Effects of vitamin E on stroke: a systematic review with meta-analysis and trial sequential analysis

Abstract

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.

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“…An RCT explored the preventive effect of vitamin E on ischemic stroke when it was used alone, and the outcome remained inconclusive [ 12 ]. When exploring the effect of isomer products of vitamin E, a former study found that serum γ -tocopherol was inversely associated with ischemic stroke in men from a large-scale cohort [ 26 ].…”

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“…Antiplatelet therapy with aspirin and clopidogrel is an established long-term regime and a cornerstone of secondary stroke prevention [23] . Previous literature also showed an 8% risk reduction of ischaemic stroke among those who take a vitamin E supplement [24] . Therefore, it was recommended to the patient that she adds tocotrienols supplementation to her medication.…”

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“…Vitamin E (α-tocopherol) is also a potent antioxidant with the ability to prevent the propagation of ROS chain reactions, mainly in membrane lipids. Vitamin E (isoforms α-tocopherol and γ-tocopherol) has been shown to reduce infarct volume by 45–55% in transient and permanent models of cerebral ischemia [ 64 , 65 ].…”