Meta-analysis suggests vitamin E stroke risk

By Nathan Gray

- Last updated on GMT

Related tags Stroke

Meta-analysis suggests vitamin E stroke risk
Vitamin E supplements may increase the risk of a rare but severe form of stroke, according to a meta-analysis published in the British Medical Journal.

The research​ from scientists at Harvard Medical School and INSERM in Paris, suggests that alpha-tocopherol vitamin E could increase the risk of haemorrhagic stroke by up to 22 percent.

The authors of the report warned against “widespread and medically uncontrolled use of vitamin E”​ until further research has clarified the role of the antioxidant in stroke and whether subgroups of individuals exist for whom vitamin E confers a substantial increased or decreased risk for specific strokes.

“This meta-analysis of randomised controlled trials of vitamin E treatment reporting on stroke outcomes indicates that the risk of haemorrhagic stroke is significantly increased by 22 percent whereas the risk of ischaemic stroke is significantly reduced by 10 percent. These associations are obscured when total stroke is evaluated as the outcome,”​ stated the researchers, led by Dr Markus Schurks, from the Division of Preventive Medicine at Harvard Medical School.

Commenting on the research, Andrew Shao, PhD, senior VP of scientific and regulatory affairs at CRN told NutraIngredients-USA that the data from the study still suggests that the benefits may outweigh the risks for stroke.

“Based on their analysis, the authors’ estimate that for every 1,000 patients exposed to vitamin E they would predict 0.8 more hemorrhagic strokes and 2.1 fewer ischemic strokes,”​ said Shao.

E uncertainty

The authors of the study noted that lipid peroxidation plays a central role in the development of atherosclerotic plaques, an important factor in cardiovascular.

“This has raised hopes that antioxidants including vitamin E may protect against cardiovascular disease. Data from observational studies support this view, suggesting a protective effect against coronary heart disease,” ​stated Dr Schurks and colleagues.

They noted that as a result, supplementation with vitamins has become popular, with more than half of the adult population in the U.S taking dietary supplements; including 12.7 percent taking vitamin E, according to data from the National Health and Nutrition Examination Survey.

Previous research has agreed that vitamin E has no overall effect on heart attacks. However, the authors noted that the evidence for stroke – including stroke subtypes – remains contradictory, with some indications that vitamin E may be beneficial for ischaemic stroke risk but detrimental for incident haemorrhagic stroke.

“As stroke remains a leading cause of death and disability and vitamin E supplements are widely used and readily available, clarification of potential opposing associations of vitamin E with ischaemic and haemorrhagic stroke is of substantial public health importance,”​ said the researchers.

Altered risk

The meta-analysis included nine trials investigating the effects of vitamin E on the incident of stroke, from which data from over 115,000 people was gathered.

The nine trials reviewed used both synthetic vitamin E (dl-alpha-tocopherol) and natural (alpha-tocopherol) vitamin E. Trials not studying the effects of alpha-tocopherol, including two using tocopheryl nicotinate were excluded from the study.

The reviewers reported that none of the results from the individual trials suggested that vitamin E significantly alters the risk for total stroke, and that overall vitamin E had no effect on the risk for total stroke.

However, the effects of vitamin E when analyzed by type of stroke showed contrasting results. The risk for haemorrhagic stroke was increased by 22 percent in people taking vitamin E, whilst the risk of ischaemic stroke was reduced by 10 percent.

“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,”​ stated the authors.


The authors noted that whilst the review data shows a significantly reduced risk for ischaemic stroke and increased risk for haemorrhagic stroke, the absolute effects are small.

“In addition, one has to keep in mind that other preventive strategies have far stronger effects on stroke. For example, the 10 percent relative risk reduction for ischaemic stroke by vitamin E is negligible compared to the substantial risk reduction achieved by antihypertensive medication or lipid lowering medication,”​ said Schurks and colleagues.

“However, given the relatively small reduction in risk of ischaemic stroke and the generally more severe outcome of haemorrhagic stroke, indiscriminate widespread use of vitamin E should be cautioned against,”​ they concluded.


Dr Shao told “The authors also acknowledge that, although the relative risk numbers appear high ….the absolute effects are quite small and may be somewhat misleading, placing in question the clinical relevance of this report.”

He added that for most consumers, who represent the general population, it is important to remember that “government surveys continue to demonstrate convincingly that Americans still fail to achieve the recommended intake for vitamin E, an essential nutrient.”

“These analyses of very specific and narrow segments of the population do not address the vitamin E inadequacy of the American diet. Supplementation still plays an important role in filling this gap for Americans,”​ said Shao.

Source: British Medical Journal
Published online ahead of print, doi: 10.1136/bmj.c5702
“Effects of vitamin E on stroke subtypes: meta-analysis of randomised controlled trials”
Authors: M. Schurks, R.J. Glynn, P.M. Rist, C. Tzourio, T. Kurth

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1 comment

Flawed from the beginning!

Posted by D J Wat,

First, the study included the synthetic (dl) form of vitamin E which is know to be deleterious to health.
Second there are 8 different forms (tocopherols) of vitamin E so for one taking Mixed Tocopherols this study does not apply.
It should be noted that beneficial Natural vitamin E supplements containing mixed tocopherols including the tocotrienols, offer well documented and proven protections that were not evaluated in this Meta-analysis.
Since this analysis did not examine the proper forms of vitamin E, I do not understand why resources were put to its undertaking.

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