Vitamin E
When scientists discovered vitamin E in 1922, they called it the anti sterility vitamin. And since then, vitamin E has been the subject of many studies on a variety of topics. In those early years, much of the research focused on the link between this fat soluble vitamin and reproduction in animals. This led some people to start taking the vitamin in the hopes of increasing sexual potency. As for most vitamins, this kind of thinking didn't pan out. Recently, however, even more exciting connections between vitamin E and a host of diseases are making headlines. Researchers have been studying vitamin E as a key player in the functioning of the immune system, which fights against viruses as well as cancer; protection against heart disease; cataracts and other eye disease; and possible treatment for AIDS, alcoholic liver disease, and Alzheimer's disease.
Vitamin E is actually two distinct groups of compounds comprising at least eight compounds. These include the tocopherols and the tocotrienols (alpha, beta, delta, gamma), and these also exist as mirror images of themselves called isomers, much the same as the carotenoids. The natural form of alpha-tocopherol is known as RRR-alpha-tocqpherol (or d-alpha-tocopherol). Adding to the chemical complexity is the fact that synthetic tocopherols, which include some vitamin supplement preparations and foods with added vitamin E, all-rac-alpha-tocopherol (or dl-alpha-tocopherol), give rise to eight more mirror images! And as with the carotenoids, scientists think these isomers may act differently in the body.
Other natural forms include beta-,delta-, and gamma-tocopherols and have small chemical differences compared to their more famous alpha sister. The tocotrienols are similar to the tocopherols, but scientists think that only one of them, only alpha-tocotrienol, appears to have important biologic activity. That important activity is antioxidant ability.
Of all the various forms of vitamin E, alpha-tocopherol is the most powerful antioxidant. And among forms of alpha-tocopherol, the natural vitamin, RRR-alpha-tocopherol, is more potent than the synthetic version, all-rac-alpha-tocopherol. This is one of the few exceptions in which our body can tell the difference between the naturally occurring vitamin and the one made in a lab. But a recent study showed that both were equally effective in preventing oxidation of LDL cholesterol, which scientists think is the reason for vitamin E's protection against heart disease.
The major role of vitamin E is as an antioxidant in body lipids. It's an essential component of all cell membranes where it performs this vital function. Since the lipids in the cell membrane are polyunsaturated and more susceptible to peroxidation, vitamin E sits in the cell membrane and stops oxidation by grabbing the free radicals before they can spread damage. The way antioxidants work is that they become oxidized, sort of sacrificing themselves for the good of the body. And they are rewarded by an ingenious system of teamwork with the other antioxidant nutrients.
Antioxidant nutrients team up to help each other and the cells and compounds they protect in two ways. Fat soluble antioxidants, vitamin E and the carotenoids, protect fat soluble compounds, while the water soluble antioxidant vitamin C provides this service in watery parts of the body, such as blood. Besides covering for each other in different parts of the body, one antioxidant can also revive another after becoming oxidized, which scientists call regeneration. The system reminds you of a baseball game: one antioxidant steps up to the plate after its teammate either strikes out or gets on base. Besides its main function as an antioxidant, vitamin E may be involved in gene expression.
Absorption of vitamin E depends on all the factors involved in dietary fat digestion and is somewhere between 20 and 40 percent. As with all the fat soluble nutrients, vitamin E may be a problem for people who have diseases that cause fat malabsorption. The body absorbs the vitamin less efficiently as you consume higher amounts. After absorption, the liver controls vitamin E's fate and the lipoproteins, LDL and HDL, carry it into the blood. Most of the body's vitamin E is in fat cells.
The RDA for vitamin E is 10 mg and 8 mg for healthy men and women, and the Reference Daily Intake (RDI) on food labels is set at 30 IU for adults. You'll see different units of measure on food products and vitamins, milligrams of alpha-tocopherol equivalents (mg) and also in international units (IU); 1 mg of all-rac-tocophry acetate is equivalent to 1 IU. Recent dietary intake surveys show tha,t many Americans are not getting enough vitamin E, with intakes well below the RDA. Surveys show that 40 percent of seniors consume significantly less than the RDA for vitamin E. And that's using the RDA as the comparison, which many scientists and nutritionists point out is nowhere near the level used in studies showing protection against diseases.
One problem is that the best sources of vitamin E are plant oils. In fact, plants provide the primary source of vitamin E in the diet with soybean, cottonseed, corn, safflower, and wheat germ oil ranking highest on the list. Other food sources include animal products such as eggs and butter, whole vegetables and fruits, and cereals and nuts, which all contain lower amounts of the vitamin in comparison to oils. Our need for vitamin E increases as the amount of polyunsaturated fat in the diet increases. Interestingly, foods that increase the need for vitamin E also provide it. Cutting back on fat makes it difficult to get enough vitamin E.
Do Americans get enough vitamin E. Many don't because they don't eat enough of the foods that contain the vitamin, and some may need more of the vitamin than others. A recent study compared vitamin E absorption and transport in young and older people. After giving the subjects a dose of vitamin E and checking blood levels, the results showed that the availability of the vitamin was lower in older people. Another group of people who may need more vitamin E are smokers. Researchers found that smokers had lower levels of essential fatty acids in their red blood cells compared to nonsmokers. When they supplemented the smokers with the vitamin, the level increased to match that of nonsmokers. Researchers believe that red blood cells need a specific ratio of vitamin E to fatty acids to protect the cell membrane against oxidative damage.
So how much vitamin E helps protect against diseases, and are those levels safe? Some studies seem to suggest that it depends on the disease. For heart disease, studies show benefits at 400 IV, and others as low as 200 IV. To boost the immune system, even less will payoff. As for safety, vitamin E appears to be relatively nontoxic, especially compared to other fat soluble vitamins (A and D in particular). Several studies have shown that adults can tolerate up to 800 mg without toxic effect. Most researchers believe that daily supplementation ranging from 100 to 400 mg is safe, and double-blind studies have demonstrated that even larger doses up to 3,200 mg didn't lead to any harmful effects.
A Closer Look at Vitamin E at Work in the Prevention of Heart Disease
Scientists have known for some time that vitamin E is a powerful antioxidant and one of the most effective scavengers of free radicals, not surprising since this appears to be its main job in the cell membrane. And it's this potent antioxidant ability which has riveted attention on fighting disease, especially as researchers add more chronic diseases to the list of those involving free radical damage. Just this past year, convincing results from a variety of studies led the American Heart Association to name vitamin E as "one of the most noteworthy accomplishments" in the battle against heart disease.
As a major risk factor for heart disease, LDL cholesterol received a lot of attention, but only recently has the antioxidant theory helped to explain why some people with normal LDL still have heart disease. It may well be that when LDL becomes oxidized, it becomes a risk for heart disease. Because of this, researchers have been studying LDL's ability to resist oxidation. In the lab, scientists can make LDL oxidize by adding metal ions, such as iron or copper, much the same as exposure to oxygen in the air oxidizes copper to a green color. Next, they measure levels of key products of oxidation; this tells them how much oxidation is going on. Then, by measuring the time during which no oxidation happens, they know how well LDL is resisting oxidation, a time frame they call the lag phase. From these studies, researchers have learned that each LDL molecule has its own characteristic resistance to oxidation and that antioxidant nutrients can increase LDL's resistance.
Several studies have shown that vitamin E significantly increases LDL oxidation resistance, and this resistance increases as vitamin E content increases. Lag-phase studies are the best evidence so far for the antioxidant teamwork theory. From these, researchers found that vitamin E depends on the involvement of other antioxidants; other fat soluble antioxidants lend a hand within LDL, and water soluble antioxidants help out in the extracellular fluid, which is water based.
Where's the Evidence?
In the early 1990s, an important international study compared blood levels of all the antioxidants in middle-aged men representing sixteen study populations in Europe. The death rate from heart disease among the groups differed by as much as six times. Talk about startling results: in the majority of the groups, two famous risk factors, blood cholesterol and blood pressure, showed no correlation to heart disease death. However, vitamin E levels in the blood showed an important relationship, with higher vitamin E protecting against heart disease death. Comparing all groups, blood pressure and cholesterol were somewhat related to death, but low vitamin E levels proved to be the strongest predictor. In addition, the study also pointed to the teamwork of the antioxidant nutrients, with better antioxidant status associated with a lower heart disease death rate.
A more recent study, the EVA, a population-based study in France, looked at antioxidant status and atherosclerosis among 1,187 men and women aged fiftynine to seventy-one. The researchers used ultrasound to measure thickening in the major arteries in the neck area and at sites with existing plaques. They also measured blood levels of vitamin E, selenium, carotenoids, and a marker of oxidation called TBARS. The results turned up some interesting gender differences and supported the concept that poor antioxidant status, especially vitamin E, plays a key role in the early stage of atherosclerosis in older people.
A similar study by the National Institute of Aging found that seniors who use vitamin E supplements were less likely to die prematurely. The Established Populations for Epidemiologic Studies of the Elderly (EPESE) followed more than 11,000 subjects over the age of sixtyfour for nine years to study the effects of vitamins C and E on death rates. People using vitamin E supplements had a 41 percent reduction in risk for heart disease and a 27 percent lower risk for death from any cause.
The Harvard Nurses Health Study followed more than 87,000 women aged thirtyfour to fiftynine for eight years. Those with the highest vitamin E intake, taking a minimum of 100 IV supplement, had a 31 percent lower risk for heart attack. In one of Harvard's earlier studies, the Harvard Health Professionals Study, researchers kept track of over 40,000 men aged forty to seventyfive for four years to see if vitamin E supplements affected the rate of heart disease. Men who took at least 100 IV of vitamin E for two years had a 40 percent reduction in heart disease.
One interesting result of the EVA study was the gender difference: women had higher levels of all antioxidants and TBARS, while men had significantly more artery-thickening and more plaques. The scientists believe that women have better antioxidant defenses. As you might expect, the higher the TBARS in men, the greater the number of plaques. In both men and women, those with higher levels of carotenoids had less artery thickening. But after taking into account other CVD risk factors such as body weight and smoking, the relationship was not significant. In contrast, people with higher vitamin E levels had lower artery thickening even after adjusting for other risk factors.
In another recent study, researchers measured TBARS in subjects supplemented with vitamin E. They found that in diabetic patients, who have a higher risk for heart disease, vitamin. E supplementation (100 IV per day for three months) significantly lowered TBARS. As an added bonus, vitamin E lowered the blood level of triglyceride, fat in the blood associated with heart disease risk, although it didn't affect cholesterol, HDL, or LDL.
The Iowa Women's Health Study included over 34,000 healthy women to determine the relationship between heart disease mortality and antioxidant intake. After adjusting for age and caloric intake, they reported that women whose vitamin E intake was higher had a lower risk of dying from heart disease. While previous studies found a benefit only from vitamin E supplements, this study showed that even modestly higher dietary intakes lowered risk of heart disease. death: 58 percent lower deaths in the highest groups of vitamin E intake of at least 12 IV than in the lowest ofless than 5.7 IV per day.
Besides helping to prevent heart disease, vitamin E may help stave off another attack in people who have heart disease. The Cholesterol Lowering Atherosclerosis Study (CLAS) reported that men with a history of bypass surgery who took 100 to 450 IV of vitamin E for two years had less progression, or worsening, of heart lesions compared to a control group.
Another type of surgery to prevent a heart attack is angioplasty, in which surgeons repair a blood vessel that is so clogged up with plaque that blood can't pass through very well, making a heart attack more likely. They insert a needle into the vessel with a tiny balloon attached to the tip. Once the needle is in place, they inflate the balloon, pushing the plaque up against the sides of the vessel, opening it up for blood to pass through smoothly again. One problem with angioplasty is that in many patients the blood vessel clogs up again, a process called restenosis.
A study of 440 angioplasty patients showed that the restenosis rate in patients taking 100 IV of vitamin E per day was 15.8 percent compared to 30 percent for the control group. Interestingly, British scientists reported that angioplasty itself, specifically balloon inflation, causes an "outpouring of free radicals" which increase the likelihood of injury to the vessel and starting the events that lead to restenosis.
Another study of over 2,000 men with heart disease, the Cambridge Heart Antioxidant Trial (CHOAS), reported a 77 percent reduction in heart attacks for men taking 400 or 800 IU of vitamin E for 18 months. CHOAS researchers stated that their findings were "the first from a prospective clinical trial to be consistent with the lipid oxidation theory of human heart disease, and support the use of a high dose of vitamin E to prevent heart attacks in patients with angina and atherosclerosis."
Besides fighting free radicals and protecting LDL, vitamin E may also playa role in another aspect of heart disease, the function of some white blood cells. These white blood cells, monocytes, are key players in the process of atherosclerosis because they stick to the insides of the blood vessel and damage it. In a study at the University of Texas Southwestern Medical Center, researchers gave 1,200 IU of vitamin E to twenty-one healthy subjects for eight weeks to see if the vitamin would affect monocytes. As the amount of vitamin E in the monocytes increased, the release of free radicals dropped and the monocytes were less sticky.
So far, the research is quite convincing: Vitamin E appears to heIp prevent and possibly treat heart disease in some patients. Of all the claims made for the vitamins these days, the evidence for vitamin E and heart disease is the most compelling. Although a few studies showed a benefit from levels you can get through diet, more' of them used higher levels achievable only with a supplement. On the plus side, vitamin E also appears to be one of the safest vitamins.
Vitamin E and Immunity
In addition to destroying free radicals, vitamin E has other antioxidant functions in the body's immune system. The immune system is responsible for warding off foreign invaders entering the body such as infectious bacteria, viruses, and toxins. Oddly enough, one of the ways the immune system fights invaders is by producing free radicals which destroy the invaders. Vitamin E protects the body's cells from any damage the free radicals might cause, even in the line of duty.
In a recent three-year study of 100 healthy men and women, high blood levels of vitamin E were associated with low infection rates. Researchers from Tufts University reported that elderly subjects using varying doses of vitamin E had enhancement immunity. At a dose of 800 IV, elderly subjects had increases in T-cell function. But the researchers also showed stimulation of immune function in subjects using 400 IU over a period of six months.
Another study evaluated the effects of vitamin E supplementation in eightyeight independent, healthy seniors aged sixtyfive and over. After four qlonths, researchers reported that seniors taking 200 mg of vitamin E every day had significant enhancement of several immune function measures compared to the control group: a 65 percent increase in response to skin antigen tests, a sixfold increase in hepatitis B antibodies, and a significant increase in the amount of antibody response to tetanus vaccine. The authors concluded that "our results indicate that a level of vitamin E greater than currently recommended enhances certain clinically relevant indexes of T-cell-mediated function in healthy elderly persons. No adverse effects were observed with vitamin E supplementation."
As for cancer and vitamin E, a recent study from Finland compared women with cancer and healthy controls: Women with the lowest blood levels of vitamin E had a higher risk of cancer than other women. The relationship was strongest for cancers involving epithelial tissue such as the mouth, digestive organs, cervix, and skin. From this study, it appears that low vitamin E intake is a risk factor for cancer in many organs, though not all. Another recent study from Finland has linked vitamin E with protection against prostate cancer. Researchers were interested in previous epidemiologic studies which suggested that vitamin E and beta-carotene might influence the development of prostate cancer. In a study of over 29,000 male smokers aged fifty to sixtynine, they gave supplements of both nutrients, separately and together. They randomly assigned subjects to groups of 50 mg of vitamin E, 20 mg of beta-carotene, both agents, or placebo daily for an average of six years. They found 246 new cases and 62 deaths from prostate cancer and a 32 percent reduction in cancer rate among the group taking vitamin E compared to subjects on placebo. In addition, the death rate from prostate cancer was 41 percent lower in the vitamin E group. This study showed a higher risk for prostate cancer among male smokers taking beta-carotene. The authors concluded that long-term vitamin E supplementation significantly reduced both the rate of prostate cancer and death from the disease in male smokers.
Diseases of the Eye
As we age, changes occur in the lens of the eye that may cause several degenerative eye diseases common among the elderly. The first step is a growing cloudiness, or opacity, of the lens, and this leads to the development of cataracts. Researchers believed that oxidative stress was an important cause of the process, and likewise that antioxidant nutrients could help to prevent or at least delay it. A recent study of 410 Finnish men reported that low blood vitamin E levels were significantly associated with increased risk for worsening of lens opacity. When they divided the men into four groups, those in the group with the lowest vitamin E had an almost four times greater risk than men in the group with the highest plasma vitamin E. Cigarette smoking was also an important risk factor for lens opacity.
Although there was strong evidence for a protective role of antioxidant nutrients in the development of cataracts, no one had linked these same nutrients to another eye disease in the elderly that is the leading cause of irreversible blindness, age-related macular degeneration (AMD). In AMD, damage occurs to the small central part of the retina, the macula, and the person loses central vision. The theory behind AMD and the antioxidants suggests that these nutrients prevent the disease by protecting the outer retina, an area containing a high concentration of polyunsaturated fatty acids, which are susceptible to oxidative damage. The antioxidants may also keep the blood vessels that feed the macula healthy.
More proof for antioxidant protection against AMD, this time for carotenoids, comes from the Eye Disease CaseControl Study (EDCCS). Researchers recruited subjects from five major American ophthalmology clinics aged fiftyfive to eighty who had a diagnosis of AMD. They found that carotenoid intake reduced AMD risk, and the relationship was linear, meaning that the higher the intake, the lower the risk. People in the group with the highest carotenoid intake had a 43 percent lower risk compared to other subjects.
The study also compared the effects of different carotenoids and found that lutein and zeaxanthin were the most effective in protecting against AMD. The EDCCS authors concluded that "increased intake of foods rich in antioxidants, especially certain carotenoids, may reduce the risk of developing advanced AMD."
Alzheimer's Disease
Not many other words conjure up more dread than Alzheimer's disease (AD). This disease now affects only 5 percent of the U.S. population, but as the number of elderly Americans continues to increase, those affected by Alzheimer's will also increase. New studies are offering hope, however, in the form of antioxidant nutrients. In 1996, an in vitro, or lab, study reported intriguing results which suggested that the degenerative damage associated with AD might be oxidative in nature.
One of the problems in studying AD is that the only way to make a definite diagnosis of AD is by doing an autopsy on a person who has died of the disease. To make the diagnosis, the pathologist looks for a protein, called amyloid, which invades the brain. Besides being a marker for diagnosis, scientists now believe that this protein causes the devastating symptoms of AD.
Based on this theory, researchers of the 1996 in vitro study placed strips of rat blood vessels in solutions containing amyloid. The amyloid interacted with cells in the blood vessels to produce an excess of free radicals, which in turn caused changes in the structure and function of the tissue. The changes included narrowing of the blood vessels, suggesting that this could occur in the brain of AD patients, causing diminished brain function.
Carrying the experiment a step further, they repeated the test but first soaked the blood vessel strips with a powerful antioxidant. When they placed the antioxidant soaked strips in the amyloid solution, blood vessel strips protected by the antioxidant did not become narrowed. The researchers think that the amyloid in the brains of Alzheimer's patients causes narrowing in the brain's blood vessels by inducing free radical damage. And, more important, antioxidants may prevent the damage that amyloid causes.
The real test for any theory of human disease, however, has to be in humans themselves. A recent study put the antioxidant hypothesis to the test in 341 patients who had moderately severe cases of AD. In this two-year study, researchers used three treatments and a control group who received no treatment: an antioxidant called selegiline (10 mg/day), vitamin E (2,000 IV a day), and both selegiline and vitamin E. They measured the time from the beginning of the study of several outcomes: the occurrence of death, the need for institutionalization, the loss of the ability to perform basic activities of daily living, and the onset of severe dementia. The results were remarkable and supported the antioxidant theory: patients taking selegiline or vitamin E and the combination therapy had major delays in the time to all of the negative outcomes compared with patients in the control group. The authors believe that in patients with moderately severe AD, treatment with selegiline or vitamin E can slow the progression of disease.