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Effects of vitamin E on stroke: a systematic review with meta-analysis and trial sequential analysis
  1. Hong Chuan Loh1,
  2. Renly Lim2,
  3. Kai Wei Lee3,
  4. Chin Yik Ooi1,
  5. Deik Roy Chuan1,
  6. Irene Looi1,4,
  7. Yuen Kah Hay5,
  8. Nurzalina Abdul Karim Khan5
  1. 1 Clinical Research Center, Hospital Seberang Jaya, Ministry of Health Malaysia, Seberang Jaya, Malaysia
  2. 2 Clinical and Health Sciences, University of South Australia, Adelaide, South Australia, Australia
  3. 3 Department of Pre-Clinical Sciences, Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman - Kampus Bandar Sungai Long, Kajang, Malaysia
  4. 4 Medical Department, Hospital Seberang Jaya, Ministry of Health Malaysia, Seberang Jaya, Malaysia
  5. 5 School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Malaysia
  1. Correspondence to Dr. Nurzalina Abdul Karim Khan; nurza{at}


There are several previous studies on the association of vitamin E with prevention of stroke but the findings remain controversial. We have conducted a systematic review, meta-analysis together with trial sequential analysis of randomised controlled trials to evaluate the effect of vitamin E supplementation versus placebo/no vitamin E on the risk reduction of total, fatal, non-fatal, haemorrhagic and ischaemic stroke. Relevant studies were identified by searching online databases through Medline, PubMed and Cochrane Central Register of Controlled Trials. A total of 18 studies with 148 016 participants were included in the analysis. There was no significant difference in the prevention of total stroke (RR (relative risk)=0.98, 95% CI 0.92–1.04, p=0.57), fatal stroke (RR=0.96, 95% CI 0.77–1.20, p=0.73) and non-fatal stroke (RR=0.96, 95% CI 0.88–1.05, p=0.35). Subgroup analyses were performed under each category (total stroke, fatal stroke and non-fatal stroke) and included the following subgroups (types of prevention, source and dosage of vitamin E and vitamin E alone vs control). The findings in all subgroup analyses were statistically insignificant. In stroke subtypes analysis, vitamin E showed significant risk reduction in ischaemic stroke (RR=0.92, 95% CI 0.85–0.99, p=0.04) but not in haemorrhagic stroke (RR=1.17, 95% CI 0.98–1.39, p=0.08). However, the trial sequential analysis demonstrated that more studies were needed to control random errors. Limitations of this study include the following: trials design may not have provided sufficient power to detect a change in stroke outcomes, participants may have had different lifestyles or health issues, there were a limited number of studies available for subgroup analysis, studies were mostly done in developed countries, and the total sample size for all included studies was insufficient to obtain a meaningful result from meta-analysis. In conclusion, there is still a lack of statistically significant evidence of the effects of vitamin E on the risk reduction of stroke. Nevertheless, vitamin E may offer some benefits in the prevention of ischaemic stroke and additional well-designed randomised controlled trials are needed to arrive at a definitive finding. PROSPERO registration number: CRD42020167827.

  • stroke

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  • Contributors Conceptualisation: HCL, KWL and NAKK; methodology: HCL, RL, KWL, CYO, DRC and NAKK; software: HCL, RL, KWL, CYO and DRC; validation: IL, KHY and NAKK; formal analysis: HCL, RL, KWL; investigation: IL, KHY and NAKK; resources: IL, KHY and NAKK; data curation: IL, KHY and NAKK; writing-original draft preparation: HCL, RL; writing-review and editing: IL, KHY and NAKK; visualisation: HCL, KWL; supervision: KHY; project administration: IL; funding acquisition: not applicable. All authors have read and agreed to the published version of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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