New analysis reemphasizes safety of vitamin E

According to a new US meta-analysis, supplementation with vitamin E does not increase mortality risk at doses of up to 5,500 IU per day.

The new meta-analysis included results from 57 randomized controlled trials with a total of 246,371 adult participants who received vitamin E supplements of up to 5,500 IU /day for a median period of 2.6 years to prevent or treat disease (1). The analysis showed that vitamin E supplementation is not associated with an increase in the risk of all-cause mortality. A reduction in mortality risk has not been proven either.

The researchers commented that many chronic diseases associated with aging, such as cancer, cardiovascular disease, cataracts and dementia, have been linked to cellular damage from oxidative stress. In theory, antioxidants like vitamin E should be able to prevent conditions associated with oxidative stress. Not surprisingly, evidence for efficient prevention or treatment of complex, multifactorial, life style-dependent chronic diseases from individual trials with vitamin E supplements alone or in combination with other antioxidants have tended to be inconclusive or contradictory.

Although vitamin E supplementation has been considered generally safe (2), a 2004 meta-analysis suggested that the risk of all-cause mortality may be significantly increased for those subjects taking at least 400 IU /d vitamin E (3). The study was criticized by experts because the trials included were mostly small and involved subjects with chronic diseases. Furthermore, studies reporting fewer than 10 deaths were excluded. A 2009 meta-analysis found the same studies to offer no evidence of increased risk of mortality associated with vitamin E at any dose (4). A 2007 meta-analysis that included additional trials reported that vitamin E supplementation was associated with a 4% increase in risk of all-cause mortality (5). Since the analysis reported on 51 trials but only found a significantly increased risk of mortality when a subset of 26 studies was considered, many researchers discounted it as invalid. In all the studies, cause-specific analysis of mortality was not possible because cause of death (e.g. disease, accident, homicide) is not typically reported in the trials that were reviewed (6).

1. Abner E. L. et al. Vitamin E and All-cause Mortality: A Meta-Analysis. Current Aging Science. 2011 ; 4.
2. Institute of Medicine: Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. A report of the Panel on Dietary Antioxidants and Related Compounds. Food Nutrition Board. Washington, DC: National Academies Pr; 2000.
3. Miller E. R. et al. Meta-analysis: High dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2004; 142:37–46.
4. Berry D. et al. Bayesian model averaging in meta-analysis: vitamin E supplementation and mortality. Clinical Trials. 2009; 6:28–41.
5. Bjelakovic G. et al. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: Sytematic review and metaanalysis. JAMA. 2007; 297:842–857.
6. Biesalski H. K. Et al. Reexamination of a meta-analysis of the effect of antioxidant supplementation on mortality and health in randomized trials. Nutrients. 2010; 2:929–949.