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Vitamin E--How Much Is Enough?

Vitamin E is an important antioxidant, with the potential for reducing risk for many diseases. But how much do people need to ingest to get the benefits? Studies by nutrition researcher Robert Parker and his colleagues may provide the answer.

There aren't many who will dispute that vitamin E is essential to good health. If you don't get enough, you'll suffer absent or altered reflexes, limb weaknesses, and sensory loss in your arms and legs. In adequate amounts, however, the powerful vitamin may reduce your risk of coronary heart disease and cancer, slow the aging process and the progress of Parkinson's disease, bolster the immune system, ease the pain of arthritis, and much more.

Despite the piles of research studies describing the benefits and antioxidant activity of vitamin E, its exact function in the body is still a mystery. Robert Parker, an associate professor in the Division of Nutritional Sciences, is changing that. With two grants from the U.S. Department of Agriculture, he and research associate Joy Swanson have been studying vitamin E since 1996. Before they recommend popping supplements and devouring foods rich in vitamin E, they want to make sense of how humans use and excrete the vitamin.

"There's compelling evidence that vitamin E is a protective factor for cardiovascular disease," Parker says. "What remains to be clarified is the overall magnitude of its importance relative to other factors and how much vitamin E is needed to achieve the maximal amount of risk reduction."

So far, the results have been exciting, he says. "The human body is much more sophisticated in dealing with this particular fat-soluble vitamin than we thought."

For certain, the body needs a sophisticated mechanism to handle this not-so-simple vitamin. Vitamin E refers to two main compounds: alpha-tocopherol, found at high levels in sunflower oil and wheat germ oil, and gamma-tocopherol, found at high levels in soybean and corn oils. Researchers have long known that alpha-tocopherol and gammatocopherol have similar chemical properties as antioxidants, but alpha-tocopherol has a much higher biopotency--that is, it is more active in the body. And people more efficiently retain alpha-tocopherol than gammatocopherol, which doesn't appear in the blood and doesn't accumulate in the tissues even though it's consumed in significant quantities.

"Beyond that, it was a complete black box," Parker says. No one understood what happened to gamma-tocopherol or how it was excreted from the body. Parker hoped that understanding how humans excrete the gamma-tocopherol form of vitamin E might shed light on why the two forms of vitamin E have different biopotencies and why individuals vary in their abilities to retain the vitamin.

Fat-soluble vitamins, like vitamin E, challenge researchers like Parker. The water-soluble vitamins, such as the B vitamins and vitamin C, are much easier to understand. Their processes of elimination are straightforward.

"The body doesn't have to do much with them," Parker says. "They often are in forms that can be excreted in the urine."

Parker suspected that urine--not bile or skin cells--was also the chief pathway for ridding the body of the gamma-tocopherol form of vitamin E. But he needed hard evidence. He and his collaborators took three consecutive urine samples at 24-hour intervals from seven healthy adults. Then they measured the concentration of a newly discovered water-soluble metabolite of gamma-tocopherol in the urine.

Parker found that a large portion of gamma-tocopherol--the major form of vitamin F people eat in the United States-does indeed leave the body via the urine. His subjects excreted between 2 and 12 milligrams of gamma-tocopherol a day as a water-soluble metabolite.

"Based on that, we concluded that urinary excretion of this water-soluble metabolite might account for 30 to 50 percent of the gamma-tocopherol that we absorb every day from our foods," Parker says. "To us, that was significant. On the other hand, we can account for less than 5 percent of the daily intake of alpha-tocopherol through urinary excretion. There is clearly a dramatic metabolic discrimination between the two forms of vitamin E that we need to understand."

After identifying and confirming the pathway for excretion of most of the gamma-tocopherol people consume, Parker and his collaborators will next study why people vary in their ability to eliminate vitamin H from the body. After all, Parker's study showed a sixfold difference among research subjects, who excreted anywhere from 2 to 12 milligrams of gamma-to copherol per day.

"We don't know how to explain that," Parker says. "Ifs likely that the major part of that variation is variation in intake."

When he asked subjects with the lowest excretion rates how often they ate margarine and mayonnaise--products generally made from foods high in gamma-tocopherol, such as corn oil and soybean oil--they reported lower in-take or use of those products.

But the differences among subjects may also be related to genetics. In other words, some people may simply be more efficient; they may more quickly excrete via urine a greater proportion of the vitamin E they take in each day.

"Tocopherols, whether they be alpha-or gamma- or naturally occurring alpha-tocopherol versus synthetic alpha-tocopherol, are all absorbed with about the same efficiency," Parker says. "So there's no discrimination among these forms at the level of their absorption by the gastrointestinal tract."

The difference is noticeable only when evaluating the way people break down vitamin E. Parker explains that because enzymes are involved in the catabolism process, genes must also be involved.

"That's the fundamental importance of understanding the metabolic pathway and how it's regulated," he says. "Because there's no regulation at the point of uptake into the body, the only variable that regulates how much vitamin E we have at any given level of intake is our ability to metabolize and excrete it. That opens up the possibility of genetic differences between different people."

It also expands his work to include diverse research models--from human metabolic studies to cell culture and molecular biological studies. To attack the multidisciplinary aspect of their research, Parker and Swanson have been working with Graham Burton of the Steacie Institute of Molecular Sciences, National Research Council of Canada, Ottawa, and with Robert Ben, a synthetic organic chemist from SUNY Binghamton.

"That has been a fun thing for me, to marshal together collaborators in these various areas all focused on a specific issue," Parker says.

They hope their current and future work will answer many questions: What is the nutritional importance of alpha-tocopherol versus gamma-tocopherol? Is synthetic vitamin E as beneficial as natural vitamin E? And how much do people need to consume to protect themselves against diseases and the aging process?

For example, alpha-tocopherol is currently considered better than gamma-tocopherol by a factor of 10 to 1. One milligram of alpha-tocopherol--but 10 milligrams of gamma-tocopherol--is one international unit (IU) of vitamin E. This ratio is particularly significant to North Americans, who consume foods that are richer in gamma-tocopherol than alpha-tocopherol. We have to eat more gamma-tocopherol to meet the dietary requirements.

Parker's group has proposed reexamining the 10-to-1 ratio of biopotency for alpha-tocopherol versus gamma-tocopherol because the official numbers come almost entirely from research on animals.

"There is much precedent in the literature, especially nutrition literature, of considerable interspecies differences with regard to metabolism of nutrients, particularly those under genetic regulation," Parker explains. "Our view is that one can carry out these animal trials in different ways and get different results. These biopotency figures are not hard and fast figures."

And it's not just a question of alpha-tocopherol and gamma-tocopherol. Whether people take natural or synthetic forms of vitamin E may affect how well they retain the vitamin. If two groups of people are fed synthetic alpha-tocopherol and natural alpha-tocopherol, respectively, the blood levels of the natural form will be about two times greater than those of the synthetic form. And regardless of age, sex, or race, the ratio remains 2 to 1.

"It's a big difference," Parker says. "The question is, why?"

Parker is completing a long and intensive study in which he gave natural and synthetic forms of alpha-tocopherol to six people. He has been fascinated by the results. As long as individuals take supplements, the natural form of vitamin E occurs in the blood at about twice the level of synthetic vitamin E. But when people stop taking the vitamin E supplement, the ratio changes, reaching as high as 2.4 to 1.0 in favor of the natural form and sinking as low as 1.2 to 1.0 in favor of the synthetic form.

"This appears to be telling us that different people have different capacities to discriminate between natural and synthetic vitamin E," Parker explains. "Some people can very strongly discriminate. Other people can less strongly discriminate."

The heterogeneity among people was masked as long as they took a large supply of supplements every day. Parker's group is now seeking to understand why some people discriminate between the different forms more strongly than others.

Another surprising discovery for Parker was that only high doses of vitamin E result in substantial increases in blood levels of the vitamin. These high rates of supplementation are those that have been linked with reduced risks for cardiovascular disease. Low doses of vitamin E, he found, are ineffective because the body seems to have mechanisms to maintain a constant level of vitamin E in the blood.

"In order to significantly increase vitamin E in the blood and those tissues that exchange with the blood--which are presumably what we're trying to influence, like arterial walls and other tissues--you need more than 100 milligrams a day," he says. "Once you get to 200 or 400 milligrams a day, those are the levels at which risks for cardiovascular disease are significantly decreased.

"This is a large paradigm shift for vitamin E and perhaps for some other fatsoluble vitamins because it has always been assumed that if you eat more, you'll have more. If you take a supplement, you'll have much more. But our study indicates that the assumption is simply not correct. The picture is much more complicated than we ever thought."

From Dietary "Factor X" to Risk-Reducing Supplement

It wasn't until the late 1800s that physicians started linking diet to diseases such as scurvy, rickets, beriberi, and pellagra, and the term vitamin was horn. Using appropriate animal models and defined diets-diets formulated using highly refined ingredients for which the chemical composition can be reasonably well known--early researchers discovered the known vitamins over the course of five decades. The fat-soluble vitamin E was one of many discoveries during that period.

The discovery of vitamin E was inspired by an interest in the nutritional properties of lipids and previous findings related to vitamins A and D, according to nutritional sciences professor Gerald Combs in his book The Vitamins. Researchers found that supplementing with new vitamins A, C, and D and thiamin improved the health of animals that were fed defined diets. But the keen eyes of two other scientists--H. M. Evans and K. S. Bishop of the University of California--observed that rats on these diets didn't reproduce normally. Only by adding small amounts of yeast and fresh lettuce to the diets did they solve the problem, restoring fertility in females and preventing infertility in both sexes. The researchers called the fertility cure factor X, and they found factor X activity in dried alfalfa, wheat germ, oats, meats, and milk fat. After distinguishing the fat-soluble factor from the known fat-soluble vitamins and having their work confirmed in 1924 at the University of Arkansas, the researchers called the new vitamin E.

Today, vitamin E is thought to play an important role in staving off disease and maintaining good health. Current research shows that vitamin E supplementation protects humans against the harmful effects of ozone in smog, relieves the pain of those with rheumatoid arthritis, and possibly plays a role in the prevention of some types of cancer, cardiovascular disease, and cataracts. One of the least toxic of the vitamins, vitamin F might be useful in managing diabetes, and topical application has been found to protect against UV-induced skin damage.

The complex nature of the biological function of vitamin E has generated great amounts of scientific interest in the vitamin-- it has kept the nutritional science community busy for the past 70-plus years. And for the general public, the "good news" discoveries have made vitamin E one of the more popular vitamins on supermarket shelves.
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Publication:Human Ecology
Geographic Code:1USA
Date:Mar 22, 2000
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