Whole Foods magazine

December 1999


Antioxidant Cocktail Update: Part 3: The Importance of Glutathione, the Master Antioxidant. An Interview With Dr. Lester Packer


By Richard A. Passwater, Ph.D.

We have been chatting with Dr. Lester Packer about the role of antioxidant nutrients in protecting us against many diseases and improving our quality of life. First we discussed the role of the antioxidant network in protecting body components. Dr. Packer emphasized the contribution of each of the antioxidant nutrients and, additionally, how several antioxidants play a role in recycling antioxidants already "expended" in terminating free radical reactions. We mentioned that, in aqueous areas, vitamin C serves as a hub of an antioxidant network that receives and passes along electrons and protons to these "spent" antioxidants so that their antioxidant function is revived. We also discussed that, in membranes, coenzyme Q-10 serves as the hub of the antioxidant network.

In Part 1, Dr. Packer also gave us his recommendations for a basic "Antioxidant Cocktail" that offers benefits for all people, as well as additional recommendations for people having certain disorders or lifestyle stresses. The basic Packer Antioxidant Cocktail includes vitamin E in both tocopherol and tocotrienol form, vitamin C as Ester C, lipoic acid, coenzyme Q-10, ginkgo biloba, and selenium. Pycnogenol also was recommended frequently We also briefly mentioned the importance of increasing levels of the antioxidant glutathione in the body, although glutathione itself is not part of the Packer Antioxidant Cocktail. We'll chat more about this shortly.

Last month, we discussed some of the reasons why glutathione is important to health and how various antioxidants can increase cellular glutathione levels. Lipoic acid is especially suited to this task, and N-acetyl cysteine (NAC), S-adenosylmethionine (SAMe) and Pycnogenol also are effective. We explained why glutathione itself and cysteine are less valuable supplements for increasing cellular glutathione levels.

Now, we will explain why glutathione is the "master antioxidant," and provide what I think will be new concepts to many readers-that different diseases require the replenishment of different antioxidants. Also, Dr. Packer will tell us why he believes that everyone taking the "statin" drugs to lower cholesterol especially needs to take coenzyme Q-10 supplements.

Passwater: Let's go back to your Antioxidant Cocktail. People are becoming fairly familiar with taking vitamin I? to reduce the incidence of heart disease. It now is recognized by many health professionals that vitamin E works by preventing the formation of oxidized-LDL that is tire cause of the so-called cholesterol deposits. For this reason, many, if not most, cardiologists even are prescribing vitamin E. However, few cardiologists in this country know of the importance of another antioxidant in the cocktail-coenzyme Q-10.

Of course, holistic physicians know about the importance of these antioxidants in heart and artery health, but they are not as familiar with all of the reasons why the antioxidants are needed for healthy arteries and hearts.

Now we can get back to the importance of the "master antioxidant," glutathione. Several times you mentioned how the antioxidant network works to improve the glutathione content of the cell. What does this mean practically? What do we know about glutathione levels and health?

Packer: Most disease has an oxidative stress component to it. Free radicals and oxidants are underlying factors in most chronic and degenerative diseases. Nor is it different with viral activation, which leads to depletion of the antioxidant defenses in our lymphocytes

It's very important for people to keep their glutathione levels high. As I mention in my book, low levels of glutathione are a harbinger for illness and premature death. Glutathione is the primary water-soluble antioxidant in the cytosol (aqueous interior of cells). Glutathione itself is a direct antioxidant, but it also plays a key role in the antioxidant network by recycling the oxidized form of vitamin C, restoring its antioxidant power. This is what I tried to show in figure 2 last month.

Glutathione is important for a strong immune system. Boosting glutathione levels can reverse the age-related slump in immune function. Glutathione also is instrumental in the detoxification of drugs and pollutants and is vital for a healthy liver. In addition, it is involved in the storage and transport of amino acids.

Passwater: Glutathione is the quartermaster corps or "supply troops" of the antioxidant defense network. Our friend Dr. Bill Pryor presented this concept in this column in January 1995. He described vitamin l: as "shock troops" that actually attack the enemy, while glutathione was like the "supply troops" that keep the shock troops supplied (in this case with reducing equivalents).

CoQ (30-2000mg.)

Carotenoids (25 milligrams plus)

Vita E (100-400 milligrams )

Vitamin C (250 milligrams to 10 grams or more)

Thiols and Bioflavonoids (several grams of each)

Figure 1. The antioxidant pyramid. The suggested dietary quantities parallel the advice given by Dr. Packer in this interview. Reprinted from WHOLE FOODS January 1995. (From a Richard Passwater drawing.)

Packer: The question you asked about the levels of glutathione is pretty important. As a generality, vitamin E is present in nanomolar concentrations, and vitamin C is present in micromolar concentrations. However, some tissues have low millimolar concentrations of vitamin C. Plasma contains 20 to 140 micromolar vitamin C and 22 to 32 micromolar of alpha-tocopherol (vitamin E). But in tissues, vitamin E levels are often nanomolar. Plasma is the carrier system for the vitamin E to the tissues but the thiols are present in millimolar concentrations. In particular, glutathione levels in certain tissues like liver cells can go as high as eight millimolar, which is very high. The glutathione that is present in the cell usually is soluble in the water compartment. But that glutathione also binds to proteins, and a lot of the glutathione is present actually on proteins. What is very interesting is that protein glutathione levels can be used to re-establish glutathione levels in the cytosol.

It isn't only the glutathione that is the supply troopers, but other thiols as well. We discussed thiols earlier (Part 1), indicating that these sulfur-containing compounds are our friends. I mentioned the thiol thioredoxin. Thioredoxin is not so well known because it is made in the body and it is not usually something that we can purposely vary in our diet. But it is an important thiol antioxidant itself as well as important because it interacts with the glutathione system to provide protection.

Passwater: You also mentioned the thiol lipoic acid for the same reason.

Packer: An important point is that in different diseases different antioxidants need to be replenished. The antioxidant network is the underlying concept but the way in which the antioxidant network works may be different in different kinds of diseases.

Passwater: That is an important point and it may be a new point of view that many professionals need to understand, as well as our readers. Please give us an example.

Packer: In heart disease, for example, it has been shown that coenzyme Q-10 can be beneficial. So people who have cardiovascular disease may want to supplement with coenzyme Q-10 to strengthen that part of the antioxidant network.

Perhaps, an even better example might be with the millions of people who are taking the so-called "statin" drugs, such as lovastatin, fluvastatin, atorvastatin, pravastatin and simvastatin. Statin drugs inhibit the biosynthesis of cholesterol and they are prescribed for millions of people who have heart disease. Many health authorities are suggesting that even healthy persons take statin drugs in the belief that they may help prevent heart disease.

Now, what many people don't realize is that the same pathway that is used in the body to synthesize cholesterol also is used to make coenzyme Q-10. So people on statin drugs may have lowered their cholesterol levels, but they now have: been made deficient in coenzyme Q-10.

Passwater: The heart has a special need for coenzyme Q-10, but as regular readers of this column know, current research suggests that antioxidants arc important to protecting arteries against cholesterol levels via their protection of the cholesterol carrier low-density lipoprotein (LDL). Free radicals can modify LDL into what is called oxidized-LDL. (Ox-HDL). Data suggests that it may be more important to protect LDL against oxidation than it is to merely lower blood cholesterol levels. Both the amount of LDL present (to be at risk of being converted to Ox-LDL), and the amount of free radicals present (to do the damage) are factors, but the more important factor is the amount of free radicals.

Packer: Precisely. Since coenzyme Q-10 is directly important to heart health and involved in the antioxidant protection of LDL, I recommend that anybody who is on a statin drug should supplement with coenzyme Q-10. This is a sub-population that is really deficient in one of the key members of our antioxidant network. The potential is enormous for side effects to occur from statin drugs. It does depend on the individual because every individual is different. But there is a large number of people who will be really adversely affected by statin treatment because of their depleted coenzyme Q-10 status.

Passwater: How ironic. Taking statin drugs cuts off the biosynthesis of a substance that we know is essential for energy production, and has been suspected of being a rate-limiting compound for the production of energy, particularly in elderly individuals. Elderly individuals are often the ones who are taking statin drugs. This really could lead to a bad situation. Supplementation with coenzyme Q10 and the other antioxidants is definitely a wise move. The statin drugs interfere with coenzyme Q-10 production, not its absorption from the diet.

Packer: It certainly makes sense.

Passwater: Earlier, we were talking about the importance of glutathione and immune function. HIV-infected persons have their immune systems destroyed because the HIV infected cells cannot make sufficient glutathione and these cells cannot import glutathione from the blood. So, in keeping with your message, HIV-infected persons and AIDS patients should emphasize taking the supplements that improve their ability to produce glutathione.

Packer: That's right. As we discussed earlier, glutathione is one of the key antioxidants in our antioxidant defense network that is critical to the antioxidant defenses within every cell and especially to our immune system. Glutathione levels arc low in HIV-infected CD4+ lymphocytes (white blood cells) of AIDS patients. The overall picture is becoming clearer; we can better see the involvement of oxidative stress that results when the balance between radicals and antioxidants is lost and radicals and other reactive oxygen species (ROS) and reactive nitrogen species (RNS) get the upper hand. Let me draw another figure to strew this:

Passwater: Well, you certainly made your point that although all of the antioxidant network members are important in the protection against some 60-plus diseases, different antioxidants should be emphasized for increased protection against specific diseases. How about lifestyle needs?

Packer: Good point. Take cigarette smokers, for example.

Heavy smokers, even those exposed to second-hand smoke, are at risk and we know that their antioxidant levels are compromised. It is common knowledge that the vitamin C levels in the blood of heavy smokers is at least 20% to 30% lower than in comparable subjects who don't smoke. And vitamin C is just one of so many antioxidant nutrients. Are the others also markedly reduced in smokers? If so, shouldn't this be known so that corrective action could be taken?

Currently, in the state of California, we are conducting a clinical trial to determine what happens to certain antioxidants. Specifically, we are providing an antioxidant cocktail based on the concepts of the network antioxidant system. One of the components we are giving people is a vitamin E combination that is rich in both tocotrienols and tocopherols.

Passwater: Many of our readers are familiar with tocotrienols, as I have chatted with researchers including Drs. Marvin Bierenbaum, Tom Watkins and Maret Traber in previous columns about tocotrienols. (WHOLE FOODS Nov 1997 through February 1998] Nevertheless, for the convenience of readers who may not be familiar with tocotrienols, please elaborate a little.

Packer: Tocotrienols are the vitamin E of the 21st century. Until recently, tocopherols have been getting most of the attention when it comes to vitamin E. Tocotrienols have the same basic functions as tocopherols but are a different shape. This difference appears to confer on them some very special qualities over and above their antioxidant function.

Studies of tocotrienols suggest that they are useful in preventing and treating atherosclerosis. They also reduce levels of thromboxane A2, a clotting factor that is a risk for strokes and heart attacks. A few studies hint that tocotrienols also may lower cholesterol levels. In addition, there are indications that tocotrienols may protect against liver cancer and, possibly, other cancers. They have been shown to inhibit the growth of several types of breast cancer cells in laboratory glassware experiments.

Passwater: Thank you. OK, before I interrupted, you were telling us about your clinical trial with smokers.

Packer: Besides vitamin E, we are giving them vitamin C, and guess what?-lipoic acid! There never has been a human clinical trial done involving smokers in which a thiol antioxidant has been given.

As we have discussed, lipoic acid increases glutathione levels and also directly protects against the damage that occurs to proteins in the blood. Smoking especially damages all proteins in the blood. They usually are damaged by oxidation to the protein thiol groups. Lipoic acid protects against this protein damage, especially when it is supplemented in combination with vitamin C.

So using the concept of an antioxidant network, we are treating passive and chronic smokers to determine whether indices of smoke-induced damage are decreased. This study is under way at the moment. I just got a progress report today telling me about the problems we are having in completing this study.

Let me mention one of the problems. It's interesting. It was not getting the money to do the study. What difficulties we ran into involved finding enough smokers, particularly passive smokers. Unfortunately, we won't have as large a study group as we had originally anticipated, but we have a substantial number of subjects in the trial and we ought to be able to have some answers on whether this network antioxidant cocktail is successful in reducing smoking-induced damage in the near future.

Packer: We now expect to finish collecting samples within a few months. After that, we will do the analyses and then we have to crunch the numbers and see what we have come up with.

Passwater: That study is very interesting and does show how health messages do get taken seriously. Obviously, people are learning that smoking not only kills people, but often kills them early and horribly. We have to get the antioxidant message out as well. First, be sure you don't smoke; then be sure you get your antioxidants.

Let's pause here. When we continue in Part 4, we'll chat about how antioxidants influence gene expression. 'this may be the most important aspect of antioxidants. I remember the gleam in your eyes several years ago when you first uncovered this relationship. Also, I want to try to go beyond the experiments and look at Dr. Packer, the person. How did you get into antioxidant research? I know our readers would be interested in learning why you chose the path you did, and how it has led to these discoveries that benefit everyone. WF

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

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