Living Longer, Feeling Better

with Durk Pearson & Sandy Shaw

 Durk Pearson and Sandy Shaw co-authored two of the best selling books on human longevity-- Life Extension: A Practical Scientific Approach (Warner Books, 1982), and The Life Extension Companion (Warner Books, 1984)-- which triggered a large amount of popular interest in the subject, and their many television talk show appearances reached a large number of people.

Although perhaps the ultimate goal of medicine all along, the idea of extending human life in otherwise healthy individuals was a completely novel concept for most people when Pearson and Shaw published their first book back in 1982. How many people could have predicted back in the early eighties, that in just a few years after the publication of their ground-breaking book, there would be such huge world-wide interest in preventative medicine?

The scientifically-sophisticated team of Pearson (with a degree in physics from MIT) and Shaw (with a degree in chemistry from UCLA) was not surprised by this swelling global interest, and had, in fact, been anticipating it. They are, without question, two of the most well-informed people on the planet regarding the biochemical mechanisms of aging, and study it full- time. They have also been very politically-active over the years with regard to protecting people's rights to access nutritional supplements, and to easily obtain available accurate information about the supplements which may benefit their health.

To this effect, they wrote the book Freedom of Informed Choice: FDA Versus Nutritional Supplements (Common Sense Press, 1993), and are presently plaintiffs in a lawsuit against the FDA, charging the government agency with restricting manufacturers from distributing truthful health information (which they view as a violation of the constitution's First Amendment guarantee of free speech) that could save many people's lives. They also design nutritional supplement formulations for their own use (some of which are also available commercially) that are as tasty as they are effective, and they could be considered biochemical "gourmets" of a sort.

I found Durk and Sandy to be fascinating. The couple makes a great team, often completing one another's sentences, and bouncing ideas and facts back and forth off each other. The breadth of their knowledge is staggering, and it doesn't take much to get them talking passionately about their favorite subjects-- life extension and freedom. A few questions can ignite an information explosion. They live on a mountain top in central Nevada, a hundred miles from the nearest traffic signal. This interview occurred on April 18, 1996.

David: What inspired your interest in life extension?

Durk: Back in 1968 my old roommate from MIT, Erwin Strauss, sent us a photocopy of an article out of Playboy about Dr. Denham Harman's free radical theory of aging. Now, that was the last thing that I expected to find in Playboy, and I certainly didn't trust it as a scientific source. But we did go down to the UCLA biomedical library, and we started looking up everything by Dr. Denham Harman and the free radical theory of aging.

And the more we looked, the more we found, and the better the theory looked. Because here was a testable mechanistic hypothesis as to what caused aging, and many age-related diseases. And all of a sudden-- it's something you just didn't think about before, like fish presumably don't think about water. They may see bubbles but they don't see the water. Aging is something that people have taken for granted, at least in western society, from time immemorial.

Sandy: This was mainly because there really wasn't much of anything you could do about it, other than have parents and grandparents that were long lived. So why bother thinking about it?

Durk: And all of a sudden to realize suddenly that-- wow-- there has to be biochemical mechanisms. Aging isn't just something that happens somehow. There are laws that govern it. There are mechanisms that make it happen.

Sandy: So here was a theory that someone proposed which sounded very interesting. We wanted to find out as much as we could about it, and see if it looked like this was a practical way that you could increase your life span.

Durk: We thought that if the free radical mechanisms are responsible for aging and many age-related diseases-- for example, cardiovascular disease and cancer-- then it should be possible to interfere with those mechanisms once you understand them, and actually reduce the rate of aging and the risk of these age-related diseases.

David: Biochemically altering the aging process was a relatively novel concept at the time; most people just took aging for granted.

Sandy: Well, you know it's not something that people never thought about before. There have been people before that like Leonardo Da Vinci, and then closer to our time Elie Metchnichov (who received the Nobel Prize for discovering macrophages) around the turn of the century, who really thought about the issue of what caused aging.

Durk: Let me give you an example. Da Vinci went around to find people who were in the process of dying of old age. Now it was very difficult to find people who died of old age, back before things like flush toilets and antibiotics. But he did find some such people, and when they died he dissected them. And he's the first person to describe atherosclerosis. In fact, he became a vegetarian, not for ethical reasons-- he had nothing against killing animals, as far as we know-- it was that he saw these fats clogging up people's arteries.

Sandy: And he thought that he might be able to avoid that by eating just plants.

Durk: He was far ahead of his time. Now around World War I, a scientist by the name of McKay did some experiments with feeding nucleic acids to mice, and he found you could get life span extensions. The problem is the mechanism was unknown. And when you don't have any mechanism-- well, there's hundreds of thousands of different chemicals you could try to dump into an animal, and what's the chances of getting a positive result?

Sandy: It's not practical for any number of reasons. Nobody would have the time or money to do it--there's too many different substances. But even if you happen to bump into a particular substance that might work, you won't necessarily use the right dose.

Durk: Not only that, but even if you found something that worked in mice and used the right dose, there'd be no reason on earth-- if you don't understand the mechanism-- to think that it had anything whatsoever to do with human beings.

Sandy: Yeah, that's right. So it was a very exciting thing finding out about the free radical theory of aging, because there was something you could study in animals, as well as in people, and find out whether interfering with these free radical reactions might have an effect on aging or life span. And there had already been some studies done-- some of them by Denham Harman himself, which showed that in some animals-- for example, rodent strains that were predisposed to die early of cancer-- you could extend their life span with anti-oxidants that would interfere with free radical reactions.

Durk: Now one of the things we also found pretty soon was that there were other theories of aging. There was one called the cross-linking theory of aging-- developed by a scientist by the name of Johan Bjorksten back in the 1930's-- and that was a mechanistic explanation. Cross links are bonds that form to improperly link sections of large molecules, such as proteins or nucleic acids; this prevents them from functioning normally. It's been subsequently found that a great deal of cross-linking is caused by free radicals. They are not mutually exclusive, and, in fact, the two theories are closely related. We know Bjorksten, and he said that he started taking very high doses of vitamin E back in the late 1930's to slow down aging.

David: What are some of the benefits that you've seen in your own lives as a result of your experimentation with health-enhancing substances and nutrients?

Durk: Well, I think that one of the most prominent ones is that our skin elasticity is much better than you'd expect for fifty- two year olds who have been exposed to a lot of sunlight. The loss of skin elasticity involves, among other things, cross- linking in the skin. Just as a windshield wiper blade that's exposed to ultraviolet light and ozone becomes stiff and brittle, and starts cracking and loses its elasticity, the same sort of thing happens to your skin. However the windshield wiper blade can't repair itself, so it's ready for the junkyard in a couple of years, whereas it takes a lot longer for people to end up in the junkyard. But people's ability to repair themselves is imperfect. Aging is basically the accumulation of improperly repaired or unrepaired damage.

Sandy: But I think that with the use of supplements we've noticed the short-term beneficial effects much more than the long-term, especially because it's hard to know what kind of condition we would be in had we not taken supplements over the past twenty- eight years. There's a number of supplements that provide compensation for aging effects in the short-term, and those things really stand out and are very noticeable.

David: What are some of the short-term benefits that you've noticed?

Sandy: We've noticed improvements in certain aspects of our mental function. An awful lot's been discovered about how the brain works. It's now known that whenever anything takes place in the brain-- whether it's a thought, or an emotion, or whether you're moving your body, or anything else-- it involves the release of neurotransmitters by some neurons, and a receipt of the neurotransmitter as a message by another neuron. And as people age their ability to manufacture and release the neurotransmitters changes.

Durk: And the ability to respond to these messages degrades with age too because of age-related damage to the receptors, and also to the re-uptake mechanisms that re-cycle these neurotransmitters.

Sandy: But it is possible to compensate to some extent by taking supplements which contain precursors to the neurotransmitters, which make it possible for your nervous system to manufacture larger supplies of the neurotransmitters.

Durk: For example, one of the things that happen as people get older is they tend to become more and more tired as time goes on. Now, I'm not talking about something due to an organic illness-- like adult-onset diabetes or a hypo-thyroidism, which can make a person feel chronically tired-- but when you're fifty you don't have the energy you had when you where twelve years old.

Sandy: There's often a loss of enthusiasm and drive and the ability to enjoy what you enjoyed before.

Durk: And a loss of a sense of wonder. But this can be restored to an extent by taking a nutrient supplement that gives you a system of nutrients that your brain can use to make more of certain neurotransmitters. For example, let's take noradrenaline-- the brain's version of adrenaline, an excitatory neurotransmitter that gives you get up and go, confidence and energy, and sort of a bright outlook on life.

Sandy: The cholinergic nervous system is another good example. The neurotransmitter acetylcholine is very important for memory, and for focus and concentration. It's particularly important for verbal memory and as people get older the cholinergic nervous system is one of the ones that declines the most, and people tend to start having old-age associated problems with remembering words.

Durk: Even when a person is young sometimes they can benefit from more cholinergic stimulation. For example, a double-blind placebo-controlled study on MIT students showed that choline supplements improved their memory of a list of words that had low imageability.

Sandy: A word can either be something that you can imagine as a picture, or it's like justice or truth, in which case you can't imagine a picture to represent a word like that.

Durk: For example, imagine memorizing a list of high-imagery words, like cat, dog, tree, house, compared to justice beauty, truth, and honor.

Sandy: And the choline supplement helped these students to remember particularly the words that had low imagery associations, which are harder to remember. So that was very interesting.

Durk: Now acetylcholine is involved in the reticular activating system, which controls focus, concentration, and organization of mental activity. One of the things that we noticed back in the 1970's, when we started taking a choline supplement, was a really dramatic improvement in Sandy's ability to organize what she was writing.

Sandy: Oh yeah, it made an incredible difference for me. If I was writing or putting together a talk, not only was I able to organize the material better, but because I was able to do these things better, I got much more satisfaction and gratification out of writing and speaking.

Durk: Well, in fact, back before the days of word processors, I'd literally cut her articles up with a pair of scissors, re- arrange it, and tape it together again with scotch tape-- I mean, literal cut and paste. And that made her pretty mad, because she knew that it really needed it.

Sandy: Well, it can be pretty discouraging to have somebody have to do that to your material. Who likes to have an editor standing over their shoulder? But that changed in a big way after I got on a choline supplement. We started out with a choline chloride liquid supplement, which tasted absolutely ghastly, but we wanted to take the supplement for the effect of it, so we more or less forced our taste buds to put up with it.

Durk: Other people had experimented with choline supplements, but we did something a little bit more than anybody else had done. We took a look at charts of intermediary metabolism to find out what other nutrients were involved in the conversion of choline to acetylcholine.

Sandy: Because it isn't just choline that's needed to make acetylcholine.

Durk: And, in fact, one of the things that's very essential is pantothenate-- pantothenic acid or vitamin B-5. That makes acetyl-co-enzyme A, the acetyl group of which is transfered to the choline by another enzyme called choline acetyl-transferase, and that's how you make acetylcholine. One can increase the conversion of choline to acetylcholine by providing above RDA doses of vitamin B-5. Initially the formula tasted absolutely ghastly, but we gagged it down every day, and we did that for years. Then one day we just looked at each other and said, "That's it! We're not going to put up with this anymore." You know, we were grimacing there, trying to gag it down. (laughter)

Sandy: We were already very interested in flavor chemistry anyway. I don't want to glorify our eating habits by saying that we were gourmets in any special sense-- we just enjoy eating. So we were starting to study flavor chemistry, and decided this would be a real opportunity to use our knowledge to find out more about the subject. We found out how to make a choline supplement that tasted good, and it became part of the collection of abilities that eventually lead us to making dietary supplements available commercially.

David: Speaking of supplements which improve concentration and memory, the first place that I ever heard of hydergine was in your book Life Extension back in 1982. What do you think of all the the new cognitive enhancers, nootropics, and so-called "smart drugs"?

Durk: There's a great many more substances being bandied about than there's good hard data on their performance. There's quite a variety of things that are available, but in many cases the data on their performance leaves a lot to be desired. For example, let's take Gingko biloba. Now I think there's probably something to Gingko biloba. The problem is that we can't really be sure because a large foreign company that manufactures it has taken to suing both scientific journals and scientists who report a lack of benefits from Gingko in papers that they publish in the scientific literature. And, of course, when you have that kind of a chilling effect it really poisons the whole well for that entire product, because you don't know what hasn't been published as a result of that.

Sandy: You don't know what would have been published that wasn't published.

Durk: On the other hand there's other things where positive cognitive effects are well-established. For example, it's well- known how most of the neurotransmitters are made. The mechanisms are understood, and it's possible to put together systems of nutrients that the brain can use to manufacture them. To make more noradrenaline you take some of the essential nutrient amino acid phenylalanine, and you also need vitamin B-6, vitamin C, copper, and folate. Well, it's interesting to note that even by the FDA's meager RDA standards, 80% of the population is not getting the RDA of vitamin B-6, which incidentally we think is much too low.

Sandy: A lot of scientists think that the RDA of vitamin B-6 is too low.

Durk: About half the people aren't getting an RDA of copper or folate. When you put all this together, it's no wonder that the number one complaint people bring to their doctors is they chronically lack energy and feel tired.

Sandy: And it's usually not due to a medical condition.

Durk: Now, of course, if you feel chronically weary, you really need to be checked out because it might be, for example, something like hypothyroidism, which a nickel-a-day worth of thyroid hormone may take care of you. But if you don't take that nickel-a-day's worth of thyroid hormone and you're hypothyroid, you could end up with serious problems, like neurological damage.

Sandy: I think that it's important for people to take responsibility and control of their own medical care, but one of the risks of that is people can make the mistake of thinking that they can diagnose a condition, and then go on and treat themselves. The diagnosis of a medical condition is a very difficult thing. It's something where a well-trained physician is needed.

Durk: It's a fine art.

Sandy: A doctor is really needed. It's often true that if you find out what medical condition you have, then you can consult data bases-- like the MEDLARS-- and find out what kind of treatments are being used and get a lot of information on how to approach it. But the diagnosis is different. There are no databases that are very good at giving you diagnostic information.

David: What do you think are the most important factors in maintaining and improving general health?

Durk: Well, the first thing, of course, is to take a look at what your ancestors died from. If your grandfather and your father both died of heart attacks, you had better look very closely at your cardiovascular system, because that means you're at elevated risk. If you have long-lived grandparents, even if you don't do anything to increase your life span, you're likely to live longer yourself, because the genetic factors are very important in how long a person lives, and knowing what killed your ancestors can be very useful in trying to prevent those things from happening to you.

Sandy: And, of course, coming up in the very near future is going to be direct information about what's contained in your DNA in terms of aging genes. People have just uncovered the genes which cause Werner's Syndrome, which is a type of accelerated aging, and there's going to be a lot more of this kind of information coming to the fore. There's information known already about genes that are involved in aging processes in nematodes (flatworms) and in Drosophila (fruit flies). And as we find out more about what genes are involved in aging in people, it's going to become possible for us to alter our own genetic make-up, so that we look more like people who were lucky enough to have had the grandparents and other relatives that lived to a ripe old age.

Durk: But if you're not genetically blessed with high levels of protective anti-oxidants, you can get them exogenously from your diet by increasing your consumption of things like vitamin E. Now in some cases no natural diet is going to give you enough to provide the sort of protection you've read about in scientific papers. It is literally impossible to get a hundred units of vitamin E per day in any diet. You'd have to eat a couple of pounds of vegetable oil per day, which would be a disaster-- to start off, you're talking about maybe eight or ten thousand calories (laughter), a huge amount of fat. That'd be no good for you at all. That's why it's necessary to take supplements to get these levels of protection. Nearly all the evidence indicates that less than a hundred units of vitamin E per day won't provide much cardiovascular protection.

Sandy: Only dietary supplements can give people a known amount-- and adjust the ratios between the different nutrients that appear to have beneficial effects. There's a lot more we need to know about that.

David: I read in one of your previous interviews that you thought people in the modern world need nutritional support beyond anything that one can get out of a natural diet.

Durk: That's correct, because, you see, in the bad old days we didn't live long enough to die from aging or age-related diseases. If you go back to the Ice-age caves of Europe-- twenty thousand years ago-- you'll find that maybe one or two percent of the population lived to the age of forty, and a handful lived to be over fifty years old.

Sandy: This is known from doing an analysis of the bones from people who died back then, that were dug out of the ground.

Durk: We have not been equipped by evolution to resist these age- related diseases very effectively, because a woman who is sixty years old is under natural conditions not going to have any children. And, in fact, back then it's very unlikely a man would live to that age to father any children either, and as a result, the diseases that come on in the later part of life, the part of life that practically nobody got to live back then, are something that we're just not too well equipped to handle. Cardiovascular disease and cancer, for example, existed a long time ago, but they were relatively rare diseases, because something else would usually kill you first.

Sandy: Not only that, but one of the things that people are discovering are genes that are called pleiotropic genes, that are beneficial to people when they're young or increase reproductive capabilities when a person is young, but then later have detrimental effects. The way that evolution is set up, it's reproduction that really drives the whole thing, and whether you're going to live twenty, thirty, or forty years after your reproductive period is over is really of no great concern to evolution.

Durk: Yeah, once your children reach an age where they can independently support themselves or reproduce themselves, you're waste material as far as evolution is concerned.

David: What do you think are some of the very most important substances and nutrients-- that most people are not familiar with-- which play an essential role in extending or improving human life?

Durk: Well, if you're talking about things that most people aren't familiar with, one of the most important ones, I'd say, is taurine, which is a sulfur-containing amino acid. It's not used in the body to make proteins, but it's very important for protecting electrically-active tissue like the heart, the eyes, and the brain.

Sandy: Also it's interesting to note that the most important dietary source of taurine is red meat. And, of course, as we know an awful lot of people have cut down or even discontinued eating red meat, so there's a very limited amount of taurine available to most people. It is possible for people to make a certain amount of taurine in their bodies, but under stressful conditions where large amounts are needed, it may not be possible to make that much.

David: Are there any other special supplements that you think people on vegetarian diets should be especially aware of?

Durk: Anybody on a vegetarian diet has got to take vitamin B-12 supplements, because vegetables don't make B-12. If you try living on a strict vegetarian diet with no milk products or fermented products in it, you'll end up croaking eventually of a B-12 deficiency unless you take a supplement. But beyond that there are many common vitamins that people don't realize the importance of taking more of them, and the consequences of not doing so. For example, when a person metabolizes an amino acid called methionine they can make an atherogenic (atherosclerosis causing) compound called homocysteine, which is also an excitatory neurotoxin. Now if you have enough B-6, B-12, and folic acid, you can convert that to a beneficial anti-oxidant called cystathione, or back into methionine. If you don't have enough B-6, B-12, and folic acid, the homocysteine can pile up. Homocysteine is probably responsible for about twenty percent of all cardiovascular deaths because of it's ability to promote atherosclerosis.

Sandy: Ten or twenty percent, depending on whose estimates you use.

Durk: Most people are simply not getting enough folic acid, B-6, and possibly B-12 to prevent that. They need to take substantially more than RDA levels, because it turns out that even the levels of homocysteine in the blood that are considered normal, are in fact atherogenic, and a risk factor for cardiovascular disease. If you take a look at the risk of cardiovascular disease, and death by cardiovascular disease, versus homocysteine levels, even people in the normal range are at substantial risk from that type of damage. And the homocysteine could be dramatically reduced by taking larger doses of B-6, folate, and B-12.

David: What do you think are some of the most common mistakes that people make with regard to caring for their health?

Durk: I think one of the biggest mistakes is, if they're taking supplements, they just take something once per day, and in the case of water-soluble vitamins-- if you want to get substantial protection-- you need to maintain relatively high blood levels, and you can't do that by taking it once per day. For example, let's take vitamin B-2. If you take a 25 mg tablet of vitamin B- 2-- which is a bright fluorescent yellow vitamin-- within half an hour or so your piss will be bright fluorescent yellow. But in four or five hours it'll be essentially back to it's pale normal self. Vitamin C leaves your body only a little bit slower than that, and the same with B-6. If a person wants to get protective levels, and to dramatically reduce their levels of homocysteine, one needs to take the water-soluble vitamins three or four times per day.

Sandy: A lot of people are taking a once-a-day RDA level type of supplement, and all you really get from that is that it prevents the classic deficiency diseases like scurvy, beri beri, and so on. You're not going to be able to maintain high serum levels that way. This is something that a lot of people don't know.

Durk: Another problem is sort of an a la carte approach to supplementation. They hear about this vitamin, and they take a lot of that. Then they hear about that vitamin, and they take a lot of that. And they don't really have a rational system of nutrients. You see free-radicals have to be handled in a rather long chain to get rid of them. A free-radical is a atom or a molecule with an unpaired electron; it's got an odd number of electrons. And because of the laws of quantum mechanics, which have to do with the symmetry of space and time, electrons like to go around in pairs, which makes free-radicals promiscuously- reactive, and that's the problem. There's about forty thousand different compounds in a typical living cell, and generally each compound is only supposed to react with one, two, or three other things in there, under very careful enzymatic controls. Whereas free-radicals can react with all sorts of things.

Sandy: Free-radicals are not substances that just come from outside the body like pollutants, radiation, ozone, or something like that. Free-radicals are created within our bodies by a great number of natural processes like respiration and metabolizing foods.

Durk: Yeah, and you can't just get rid of all free-radicals, as they're necessary for life. One of the reasons that cyanide kills you is it shorts out a series of free-radical reactions that are supposed to occur in the mitochondria.

Sandy: Yeah, it's a perfect free-radical quencher.

Durk: And it will kill you real fast.

Sandy: Yeah-- kaput!

Durk: So what you need is something that quenches free-radicals where they don't belong, and allows them to do what they're supposed to do where they're supposed to be doing it. Anytime you have oxidative metabolism-- anytime you're burning something with oxygen to produce energy-- free-radicals are an inherent part of that process. And when they get out of control, then you have problems.

Sandy: And anytime you increase your metabolic rate-- whether from exercise or emotional excitement, or you're on a diet and you're burning off more fat-- then you're creating more free- radicals, and you've got to be able to handle that.

Durk: Now, let's suppose you create a free-radical in the mitochondria (the cellular energy factory), and it escapes to the fatty membrane around it. That can cause peroxidation of the fat there, and you can get a chain-reaction from one free-radical which oxidizes thousands of fatty molecules. Now if you have vitamin E around, it can scavenge the free-radical, but the radical doesn't disappear. It becomes a lower energy, less reactive, more stable radical called a tocopherol radical.

Sandy: But you still have to get rid of it.

Durk: Yeah, it's less dangerous than what you had before, but it's not harmless. The way you get rid of that is it bumps up against an ascorbate ion-- vitamin C-- and that free electron hops on over. So now you have an ascorbyl radical, but you've regenerated the alpha tocopherol and it's ready to do its job again. You get rid of the ascorbyl radical with glutathione peroxidase, a selenium-containing enzyme. There's a long series of these reactions. At each step the radical has less energy. It becomes less reactive, less dangerous, and more stable, until you can finally pair it up with another unmatched electron. Then they cancel each other out, and you get rid of it. But this is why it's necessary to have a system of free-radical scavengers, and to not just stuff yourself with only vitamin C or E.

Sandy: That's one of the problems with some of the current vitamin studies. They run these clinical trials where they're looking at what happens to people when you give them huge supplements of something like beta carotene, but they're not giving them a system of nutrients such as you'd normally find in a plant carrying beta carotene.

Durk: For example, at high levels, beta carotene alone can act as a pro-oxidant, and it can speed up free-radical reactions. However, in conjunction with other anti-oxidants, like vitamin E for example, it can act as an anti-oxidant. So if you just give a person a large dose of beta carotene, and expose them to a lot of free-radicals-- like in the case of a heavy smoker-- you're really asking for trouble.

David: I take it that you're referring to the Finnish studies that showed a greater incidence of lung cancer among smokers who took just beta carotene supplements?

Sandy: Well, that was one of the problems, and of course, the average person in the study had over a thirty-five year history of heavy smoking. So we're talking about people who already had done very extensive damage, and most of them may have already had pre-malignent conditions by the time they started on the beta carotene supplements.

Durk: And when you give them the beta carotene-- without high levels of other anti-oxidants along with it-- in conjunction with the free-radicals in the cigarette smoke (of which there's a hell of a lot), you could actually end up causing more free-radical damage, rather than preventing it. Beta carotene alone, in the absence of other anti-oxidants in adequate quantities, can actually increase the level of free-radicals, rather than decrease it.

Sandy: This is especially true under conditions where there's high oxygen pressure--such as is the case in the lungs. There's a lot of oxygen in the lungs, compared to places where there's low oxygen partial pressures, like in atherosclerotic plaques.

Durk: Beta carotene reduces the risk of atherosclerosis, but it might increase the risk of lung cancer, unless it's taken in adequate quantities with other anti-oxidants, and this is one area where the experiments were not very well planned. I don't think the people planning them understood what free-radicals were in a sense, because you can't get rid of them by just giving one magic bullet. For example, in the Finnish study the authors themselves proposed that they did not have enough vitamin E along with the beta carotene, and they found that out in retrospect.

Sandy: They only had fifty miligrams of vitamin E, which is quite small.

Durk: And no study has ever shown any benefits from that, other than preventing vitamin E deficiency. Also people in Finland suffer from pathologically low levels of selenium. Remember what I said before about how, in order to get rid of that ascorbyl radical that you get from the tocopherol radical, you have to have a selenium-containing enzyme called glutathione peroxidase? Well, in Finland the levels of selenium are so low in the soil and food there that the health authorities are now requiring fortification of all fertilizer with selenium. And it's going to take many years to get people's selenium levels up to a decent amount that way. And if you don't have enough glutathione peroxidase, simply adding another anti-oxidant may cause more mischief than benefit. That's why we suggest people take a hundred or two hundred micrograms a day of a selenium supplement to make sure they have an adequate amount. In some of the other studies, for example the CARET study, they gave very large amounts of vitamin A along with the beta carotene...

Sandy: They gave the study subjects beta carotene plus seven and half times the RDA of vitamin A, and that's enough to cause hyper-vitaminosis A symptoms in some people.

David: Because vitamin A is stored in the body, and it's not water-soluble.

Durk: Right, and again, I think one of the big things to stress is that when a person's been subjecting themselves to a lot of genetic damage for thirty years, there's no evidence that beta carotene, or any other substance, is going to be able to correct that.

Sandy: The beta carotene was being used as a treatment in that study, rather than as a preventative, which is what the studies on anti-oxidant vitamins and beta carotene have shown-- an ability to protect cells against certain types of damage before the damage takes place, not necessarily to cause the damage to go away once it's happened.

Durk: Now there are other types of damage that are more readily reversible, but once you've accumulated genetic errors in your cells, you've got a problem. They're not going to go away. On the other hand, something like atherosclerotic plaques can regress on a diet that's lower in fats, particularly the saturated fats, and if one takes large amounts of anti-oxidant vitamins-- particularly C and E-- they can substantially reduce their risk of subsequently dying of cardiovascular disease.

David: What do you think are some of the strengths and weaknesses of modern Western medicine and medical research?

Durk: I think that the biggest problem that we have with modern medicine is a regulatory and institutional problem due to the FDA. America has the finest illness-treatment system in the world. If you're sick, and you have any brains at all, and you can get to America, by God, you're going to come to America to get yourself fixed. The problem is that the FDA treats the prevention of disease by nutritional means exactly the same way it treats the cure of disease with synthetic drugs that have never naturally existed in a living tissue.

Sandy: You have to spend as much money proving that vitamin E is safe and efficacious, as you do if you've got some cytotoxic drug that's going to be used for chemotherapy.

Durk: No one is going to spend 200 or 250 million dollars, and wait eight to twelve years to be able to make a claim about vitamin E reducing the risk of cardiovascular disease. There's no patents on vitamin E and it's been used since the 1940's for that purpose. The same thing applies to low-dose aspirin, another thing which is very useful for reducing your risk of a heart attack.

Because of this we have an excellent illness-care system, but we don't have a preventive health-care system. They're two entirely different things. A health care system is one that cares for your health, and keeps you healthy. We have a great illness- care system, albeit very expensive because of other regulatory problems, but we have essentially no health-care system, because the FDA treats nutrient supplements that are very useful in health care as if they were drugs.

Sandy: Then there's the matter of off-label usage. It's very common for a company to get a drug approved for whatever is going to be the easiest thing to get it approved for, and then later on, in the course of medical practice, doctors discover other uses for the drug. There are many drugs that have a common off- label use, that is, a use for which a drug was not approved, yet is common in medical practice. That doesn't mean that the company selling the drug is permitted to tell anybody about it, or even to tell doctors. In the treatment of cancer, for example, forty percent of patients who receive chemotherapy receive at least one drug that is being used for an off-label use. This is because that use is actually an effective way of using that drug, but it's not something that the company selling the drug is permitted to educate people about.

Durk: And as result there's a greater risk that the doctor will use the drug inappropriately, at the wrong dose, or at the wrong time in a sequence of drugs, because he has to find out about it on a golf course, rather than from a paper sent out by the pharmeceutical manufactuer, which gives the results of a double- blind placebo-controlled experiment.

David: What sort of supplements would you suggest to someone looking to improve their sex life?

Durk: Oh, I'd say take an arginine-choline-B-5 supplement about thirty minutes before sex, and, boy, you will find out how nutrients can affect sex. The mechanism for erections in males, and the analogous increase in the blood flooding into vaginal tissue in the woman, is due to the release of nitric oxide. Acetylcholine is a neurotransmitter that makes muscles contract, and it also activates an enzyme called nitric oxide synthase, which manufactures nitric oxide from the nutrient amino acid arginine. Arginine is the only nutrient that can be used to make nitric oxide.

When you get that cholinergic signal, the nitric oxide causes vasodilation (opening of blood vessels), which allows the corpus cavernosum in the penis, and the blood vessels in the vagina, to become engorged with blood causing an erection. You will be very pleasantly surprised to find out what happens if you take an arginine-choline-B-5 supplement about half an hour before sex. The results can be quite dramatic. Also, I might add, arginine has been used to increase fertility in male agricultural animals since the 1950's.

Sandy: It's been known since the fifties, that you can increase sperm counts dramatically in male animals by giving them arginine supplements. It's been particularly used for prize animals that are going to be the father of many offspring, and need to be reproductively competent for a long time.

David: What role do think the mind plays in health and illness?

Durk: Oh, it's tremendous. The mind controls biochemically and electrically a tremendous amount of what happens in your body. For example, the brain gives orders to the thymus gland, which is the heart of your T-cell immune system. People who are depressed, for whatever reason, have a much higher chance of dying. I was just reading that in the latest The Lancet I believe it was, that people in the highest quintile of depression scores have about five times the chance of dying-- from all causes-- than people in the lowest quintile.

Sandy: Actually, it's a paper we haven't had a chance to read yet, but we saw a review of it in Science News. What they talked about was not people who were depressed, but people who had very high levels of hopelessness-- who just didn't think that there was any hope or any future for them. It went beyond just being depressed. And those people had a very high risk of suffering a very severe illness.

Durk: In fact, I think any physician will tell you that the number one factor in prognosis, if a person's diagnosed with cancer, is how they react to it-- if they give up, chances are they're going to die.

Sandy: That's right. If they fight it, and remain actively resisting, then they've got a much better chance.

David: I recently interviewed Timothy Leary, who's dying right now of prostate cancer. He told me that he thought that "fighting" was a terrible metaphor for approaching an illness. We don't have to fight everything, he told me, and in fact, he says that he's "thrilled and ecstatic" that he's dying. What do you think of his response to cancer?

Durk: Well, you know, that's a personal value judgment that he makes. He's not fighting the cancer, he's just looking forward to death.

Sandy: We only just heard about the fact that he had terminal prostate cancer-- and that it had metastasized all over his body- - within the last month. It may be that after having made quite a bit of effort to have something done about it, and to find an effective treatment over a period of time, it's now gotten down to where he seems to have exhausted all possibilities. I certainly hope that he's tried to find an effective treatment.

Durk: It's interesting to note that some of the earliest experiments with LSD in human beings that resulted in published scientific papers, were on terminal cancer patients. It altered their view of things. I mean, they were going to die, but instead of being terribly depressed by it, they were able to accept it and make the best of what they had for as long as they had it, which is definitely better than just being horribly depressed.

Sandy: Absolutely. But, nevertheless, it's not our nature to just give up, and say, okay great, I'll enjoy the dying experience. I wouldn't be inclined to give up until the day I die. (laughter)

Durk: In fact, if we had given up when Sandy was diagnosed with terminal cancer many, many years ago, she'd be dead by now. We did some fairly heroic things, and they worked. The case history is all written up in Life Extension: A Practical Scientific Approach.

David: What types of life extension advances do you foresee in the future?

Durk: There's an awful lot of work being done in the area of phytochemicals. If you take a look at incidences of various age- related diseases around the world, you find that there are very dramatic differences. For example, let's take cancer. Cigarette smoking is a very major cause of cancer of lungs, bladder, and so forth. Now, if you take a look at Japanese males, the percentage of Japanese males in Japan who smoke is much higher than the percentage of males in America that smoke, and yet you do not have a higher death rate in Japan from lung cancer.

Sandy. It's lower, considerably lower.

Durk: So the first thing that scientists thought is that maybe the Japanese have a greater genetic resistance to smoking-induced lung cancer. Well, the way you test for that is you take a look at Japanese who have come over to America, or second-generation Japanese in America.

Sandy: Who adopted a western style diet.

Durk: And you find that they croak just as much as Caucasians do in this country from lung cancers if they're smokers. So that wasn't the answer. They're not genetically resistant. The next thing you take a look at is-- what else are they putting into their bodies, other than the tobacco smoke, that might make a difference?

Sandy: You look at the difference between the diet they were eating in Japan, and compare that to the diet they adopted when they came to this country, and assumed essentially the same risk of lung cancer as people living here.

Durk: One of the important factors that was found to be different-- and there's several-- is apparently green tea poly- phenols. Green tea is very popular in Japan, and nowhere near as popular over here. The polyphenols in green tea are structurally and functionally very similar to the synthetic anti-oxidant BHT, which is one of the first compounds that was shown to extend the life span of experimental animals. It's interesting to note that you get a bigger increase in the life span of experimental animals that are genetically prone to die of cancer than those that are relatively long life span animals and which don't generally die of cancer.

Sandy: BHT is a synthetic phenolic anti-oxidant.

Durk: But unlike BHT, where very few people have taken large amounts for a long period of time, the green tea polyphenols have been consumed by hundreds of millions of people for thousands of years, and if that was going to make your liver turn green and fall out we would have known about it a long time ago. In fact, one of the nutrient supplements that we take now-a-days is green tea polyphenols. We take the equivalent of about six cups of green tea polyphenols per day, and in epidemiological studies that amount has been shown to provide substantial protection from cancers of the epithelial tissue-- that is, skin, lungs, and gut-- and also looks as if it probably provides protection from cardiovascular disease as well.

Now, I hasten to add, there is a difference between green tea and the teas people drink in this country, like oolong tea, grey tea, or black tea, which are fermented. In that fermentation process, the polyphenols become oxidized and less active. Now the reason this is done is that the polyphenols tend to be very bitter substances. That's why most people will just grit their teeth at green tea, but we have flavor systems that make the green tea polyphenols delicious, not merely palatable. I might also add that if it was just epidemiological data on human beings, then there's always other possible explanations, but there is mechanistic data and experimental data on animals as well.

Sandy: In addition to the animal studies and the mechanistic studies, there have also been short-term human studies that show beneficial effects of green tea polyphenols on things like the oxidation of LDL cholesterol.

Durk: If you take mice and paint tobacco combustion tars on their skin, and if they're given green tea polyphenols, you have fewer incidences of cancers developing. It's the same with ultra-violet exposure of the skin, or with feeding them those carcinogens orally-- you get fewer cancers developing in the animals. We think that there's going to be an awful lot of work coming out in the next few years about this. There's already hundreds of papers on the polyphenols. There'll be a lot of other substances-- which are found in foods-- that a person can take to provide substantial amounts of protection.

Sandy: One important thing that's taken place in this country is that there's been a change in the FDA's process of controlling the flow of information about substances like phytochemicals and other dietary supplements that have healthful effects.

David: A change in what way?

Sandy: Actually, what's going on now is the result of a very long period of political warfare which started in the 1970's over whether people should have access to high potency dietary supplements that contain substances you can get in much smaller amounts in a diet.

David: Are you talking about control of the supplements themselves or control of the information about the supplements?

Sandy: Both.

Durk: Initially the FDA tried to control the supplements by restricting as prescription items any supplement that was more than fifty percent over the RDA.

Sandy: That was back in the 1970's that they were proposing to do that.

Durk: But Congress got some six million letters on that, and a law was passed prohibiting the FDA from regulating vitamins as drugs.

David: What is the RDA based upon?

Durk: The RDA is based on the opinions of scientific panels published by the National Research Council of the National Academy of Science. They are basically set high enough so that most people will not have any symptoms of classical deficiency diseases. For example, sixty milligrams of vitamin C a day is enough so that you won't get scurvy.

Sandy: In other words, if you don't have bruises all over your body, your gums aren't bleeding, and your teeth aren't getting loose and falling out, then you don't have scurvy, and you're getting your RDA of vitamin C.

Durk: There's a real conceptual problem here. The idea that vitamin C merely prevents scurvy is false. While it's true that it prevents scurvy, and that a deficiency of it will result in scurvy, that doesn't mean that's the only thing that vitamin C does. In fact, scurvy is a free-radical disease, and there are other free-radical diseases, such as cardiovascular disease and many types of the processes that causes the initiation and promotion of cancer. There are many other free-radical diseases that vitamin C can reduce your risk of, provided you take enough of it, and that takes more than sixty milligrams. You are not going to reduce your risk of heart attacks by taking only the RDA of vitamin C-- sixty milligrams.

Sandy: The recent political battle is over the FDA's control of the flow of truthful non-misleading information concerning dietary supplements. They set up a system in which you can not communicate any information whatsoever on labels or in ads-- no matter how much supporting evidence you have for it in the way of the scientific studies-- unless the FDA first gives you permission to do so. Well, this is a violation of the First Amendment to the Constitution.

Durk: Now this just applies to people selling nutrient supplements, not to scientists or other third parties who don't benefit from the sale of the nutrient supplements.

Sandy: The FDA's restrictions on the communication of truthful information is a violation of the Constitutional rights of people who offer supplements, because if something is truthful, the First Amendment of the Constitution says that the government is not supposed to have the power to be able to stop you from saying it.

Durk: It's also a violation of the Constitutional rights of people who want to hear these things, and would otherwise benefit from it.

Sandy: This battle's been going on for quite some time. We recently sued the FDA for Constitutional violations of the First Amendment, because they have continued to claim that they have the right to decide what you can and can't say-- that you have to get their permission to say anything. This is a scientific orthodoxy. It's like what happened in the Soviet Union when they had Lysenkoism, and Lysenko controlled what people could say about biology. The FDA has long controlled what information could be provided about dietary supplements, and the FDA is a slow rigid bureaucracy. They have fallen far behind the data.

Durk: And that's why we're suing them-- because the FDA's prohibition on truthful, non-misleading claims is costing literally at least a couple of hundred thousand lives per year. For example, most of the people who could benefit from low-dose aspirin do not know that taking a quarter to a half aspirin per day can very dramatically reduce your risk of a heart attack and death from a heart attack. We're talking about roughly a forty percent reduction in risk for a man over fifty, and for post-menopausal women it's about the same.

Durk: But most people do not know this, and the people who would love to tell you-- like the Bayer aspirin company-- are forbidden from doing so. They're allowed to tell doctors about low dose aspirin reducing the risk of a second heart attack, but not about its protective effects against first heart attacks, even though the mechanisms of preventing that second heart attack are exactly the same as the mechanisms for preventing the first heart attack. Even though there is overwhelming evidence you can prevent many first heart attacks, you can't say it. The patents on aspirin ran out almost a hundred years ago.

Sandy: Nobody is going to be able to get exclusive use of a claim after spending 200 to 250 million dollars in order to get the FDA to approve the claim. So no one's going to do it.

Durk: In fact, the aspirin component in the Physician's Health Study was terminated for ethical reasons. The ethics committee overseeing the study decided there would be a lot of unnecessary and preventable deaths from heart attacks if the people on the placebo were not given the opportunity to start taking low-dose aspirin. As a result, in order to get permission to say that low- dose aspirin prevents first heart attacks, the FDA would require more double-blind placebo-controlled studies, and there is no way that could be ethically done. It's a Catch-22.

Sandy: You can't take twenty thousand people and put half of them on a couple of hundred units of vitamin E, and then give the other half a placebo, and tell them that they can't take any vitamin E for the next ten or fifteen years.

David: You're saying the FDA actually won't allow people to state facts?

Durk: That is correct. The FDA says that unless we, the FDA, give you our permission to say it, it's a crime to say it.

Sandy: It's not in the criteria of the crime whether the statement is true or not. Whether the statement is true or not is totally irrelevant. It's just that you are not getting the FDA's permission to make the statement. That's what the crime is. (interview cont...in part two)