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Effects of vitamin E on stroke subtypes: meta-analysis of randomised controlled trials

BMJ 2010; 341 doi: (Published 05 November 2010) Cite this as: BMJ 2010;341:c5702
  1. Markus Schürks, instructor of medicine16,
  2. Robert J Glynn, associate professor of medicine and biostatistics13,
  3. Pamela M Rist, doctoral student in epidemiology12,
  4. Christophe Tzourio, senior director of research45,
  5. Tobias Kurth, director of research1245
  1. 1Division of Preventive Medicine, Department of Medicine; Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02215-1204, USA
  2. 2Department of Epidemiology, Harvard School of Public Health, Boston
  3. 3Department of Biostatistics, Harvard School of Public Health, Boston
  4. 4INSERM Unit 708 - Neuroepidemiology, Paris, France
  5. 5UPMC Univ Paris 06, F-75005, Paris
  6. 6Department of Neurology, University Hospital Essen, Germany
  1. Correspondence to: M Schürks mschuerks{at}, T Kurth tobias.kurth{at}
  • Accepted 25 August 2010


Objective To evaluate the effect of vitamin E supplementation on incident total, ischaemic, and haemorrhagic stroke.

Design Systematic review and meta-analysis of randomised, placebo controlled trials published until January 2010.

Data sources Electronic databases (Medline, Embase, Cochrane Central Register of Controlled Trials) and reference lists of trial reports.

Selection criteria Randomised, placebo controlled trials with ≥1 year of follow-up investigating the effect of vitamin E on stroke.

Review methods and data extraction Two investigators independently assessed eligibility of identified trials. Disagreements were resolved by consensus. Two different investigators independently extracted data. Risk ratios (and 95% confidence intervals) were calculated for each trial based on the number of cases and non-cases randomised to vitamin E or placebo. Pooled effect estimates were then calculated.

Results Nine trials investigating the effect of vitamin E on incident stroke were included, totalling 118 765 participants (59 357 randomised to vitamin E and 59 408 to placebo). Among those, seven trials reported data for total stroke and five trials each for haemorrhagic and ischaemic stroke. Vitamin E had no effect on the risk for total stroke (pooled relative risk 0.98 (95% confidence interval 0.91 to 1.05), P=0.53). In contrast, the risk for haemorrhagic stroke was increased (pooled relative risk 1.22 (1.00 to 1.48), P=0.045), while the risk of ischaemic stroke was reduced (pooled relative risk 0.90 (0.82 to 0.99), P=0.02). There was little evidence for heterogeneity among studies. Meta-regression did not identify blinding strategy, vitamin E dose, or morbidity status of participants as sources of heterogeneity. In terms of absolute risk, this translates into one additional haemorrhagic stroke for every 1250 individuals taking vitamin E, in contrast to one ischaemic stroke prevented per 476 individuals taking vitamin E.

Conclusion In this meta-analysis, vitamin E increased the risk for haemorrhagic stroke by 22% and reduced the risk of ischaemic stroke by 10%. This differential risk pattern is obscured when looking at total stroke. Given the relatively small risk reduction of ischaemic stroke and the generally more severe outcome of haemorrhagic stroke, indiscriminate widespread use of vitamin E should be cautioned against.


  • Contributors: MS and TK conceived and designed the study, analysed the data, and drafted the manuscript. MS, PMR, and TK were responsible for the acquisition of the data. All authors interpreted the data, critically revised the draft for important intellectual content, and gave final approval of the version to be published. MS and TK are guarantors for the study. All authors had full access to all of the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis.

  • Funding: No specific funding for this study.

  • Competing interests: All authors have completed the Unified Competing Interest form at (available on request from the corresponding author) and declare: that for the specific matter of this research, no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work.

  • Data sharing: No additional data available.

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