|This is a copy of the now-defunct webpage: http://www.krysalis.net/antiox.htm|
The power of science has always been guided by theories or theoretical constructs that make it possible to progress to greater understanding and accomplishments by a process that is far more efficient than a random walk. Also, in science, the correct theory is no more than the best theory at the time. As different fields advance, their theoretical foundation usually changes to accommodate new knowledge, which is usually essential for making further steps of progress possible. For years we have accepted the "free radical" theory of damage to explain many observed diseases or degenerative processes and the companion "antioxidant" theory to explain the many health benefits derived from numerous foods and dietary supplements, which work to prevent the damaging effects of the free radicals. These theories have served us well in that they have brought us a long way. However, I now believe they have reached their useful limit and there is a need for a substantially new insight for further organized progress to be made. I would like to propose a new theory for both the cause of such degenerative processes, and the biochemical repair mechanism of materials presently named antioxidants. In the immediate term, I hope it will serve to give people a better understanding of antioxidants and thus enable them to make better choices. As time goes on, I hope this will serve as a useful guide for the development of the next generation of even more effective "antioxidants".
Lets first look at the overall biochemical oxidative system and assume that the bioactive materials called antioxidants do work to lower the potential for oxidative damage. First we have to consider something more global than a few postulated, free radical reactions. As any physical chemist knows, the character of a liquid solution must include not only the pH, but also the Eh. Most of us are familiar with pH. It is the measure of the degree to which a liquid is either acidic or basic. It is not adequate to describe a solution simply as acidic or basic, it is critically important to describe just how acidic or basic it is. The change from very acidic to very basic is a continuum with the standard unit of measurement being the pH. Similarly, a less well-known characterization of a solution is the degree to which it is oxidizing or reducing. Again it is not sufficient to simply say it is oxidizing or reducing, but rather it is a continuum of change with the standard unit of measure being the Eh. The reason the pH and Eh are so important is because together, they exert a powerful action on any other chemistry that is taking place in the solution. This is true, not just for laboratory solutions, but also for the biochemistry taking place in cells. For this discussion, we will ignore changes in pH, as important as they are, and consider only changes in Eh.
Taking an overall look at the oxidation potential (Eh) as oxygen progresses through our bodies, it is highest where oxygen first enters the lungs. It is slightly lower as it diffuses into the blood and even lower as it diffuses from the blood into cells. Once it enters the cells it is continually lowered as the state of the oxygen is transformed in the multitude of steps associated with metabolizing food. Eventually it exits our bodies at a very low oxidation potential as carbon dioxide and water in our urine, feces and breath.
Free Radicals: All chemical reactions involve the formation of free radicals as intermediate steps since they all require the transfer of unpaired electrons. As food is metabolized in cells, free radicals are formed with every reaction step as a necessary part of the step. If they were not formed, metabolism would stop and we would not be here. Yes, free radicals are responsible for biological damage since all chemical reactions, beneficial and damaging, involve free radicals. However, this is not a very useful concept since it does not help distinguish between good (essential) reactions and bad (damaging) ones.
It takes a great deal of energy to keep our bodies operational. The shear mass of food consumed and metabolized should provide the insight that metabolism is the dominant chemical process that takes place in our bodies. It is also the process that creates almost all the chemically active free radicals in our bodies and eventually processes them into chemically inactive carbon dioxide and water.
If we compare the mass of food eaten with the mass of any set of antioxidants consumed, the mass of the antioxidants is minuscule. So, how can such antioxidants be a significant factor in reacting with any set of free radicals, damaging or not? There is little doubt that they can have a large effect on our health, but it is unreasonable to assume that they act as simple reactants consuming oxygen free radical species, thus competing with food. Their dominant influence has to be their role as catalysts. Catalysts play an enormous role in chemistry. They serve to promote chemical reactions but are not consumed in them. They are thus free to be used over and over again. In this way extremely small amounts can have very large effects. In biochemistry, catalysts are called enzymes. The large number of such enzymes operating in our cells does not seem to be common knowledge. There are more than 4,000 such enzymes that have been identified as playing discrete, specialized roles in our biochemistry. These too have to be synthesized in our cells. This should give another insight into enormity of the complexity of the chemistry that must take place properly in healthy cells.
Conclusion: The primary biochemical role of antioxidants is as enzymes or essential active components of enzymes (coenzymes). Specifically including the enzymes that support/enhance metabolism. This is not a revolutionary concept since the enzyme or coenzyme roles of many antioxidants have been identified. However, the understanding that this is the primary role of antioxidants has not been generalized to the extent it should be.
Conclusion: If we focus on the dominant chemical process in our body based on simple quantity, the energy supply process of metabolism, the true beneficial effect of antioxidants is not the selective elimination of damaging free radicals, but rather the enhancement of metabolism. This will increase the rate of consumption of oxygen, lowering the local oxidation potential, making oxidative damage less likely. As a natural unavoidable consequence, it will increase cellular energy, which can be used for everything including the prevention or repair of damage. Concerning cellular damage, it is very likely that the increased availability of cellular energy is considerably more important than the reduction of oxidation potential (oxidative free radicals).
I have a chart on my wall that presents an attempt to trace all the biochemical pathways of cellular metabolism and their interactions. This is only part of the chemistry that takes place in every one of your cells, and the magnitude of the complexity boggles the mind. To say it is extraordinarily complex is a gross understatement. Just looking at this overview chart is a simple way to be convinced that in order for this system to function, it must be highly organized and controlled. If we now view this from a straight thermodynamic argument, it requires energy to establish and maintain order, and diminishing energy progressively leads to increased disorder (increased entropy). As the energy available to a cell diminishes, for any reason, it is reasonable to assume that the highly ordered cellular chemistry will gradually become less well ordered and controlled. As this progresses, cellular reactions will start to malfunction. The ones that malfunction first will vary depending on the cell type and genetic makeup of that individual. Thus, the resulting degenerative "disease" will be expressed differently, but the root cause will be the same.
Conclusion: The primary cause of degenerative diseases is not due to damaging free radicals, but rather it is due to the required highly ordered cell biochemistry becoming disordered due to insufficient cellular energy to maintain the normal state of order. Once disorder starts, it can result in a multitude of different disease expressions, depending on which cell types are involved and the basic genetic makeup. The weakest link will go first, which will be unpredictable. You will end up with what looks like many different diseases, but they will have the same root cause.
Of course, superimposed on this cellular energy argument is the need for special nutrients that may not be required directly for the generation of cellular energy, but are required building blocks for other specialized biochemical reactions that are powered by adequate cellular energy, but cannot be accomplished by the availability of energy alone.
It is difficult to say how far this viewpoint can be taken. Is the formation of some unusual protein molecules found in the brains of deceased Alzheimer's disease patients simply due to disordered brain chemistry due to a lack of cellular energy? Are autoimmune diseases caused by low cellular energy altering the chemistry just enough to cause the immune system to recognize the cells as "foreign" and attack them? Is this the root cause of cancer? There is a great deal of well-documented studies showing that "antioxidants" in the diet can result in dramatically lower cancer rates. If this concept of a lack of cellular energy causing disease is as general as this, then the development of more advanced antioxidants (more likely blends of antioxidants), which more accurately should be called "metabolic enhancers" (as well as enhancers of other cellular reactions), should lead us to new revolution in health and medicine.
The necessary, incredible complexity of the biochemistry of every cell, required for the continuation of health and life itself, reinforces that realization that we depend totally on our natural, genetically controlled chemistry to keep us operational on a day-to-day basis. With few exceptions, we are totally at the mercy of this system operating correctly, on its own. We can influence it constructively in very few ways. Most powerfully, we can provide the basic building blocks (nutrients) that enable it to perform as designed. In only a very few ways, compared with all that happens in a cell, we have designed drugs that can intervene constructively in specific reactions or functions. Also, another important aspect for many, the nutritional approach is usually inexpensive, and the drug approach expensive. It is thus my belief that as a general rule, nutrition (and exercise) should always be the starting point for dealing with any disease. This will most likely correct a vast majority of diseases. It is only after this approach has been tried and failed, that treatment with drugs should be employed. Of course, there will always be obvious exceptions, such as medical emergencies, where conventional emergency procedures will be the safest bet.
I have another insight that I found important for me. Drugs very often operate by inter fearing with a natural biochemical process, such as lowering blood cholesterol by interfering with the production of cholesterol in the liver, or by lowering blood pressure by inter fearing with the reabsorption of water in the kidney. So many of them follow this basic principal of interference with a biochemical process. And, this is often very successful for treat a disease or problem, but it also runs a high risk of negative side-effects by inter fearing with some other process that results in damage. In contrast, dietary supplements operate by enhancing biochemical processes. Thus, when addressing a particular disease in this manner, the chances are that while the supplement is enhancing the desired process, it is also enhancing some other one that you were not planning for, with a very positive side-effect. Because of this, the risk of negative side effects from the supplement approach to treatment should be far less than that from drugs, and thus such an approach should be far safer.
How does this influence how we address antioxidants? We can assume individual antioxidants enhance different parts of the very extensive and complex metabolic process, and there is no single one that enhances every aspect. Therefore, to be complete, we need a matched set of antioxidants that covers the entire range of metabolic processes. Individual ones will enhance only one part of the metabolic chain, shifting the "choke point" to the next slowest part. We would like to know what that best complex of antioxidants is, but, at our present state of knowledge, not enough is known to design it. This leads to the following:
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David W. Gregg, Ph.D.
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