LINUS PAULING INSTITUTE RESEARCH REPORT

Maret Traber

All About E

An Interview with Maret G. Traber, Ph.D.
Professor of Nutrition
LPI Principal Investigator

Q: What is vitamin E?

A: Vitamin E is a family of eight fat-soluble antioxidants, four tocopherols and four tocotrienols, but only one of those eight is useful for humans—alpha-tocopherol. This is commonly called vitamin E on supplement labels.

Q: Do all the tocopherols and tocotrienols have vitamin E activity?

A: They all have antioxidant activity, so for floor wax and for skin creams, those forms of vitamin E are great, but we are finding that the body works very hard to exclude forms of vitamin E other than alpha-tocopherol.

Q: Why does the body prefer alpha-tocopherol?

A: The liver picks out alpha-tocopherol to put back in the plasma, using a special protein called the alpha-tocopherol transfer protein. If you have a genetic defect in this protein, then you will have vitamin E deficiency symptoms by the time you are five- or six-years old.

Q: Do all animals preferentially use alpha-tocopherol?

A: I have seen studies in mice, rats, cats, pigs, sheep, monkeys, salmon, and humans. I don’t believe that there is any animal that does not prefer alpha-tocopherol to other forms.

Q: Is vitamin E synthesized in any animal?

A: No, only plants can make vitamin E, and different plants make different amounts of the various vitamin E forms.

Q: Has vitamin E deficiency been observed in humans?

A: Yes. About 15 years ago, there was a flurry of reports demonstrating that vitamin E deficiency occurs in humans. The initial symptom is a lack of feeling in the hands and feet. The disorder, called sensory neuropathy, progresses until even walking becomes impossible.

Q: How common is it?

A: I think there are a hundred people in the world who lack the alpha-tocopherol transfer protein, resulting in vitamin E deficiency. Also, human vitamin E deficiency can result from fat malabsorption syndromes, such as cholestatic liver disease or from cystic fibrosis. These are more common disorders.

Q: Since vitamin E deficiency is so uncommon, how is the recommended dietary allowance (RDA) determined?

A: It’s almost like asking, “How much car insurance do you need?” If you never get into a car wreck, all that money that you’ve spent on insurance is wasted. If you have adequate vitamin E and your levels of oxidative stress are low, then maybe you don’t need so much vitamin E. However, if your level of vitamin E is low, and then you have increased oxidative stress, say, by running a marathon or breathing polluted air, you may have increased oxidative damage. For example, if you stress plants by not giving them sufficient water or providing too much sunlight, they actually make more vitamin E to protect themselves.

Q: Free radicals are generated in the body through normal biochemical processes and respiration. When does that become excessive and potentially harmful, and how can one determine one’s level of oxidative stress?

A: Since vitamin E is safe, you can take a supplement, and you won’t have to wonder if you have enough vitamin E. But cigarette smoking, pollution, sun exposure, and vigorous exercise produce oxidative stress, so daily activities could increase your requirements.

Q: What are the dietary sources of vitamin E?

A: Spinach, almonds, and other nuts are good dietary sources. Vegetable oils really are the major sources, especially olive oil and sunflower oil.

Q: What form of vitamin E predominates in these food sources?

A: Those foods contain primarily alpha-tocopherol. Other oils, like corn oil or soybean oil, contain mostly gamma-tocopherol.

Q: Have there been many studies with gamma-tocopherol?

A: We are currently studying gamma-tocopherol. We found that the body works hard to excrete it, while alpha-tocopherol is retained. Some studies in rats have found that gamma-tocopherol inhibits platelet aggregation, but it isn’t clear if this is related to an antioxidant function or something else.

Q: Do you think that transfer proteins for other forms of vitamin E might be discovered?

A: Dr. Angelo Azzi’s group is working very hard to find tocopherol transfer proteins. They found a protein that is in virtually every cell in the body, which really excited the vitamin E community. We thought that a protein that regulates intracellular vitamin E had been discovered, but it turns out to actually regulate cholesterol. So researchers are still searching for other molecules that might move vitamin E around.

Q: How does vitamin E interact with other antioxidants?

A: We know that you can generate a vitamin E radical in the test tube, which can interact with vitamin C and be reduced back to its unoxidized form, oxidizing vitamin C in the process. Now that's been known probably for 20 or 30 years. We are still studying what actually occurs in humans.

Q: Is oxidation the same as metabolism?

A: Oxidation is the process your body uses to get energy from your food. The body oxidizes glucose or fats to CO2 and water, much like burning logs in your fireplace makes heat, CO2, and water. However, the body frees energy using enzymes in the mitochondria. Although the mitochondria are pretty efficient, some free radicals leak from the mitochondria and generate oxidative stress. Metabolism is a process in the body to make a substance easier to excrete. For example, vitamin E is metabolized to other products, which we can measure in body fluids. Metabolized vitamin E is not the same as oxidized vitamin E.

Q: Why do you measure vitamin E metabolites?

A: We would like to have a really nice biomarker that would help us answer the question, “Does the body have enough vitamin E?” A metabolite may be the body’s way of getting rid of extra vitamin E by converting it to a metabolite that can be excreted. The more metabolite you have, the better off you are with respect to vitamin E status.

Q: Does the metabolite itself have any special biochemical function in the body?

A: We don’t know a lot about the metabolite. It was first described back in 1984, and almost nobody worked on it until about the middle of the 1990s. In the last year, there have been 10 or 12 papers published on vitamin E metabolites. The metabolite’s carboxyl group makes it water soluble, and it still has vitamin E antioxidant activity, so many interesting functions and effects have been reported. But what you observe in the test tube or in cell culture may not be what happens in the body.

Q: Does vitamin E have any function unrelated to its antioxidant activity?

A: According to some people, vitamin E is not an antioxidant! The problem is that it’s very difficult to distinguish antioxidant from biologic effects because vitamin E can change the fluidity of the cellular membrane. For example, there are all kinds of factors that have been shown to be modulated by vitamin E in cell culture. It is still an open question—what does vitamin E do? It is certainly an antioxidant, but if that is the only answer, why do we need only alpha-tocopherol and not theother forms? If vitamin E acts as an antioxidant, why does the body exclude those other forms? And if it is not working only as an antioxidant, what else does it do? We still don’t know.

Q: Vitamin E has a long history of use for heart disease. Do you think that it prevents heart disease or has any value in treating it?

A: We really can’t answer this yet. Results from intervention studies in which vitamin E is given to subjects who have heart disease in order to find out if it prevents second heart attacks have been mixed. The atherosclerotic lesion is packed full of oxidized LDL cholesterol. We know that vitamin E can delay LDL from getting oxidized. This is such a compelling argument that probably 100,000 people have been studied in clinical trials with vitamin E. However, since no one wants to do a clinical trial that fails, they recruit people with high levels of oxidative stress or manifest disease. These studies are done in people with symptoms who generally take many medications. Then the question is asked, “Will vitamin E prevent a heart attack?” That is a very different scenario from studying subjects who take supplements from the age of 45 or so for 30 years. Are those individuals less likely to have a heart attack if they have no signs of heart disease when they start taking vitamin E? The problem is that if vitamin E has, say, a 5% benefit, this means that a fatal heart attack would be prevented in 50,000 people in a population of 1,000,000. But to find a 5% benefit, an enormous number of people would have to be studied for 30 years. So it becomes outrageously expensive, and you can’t do it. Some statements in the medical literature suggest that supplemental vitamin E is dangerous because it misleads people into believing that they don’t have to exercise or eat right, that they can do whatever they like as long as they take their vitamin E, and they won’t have a heart attack. I think that it is wrong to say vitamin E is dangerous. Certainly it is true that vitamin E won’t cure bad habits. Many factors contribute to optimum health—a healthy diet with lots of fruits and vegetables, exercise, and taking a vitamin E supplement. The Nurses’ Health Study found that women who exercised, ate lots of fruits and vegetables, and took vitamin E supplements had 45% less coronary heart disease mortality.

Q: You said the results of the secondary prevention trials have been equivocal. Do you think that one possible explanation for this may be lack of instruction about the way to take vitamin E, since it’s fat soluble and should be taken with food?

A: When you carry out a study with thousands of people, compared to the studies we do with 10 people, there are limitations in what you can discover about the subjects. I can spend time finding out lots of information about those 10 people, what their diets and habits are, and know a lot about the subjects. I think many doctors are unaware of the importance of dietary and nutrition information. People have said to me, “Oh, I thought it was important to take my vitamin on an empty stomach so food doesn’t interfere!” This is exactly the opposite of what they need to do. Fat-soluble vitamin E should always be taken with a meal so that it will be properly absorbed. These instructions may not have been provided to subjects in many of the clinical trials. Also, we don't know what an effective dose might be or how long it might need to be taken for an effect to be observed.

Q: Does topical vitamin E improve skin appearance?

A: Most skin creams actually contain vitamin E. It’s listed on the label as alpha-tocopheryl acetate. This form of vitamin E is useful because it doesn’t get oxidized. That’s actually good because the alpha-tocopheryl acetate can penetrate through the skin surface and get to the living cells. About 5% of the amount that's smeared on the skin is actually converted to the free tocopherol once it’s inside those deep skin cells and provides beneficial antioxidant effects.

Q: A recent study showed that supplementation in elderly nursing home residents with 200 IU/day of vitamin E for one year decreased the incidence of the common cold. What role does vitamin E play in immune function?

A: Dr. Simin Meydani carried out that study in a large number of nursing home patients. I think her data emphasizes that vitamin E improves immune function—the patients on vitamin E had fewer colds. Dr. Meydani has done some other studies suggesting that vitamin E, as well as a multivitamin supplement, enhances immune function. I recommend that everyone take a good multivitamin supplement.

Q: What about possible interactions between vitamin E and anticoagulant drugs?

A: This potential problem was recognized in animal toxicology studies. If you add vitamin E to an animal diet in amounts that would be equivalent to 10 grams for a person— maybe 20 or 30 vitamin E capsules—the animals have a tendency to bleed. Extra vitamin K can prevent this abnormal bleeding. Some people who take vitamin E have reported that they bleed more easily. The upper limit for safe intake was set by the Food and Nutrition Board at 1,000 mg per day (1,100 IU dl-alpha- or 1,500 IU d-alpha-tocopherol). If you are taking vitamin E and get bruised easily, you may be taking too much. On the other hand, blood clotting causes heart attacks and many strokes, so vitamin E may have some benefit there. Some physicians have advised patients taking anti- coagulant drugs not to take really large doses of vitamin E.

Q: Are there other side effects of very large intakes of vitamin E? Is vitamin E toxic at high doses?

A: Bleeding is the only side effect that the Food and Nutrition Board could find. I think it should be noted that there aren’t any studies in humans that demonstrate adverse effects of vitamin E, possibly because the studies are not of sufficient size, length, or control.

Q: In general, do you recommend vitamin E supplements for healthy people?

A: Only if they don’t bleed abnormally!

Q: What daily amount would you suggest?

A: The RDA is 15 mg alpha-tocopherol. To get that from your diet you have to eat food high in vitamin E like olive oil, sunflower oil, almonds, and spinach. There is not much vitamin E in most fruits and vegetables. If you’re going to take a vitamin E supplement, take it with a meal. If you take many different supplements or pills, don’t take all of them together. It’s better to take vitamin E with dinner to avoid possible interference with drugs that may be taken in the morning.

Q: Is 200 IU of d-alpha-tocopherol a reasonable amount to take?

A: Synthetic vitamin E is cheaper than d-alpha-tocopherol, or natural source vitamin E, but only half as effective. The body is clever enough to figure out the one it wants. It’s really a wash. If you want to get 200 IU of natural vitamin E, you can buy 400 IU supplements of synthetic vitamin E at maybe half the cost of 200 IU natural vitamin E.

Q: So synthetic vitamin E, or dl-alpha-tocopherol, also contains d-alpha, and you get about half the dose of d-alpha-tocopherol in those supplements?

A: Correct.

Q: What projects are you currently working on in the lab?

A: The one I am most excited about is the one Dr. Richard Bruno has been working on. (more)

Last updated November, 2004

 

Micronutrient Research for Optimum Health

 
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