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August 2005

By Terri Mitchell

It’s hard to imagine a health world without antioxidants. They stand alongside aspirin and Band-Aids as mainstays of the American landscape. Hundreds line the shelves of Wal-Mart and Rite Aid, avidly sought by the masses. Yet 25 years ago, antioxidants didn’t exist for most people.

It was a strange turn of events that made antioxidants mainstream. In a brew that threw together a physicist, an oil chemist, an adventurer, and a Hollywood talk show host, what emerged was the idea that average people could use science to advance their health, and the antioxidant boom was born.

Oh, and Playboy. In 1968, MIT wunderkind Durk Pearson read an article from the magazine about Dr. Denham Harman’s theory on free radicals and aging. Intrigued, Pearson and Sandy Shaw dug into the UCLA library and pulled out Harman’s scientific publications. Harman, a chemist working in the then-obscure field of oxygen chemistry for the research arm of Shell Oil, had come up with the notion that the by-products of oxygen reactions (“free radicals”) cause aging. (Anything that aged rubber probably wouldn’t do much for internal organs, Harman rightfully reasoned.) Armed with degrees in physics and chemistry, Pearson and Shaw immediately took to Harman’s scientifically based concept, and began looking into it further. That was fine, and it might have been the end of it except for the well-timed entrance of a genuine Indiana Jones-type adventurer named Jack Wheeler.

Wheeler was a regular guest on the then-popular Merv Griffin talk show, and when he went to California for filming, he hung out with Durk and Sandy. They had become immersed in the idea of testing Harman’s theory, and every time Wheeler showed up, they regaled him with their latest ideas about aging and free radicals. Durk’s knack for whacking complicated science down to size got Wheeler to thinking there might be a wider audience for the finer points of free radical chemistry (hey, the stuff was interesting the way Durk explained it). So Wheeler approached Merv about Durk going on the show. Incredibly (it seems now), Merv consented, and the rest is history. Durk’s second visit provoked over 100,000 letters—the single most popular appearance ever recorded for a talk show. As Wheeler tells it, Merv’s entire office was covered in letters asking Durk and Sandy questions about health and aging.

Clearly, the idea that average people could use science for their own benefit was immensely popular. Until then, science on free radicals wasn’t even known to most chemists, let alone medical doctors. TV viewers of the time had two health care options: they could go to a doctor who would give them a drug, or consult a nutritionist who would make them eat wheat germ and desiccated liver. Here was something different. Here was a guy in lederhosen talking about a whole new world of antioxidants: vitamins and drugs, amino acids and hormones—things that a person could get ahold of and actually try. This was beyond prednisone and liver tablets. Now people could actually do something about their widening girth, chronic allergies, and cross-linked skin. And aging of all things! Durk said you could actually do something about aging! The fact that the man looked like an escapee from a commune was of no importance. Free radicals—boo! Antioxidants—yea! Americans had new weapons against the things that plagued them.

That was then and this is now. Things are a little more complicated than they seemed to be back in the Merv era. The connection between oxidative damage and the degenerative diseases of aging, as well as aging itself, remains strong. Yet the world of antioxidants has gotten substantially more complex.

The Vitamin E Shield

Vitamin E is one of America’s most popular antioxidant supplements. According to a recent USDA study, that’s a good thing, because only 2.4% of American women and 8% of men get enough of the vitamin from food.1

Vitamin E is fat-soluble and reduces the level of free radicals associated with lipids, such as those that affect cholesterol and those that affect the brain. For this reason, vitamin E has been intensively studied for its ability to prevent cardiovascular and Alzheimer’s diseases.

Taking relatively high doses of vitamin E (2000 IU/day) may protect against Alzheimer’s disease, especially if begun early in life and combined with relatively high doses of vitamin C (1000 mg.)2-4 There are two good reasons for people worried about Alzheimer’s to take vitamin E: Alzheimer’s patients have significantly reduced levels of antioxidants in their brains and blood, which can be raised with supplements such as vitamin E; and biochemical studies show that the high level of oxidative stress found in Alzheimer’s patients is ameliorated with antioxidants, including vitamin E.5-9 Vitamin E is one of the bestknown antioxidants, but by no means the only one.

Free Radicals and Inflammation

One of the most important medical discoveries of the past decade is the connection between inflammation and diseases like cancer and Alzheimer’s. The finding that people who take anti-inflammatory drugs have a lower risk of cancer was, at first, very surprising. How could something that lowers pain and reduces swelling possibly inhibit cancer? Researchers soon discovered inflammatory factors that enhance the ability of cancer cells to multiply and spread. Now we know that things that block inflammation—including aspirin—also impede cancer.

Things have been ratcheted up in the antioxidant world with new research showing that some antioxidants have powerful anti- inflammatory action. Although inflammation involves free radicals, it’s somewhat more complicated, involving the activation and inactivation of genes as well. Some antioxidants also block inflammation in addition to having radical-scavenging effects.

For example, when the antioxidant curcumin is given as a dietary supplement to animals with a mouse model of Alzheimer’s disease, it blocks the oxidation of certain proteins. This is the antioxidant effect, which in turn lowers the activation of inflammation signals. The net result is that abnormal Alzheimer’s proteins are lowered by about 40%.10 This may slow disease progression. If this experiment held up in humans, and abnormal proteins could be retarded by 40%, it might translate into years of life that would otherwise be lost to a disease for which there is presently no cure.10

Combinations of antioxidants can have greater effects than single agents on certain types of inflammation. A recent study focuses on an inflammation marker known as C-reactive protein (CRP), which is elevated in people who may appear healthy but could have a sudden heart attack and die. This study is important because it used baboons, whose biochemistry is more human-like than that of rodents.11 It shows that elevated CRP can be dramatically reversed with a combination of two antioxidants. Vitamin E (DL-alpha-tocopheryl acetate) at a human dose of approximately 200 IU/day reduces CRP by 50%. Adding coenzyme Q10 further reduces CRP by about 20% more, for a 70% reduction overall.11 Two other studies of primates demonstrated beneficial effects of vitamin E, for both the prevention and treatment of cardiovascular disease.12,13

Curcumin and vitamin E are only two of the many antioxidants that inhibit inflammation. Information on others can be found in past and future issues of this magazine. The important thing is to be aware that some antioxidants go a step further and reduce inflammation, which may block serious diseases including cancer.

Does Diet Increase Free Radicals?

When free radicals first hit the radar screen, the emphasis was on taking antioxidants to counteract them. While this is still a good idea, the complementary approach is to generate as few free radicals as possible in the first place. Diet, it has been discovered, can undermine this goal.

Iron and copper are required elements of human nutrition. However, an overabundance of either or both promotes free radicals that destroy healthy tissue. Iron has been the focus of several recent studies that are extremely important.

One of them shows that the risk of type II diabetes increases with greater amounts of iron in the diet. In a 12-year study of more than 30,000 men, “heme” iron from red meat doubled the risk of type II diabetes.14 Dietary heme from red meat is also a potent promoter of colon cancer.15 And an analysis of two large American studies shows that excess iron increases the risk of a fatal heart attack more than fivefold and raises the risk of all-cause mortality over threefold.16 Iron from plant sources is known as “nonheme” iron and doesn’t appear to carry the same risks. One reason may be that it’s not absorbed as well. Plants contain natural metal inhibitors.

The principal source of iron in the American diet is fortified cereals such as Kellogg’s Product 19, which contains 18 mg in a one-cup serving. The iron in fortified cereal, however, is non-heme iron, and its absorption is impeded by the phytate in the cereal. By comparison, three ounces of beef contain 3 mg of heme iron that is readily absorbed.17 The US Food and Nutrition Board has set an upper limit on iron intake of 45 mg/day. Postmenopausal women and men are advised to avoid highly fortified foods and iron supplements.18

Copper is another metal that promotes damaging free radicals. Copper combined with homocysteine (a natural byproduct of methionine metabolism) creates a lethal brew that can harm the brain and heart.19,20 Copper promotes the spread of cancer, and a copper chelator known as tetrathiomolybdate has been successfully used to combat some types of cancer, including squamous cell.21,22

Copper accumulates in the brains of Alzheimer’s patients.23 The phytocompound curcumin again appears on the scene. It has been proposed that curcumin be used as a treatment to chelate copper and prevent it from triggering free radical damage.24 Curcumin naturally chelates both iron and copper.24 Resveratrol, from wine and grapes, is also a copper chelator that keeps the metal from oxidizing LDL (low-density lipoprotein),25 which can be found in the brain as well as the heart and blood vessels.

Although resveratrol doesn’t chelate iron, it’s one of the strongest antioxidants ever discovered for protecting against iron-induced free radicals.26 Quercetin, a natural cousin of resveratrol in grapevine and other plants, neutralizes both iron and copper better than 10 other phytocompounds.27 “Remarkable protection against lipid peroxidation” is how researchers in Italy described quercetin after studying its ability to chelate iron in LDL.28 This is important, because current research indicates that it’s not cholesterol per se that’s bad, it’s oxidized cholesterol—that is, oxidized LDL.

The number-one source of copper in the American diet is beef. According to the USDA database, beef contains whopping amounts of copper. Three ounces of American beef contain nearly 4 mg of copper. By comparison, one cup of chickpeas contains 0.58 mg.29