Whole Foods magazine

October 1999

An interview with Dr. Lester Packer


Antioxidant Cocktail Update: Part 1 The take-home message is to use antioxidant supplements

By Richard A. Passwater, Ph.D.

Once again I am calling upon Dr. Lester Packer to update us on his antioxidant research. In his new book, The Antioxidant Miracle, he has made recommendations that are important to the health of everyone. We will chat with Dr. Packer about his research and the "Antioxidant Cocktail" that he recommends for improved well-being.

Dr. Packer is a professor in the Department of Molecular and Cell Biology at the University of California at Berkeley. He received a Ph.D. in Microbiology and Biochemistry from Yale University in 1956. At Berkeley he has been professor of physiology since 1961. Also, he has been director of the Membrane Bioenergetics Group at the University of California at Berkeley and a senior scientist at the Lawrence Berkeley Laboratory since 1972. His research in the area of biological oxidation and bioenergetics has emphasized studies on the roles of oxidants and antioxidants in biological systems.

Dr. Packer is one of the world's leading researchers on vitamin E and other biological antioxidants. His recent work has elucidated new areas in the biochemistry of vitamin E, including the vitamin E cycle and the antioxidant network. This is relevant to the understanding of new enzymic reactions of vitamin E, the vitamin E radical, and the biological consequences of the action of vitamin E. Recent work concerns the prevention of oxidatively induced injury in biological systems by antioxidants and how vitamins E, C, and lipoic acid affect other antioxidants, particularly bioflavonoids, through the antioxidant network, gene expression and cell regulation. These investigations are helping to develop a new broader understanding of biological antioxidant defense mechanisms.

Dr. Packer has written or edited more than 70 books, authored over 700 articles, is a member of eight professional societies and six editorial boards of scientific journals, and has organized numerous conferences in the area of his research interests. Currently he is president of The Oxygen Club of California (OCC), immediate past president and chair of the International Committee of the International Society for Free Radical Research (ISFRR), and vice president of UNESCO's Global Network on Molecular and Cell Biology (UNESCO-MCBN).


Passwater: The health food community in general, and our regular readers in particular, long have been familiar with the antioxidant research of scientists such as Drs. Denham Harman, Al Tappel, Bill Pryor, and yourself, as well as some of my research. You have discussed oxygen free radicals with us three times in past "Vitamin Connection" columns, beginning in February 1993. You now have written a new book. Previously, you had written or edited more than 70 books mainly for the scientific audience. This is for the popular audience. Why did you decide to bring the public up to date on all this research that you have been doing? And what is your "take-home" message from the book?

Packer: Motivation for writing the book was to bring to the general public some of the exciting developments that have been happening in the field of antioxidant research, where we have a growing appreciation of the importance of oxygen and glucose in our lives. We can't live without them. They are indispensable for our energy but they are awfully toxic. During evolution, oxygen and glucose were chosen as the way in which to generate energy by the body. They were the best choices available. All other choices seemed to be more toxic.

Passwater: We often say that everything is toxic to the body at some level, even oxygen and water. And our readers know that high blood sugar levels are not good. Please explain why these seemingly innocuous chemicals are toxic-even though they are less toxic than the other choices.

Packer: The toxicity of oxygen and glucose often arises from free radicals that are produced from them. Free radicals are reactive substances that have an unpaired electron in the terms of the chemist. Free radicals are essential for many aspects of our energy metabolism.

Passwater: In the right place at the right time they have a purpose, but ...

Packer: Well, as your readers know, the problem is that they are potentially toxic. They can damage molecules and tissues, which can lead to various disorders. In fact, the body often uses the toxicity of free radicals to its own advantage. The immune system cells become induced to generate free radicals when we have an infection to destroy bacteria or viruses and this is important in body defense.

The problem in that case, however, is that the overproduction of free radicals under these circumstances may damage normal tissues. I thought it was time to write a book in which the science of free radicals-and the explanation of how antioxidants combat or regulate them-should be written in a way in which the science is presented so that it could be understandable to the General public. Yet, at the same time, the book should bring out some of the scientific aspects of how free radicals and antioxidants work.

As your readers know, it is becoming generally accepted that the balance between free radicals, oxidative processes and antioxidants is very important for healthy aging. If that balance is disrupted in a person, then aging may be accelerated, and the person becomes at greater risk of developing age-related diseases the chronic and degenerative diseases associated with aging. These age-related diseases include cardiovascular diseases, cancer, neurodegenerative diseases, cataract formation and so forth. All these diseases, some 60-plus, have been linked at some stage in their progression to free radicals. Thus, the importance of antioxidants is in their ability to maintain the critical balance that slows aging and is protective against these disorders.

Passwater: This is one of the major points of your book.

Packer: Yes, and another theme of The Antioxidant Miracle is that antioxidants work in a coordinated manner. They interact with one another, and this interaction, which we like to call the antioxidant network, is very important to the overall antioxidant defense that we possess. The key members of the antioxidant network are vitamin E and vitamin C, but there are other participants in this network. These are thiol antioxidants, antioxidants that contain sulfur groups in the body. Glutathione perhaps is the best known of these, but there are other sulfur-containing antioxidants that also are very important.

Passwater: We need to do a better job of informing people about the benefits of glutathione. You have written or edited several technical books on glutathione, and I wrote the foreword to Dr. Alan Pressman's The GSH Phenomenon, which now is available in paperback as Glutathione: The Ultimate Antioxidant. Also, 1 am presently writing a basic book oil glutathione. As many of our readers know, I have always had a keen interest in sulfur-containing nutrients. You have done much research with sulfur-containing antioxidants. You also have written or edited several books on lipoic acid, and I wrote Lipoic Acid: The Metabolic Antioxidant in 1995. In December 1995, you chatted with us about the health benefit of lipoic acid.

Packer: Yes, sulfur-containing nutrients are very interesting. Glutathione is a small

molecule; it is a tripeptide consisting of the three amino acids, glutamate, cysteine, and glycine. Glutathione regulates the oxidation reduction state of thiol groups (parts of molecules that contain both sulfur and hydrogen) that are important in the structure and activity of proteins and enzymes. Lipoic acid is another very important sulfur-containing antioxidant that is a key member of the antioxidant network.

So we have glutathione and lipoic acid, and we have others such as thioredoxin, a protein cofactor. Thioredoxin is a 12,000-molecular weight protein. As proteins go, it is not very big, but it contains two sulfur atoms that can be alternately oxidized and reduced and thus can effect the status of sulfur oxidation and reduction in key enzymes and proteins. Thus, thioredoxin can destroy free radicals much as glutathione can.

Some things that I think are important to remember about how the network antioxidants work is that some steps are non-enzymatically driven. Lipoic acid, when it is reduced to dihydrolipoic acid, has such a powerful reducing capacity that it can non-enzymatically reduce oxidized cytochrome c.

Passwater: Many of our readers may not be familiar with cytochrome c, and 1 haven't discussed it much in previous columns. So let me take a moment to provide this explanation: the cytochromes are iron-containing proteins in which the iron atom oscillates between the reduced form of iron (Fe+2) and the oxidized form (Fe+3) during oxidation and reduction re actions. Cytochrome c is a water-soluble cytochrome in the respiratory chain (electron transport chain) That produces 110$ energy that Dr. Packer referred to in (he inner membranes of mitochondria. Mitochondrial enzymes reduce lipoic acid to its antioxidant potent form, the reduced form of lipoic acid called dihydrolipoic acid

Packer: Reduced lipoic acid can donate electrons (reduce) to the completely oxidized form of vitamin C called dehydroascorbic acid to reduce it back to its partially oxidized form, the semi-ascorbial radical (ascorbate radical). This partially oxidized form can be reduced further by lipoic acid non-enzymatically to vitamin C (ascorbic acid). And, of course, vitamin C can, in turn, regenerate vitamin E from its vitamin E radical.

Other components of the antioxidant network besides the thiols are the bioflavonoid and polyphenols, of which there may be more than 4,000 in nature and perhaps about 400 common in our diet. These substances interact in the antioxidant network by regenerating vitamin C. Vitamin C works in the antioxidant network by regenerating vitamin E. The thiols work in the network by regenerating the vitamin C, so vitamin C is sort of like the hub of the antioxidant network. In the cytosol, the aqueous part of the cell, these substances, which are water soluble, interact with each other and vitamin C is the hub. Here vitamin C feeds electrons and protons to convert "used" vitamin E, the harmless vitamin E radical formed when vitamin E sacrifices itself to terminate a harmful free radical, back into active antioxidant vitamin E.

Of course, in this process, vitamin C becomes a harmless free radical, but it can be regenerated by the thiol antioxidants and by bioflavonoids back to the active antioxidant vitamin C. There is one other component of the antioxidant network, a fifth component that is very important and that is coenzyme Q-10. Coenzyme Q-10, unlike vitamin C, bioflavonoids, and thiols, is completely insoluble in water and only resides in biological membranes or in lipoproteins (the carriers of cholesterol and other fat-soluble substances in the bloodstream).

In membranes, an antioxidant network also exists. Here the difference is that the hub of the antioxidant network is coenzyme Q-10. Coenzyme ()-10 can interact with vitamin I: radicals to regenerate vitamin E. In fact, many scientists are thinking, we in particular, that this is perhaps the chief (unction of coenzyme (,1-10 in most membranes. The exception is the inner-membrane of mitochondria, where coenzyme Q-10 has a special function in the energy-generating system associated wily Ill(, respiratory drain. Coenzyme Q_ 1(1 also can beat affected by aqueous antioxidant, used as ascorbic acid and most important, lipoic acid.

Passwater: So one antioxidant may be affected by other antioxidants.

Packer: This whole antioxidant network works like an orchestra depending on individuals who have, of course, different complements of antioxidants depending upon their nutritional regimens and the individuality of their own body metabolisms. The idea behind having a network of antioxidants is that if one antioxidant happens to be deficient the others can compensate and still keep the antioxidant defense system strong.

For example, let's suppose a person is deficient in vitamin C. The vitamin C that is present can be made to be more efficient thanks to components of the network like bioflavonoids or lipoic acid. The presence of these nutrients keeps the vitamin C always in its biologically active state. So there are five key members of the antioxidant network and we think this network is important in maintaining healthy aging.

Scientists used to think that antioxidants worked by themselves and vitamin C had its own antioxidant activity, vitamin E had its own antioxidant activity and so on. But now we have a greater appreciation of the sophistication that the biological system uses in targeting free radicals that can be damaging.

Passwater: You have added to the understanding of the antioxidant network over the years. I first found that antioxidants had biological synergism in longevity studies I was conducting with laboratory animals in 1962. This biological synergism also was apparent in my cancer prevention studies in 1970 and became the basis for my patent applications filed in 1972. The U. S. Patent Office informed tile in May that this patent finally will be granted late this year.

I had empirical evidence that the antioxidants were synergistic, but had little idea its to why. The effect was more than could be accounted for by considerations such as free radical profile efficiencies or tissue affinities differences.

You have so many areas of antioxidant research going at once that it's hard let keep front jumping around among the various studies. I want to go into the health bell benefits of glutathione and lipoic acid with you in more depth later, but right now 1 feel compelled to follow up with more on coenzyme Q-10. I noticed an extra twinkle in your eyes when you were talking about it just now. This usually means that we should pay attention because you'll be soon reporting something that will have a major impact on our understanding of the health benefits of antioxidant nutrients.

Scientists normally think of coenzyme Q-10 in terms of the respiratory chain as it produces energy in the inner membrane of the mitochondria. Yet, when people are fed large amounts of coenzyme Q-10, they see increased health benefits beyond what one might expect from merely having improved energy production. Now you are talking about coenzyme Q-10 being the antioxidant hub in the lipid portion of membranes. There we have an antioxidant network with coenzyme Q-10 as the hub, whereas in aqueous regions in the body, the cell cytosol and even the bloodstream, vitamin C is the antioxidant hub.

Are you telling us that we should be looking at the antioxidant network as having different hubs in different regions of the body, and with the networks consisting of different combinations of antioxidants working together, and even different antioxidant compounds at work in the different regions? Please elaborate for our readers on how the different networks might function in different regions of the body and how this is going to affect us.

Packer: The question is very good. The answer unfortunately is not as good as the question. This is because most of the evidence that we have on how the network antioxidants interact comes from in vitro (in scientific glassware as opposed to in the body) studies. It comes from test-tube studies, from studies that mimic biochemical systems, from studies with cells in cultures. It is very difficult to get this information in vivo (in living animals). There is information about this in vivo, but it is fragmentary. But, based on what we know about the different distribution patterns of these antioxidants and different tissues in the body in different compartments within cells, it's logical to thinly that the way in which the orchestration of the network antioxidants is going to he played out is going to be different. I1 is going to be based upon time and space. Where are these antioxidant molecules? How many antioxidant molecules arc there in the membrane? How many arc in the cytosol? These questions arc important to the overall system.

Passwater: Also, what kind of stress has he'll applied to tile system to gel tile antioxidants to respond? Because, after all, antioxidants respond to an oxidative stress

Packer: Within the antioxidant network, the component most vulnerable to stress probably is vitamin E. That's because of the great susceptibility of unsaturated fatty acids to be oxidized. When fatty acids are oxidized, free radicals arise and propagation of free radicals can lead to biological damage unless vitamin E intercedes and intercepts and stops the chain propagation of free radicals. As we discussed earlier, in the process vitamin E itself becomes a weak and harmless free radical. When vitamin E is "spent" in terminating a free radical, the whole network antioxidant cascade is activated. Depending upon what network antioxidants are available, the ability of vitamin E to be regenerated and to sustain its action in quenching free radicals will be dependent upon that antioxidant network status, and that is different in every individual.

Passwater: Earlier, you mentioned that when people think of vitamin C for its antioxidant capabilities, they consider it as an isolated substance and they have only a limited appreciation of its capabilities. Going back to the days before vitamin C was understood to be antioxidant, it was thought to be useful in the prevention of scurvy, and nothing more. Commonly, in the past, the medical and nutritional profession held very narrow concepts of what antioxidants could do for human health. Now they have become educated, thanks to research like yours. There is a new understanding that these substances operate in a network and are not independent. In your book, The Antioxidant Miracle, I believe that the take-home message is that a good diet and supplementation program can take advantage of the antioxidant network to rejuvenate the heart, strengthen the immune system, maximize brain power (many of us could use that) and perhaps slow or reverse the aging process.

Today we have drifted off into some fairly technical discussions. In your book, you keep it simple. You present tile information in such an easy-to-understand manner. One does not have to know how the antioxidant network operates to take advantage of tile health benefits of antioxidants. You provide very easy-to-follow instructions as to what to take and how much to lake.

The sophistication of understanding that you arc now developing is new. Ii is not yet shared by the majority of conventional nutritionists and health cam practitioners. Most haven'( yet been educated about tile connection between free radicals, antioxidant balance and the efficiency of the immune system. Could you tell us a little bit more about these concepts?

Packer: One of my lake-home messages, as you call them, is that besides the usual recommendations of having a well balanced diet and a proper program of exercise, we think it is important to supplement your diet with antioxidants to shore up your antioxidant network defense. The basis for this recommendation is our conviction that the underlying factors important in healthy aging and in prevention, and in some cases treatment of disease, involve a proper defense.

So we have formulated a basic "antioxidant cocktail" that is designed to fortify the entire antioxidant network.

I fully believe that, in the next century, this concept of network antioxidants is going to become a very important paradigm for health. It's not so well recognized now, but, considering that we are at the end of a millennium and about to go into a new one, perhaps it's a good time to evaluate where we stand and where we may be going in the future in terms of nutritional antioxidants and in optimizing our diet to improve our lifestyle.

The Packer Plan has been formulated; it represents our best educated guess of what antioxidants to take, particularly the five key members of the antioxidant network in order to shore up the network antioxidant defense system. We have a basic antioxidant cocktail that is designed for this purpose. A key component of this formulation is lipoic acid.

Passwater: In the next part of this interview, we'll get around to discussing the importance of lipoic acid and Pycnogenol, paying specific attention to how they increase the body's glutathione production and why this is so important. We'll close this part with a brief description of the "Packer Antioxidant Cocktail."

Packer: There is a basic antioxidant cocktail for all adults. To this, adjustments are made for certain conditions. For example, smokers or those at high risk for cancer should modify the plan to better fit their increased needs. Meanwhile, the basic antioxidant cocktail is divided into two servings a morning portion and an evening portion.

The A.M. regimen is as follows:

-100 milligrams of tocotrienols (a form of vitamin E having its own actions)

-200 milligrams of natural mixed tocopherols (regular mixed ester vitamin E)

-30 milligrams of coenzyme Q-10 -50 milligrams of lipoic acid -250 milligrams of Ester C vitamin C -400 micrograms of folic acid -300 micrograms of biotin -2 milligrams of vitamin 13-6.

The P.M. regimen is as follows:

-200 milligrams of natural alpha tocopherol (regular vitamin E) -50 milligrams of lipoic acid -250 milligrams of Ester C vitamin C -30 milligrams of ginkgo biloba -200 micrograms of selenium Some of the other recommendations include:

Diabetics should add the following (either A.M. or PM.):

-100 milligrams of lipoic acid

-1,000 milligrams of GLA

-200 micrograms of chromium

Smokers and people at high risk of developing cancer or heart disease need an additional daily amount of the following:

-100 milligrams of lipoic acid

-100 milligrams of tocotrienols

-50 milligrams of coenzyme Q-10

-20 milligrams of Pycnogenol

Passwater: OK, there it is-the Packer Plan. Developed by the foremost antioxidant researcher in the world. That's good advice and we'll examine why in Part 2. WF


1999 Whole Foods Magazine and Richard A. Passwater, Ph.D.

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