Unnecessary Concern Raised Over Vitamin E Safety
The Annals of Internal Medicine recently published an article entitled Meta-Analysis: High-Dosage Vitamin E Supplementation May Increase All-Cause Mortality. This is a very dramatic statement, to say the least. The problem, however, is that there is no substantial basis for it. As is the case in many studies, this incompetent and shoddy work has garnered the attention of a news media that usually takes press releases from journals such as the Annals of Internal Medicine at face value, rather than delving into the specifics of the article. Consequently, the media attention created by the report has stirred up unnecessary fear regarding the safety of vitamin E supplementation. According to the Council for Responsible Nutrition (CRN), the meta-analysis "inappropriately tries to draw conclusions for the whole population based on a combination of studies of people who were already at grave risk with existing diseases including cancer, heart disease, Alzheimer's, Parkinson's, and kidney failure."
The researchers themselves concede the following: "High-dose (>= 400 IU/d) trials were often small and were performed in patients with chronic diseases. The generalizability of the findings to healthy adults is uncertain. Precise estimation of the threshold at which risk increases is difficult." But this did not stop them from making extrapolations to the general population, as they stated in their conclusion, "High-dose (>= 400 IU/d) vitamin E supplements may increase all-cause mortality and should be avoided." Their extrapolations went further (and far beyond the scope of their study) when they said, "…use of any high-dose vitamin supplements should be discouraged…" [emphasis added].
The premise for their argument is based on data from 19 independent clinical studies involving a collective 135,967 participants. Of these 19 trials, nine tested vitamin E alone and 10 tested vitamin E combined with other vitamins or minerals. The dosage of vitamin E ranged from 16.5 to 2,000 IU/day (median 400 IU/day).
The meta-analysis combined the individual trials to create an overall finding of risk. By combining 19 studies into a single cohort the investigators attempted to show a possible trend in mortality associated with "high-dosage" vitamin E. Although this may have given the study more statistical grounding, it did not account for limitations associated with each study.
"The overall conclusion of this meta-analysis is driven by the results from a few of these clinical trials, some of which are suspect and/or dated. For example, the WAVE trial made no correction for multiple comparisons, and found one of 22 comparisons 'significant.' This is 1/22 whereas 1/20 would have been expected on a random basis. In other words, they found nothing," commented John Hathcock, Ph.D., vice president of scientific and international affairs for CRN.
Interestingly, of the 19 studies highlighted, 18 showed no statistically significant increase in all-cause mortality. In the CHAOS trial, the one study that showed a statistically significant mortality increase, compliance in the vitamin E group who died during the study was only 22 percent, compared to an overall compliance of 43 percent. Might these people have survived if they had actually taken the vitamin E?
Furthermore, at least four of the studies that used dosages > 400 IU/d reported some statistically significant benefit from supplementation. For example, researchers involved with the SPACE study reported patients given vitamin E suffered 70 percent fewer heart attacks than those given placebo. A similar phenomenon was observed in the CHAOS study, which reported a 77-percent decrease in non-fatal MI.
Some things to consider:
The Annals of Internal Medicine report was not a new clinical study, but an analysis of data from pre-existing clinical trials.
Most of the trials involved the elderly, people with serious pre-existing illnesses, or people with increased risk of disease. Data from a number of the studies may be suspect.
Only studies with an occurrence of at least 10 deaths were considered.
No distinction was made between the various isomers of vitamin E used in the studies. For example, some used dl-alpha tocopherol (synthetic), while others used d-alpha tocopherol (natural source).
No distinction was made between use of vitamin E by itself or in combination with other nutrients.
The investigators acknowledged important limitations to the meta-analysis study.
Individuals taking supplemental vitamin E can be assured it is not harmful, and should not discontinue its use based on the questionable findings of this statistical re-working of other studies. Numerous studies on vitamin E show it is a non-toxic and beneficial nutrient.
For the free full-text article in Annals of Internal Medicine:
http://www.annals.org/cgi/content/full/0000605-200501040-00110v1
-or-
http://www.annals.org/cgi/reprint/0000605-200501040-00110v1
For more issues concerning the meta-analysis report, or general information regarding vitamin E, click on the links below:
FAQ on vitamin E meta-analysis in Annals of Internal Medicine (PDF):
http://www.crnusa.org/pdfs/CRN_VitaminE_FactSheet1104.pdf
FAQ on Vitamin E: (PDF)
http://www.crnusa.org/pdfs/CRN_VitaminE_QandA1104.pdf
