A New Antioxidant

Its Workings Unrecognized for Decades, Alpha-lipoic Acid Is Potent and May Be Useful in Preventing Disease

by Robert Sanders

A relatively unknown antioxidant is actually more potent than its better-known cousins, such as vitamins C and E, and could prove useful in treating disease and protecting the body against the daily assaults that lead to disease and aging, according to a Berkeley scientist.

The antioxidant is alpha-lipoic acid, currently used in Europe to treat peripheral nerve degeneration (neuropathy) resulting from diabetes.

It could have much broader use in treating disease, however, and may have general health benefits when taken as a daily supplement like other antioxidants. It is already available in some health food stores as a "metabolic antioxidant."

"Alpha-lipoic acid could have far-reaching consequences in the search for prevention and therapy of chronic degenerative diseases such as diabetes and cardiovascular disease," says Lester Packer, one of the leading researchers in the area of antioxidants--vitamin E and alpha-lipoic acid in particular--and a professor of molecular and cell biology here.

"And because it's the only antioxidant that can easily get into the brain, it could be useful in preventing damage from a stroke," he says.

Packer and other scientists discussed new data on the effects of oxidants and antioxidants in various areas of biology at a meeting earlier this month in Santa Barbara of the Oxygen Club of California, an international group of scientists.

Antioxidants are chemicals that defuse free radicals--destructive chemicals produced by the body and thought to contribute to aging and ailments ranging from heart disease to stroke.

Known for more than 30 years and once thought to be a vitamin, alpha-lipoic acid was recognized as an antioxidant a mere seven years ago, and only recently have scientists discovered how it works in the body.

New data from Packer's laboratory reported in this month's issue of Brain Research show that alpha-lipoic acid can significantly increase survival in rats that have suffered a stroke, if given before the stroke occurs. Though pretreatment with alpha-lipoic acid is impractical, the results prove the importance of this antioxidant in preventing cell and tissue damage, Packer says.

Studies several years ago showed a similar role for lipoic acid in preventing tissue damage and death after a heart attack.

All antioxidants--the best known are vitamins C and E, beta-carotene and related carotenoids, and a family of chemicals called flavonoids--work by disarming deadly free radicals before they wreak havoc on cells and tissue in the body. Essentially "toxic waste" generated by most normal processes in the body, from breathing to digestion, free radicals are thought to contribute to disease and aging.

While the body's normal load of antioxidants is thought to be sufficient to limit damage from free radicals, many people take supplements in hopes of reducing free radical damage even further, and maybe reducing the chance of developing cancer, heart disease and diabetes.

Also, part of the reason nutritionists recommend eating fruits and vegetables is because they provide large doses of antioxidants. Citrus and tomatoes contain vitamin C, yellow and orange vegetables provide large amounts of beta-carotene, fruits have loads of flavonoids and many natural foods, especially grains, contain vitamin E.

Over the years evidence has accumulated to support the value of taking extra antioxidants, to the extent that the FDA is now considering whether to allow health claims on bottles of these supplements.

"Though the evidence is largely circumstantial that antioxidants are beneficial, it continues to become stronger," Packer said. "We would be foolish not to take account of this evidence."

What Packer has fleshed out in recent years is how alpha-lipoic acid and other antioxidants interact in a complex recycling process in the body.

He showed several years ago, for example, that vitamin E "recycles" vitamin C in the body--that is, after vitamin E has disarmed or oxidized a free radical, vitamin C can come along and return vitamin E to fighting form. The two vitamins thus work together to prevent free radical damage in the body, Packer says.

Since then he and his colleagues have shown that, in turn, vitamin C can be recycled by glutathione, an antioxidant produced only in the body. The cycle continues with another antioxidant, NADPH--a coenzyme, or chemical essential to the action of other enzymes--recycling glutathione.

Despite this detailed understanding of the antioxidant cycle, when Packer and other researchers tried to boost antioxidant levels to determine whether they can protect against disease, they were unable to find a way to increase glutathione levels.

Glutathione cannot be taken by mouth like vitamins C and E because it is broken down in the stomach before it reaches the bloodstream.

Alpha-lipoic acid proved to be the missing link, Packer says.


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