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Of the many aspects of life extension research, perhaps none is as basic to the retardation of the aging process as the interaction between free radicals and antioxidants. Durk Pearson and Sandy Shaw were among the first to openly discuss the menace of free radicals in the human body, along with the various antioxidant solutions. They were early advocates of the use of beta carotene supplements, which are now widely acknowledged as helpful and beneficial. In 1982 they wrote, "Since you life depends on very careful control of the chemical reactions within you, free radicals can be deadly." In this month's exclusive interview, Durk and Sandy discuss some of the progress that's been made in antioxidant research in the decade since they wrote those words.

SMART: What exactly is a free radical?

SANDY: Normally, compounds have an even number of electrons. A free radical is an atom or molecule with an unpaired electron. In a typical cell you may have 40,000 different chemical compounds and each one reacts with maybe one or two specific other molecules. The reason free radicals are dangerous is that they are promiscuously chemically reactive; free radicals will react with anything in sight. This is especially true for the hydroxyl (OH) radical. That is a terribly active compound. At room temperature, the hydroxyl radical can oxidize xenon, which is an otherwise inert gas. So you have something here that is promiscuously reactive and can tear up anything it touches. Fortunately, we have antioxidant molecules to protect us. An antioxidant is a molecule that can block the damaging effects of free radicals.

SMART: The interest in antioxidants in the scientific community seems to be heating up. Do you think that there is enough here to represent what might be a paradigm shift?

SANDY: Yes, very definitely so. In fact that is almost the term that was used by Dr. William Pryor, the organizer of the conference that was held in October 1989 in London on antioxidant vitamins and beta carotene for the prevention of disease. The conference dealt particularly with cardiovascular disease, cancer, cataracts, and some of the aspects of aging itself. In fact, several of the scientists at the meeting said that here's a growing attitude that there really should be two different RDAs for two different purposes. The lower amount would be to prevent the classical disease like scurvy, beriberi, pellagra, and so on. The higher amount would be appropriate for optimal disease-preventing properties.

DURK: It's now a very widely held view among scientists studying nutrients that there are levels of nutrients that have disease-preventing properties, but that you don't generally get these protective effects at the RDA level.

SMART: Let's go back in history a little bit. The knowledge of how antioxidants operate is really embodied in the free radical theory of aging put forth by Dr. Denham Harman, isn't it?

DURK: No, actually the way that antioxidants work has been known for a lot longer, because they have been used in foods, plastic, rubber, petroleum, and so on.

SANDY: In fact, that is how Dr. Denham Harman got involved with this, the free-radical theory, in the first place. He was an industrial scientist.

DURK: At the Shell oil company. In fact he was the inventor of the Shell Strip.

SANDY: Exactly. He was the first to see the parallel between free-radical activity in things like petroleum and changes that occur in aging. DURK: When a free-radical hits a polyunsaturated fat molecule in the body, for example, it's just like a free radical hitting a olefin molecule in gasoline. In each case, you end up forming a polymerized sludge. The varnish that develops in the carburetor of your trail bike or your lawn mower when it has been sitting around all winter, is the same sort of crap you get in your body as you age, produced by the same sort of mechanisms, free-radicals attacking fatty materials. In the opening scene of our "Life Extension Video" Sandy and I are in a junk yard doing an autopsy on a Cadillac that died without a mark on it. In fact, what killed it was the same sort of thing that kills most people, free-radical reactions gumming up the works.

SANDY: We autopsied the vehicle and removed some of the hoses that had become all stiff and brittle, just like hardening of the arteries. It's interesting to note that, without understanding the mechanisms of oxidation and free-radicals, people have been using free-radical scavengers for thousands of years. Take spices, for example. Hundreds of years ago there was a tremendous demand for spices. People like Magellan and Drake and Columbus weren't just explorers; they were looking to make a fortune by locating sources of spices.

DURK: When Magellan went around the world as I recall, only about 85 people of the hundreds and hundreds that originally left with him came back alive. You'd think after a debacle like that, nobody would ever try to go around the world again. But in fact, hundreds of ships went out, because if they came back with one ship full of spice they could afford to pay for the five ships they lost.

SANDY: And it wasn't because there were a lot of gourmet chefs back then. Spices were used largely for preserving foods. The didn't have refrigerators back then. Instead, they had a number of techniques like salting fish or smoking meat that stopped the bacterial decay of the food.

DURK: Yes, salting it and drying it will prevent bacterial degradation, but it does nothing to prevent the fats from going rancid, and of course, the rancid fats not only don't taste good, they suppress the immune system. Back then there were all kinds of plagues and epidemics. It was a real disaster to have your immune system suppressed. And of course they didn't understand the connection, but they realized that when the food gets bad, you get sick.

SANDY: And they knew that if they used spices, the food would be palatable longer.

DURK: One of our museum catalogs has a little clove cross that one of the popes wore back in the 1550's.

SANDY: And the clove must have been venerated to have been put on the highest religious symbol, the cross.

DURK: And in fact your classic Virginia smoked ham studded with cloves is loaded with antioxidants-both the smoke and the cloves contain phenolics, which are potent antioxidants. BHT, incidently, is a phenolic too. Much better than the clove oil because it is more stable and lower in toxicity.

SMART: What are the various types of antioxidants?

DURK: A fundamental distinction is in terms of water-soluble vs. fat-soluble antioxidants. In general, your body can store the water-soluble ones for very short periods of time in large quantities, whereas the fat-soluble can be stored much longer. This is why if you want to get the most antioxidant benefits out of high doses of water-soluble vitamin C, you really need to take it 3 or 4 times a day.

On the other hand, you can take beta-carotene, which is fat soluble, every other day and get good results, especially if you take it with the fattiest meal of the day to facilitate absorption. Another division is between xenobiotic antioxidants and those that are normally found in the body. BHT is xenobiotic; it doesn't occur naturally in your body. You normally find ascorbate (vitamin C) and tocopherol (vitamin E) in your body.

SMART: Does the fact that a vitamin is synthetic or naturally occurring make any difference?

DURK: No. The structure of a molecule, not its history, determines its function. Whether the vitamin C was made in a stainless steel and glass plant or a green leafy plant doesn't make any difference. It has the same molecular structure and is going to function in the same way.

SMART: What do you think is the future for antioxidant use?

SANDY: There's plenty going on right now. I think the FDA is going to have to change their present stance towards vitamins; they recommend that people not take supplements; that people shouldn't even take supplements with 100% of the RDA in them! For example, the FDA has fought for years against the fortification of cereals. Unfortunately, policy is not made by scientists; it is made by politicians and bureaucrats. And it takes them a lot longer to come around to accepting scientific positions.

SMART: Are there any promising new antioxidants that you have been looking at?

DURK: I think that taurine is probably the most important one.

SANDY: Taurine is an excellent one. The big problem with the antioxidant area is with the tremendous growth of FDA regulations and the extreme expense of getting material approved. Since there's no way for a company to get a patent on something like taurine, and it's a natural substance that you get in your diet, there's not all that much research being done on it. We would like to see a lot more research being done on taurine.

SMART: What does taurine do in the body?

DURK: Let me tell you a story about taurine. A friend of ours called up and said that his cat was dying. It was an old cat -13 years; its eyes were opaque with cataracts and it was also bleeding from the eyes. It could barely crawl around, because its hind legs were paralyzed. His vet said it had terminal congestive heart failure and should be put to "sleep," but he didn't want to do that. He wanted us to pull off a miracle.

So I said, "Hey, it sounds like a taurine deficiency." There was taurine in the cat food, but I thought that the amount in cat food might not be sufficient for such an old cat. So I told him to add about a quarter of a gram of taurine to the cat's food three times a day. Now the cat could barely get its nose over the bowl at first, but by the end of the day, it was crawling around pretty strongly and by the end of the week it was walking around. Two weeks later, the cat was running around like nothing had ever happened. The cataracts were gone, the bleeding was gone.

SMART: The cataracts actually reversed?

DURK: They were gone. They went away. There's a special pump in the eye for taurine. There are also taurine pumps in the heart and the brain so that taurine can be concentrated in those organs. In fact, it turns out that in the heart, the brain, and the eyes, taurine is the free amino acid with the highest concentration.

SMART: There is 1.25 gm of taurine in 12 capsules of PERSONAL RADICAL SHIELD. What levels do you recommend for those who want to take more?

DURK: I'd have no problem with a person taking about 5 grams of taurine per day provided they don't have a history of ulcers. Some people who've had ulcers may get a reactivation at that high a level. Also remember that taurine is water soluble, so, as with vitamin C, you need to take it frequently. A person who is really interested in free radicals ought to get the special supplement of the January 1991 issue of the American Journal of Clinical Nutrition.

SANDY: It has over 200 pages of solid information on how nutrients, antioxidant vitamins, and beta carotene can help prevent cancer, cardiovascular disease, and diseases of aging like cataracts and Parkinson's disease. Although there is some theoretical material in this issue, it consists mostly of practical studies of the disease-preventing properties of many nutrients. This volume is a culmination of what has been going on in the field for decades. It has gotten to the point now that to tell people they shouldn't be taking supplements of vitamin E, vitamin C, and beta-carotene is unethical and irresponsible, if not outright criminal.

DURK: For example, they have a study which is a meta-analysis of several major European epidemiological studies of factors involved in cardiovascular disease. They found that the single most important predictor of cardiovascular disease in people with reasonably normal cholesterol levels (in the range 220-240) was low serum vitamin E levels. In fact, 62 percent of cardiovascular problems were predictable by low serum levels of vitamin E. And, four factors, when combined, predicted 87 percent of the ischemic cardiovascular disease. there were low serum vitamin E, low serum vitamin C, high diastolic blood pressure, and low serum vitamin A.

SMART: How important is genetics in terms of the effect of antioxidants? Are some people more susceptible than others because of their heredity?

SANDY: There's been a lot of evidence of genetic effects on longevity. Now some people are saying that maybe aging is a genetic thing, and that free radicals are not important, or they are just a side issue. But if you really look at what is going on, I think a better theory is what Cutler talked about in the supplement to the American Journal of Clinical Nutrition we spoke about earlier-an interaction between genes and free radicals. Free radicals have an important effect on the way genes regulate metabolic processes. Genes can be damaged by free radicals. Cutler suggests that free radicals may cause improper gene regulation that results in the other changes that are associated with aging, neuroendocrine dysfunction, and so on. So you'd expect that if you reduce free radical damage, you would reduce genetic damage as well. The two are not independent of each other, they're interrelated.

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