UC Berkeley press release


UC Berkeley and Australian researchers call into question current formulation of Vitamin E supplements

by Robert Sanders

Berkeley -- Health conscious consumers may be shortchanging themselves by taking vitamin E supplements because those available today contain an imbalance of the two major forms of the vitamin, say a team of researchers from UC Berkeley and Australia.

Commercially available vitamin E supplements contain primarily alpha-tocopherol, but the researchers have found evidence that gamma-tocopherol also plays a crucial and complementary role in the body, and perhaps is equally important in staving off degenerative diseases and aging.

Because alpha-tocopherol is the main form of vitamin E in the body it has been the form most studied. Research studies have shown that alpha-tocopherol is the most potent antioxidant, and appears to protect the body from the ravages of heart disease, cancer and aging.

In the April 1 issue of the Proceedings of the National Academy of Sciences, the researchers report that a second form of vitamin E, gamma-tocopherol, may play an equally important role in disarming destructive chemicals -- chemicals that alpha-tocopherol cannot completely neutralize.

"We can't say for sure, but the initial evidence is pretty clear," says visiting postdoctoral researcher Stephan Christen of the University of California at Berkeley. "We should not be taking only alpha-tocopherol in supplements."

Christen, a member of Bruce N. Ames's laboratory in the department of molecular and cell biology at UC Berkeley, notes too that people who take large doses of alpha-tocopherol exhibit lower levels of gamma-tocopherol.

"Based on our study, vitamin E supplements should contain a ratio closer to what is found in the diet, which is 70 percent gamma-tocopherol. I think a better formulation would be a 50-50 mixture of alpha- and gamma-tocopherol," Christen recommends.

"There's no reason not to do this, either, since supplements with a mixture of alpha and gamma would be cheap to make. Both are readily extracted from plants such as soybeans."

Some vitamin E supplements do include gamma-tocopherol, he says, but typically in proportions no greater than 10 or 20 percent.

"We have to evaluate the importance of vitamin E supplements, because they contain only alpha-tocopherol," adds Maret G. Traber, a research biochemist at UC Berkeley who has extensively studied alpha- and gamma-tocopherol metabolism in humans and animals. "Vitamin E was discovered at UC Berkeley 75 years ago, and we are still finding new effects of it."

The researchers found that gamma-tocopherol is particularly important in getting rid of destructive chemicals that are derived from nitric oxide, which is produced copiously in the body at sites of inflammation. Nitric oxide, which itself is only moderately toxic and in fact is an important cellular regulator, is produced at elevated levels by phagocytic cells to kill invading organisms.

Nitric oxide quickly reacts with other substances, forming reactive chemicals such as peroxynitrite, but can also damage healthy tissue. Peroxynitrite is a powerful mutagen, reacting readily with DNA, proteins and fatty compounds called lipids, and causes extensive cell damage.

In cases where inflammation becomes chronic, tissue damage from these reactive substances is thought to lead to cancer, cardiovascular disease, neurodegenerative diseases such as Alzheimer's disease, and in general speed the ravages of aging.

Though the main form of vitamin E in the U.S. diet is gamma-tocopherol, Christen says, the gamma form quickly disappears from the blood so that the majority of vitamin E found in blood plasma and organ tissues is alpha-tocopherol. That is why researchers have concentrated on study of alpha-tocopherol.

With so little known about the role of gamma-tocopherol, however, the research team decided to look at its ability to protect against damage mediated by reactive nitrogen oxides, often referred to by air pollution experts as NOx. The team consisted of Christen, Ames and their colleagues Alan A. Woodall and Mark K. Shigenaga at UC Berkeley; plus chemistry professor Peter T. Southwell-Keely and Mark W. Duncan of the Biomedical Mass Spectrometry Unit, University of New South Wales.

The researchers found that gamma-tocopherol was more effective than alpha-tocopherol in limiting peroxynitrite damage to lipids, in the form of liposomes and low density lipoproteins. In addition, only gamma-tocopherol was able to permanently trap NOx, Christen says.

The implication, the researchers say, is that alpha and gamma-tocopherol play complementary roles in limiting cell damage: alpha to neutralize oxidants such as free radicals, and gamma to trap nitrogen oxides (NOx).

These results support the work of Robert V. Cooney of the Cancer Research Center of Hawaii, who in 1993 showed that gamma-tocopherol detoxifies nitrogen dioxide, the yellow gas found in smog, more effectively than alpha-tocopherol.

"Evidence is now emerging that gamma-tocopherol may be as important as alpha-tocopherol in the prevention of degenerative diseases such as cancer and heart disease," the researchers conclude.

The research was supported by the National Cancer Institute, the National Institute of Environmental Health Sciences and the Swiss Foundation for Medical-Biological Stipends.

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