Measuring Your Antioxidant Status: Interview with Dr. Charles A. Thomas
by Richard Passwater, Ph.D.
Forget about your cholesterol number - what are your levels of CoQ-10, vitamin E, selenium, beta-carotene and vitamin C? You may eat well and take supplements, but do you know if they actually get into your system? Are the concentration levels of these protective substances in your blood below par, middling, or in the higher protective range?
In recent Health Connection columns, the world's leading researchers on antioxidants, heart disease, cancer and aging have explained how our antioxidant defenses help us live better and longer. Our antioxidant defense system includes large molecules such as the antioxidant enzymes and coenzymes, together with small molecules such as the antioxidant micronutrients - many of which turn out to be the familiar vitamins. Our diet helps determine both the amount antioxidant micronutrients in our blood and cells, as well as the levels of antioxidant enzymes and coenzymes that our bodies produce is determined partly by heredity and partly by diet.
I stress that our diet is a factor in our antioxidant defenses, because the needed nutrients must be in your diet in the first place. However, they won't help you unless they are absorbed. It is not just what we eat, but how well we absorb nutrients from our food and supplements. We can determine out diets, but our antioxidant defenses are influenced by other variables that are outside our control. The only solution is to MEASURE the blood levels directly and then make adjustments as necessary based on these measurements.
Let me emphasize the importance of the latter with the research of Dr. Richard Donaldson of the St. Louis Veterans' Administration Hospital. Dr. Donaldson conducted a clinical trial with terminally ill cancer patients. He found that when he could raise the patients' blood levels of selenium into the normal range, their pain and tumor sizes were often reduced. The amount of selenium needed to obtain normal blood levels varied from person to person. Normal healthy people usually have normal blood selenium levels on normal diets. However, cancer patients usually have low selenium levels on normal diets. Apparently they could not get enough without supplements. Dr. Donaldson found that he had to supplement the cancer patients with at least 200 to 600 micrograms of selenium per day and in some cases 2,000 micrograms of selenium per day were required to obtain normal blood selenium levels.
As Dr. Gerhard Schrauzer told us in the December 1991 column, blood selenium levels often indicate the presence of cancer and even the severity of cancer in a patient. This is how he became interested in the role of selenium in cancer. It seems that low blood selenium levels increase the risk of cancer and that tumors may also deplete the blood of selenium. Some people absorb selenium poorly and this increases the probability of developing cancer.
Selenium, of course, is just one element in the complex and overlapping antioxidant defense system that includes nutrients such as vitamin E, beta-carotene, vitamin A, coenzyme Q-10, vitamin C, and many others. Blind supplementation is not a good idea, because some of these micronutrients like selenium and vitamin A can be toxic at higher levels. When I first pointed this out several years ago, many people wrote to me asking where they could get the blood levels of these substances measured. Now, at last, there is such a laboratory that can do just this. They measure the blood concentrations of more than 20 different substances that are related to the antioxidant defense system. The results are plotted in graphs that make it easy to see exactly what relative deficiencies actually exist so that they can be targeted for correction.
Do you know what your antioxidant profile is? Dr. Charles A. Thomas will tell us some of the reasons why this information should be of interest to you.
Passwater: Dr. Thomas, you taught biophysics at Johns Hopkins University and were a professor of biological chemistry at Harvard Medical School before moving to San Diego to become Chairman of the Cell Biology Department of the Scripps Research Foundation. I know that during this time your research programs were funded by the NIH and that you are the author and co-author of many papers. Exactly what kind of research was this?
Thomas: Most of my research has been on the structure and mode of replication of viral DNA molecules. For example, we were the first to show that a virus particle contains a single molecule of nucleic acid - which turns out to be a general, but not unbroken rule. We demonstrated that many of these DNAs begin and end with the same sequence of nucleotides and how there were involved in replication and integration.
Passwater: Sounds like molecular biology to me! This is a far cry from what you are doing now. How would you characterize your work at present?
Thomas: We are doing analytical biochemistry. We are measuring the concentration of over 20 different substances in human blood serum that are somehow related to the individual's ability to avoid degenerative diseases.
Passwater: Your present work seems completely different from molecular biology - why did you switch fields?
Thomas: Well, actually there is a connection. My interest in the replication and transcription of nucleic acids led me to think about how DNA was damaged; how mutations arise; what are the damaging agents and where they come from. In those days everyone was concerned about low levels of radiation and toxic residues from pesticides and effusions of industry. This was politically correct and well-funded by government agencies. When I looked into this question, I discovered that radiation and toxic residues could only be responsible for a negligible portion of the damages that are actually observed.
Passwater: If these environmental agents are not especially significant, what are the most damaging agents and where do they come from?
Thomas: The most mutagenic agents are oxygen radicals that are being generated by the normal biochemistry of every cell in our bodies (and in the bodies of every other animal that lives in air). Early in my reading, I came across a paper by Drs. Helmut Sies and Britton Chance. This work summarized evidence that about one-to-two percent of all the oxygen we breathe was not converted to water and energy, but rather to the formation of superoxide radical (O2.-) and its descendants such as hydrogen peroxide (H2O2). This paper had a strong influence on my thinking.
Passwater: It's uncanny how the academic lives of many of the scientists in this series are entwined. Both Dr. Packer and myself have personally been involved with the research of Dr. Britton Chance and Dr. Helmut Sies will be the subject of a future interview. But, before I wander too far off the subject, please explain why their paper had such a powerful influence on you.
Thomas: Yes, I quickly made a calculation that if all this superoxide radical (O2.-) and hydrogen peroxide (H2O2) were converted to hydroxyl radical (OH.), the cell and the animal would be killed instantly.
Passwater: Please elaborate.
Thomas: You see, when x-rays (or any ionizing radiation) pass through body tissues, the largest portion of the damaging effects are due to the splitting of water molecules and the formation of the hydroxyl radical. The fact that one percent of the oxygen was shunted into the path of radical formation, meant that the cell would, in effect, be receiving the equivalent of more than a million rads per day, when a thousand rads is enough to kill most anything, including humans.
Passwater: That's an interesting approach, comparing the amount of radicals produced in normal metabolism to the amount produced by ionizing radiation.
Thomas: Yes, in a sense we are producing the same radicals by normal metabolism as are produced by x-rays. My calculation could have been wrong, but probably not. What was more likely is that even though these radicals are produced, there is some highly efficient way of preventing them from doing most of the damage that they would otherwise do. There was some kind of antiradical defense system that Nature had put into place and that prevents all but a small fraction of the damages.
Passwater: Aha! This gets us to the antioxidant defense system.
Thomas: Yes, we would not be alive without it. However, with the passing of time, nutritional deficiencies, disease states, emotional stress, the consumption of toxic materials like tobacco smoke and alcohol, or whatever, the antiradical defense system becomes impaired and the rate of damage increases. Mutations and cancer result.
Passwater: Can you explain what is known about the anti-oxygen-radical-defense system?
Thomas: Sure, but remember that entire books are devoted to this subject. Briefly stated, most of the radicals are generated in the mitochondria where 98 percent of the oxygen that the cell consumes is reduced to water by an efficient process called "respiration." The radical by-products of respiration promptly encounter detoxifying enzymes that efficiently convert them to water.
Passwater: But nothing is ever 100% perfect?
Thomas: Right - even a tiny percentage of unwanted radical production can do a lot of damage. This tiny percentage that gets through the antiradical defense system is probably responsible for a major part of what we know as "aging."
Passwater: What are you doing at PANTOX Laboratories to help us reduce this damage?
Thomas: We are measuring the blood serum levels of many of the small-molecule components of this antioxidant defense system. Many of these are familiar vitamins; some are not. They represent the last and final layer of defense. If they are not around, the tissue components are oxidized at a significantly higher rate.
Passwater: This means to me that we would expect that people who have low levels of these micronutrients would experience higher levels of heart disease and cancer etc. Is this right?
Thomas: Indeed it is, and this is what attracted me to this field. There are published papers describing the higher incidence of almost every degenerative disease with lowered levels of vitamin E, vitamin C, carotenoids, coenzyme Q-10, bilirubin, or selenium. You yourself introduced your readers to the importance of monoriting their blood levels of antioxidants -- especially selenium and vitamin E in terms of cancer prevention and treatment -- in 1987 in the March issue of Let's Live. Very basic ideas sometimes take a long time to gain recognition.
Passwater: Let's say a person has a poor PANTOX Profile where he is pretty low in just about everything. Can he do anything about it?
Thomas: Absolutely! By consuming significantly higher levels of micronutrients in the form of supplements, he usually can elevate his serum levels.
Passwater: This will reduce his risk for cancer and heart disease?
Thomas: You and I certainly are convinced, but we have to be careful here. There are a few intervention studies that support this conclusion, but the most important intervention studies are yet to be completed. Based upon what we know about the biochemistry and physiology of antioxidant protection, we are expecting these intervention studies to confirm our expectation.
Passwater: What have you learned from measuring PANTOX Profiles on thousands of people?
Thomas: Well, the first thing you have already mentioned above: "What you eat is definitely NOT what you get!" We have some people who have never touched a nutritional supplement who have near-ideal PANTOX profiles (although they admit to eating plenty of fruit and vegetables). We have others who have high beta-carotene but no significant vitamin A. This means to me that they no longer have the enzymatic ability to convert beta-carotene to vitamin A. We have others who have high levels of vitamin A, but no carotenoids. It's a zoo out there. I never expected that people could be so individually different.
Passwater: Another example of Dr. Roger William's teaching of biochemical individuality! Are there any special groups of people who would benefit from having their profiles measured.
Thomas: Yes, of course. Those who have experienced cancer or heart disease, cataracts, macular degeneration etc. They should optimize their present antioxidant defenses. This also applies to members of their families, because family members often share the same diet and lifestyle. PANTOX is participating in a large number of clinical studies relating to heart disease, cancer, Alzheimer's and other diseases of aging.
We have recently started providing PANTOX Profiles on Downs Syndrome children. Most Down's individuals have an extra chromosome 21, so they have a fifty percent excess of every gene on that chromosome. Among them is the gene for superoxide dismutase (SOD) which converts superoxide anion radicals to hydrogen peroxide. This leads to a fifty percent increase in the amount of SOD in their cells and probably an increase in the concentration of hydrogen peroxide, although this has not been measured. Therefore, Down's individuals would be expected to be under greater oxidative stress. In the limited number of children that we have studied, they do indeed seem to have depleted serum levels of lipid-soluble antioxidants and vitamin C. These results are guiding special supplementation programs for these children.
Passwater: The extra SOD is beneficial when it dismutates superoxide anion radicals to peroxide, but unless there is also additional catalase to reduce the peroxide to water, the person is still under oxidative stress from the accumulating peroxide.
Pro-oxidants are also of interest in determining the antioxidant statue. Does the PANTOX Profile include iron?
Thomas: Indeed it does. We measure serum iron, total iron-binding capacity (TIBC) and serum ferritin. (Ferritin is a protein that stores iron.) There are now many publications that demonstrate the key role of iron as a catalyst for the formation of the hydroxyl radical. Since the hydroxyl radical reacts very close to the iron ion that catalyzes its formation from hydrogen peroxide, iron ions are responsible for directing oxidative damage to the site to which they are bound.
Passwater: In vitro studies suggest that free iron ions in the body might catalyze oxidative damage. The body takes great care to scavenge free iron ions so that this damage is minimized if it does occur in vivo. There is considerable debate and a great deal of scientific interest in the possible involvement of stored iron in radical formation in vivo. In any case, in normal individuals, stored iron does not appear to be dependent on the amount of iron in the diet. Iron, in contrast to many other minerals, is regulated in the body primarily by absorption rather than by excretion. The absorption of dietary iron is strongly regulated by body iron stores. When iron stores are low, the body is more efficient at absorbing dietary iron and vice versa.
However, there are individuals with abnormal iron regulation who accumulate too much iron stored in the blood. Hemochromatosis and hemosiderosis are examples of iron-storage diseases.
Thomas: Yes, an excessive amount of stored iron is bad for you, but we have to have some iron in order to live. We need it in hemoglobin, for example and hundreds of vital enzymes, including the antioxidant enzyme, catalase which reduces hydrogen peroxide to water. We want to avoid excessive amounts of stored iron. Excessive amounts of stored iron leads to "homeless iron" which targets the damages that I just mentioned. This is a perfect example of why measurement is so important. If we have too little iron we are likely to experience iron-deficiency anemia. Too much stored iron and we are likely to experience a faster rate of aging. On a typical office visit to a physician, iron-deficiency anemia is easy to detect and correct, the other, too much stored iron, will not cause problems for many years and is likely to be overlooked or dismissed by the physician.
Passwater: If a person has too much stored iron, what can be done to correct that?
Thomas: Actually, its very easy: you make a blood donation, or a series of blood donations at two-month intervals. Each unit of blood removes almost 1/4 a gram of iron from the iron stores in the body. New blood cells must be made and the iron required to do so is removed from the major iron-storage depots in the liver.
Passwater: Good advice. Not only would that help the person with too much stored iron, it would help another person needing a transfusion. As a paramedic (EMT-A) I have treated a great many accident victims who have needed blood transfusions to save their lives. I have also spilled appreciable quantities of my own blood on a couple of occasions -- once to the point of no detectable pulse or blood pressure -- so I can personally attest that giving blood saves lives. But too many people fear donating blood.
Thomas: Nothing in medicine is safer. There are 12 million blood donations made every year, and some individuals have given many gallons over time, all with no recorded ill-effects. Cycling females lose up to 3 pints of blood per year, and they are the most healthy humans alive.
Passwater: Do you donate blood regularly?
Thomas: Of course. My stored iron levels are now comparable to a 25 year old female.
Passwater: What effect does high levels of stored iron have on the PANTOX Profile?
Thomas: We have found a most astonishing thing. Those people who have high levels of stored iron (as indicated by high serum ferritin values and low TIBC) have sharply lower beta-carotene values - it is as though they are using up their carotenoids (although there are other explanations). Among those people with "HiFer-LoBeta-Car," we find many who have depleted levels of vitamin C, E, and A. If this is the case, the serum level of glucose almost always is elevated. I imagine that the body is increasing the glucose level as an "antioxidant of last resort." There are papers indicating that if serum iron is lowered, the serum glucose levels are normalized. I believe that the relationship between iron loading, depleted antioxidants and late-onset diabetes should be more carefully studied.
Passwater: Now that is interesting and it is something researchers ought to follow up. By the way, how does PANTOX operate?
Thomas: PANTOX Laboratories is a CLIA-approved reference laboratory that is licensed in California. To date we have measured PANTOX Profiles in over 3,000 blood samples. The PANTOX Profile must be ordered by a licensed practitioner in the State where the sample of blood is taken. Most of our orders come from physicians but many come from other practitioners.
Passwater: How can readers get their Profile done?
Thomas: If readers would like to have their own PANTOX Profile done, they can call Pantox Laboratories at 800-PANTOX6 (800-726-8696). We can send information and a specimen kit (including simple instructions on how to transport the sample) to their physician or other qualified health practitioner, or perhaps recommend a doctor in their area who is already familiar with the PANTOX Profile and how to interpret and use the results.
Passwater: How much does it cost and is it covered by insurance?
Thomas: Clinically, PANTOX Profiles are used both as part of diagnostic and treatment protocols and as preventive diagnostic screens. The cost (currently $275, $250 if payment is sent with the specimen) is typically reimbursable when a valid ICD-9 diagnostic code is included on the Patient Information/Requisition form. In that case, the panel is considered eligible for coverage by virtually all insurance plans and we accept Medicare assignment. We will bill patients (and submit insurance claims on their behalf, if their insurance information is included with the sample), or we will bill the doctor directly, if preferred.
Passwater: How often should a PANTOX Profile be repeated?
Thomas: For a person who has a poor profile and has taken steps to improve it, we suggest a repeat four to six months later. For a person who is maintaining a good profile, a simple annual biochemical checkup is recommended.
Passwater: Good advice. Would you like to leave our readers with any parting message?
Thomas: Almost everyone in the US dies of the diseases of aging. To reduce the rate of aging - that is to maintain optimal health - is a matter of personal responsibility; no government and no insurance company will ever be able to provide health for the individual: he must do this for himself. I hope that PANTOX will enable the individual to assume more responsibility for his own health.
Passwater: Thank you Dr. Thomas.
All rights, including electronic and print media, to this article are copyrighted to Richard A. Passwater, Ph.D and Whole Foods magazine (WFC Inc.).