Hey, vitamin E was supposed to be good for the heart. That’s what “they” said. And you can count me in that “they.” Several years ago, I wrote a pretty optimistic piece on vitamin E, based on some interesting observational studies and some promising laboratory findings. A number of studies had shown that people taking vitamin E had fewer heart attacks and strokes, and investigators had demonstrated that the vitamin had powerful antioxidant effects—at least in the test tube. The only downside seemed to be an anticoagulant effect at high doses. I did have a lingering concern about that, but upon looking into the issue, I concluded that at a dose of 200 iu this was not a concern, and I was quite comfortable suggesting a daily intake of that amount. Couldn’t do any harm, and might do some good. I figured that intervention studies, which were just getting started at the time, would nail down the details about the most appropriate dose. They would also eliminate the possibility that vitamin E takers were seeing benefits not because of the supplement, but because they were eating healthier diets and exercising more.
Well, those intervention studies served up a surprise. Study after study showed that people taking vitamin E were no better off, in terms of cardiovascular disease, than those taking a placebo. Even the studies about preventing macular degeneration, a serious eye condition, were disappointing. And then came the analysis of some nineteen vitamin E studies by Dr. Edgar Miller of Johns Hopkins University. In a paper published in the Annals of Internal Medicine, Miller reports that, when the results of these studies involving over 136,000 patients are combined, no protection against cardiovascular disease is evident. Then comes the shocker. Not only did the vitamin not protect against disease, but it also appeared to increase mortality from all causes!
This finding startled the millions of people taking vitamin E supplements, and shook supplement producers to the core. The supplement industry is monumental, and profits are huge. Understandably, then, the industry was quick to mobilize and point fingers at what it claimed were shortcomings of Miller’s “meta-analysis.” Most of the studies involved people who already had cancer, Alzheimer’s, or heart disease, and therefore the results would not be expected to apply to a healthy population. While it is certainly correct that the subjects of these studies already had some sort of disease, the inference that the results therefore do not apply to healthy people is not necessarily valid. Indeed, one normally expects an intervention to be most effective in people already burdened with disease. Aspirin, for example, is of great use in preventing heart attacks in people with existing heart disease, but the jury is still out on the effectiveness of healthy people taking aspirin. So if vitamin E offers no help to those who suffer from an ailment, it is unlikely to benefit the healthy.
Another criticism aimed at the study suggests that most of the participants took synthetic, rather than natural, vitamin E. That’s true, but it is the synthetic version that is most commonly available, and that’s the one people tend to take. There are eight different naturally occurring forms of vitamin E: four different “tocopherol” forms, and four corresponding “tocotrienols.” It certainly is possible that supplements composed of a blend of all of these would have a different effect than just alpha-tocopherol, which is the base of most supplements, whether synthetic or natural.
Just as the smoke was clearing from Miller’s meta-analysis, the scientific community and the public were stunned by the results of HOPE-TOO, published in March 2005 in the Journal of the American Medical Association. The Heart Outcomes Prevention Evaluation Ongoing Outcomes trial (who says scientists don’t have imagination when it comes to names?) began in 1993, when more than 9,000 people over the age of fifty-five, with a history of either diabetes or heart disease, were randomly assigned to take either 400 iu of natural source vitamin E, or a placebo. The hope of HOPE was that vitamin E would provide some benefit against heart disease, and perhaps cancer. Alas, such was not to be the case. To the surprise of the researchers who monitored the study, not only did the vitamin prove ineffective, but it actually increased the risk of heart failure by up to 19 percent! Again, we have to remember that the results may have been different in a healthy population. The study used natural source alpha-tocopherol, and, as mentioned above, some critics have suggested that the results would have been different if the supplement reflected the ratio of the four different forms of tocopherol as they occur in the diet. Possibly, but that’s conjecture. In any case, alpha-tocopherol is what is commonly found in the supplements people take to ward off disease.
So is vitamin E hopeless? No study can provide a final answer, but the Miller analysis showed no benefit with vitamin E use in 136,000 people, as well as a dose-response relationship in terms of mortality. In general, when an effect, either positive or negative, increases with dose, it usually means that it is real, rather than a statistical artifact. In this case, the researchers noted that risk of premature death began to rise at around a daily dose of 150 iu of vitamin E, and at a dose of 400 iu per day, the risk of dying from any cause becomes about 10 percent higher than for people not taking the vitamin. HOPE-TOO added more fuel to the burning controversy with its finding of a cardiac risk instead of a benefit from vitamin E supplements.
Of course, it is always possible that vitamin takers don’t take as much care with their diet and exercise habits because they feel they are protected, but this is not a likely explanation, given the large number of subjects involved in the studies. The fact is that, as more and more high-quality studies about supplements come to light, we begin to see an emerging pattern. While anti-oxidants undoubtedly play an important role in health, their relative amounts are of essence. More is not necessarily better. Food seems to contain the best balance of these nutrients, and when we flood the body with antioxidants from an outside source, the antioxidant balance is upset to the extent that adverse reactions may occur.
More evidence about the ineffectiveness of vitamin E in preventing cardiovascular disease or cancer comes from the Women’s Health Study conducted between 1992 and 2004. Almost 40,000 women over the age of forty-five were given either a placebo or 600 iu of natural source alpha-tocopherol on alternate days. The researchers found no overall benefit for major cardiovascular events or cancer and concluded that the data do not support recommending vitamin E supplementation for the prevention of these diseases in healthy women.
Given the fact that we have no clear indication of benefit from high doses of vitamin E, and that there are suggestions of possible harm, the prudent advice is to avoid high doses. Moderate amounts, though, may provide some benefit. In seniors, 200 iu a day seems to offer some protection against respiratory tract infections, and vitamin E may play a role in preventing Alzheimer’s disease. A study of 5,000 elderly people in Utah found that vitamin E supplements protected against Alzheimer’s, but only when taken together with vitamin C. This actually has a theoretical rationale: vitamin C can recharge the activity of vitamin E after it has performed its role as an antioxidant. A combination of 400 iu of vitamin E with 500 milligrams of vitamin C was found to be useful. Such amounts are not dangerous. So while vitamin E may not do much for your heart, it may help your memory. You just have to remember to take vitamin C along with it! But once memory problems have appeared, vitamin E is useless. In a study reported in the New England Journal of Medicine in 2005, researchers followed 769 older people (ranging in age from fifty-five to ninety years) who had experienced mild cognitive impairment. Some were treated with high doses of vitamin E (2,000 iu per day), and some with a placebo. Vitamin E was ineffective in warding off Alzheimer’s disease. The same study showed that donepezil (Aricept) slowed the progression of the disease during the first year, but this benefit was not maintained thereafter.
The jury is still out on the possible benefits of vitamin E in slowing the progress of macular degeneration, an eye disease characterized by the breakdown of cells in an area of the retina known as the macula. In 2001 the Age-Related Eye Disease Study (areds) created a great deal of excitement when it revealed that a supplement consisting of 500 milligrams of vitamin C; 400 iu of vitamin E; 15 milligrams of beta-carotene; 80 milligrams of zinc as zinc oxide; and two milligrams of copper as cupric oxide significantly slowed the progress of the disease. The role of vita-min E here is unclear, but in any case, there is no evidence that such supplements may prevent people from getting macular degeneration in the first place.
I must admit that I had greater hopes for vitamin E, based on its antioxidant potential and a few promising epidemiological studies. But placebo-controlled intervention trials have unfortunately not lived up to expectations. Such is the nature of science! It is a self-correcting discipline, and in the long run, science eventually manages to focus in on the truth. The truth may not always be what we wish, but the mark of a scientist is to go according to the results of research, not according to his or her wishes.