Table of Contents
- Introduction: Vitamin E and Disease Prevention
- Vitamin E and Heart Disease
- Vitamin E and Cancer
- Could Vitamin E Supplements Be Harmful?
- Vitamin E and Other Chronic Diseases
Vitamin E’s main function in the body is to work as an antioxidant, scavenging loose electrons—so-called “free radicals”—that can damage cells. (1) Antioxidants, including vitamin E, came to public attention in the 1980s, when scientists began to understand that free radical damage was involved in the early stages of artery-clogging atherosclerosis, and might also contribute to cancer, vision loss, and a host of other chronic conditions. Studies since then have dimmed some of the promise of using high dose vitamin E to prevent chronic diseases.
For a time, vitamin E supplements looked like an easy way to prevent heart disease. Promising observational studies, including the Nurses’ Health Study (2) and Health Professionals Follow-Up Study, (3) suggested 20 to 40 percent reductions in coronary heart disease risk among individuals who took vitamin E supplements (usually containing 400 IU or more) for least two years. (4)
The results of several randomized trials have dampened enthusiasm for vitamin E’s ability to prevent heart attacks or deaths from heart disease among individuals with heart disease or those at high risk for it. In the GISSI Prevention Trial, the results were mixed but mostly showed no preventive effects after more than three years of treatment with vitamin E among 11,000 heart attack survivors. (5) Results from the Heart Outcomes Prevention Evaluation (HOPE) trial also showed no benefit of four years worth of vitamin E supplementation among more than 9,500 men and women already diagnosed with heart disease or at high risk for it. (6) In fact, when the HOPE trial was extended for another four years, researchers found that study volunteers who took vitamin E had a higher risk of heart failure. (7) Based on such studies, the American Heart Association has concluded that “the scientific data do not justify the use of antioxidant vitamin supplements [such as vitamin E] for CVD risk reduction.” (8)
It’s possible that in people who already have heart disease or are high risk of heart disease, the use of drugs such as aspirin, beta blockers, and ACE inhibitors mask a modest effect of vitamin E, and that vitamin E may have benefits among healthier people. But large randomized controlled trials of vitamin E supplementation in healthy women and men have yielded mixed results.
In the Women’s Health Study, which followed 40,000 women for 10 years, vitamin E supplements of 600 IU every other day did not significantly reduce the risk of so-called “major cardiac events” (heart attack, stroke, or cardiovascular death). But there was some encouraging news in the findings: When these major cardiac events were analyzed separately, vitamin E supplementation was linked to a 24 percent lower risk of cardiovascular death. (9) And among women ages 65 and older, vitamin E supplementation reduced the risk of major cardiac events by 26 percent. A later analysis found that women who took the vitamin E supplements also had a lower risk of developing serious blood clots in the legs and lungs, with women at the highest risk of such blood clots receiving the greatest benefit. (10)
Other heart disease prevention trials in healthy people have not been as promising, however. The SU.VI.MAX trial found that seven years of low-dose vitamin E supplementation (as part of a daily antioxidant pill) reduced the risk of cancer and the risk of dying from any cause in men, but did not show these beneficial effects in women; the supplements did not offer any protection against heart disease in men or women. (11) Discouraging results have also come from the Physicians’ Health Study II, an eight-year trial that involved nearly 15,000 middle-aged men, most of whom were free of heart disease at the start of the study. Researchers found that taking vitamin E supplements of 400 IU every other day, alone or with vitamin C, failed to offer any protection against heart attacks, strokes, or cardiovascular deaths. (12)
More recent evidence suggests that vitamin E may have potential benefits only in certain subgroups of the general population: A trial of high dose vitamin E in Israel, for example, showed a marked reduction in coronary heart disease among people with type 2 diabetes who have a common genetic predisposition for greater oxidative stress. (13) So we certainly have not heard the last word on vitamin E and heart disease prevention.
The story on vitamin E and cancer prevention has been a bit less encouraging than the story on vitamin E and heart disease. Taken as a whole, observational studies have not found vitamin E in food or supplements to offer much protection against cancer in general, or against specific cancers. (14–23) Some observational studies and clinical trials, however, suggested that vitamin E supplements might lower the risk of advanced prostate cancer in smokers. (16,24–26)
Investigators had hoped that the Selenium and Vitamin E Cancer Prevention Trial (SELECT) would give more definitive answers on vitamin E and prostate cancer. SELECT’s 18,000 men were assigned to follow one of four pill regimens—vitamin E plus selenium, vitamin E plus a selenium placebo, selenium plus a vitamin E placebo, or a double placebo—and were supposed to be tracked for 7 to 12 years. But investigators halted the study halfway though, in 2008, when early analyses showed that vitamin E offered no cancer or prostate cancer prevention benefit. (27) Though the trial ended, researchers continued to follow the men who had participated. In 2011, they reported a 17 percent higher risk of prostate cancer among men assigned to take vitamin E; there was no significant increased risk of prostate cancer among men who took vitamin E and selenium. (28)
Though these results, on the face of it, sound worrisome, two other major trials of vitamin E and prostate cancer had quite different results: The Alpha Tocopherol Beta Carotene randomized trial, for example, followed nearly 30,000 Finnish male smokers for an average of six years. (24) It found that men assigned to take daily vitamin E supplements had a 32 percent lower risk of developing prostate cancer—and a 41 percent lower risk of dying from prostate cancer—than men given a placebo. Vitamin E’s protective effect was strongest for men whose cancers were far enough along that they could be detected by a clinical exam. The large and long-term Physicians’ Health Study II trial, meanwhile, found that vitamin E supplements had no effect on the risk of prostate cancer or any other cancer. (29)
Why were the SELECT findings on vitamin E and prostate cancer so different from those of earlier studies? Previous studies of vitamin E and prostate cancer found the greatest benefit in men who were smokers, as well as men who had more advanced cancers. (16,24–26) In the SELECT trial, however, fewer than 10 percent of the men were smokers, and most had their cancers discovered at an early stage, through prostate specific antigen (PSA) blood tests. (27,28) Many early-stage, low-grade prostate cancers identified by PSA test would not go on to become advanced cancers. And there’s other evidence that different processes may be at work in early- and late-stage prostate cancers. A large trial of a drug to prevent prostate cancer found opposite effects for early and advanced prostate cancers. (30)
Bear in mind that prostate cancer develops slowly, and any study looking at prostate cancer prevention needs to track men for a long time. By stopping the SELECT trial early, there’s no way to tell if vitamin E could have helped protect against prostate cancer in some men if they had continued the trial over a longer period of time. Very few cases in the SELECT Trial were of advanced prostate cancer, further limiting the interpretation of the findings.
The occasional reports of harm from studies of high-dose vitamin E supplements highlight a question that researchers have been debating for years: Could high-dose vitamin E supplements potentially increase the risk of dying? Researchers have tried to answer this question by combining the results of multiple studies. In one such analysis, (31) the authors gathered and re-analyzed data from 19 clinical trials of vitamin E, including the GISSI and HOPE studies; they found a higher rate of death in trials where patients consumed more than 400 IU of supplements per day. While this meta-analysis drew headlines when it was released, there are limitations to the conclusions that can be drawn from it. Some of the findings are based on very small studies, and in some of these trials, vitamin E was combined with high doses of beta-carotene, which itself has been related to excess mortality. Furthermore, many of the high-dose vitamin E trials included in the analysis were done on people who had chronic diseases, such as heart disease or Alzheimer’s disease. Also, other meta-analyses have come to different conclusions. So it is not clear that these findings would apply to healthy people. The Physicians’ Health Study II, for example, did not find that any difference in death rates between the study participants who took vitamin E and those who took a placebo. (12)
Investigators have explored whether vitamin E supplements can protect against other chronic diseases, and here, too, the findings have been mixed:
Age-Related Vision Diseases
A six-year trial found that vitamin E, in combination with vitamin C, beta carotene, and zinc, offers some protection against the development of advanced age-related macular degeneration (AMD), but not cataract, in people who were at high risk of the disease. (32,33) On its own, however, vitamin E does not seem to offer much benefit against either AMD or cataract. (34,35)
Cognitive Function and Neurodegenerative Diseases
Scientists seeking to untangle the causes of Alzheimer’s, Parkinson’s, and other diseases of the brain and nervous system have focused on the role that free radical damage plays in these diseases’ development. (36) But to date, there is little evidence as to whether vitamin E can help protect against these diseases or that it offers any benefit to people who already have these diseases.
- Dementia: Some prospective studies suggest that vitamin E supplements, particularly in combination with vitamin C, may be associated with small improvements in cognitive function or lowered risk of Alzheimer’s disease and other forms of dementia, while other studies have failed to find any such benefit. (37–40) A three-year randomized controlled trial in people with mild cognitive impairment—often a precursor to Alzheimer’s disease—found that taking 2,000 IU of vitamin E daily failed to slow the progression to Alzheimer’s disease. (41) Keep in mind, however, that the progression from mild cognitive impairment to Alzheimer’s disease can take many years, and this study was fairly short, so it is probably not the last word on vitamin E and dementia.
- Parkinson’s Disease: Some, but not all, prospective studies suggest that getting higher intakes of vitamin E from diet—not from high-dose supplements—is associated with a reduced risk of Parkinson’s disease. (42–44) In people who already have Parkinson’s, high-dose vitamin E supplements do not slow the disease’s progression. (45) Why the difference between vitamin E from foods versus that from supplements? It’s possible that foods rich in vitamin E, such as nuts or legumes, contain other nutrients that protect against Parkinson’s disease. More research is needed.
- Amyotrophic Lateral Sclerosis (ALS): One large prospective study that followed nearly 1 million people for up to 16 years found that people who regularly took vitamin E supplements had a lower risk of dying from ALS than people who never took vitamin E supplements. (46) More recently, a combined analysis of multiple studies with more than 1 million participants found that the longer people used vitamin E supplements, the lower their risk of ALS. (47) Clinical trials of vitamin E supplements in people who already have ALS have generally failed to show any benefit, however. (48) This may be a situation where vitamin E is beneficial for prevention, rather than treatment, but more research is needed.
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