAS  PubMed  Google Scholar 

  36. Hoffman RM, Garewal HS. Alpha-tocopherol supplementation for men with existing coronary artery disease: a feasibility study. Prev Med. 1999;29(2):112–8.

    Article  CAS  PubMed  Google Scholar 

  37. Wluka AE, Stuckey S, Brand C, et al. Supplementary vitamin E does not affect the loss of cartilage volume in knee osteoarthritis: a 2 year double blind randomized placebo controlled study. J rheumatol. 2002;29(12):2585–91.

    CAS  PubMed  Google Scholar 

  38. Sanyal AJ, Chalasani N, Kowdley KV, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362(18):1675–85.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. de Waart FG, Kok FJ, Smilde TJ, et al. Effect of glutathione S-transferase M1 genotype on progression of atherosclerosis in lifelong male smokers. Atherosclerosis. 2001;158(1):227–31.

    Article  PubMed  Google Scholar 

  40. Hodis HN, Mack WJ, LaBree L, et al. Alpha-tocopherol supplementation in healthy individuals reduces low-density lipoprotein oxidation but not atherosclerosis: the Vitamin E Atherosclerosis Prevention Study (VEAPS). Circulation. 2002;106(12):1453–9.

    Article  CAS  PubMed  Google Scholar 

  41. Magliano D, McNeil J, Branley P, et al. The Melbourne Atherosclerosis Vitamin E Trial (MAVET): a study of high dose vitamin E in smokers. European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology. 2006;13(3):341–7.

    Google Scholar 

  42. Salonen JT, Nyyssonen K, Salonen R, et al. Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study: a randomized trial of the effect of vitamins E and C on 3-year progression of carotid atherosclerosis. J Intern Med. 2000;248(5):377–86.

    Article  CAS  PubMed  Google Scholar 

  43. Graat JM, Schouten EG, Kok FJ. Effect of daily vitamin E and multivitamin-mineral supplementation on acute respiratory tract infections in elderly persons: a randomized controlled trial. JAMA : J Am Med Assoc. 2002;288(6):715–21.

    Article  CAS  Google Scholar 

  44. McNeil JJ, Robman L, Tikellis G, et al. Vitamin E supplementation and cataract: randomized controlled trial. Ophthalmology. 2004;111(1):75–84.

    Article  PubMed  Google Scholar 

  45. Milman U, Blum S, Shapira C, et al. Vitamin E supplementation reduces cardiovascular events in a subgroup of middle-aged individuals with both type 2 diabetes mellitus and the haptoglobin 2–2 genotype: a prospective double-blinded clinical trial. Arterioscler Thromb Vasc Biol. 2008;28(2):341–7.

    Article  CAS  PubMed  Google Scholar 

  46. Cook NR, Albert CM, Gaziano JM, et al. A randomized factorial trial of vitamins C and E and beta carotene in the secondary prevention of cardiovascular events in women: results from the Women’s Antioxidant Cardiovascular Study. Arch Intern Med. 2007;167(15):1610–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Lonn E, Bosch J, Yusuf S, et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA : J Am Med Assoc. 2005;293(11):1338–47.

    Article  Google Scholar 

  48. Gaziano JM, Glynn RJ, Christen WG, et al. Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians’ Health Study II randomized controlled trial. JAMA : J Am Med Assoc. 2009;301(1):52–62.

    Article  CAS  Google Scholar 

  49. Virtamo J, Pietinen P, Huttunen JK, et al. Incidence of cancer and mortality following alpha-tocopherol and beta-carotene supplementation: a postintervention follow-up. JAMA : J Am Med Assoc. 2003;290(4):476–85.

    Article  CAS  Google Scholar 

  50. Lippman SM, Klein EA, Goodman PJ, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA : J Am Med Assoc. 2009;301(1):39–51.

    Article  CAS  Google Scholar 

  51. Lee IM, Cook NR, Gaziano JM, et al. Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women’s Health Study: a randomized controlled trial. JAMA : J Am Med Assoc. 2005;294(1):56–65.

    Article  CAS  Google Scholar 

  52. Fortmann SP, Burda BU, Senger CA, et al. Vitamin and Mineral Supplements in the Primary Prevention of Cardiovascular Disease and Cancer: An Updated Systematic Evidence Review for the U.S. Preventive Services Task Force. Annals of internal medicine 2013

  53. Abner EL, Schmitt FA, Mendiondo MS, et al. Vitamin E and all-cause mortality: a meta-analysis. Current aging sci. 2011;4(2):158–70.

    Article  CAS  Google Scholar 

  54. Shekelle PG, Morton SC, Jungvig LK, et al. Effect of supplemental vitamin E for the prevention and treatment of cardiovascular disease. J Gen Intern Med. 2004;19(4):380–9.

    Article  PubMed Central  PubMed  Google Scholar 

  55. Albanes D. Antioxidant supplements and mortality. JAMA : J Am Med Assoc. 2007;298(4):400. author reply 02–3.

    Article  CAS  Google Scholar 

  56. Willcox BJ, Curb JD, Rodriguez BL. Antioxidants in cardiovascular health and disease: key lessons from epidemiologic studies. Am J Cardiol. 2008;101(10A):75D–86D.

    Article  CAS  PubMed  Google Scholar 

  57. Cordero Z, Drogan D, Weikert C, et al. Vitamin E and risk of cardiovascular diseases: a review of epidemiologic and clinical trial studies. Crit Rev Food Sci Nutr. 2010;50(5):420–40.

    Article  CAS  PubMed  Google Scholar 

  58. Steinberg D. The LDL modification hypothesis of atherogenesis: an update. J Lipid Res. 2009;50:S376–81.

    Article  PubMed Central  PubMed  Google Scholar 

  59. Li H, Horke S, Forstermann U. Vascular oxidative stress, nitric oxide and atherosclerosis. Atherosclerosis. 2014;237(1):208–19.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Lorena Romero, Senior Librarian, Ian Potter Library at Alfred Health for her assistance with the search strategy, also Dr Lisa Demos and Dr Kathlyn Ronaldson (School of Public Health and Preventive Medicine, Monash University) for their constructive comments on the manuscript. We would like to acknowledge the contribution made by the late Associate Professor Damien Jolley to the discussion and planning for this study.

Conflict of Interest

AC, MB and LP declare that they have no conflict of interest. JM has received honoraria for service on advisory boards for Pfizer, Bayer and Janssen-Cilag.

Author information

Authors and Affiliations

  1. Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Level 6, Alfred Centre, 99 Commercial Road, Melbourne, 3004, Australia

    Andrea J. Curtis, Michael Bullen, Loretta Piccenna & John J. McNeil

Authors
  1. Andrea J. Curtis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Bullen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Loretta Piccenna
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. John J. McNeil
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrea J. Curtis.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(DOC 68 kb)

ESM 2

(DOC 16 kb)

ESM 3

(DOC 18 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Curtis, A.J., Bullen, M., Piccenna, L. et al. Vitamin E Supplementation and Mortality in Healthy People: A Meta-Analysis of Randomised Controlled Trials. Cardiovasc Drugs Ther 28, 563–573 (2014). https://doi.org/10.1007/s10557-014-6560-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10557-014-6560-7

Keywords

Search

Navigation