PROPOSED COMMON CAUSE AND CURE FOR ALL FORMS OF CANCER: ITEMS 1-21 (SECTION 2)Prepared for educational use by David W. Gregg, PhD.
Used with permission.
These web pages are for information only. They represent the observations, views and opinions of the author, and are not a recommendation for treatment. Anyone reading it should consult his/her physician before considering treatment.
Items 1-22 (Section 2)
1. DMSO (& MSM)
2. Carbon Dioxide
3. An Added Insight
5. A Vegetable Diet
6. Vitamin C
7. Vitamin C + MSM
8. Inositol Hexaphosphate (IP6)
9. Synthetic Blood
10.Oxygen Transport Summary
11. Coenzyme Q 10 (CoQ10)
12. Vitamin B12 and Folic Acid
13. The Inner Membrane of the Mitochondria
15. The Citric Acid (Kreb's) Cycle
16. Fruits, Vegetables & Herbs
18. Glutamine and Glucose—Cancer Foods
21. Mental Exercise—Glucose
1: DMSO (& MSM)
In my Health Note DMSO I describe how in the body DMSO forms equilibrium with MSM (the oxidized form of DMSO) and the combination becomes an oxygen transport system, enhancing aerobic metabolism. This operates at only one point, the respiratory chain (at the inner membrane of the mitochondria). John Boik, in his book "Cancer & Natural Medicine" (1996) cites a number of publications where DMSO solutions have caused fifteen different forms of cancer (in vitro) to differentiate (and thus turn into normal cells). The biochemical mechanism was not understood, however, it is fully consistent and explained by the mechanism proposed here. It also demonstrates a most essential point: It is possible to convert cancer cells back into normal cells, and it is logical to conclude that it happened by restarting aerobic metabolism.
So it works in vitro, but does it work in vivo (in living people)?
More than a year ago I was contacted by a lady who was interested in my discovery that DMSO can help Crohn's Disease (Health note: Crohn's Disease). During our discussion she mentioned that she had a basal carcinoma and had a date to have it removed surgically, something that she had to go through several times before. Thus, she was quite familiar with what they looked like. I told her about some of the reports of DMSO helping cancer, and she decided to try it. She told me she applied DMSO twice a day and by the time her surgery date arrived a month later the basil carcinoma had completely vanished (no surgery took place). This may be evidence of two important processes, reversal of cancer through the reestablishment of aerobic metabolism, and the eventual elimination of the cancerous cells through apoptosis. Apoptosis is programmed cell death that happens to most normal cells in a matter of 1-2 weeks or less. Even though anaerobic metabolism is the cause of the cancer, genetic damage is the cause of anaerobic metabolism. Reestablishing aerobic metabolism with DMSO could not correct the primary initiator, genetic damage. However, holding the cancer cells in a normal state long enough gives the natural process associated with healthy cells, apoptosis, time to eliminate the cancer cells. This approach kills cancer cells through making them healthy. Thus, unlike conventional chemotherapy, it makes normal cells even healthier in the process. This is addressed in more detail in later Items (below).
More recently I attended a medical conference (on alternative medicine) sponsored by the Orthomolecular Health Medicine Society in San Francisco (Feb. 26-28, 1999). One of the talks addressed DMSO. Numerous effects and benefits were described, but nothing was said about its oxygen transport characteristics or its affect on cancer. I joined a discussion group with the presenter afterwards and one lady (MD) said she had an experience where she had a melanoma on her leg and when she treated it with DMSO, it went away. She didn't go into detail so I wasn't able to find out how often she applied it and how long it took to go away.
My interpretation, if these reports can be trusted, is that the DMSO reversed the effect of a carbon dioxide deficiency depriving the cells of oxygen and thus stabilizing the cancer state. The DMSO-MSM complex would deliver oxygen by a mechanism that is independent of hemoglobin and thus would not be stopped by the lack of carbon dioxide. Once the cells had returned to normal they then produced enough carbon dioxide to reestablish stability in that mode. However, I would expect that the primary initiating cause may still be present and the normal state would be precarious. It also has the advantage of being able to apply a relatively high concentration of DMSO to the cancer (it is on the skin) and the DMSO has an abundant source of oxygen to transport (the surrounding air). It isn't at all clear that this would be effective on internal cancers. The required concentration may be far higher than the body can tolerate, and the primary source of oxygen (the lungs) may not be sufficient.
This is certainly not enough experience to draw firm conclusions, but as Chairman Mao once said, "The journey of 1000 miles begins with the first step". Any valid treatment of cancer will begin with the first case.
2. Carbon Dioxide
Most of us are familiar with the experience of breathing very rapidly for a while and becoming dizzy. You are not becoming dizzy because of too much oxygen, but rather too little. What you have done is to exhaust too much of your carbon dioxide. Carbon dioxide is essential for displacing oxygen from your hemoglobin (red blood cells) so it can be delivered to your cells where it is needed. When the carbon dioxide concentration falls too low, oxygen is no longer displaced from the hemoglobin and thus is no longer available to your cells. At this point aerobic metabolism stops and so do you. If all is working normally, when you stop breathing, the carbon dioxide level builds back up quickly and you recover.
Now lets consider a cancer cell (with anaerobic metabolism). Anaerobic metabolism (glycolysis) derives energy by converting glucose to lactic acid (& sometimes ethyl alcohol). This process produces no carbon dioxide if lactic acid is the product and only one carbon dioxide is ethyl alcohol is the product. This is compared to six carbon dioxide molecules per molecule of glucose for aerobic metabolism. Thus, once a cell starts to turn cancerous due to some other blockage in the aerobic metabolic sequence, it will start to produce less carbon dioxide, which will further reinforce the transition to cancer (anaerobic metabolism) by reducing the availability of oxygen. In a sense, this process serves to stabilize the state of cancer.
3. An Added Insight
The first stages of anaerobic metabolism produce pyruvate and NADH (along with two ATP's). In the case of cancer, the next stage involves the reaction of NADH reducing pyruvate to lactic acid, liberating a little more energy and consuming the NADH. Cancer always takes this second step making lactic acid. This provides a special insight. If the final stage of aerobic metabolism was operating, the respiratory chain, (and the aerobic metabolism blockage was earlier) then the NADH would preferentially be consumed by this stage and the conversion of pyruvate to lactic acid would not occur. However, the pyruvate is converted to lactic acid and thus the respiratory chain is not operable. This further identifies a specific problem area within the total aerobic sequence, and this problem always occurs in cancer cells.
This could be explained simply by the discussion presented in the Carbon Dioxide discussion above, describing why oxygen is not being transported to the mitochondria and thus the respiratory chain. This is likely to be a major part of it, but it may not be the full explanation for all cancers. The inner membrane of the mitochondria and thus the respiratory chain could also be disabled by the lack of coenzyme Q10 (CoQ10) or the combination of vitamin B12 and folic acid as discussed in items 11 and 12 below.
We all know that the cancer danger increases significantly when the tumor becomes metastatic, spreading tumor cells to distant parts of the body, starting more tumors. If this approach of supplying missing enzymes works, it should work on all the tumors, no matter where they have spread. The spread tumors should have the same source of metabolic disorder and thus should be fixed by the same method/treatment. However, I am going to postulate a new, unrecognized hazard that could be very damaging, but could also be avoided. To do this, I am going to have to invoke some biochemical processes that have not yet been demonstrated, at least not rigorously, but I firmly believe exist. However, I hope you will still hear me out.
I believe that the process of metastasis is not unique to tumors. Rather, I believe it is a natural process that occurs with all organs (heart, liver, kidney, etc.) to some extent where their cells get released and some take up residence in other organs where they don't belong. My primary argument is that there are too many cells in any organ for them to be perfectly contained. Thus, the body must have a mechanism for dealing with this process. If the body could not provide a remedy, our organs would gradually turn into a diversity of organs, not all in the right place. So what happens? Cells from one organ that get misplaced in another organ redifferentiate and turn themselves into the right type of cells. This redifferentiation process with cells that had already reached their final state of differentiation was once thought to be impossible. However, very recently it was reported that it can and does happen. Thus, we can now understand how the body can protect itself from natural metastasis of normal organs gradually converting each of your organs into a potpourri of organ cells.
What is the implication for cancer? Lets start with a metastasized cancer and then convert all the cancer cells back to normal cells via. the treatments proposed above. Lets say that the cancer started in the colon. Then the normalized cells would all be colon cells no matter where they have spread. What now? If we invoke redifferentiation as discussed above, these cells will then convert themselves into the type of cells of the organ they are in. However, even though they are now a different cell type, they still have the same enzyme deficiency that made them cancerous in the first place. Now let us remove the external source of enzymes. The cells will become cancerous again, but this time they will become a cancer that is characteristic of the organ they are now in. So, suddenly we not only have the original cancer form, but also all the different forms that are characteristic of the all the organs that have become host to the metastasized cells from the original cancer. Different cancers (characterized by their organ starting point) have different growth rates. Thus, this process is likely to produce a far more rapidly moving and deadly cancer.
5. A Vegetable Diet
There are numerous reports/claims that a diet consisting almost entirely of a diversity of vegetables can cause cancer tumors to shrink or even vanish. If these reports are correct, they make sense in the context of the theory that is presented here. I am postulating anaerobic metabolism and thus cancer can be caused by the blockage of the aerobic process at any point in the Kreb's cycle or the respiratory chain. There are numerous chemical steps that are involved in sequence and if any of them is blocked you have the potential of arresting the entire aerobic process. Each of these steps are catalyzed by specific enzymes and regulated by other enzymes. If any of these are missing, aerobic metabolism could stop.
Each vegetable has its own distribution of enzymes, some of which our bodies can incorporate sufficiently intact to help us supply our own essential enzymes. It is unlikely that one vegetable will have a distribution of enzymes that will supply all of out needs. However, a wide diversity of vegetables might. At least, the possibilities improve with the diversity of supply. This would include herbs. It is my belief that Chinese herbal medicine can be interpreted into western medicine or biochemical understanding by assuming they provide specific enzymes that are needed to remedy a particular disease that is caused by a particular enzyme deficiency. The problem, of course, is to try to identify what enzymes are missing for a particular disease state, and which vegetable or herb can provide it. This information is not available, most likely because the problem has not been clearly presented before. Since this information is not available, the safest approach is to resort to a "shotgun" approach using all vegetables in the hope that one or more will provide what is needed. I personally am comfortable with taking this approach with vegetables, but do not know enough about herbs to know when to worry about toxic effects.
I believe we need a focused research effort that identifies the enzymes that are missing in different cancers and the enzyme distribution that is provided by each vegetable or herb. Once that is in hand, treatment of cancer may become far more successful.
The primary focus that I have heard about is on maintaining a rigorous, strict vegetable diet. Fruits are avoided because they provide a ready source of sugar. Cancer cells love glucose and thus sugar, and if they can obtain that easily they will. If the sugar (glucose) is not so available, they are encouraged to go through the effort to incorporate a needed enzyme to start up the aerobic metabolism process. (This is my simplistic interpretation.)
This treatment mechanism is directed towards providing an external supply of essential enzymes that are produced internally in normal cells. As would be expected, when the external supply is terminated, by termination of the diet, one would expect the cancer to return and that is the reported experience.
6. Vitamin C
Vitamin C has many well-known health benefits, which I won't attempt to list here. However, there are two that should have special significance for preventing the initiation and progression of cancer.
Heavy Metal Elimination: I recently attended a paper presented at a medical conference (on alternative medicine) sponsored by the Orthomolecular Health Medicine Society in San Francisco (Feb. 26-28, 1999). The paper was focused on methods to encourage your body to excrete toxic heavy metals such as mercury, lead and cadmium. There were a number of promising treatments discussed, one of which was vitamin C. It wasn't necessarily the most effective treatment in all cases, but it was found to be significantly effective in mobilizing such toxic metals out of the cells and causing them to be excreted in the feces. Since such toxic metals could be a root cause for genetic damage, causing anaerobic metabolism and thus cancer. Removing them from your body could help in the prevention of cancer.
Oxygen Transport: Vitamin C has often been touted as having powerful "antioxidant" properties. As explained in my Health Note Antioxidants, I interpret this to mean that it can enhance metabolism. I thus decided to look more carefully at its biochemical properties. I discovered that vitamin C can be oxidized or reduced in your body. This is not a big surprise to most. However, specifically, when it is oxidized, it gives up two hydrogen atoms forming a new internal bond between oxygen and the two hydrogen's go into forming water. When it is reduced back again, it bonds with two hydrogen's again, forming the original form of the vitamin C. How lets look at the oxidation reaction that takes place at the inner membrane of the mitochondria, which powers the respiratory chain of aerobic metabolism. The conventional understanding is that oxygen diffuses to this membrane and reacts with hydrogen (in the form of NADH and FADH2), picking up two hydrogen atoms per oxygen atom, to form water. It is this reaction that powers the respiratory chain to form most of the ATP that is produced in the mitochondria. Now lets look at what can happen if oxidized vitamin C diffuses up to the same membrane. It too can react with two hydrogen atoms in the same way that oxygen can, but it will form reduced vitamin C instead of water. Since this can be an exothermic reaction, it too can provide energy to power the respiratory chain in the same way that oxygen can. Thus, in effect, vitamin C can participate in the transport of oxidation potential to the mitochondria and thus help facilitate the operation of the respiratory chain, with all its anticancer implications. I believe that this oxidation transport capability might be the major explanation as to why large doses of vitamin C seem to have powerful, general health benefits. It could be giving every cell more energy to cope with a variety of health issues. Basically, the vitamin C is transported to the lungs in the blood where it is oxidized. It then is transported to the cells where it diffuses to the mitochondria and delivers its oxidation potential, powering the respiratory chain, and cycle repeats. It should be noted that there have been many reports where mega doses of vitamin C have been attributed to causing the shrinking of cancer tumors.
7. Vitamin C plus MSM
It appears that the DMSO-MSM equilibrium can act as an oxygen transport system and vitamin C can also. What about the combination? One would expect the effects to additive. There is no reason to expect them to conflict and thus diminish the other's contribution. As an interesting single observation, I have a friend who is a very competitive athlete. When I told him about this theory, he decided to get some MSM powder and Vitamin C powder and mix them (about equally). They are both available in our local health food stores. He said that he then put about a quarter of a teaspoon of the mixture in water and drank it in the morning. It gave him an extreme rush of energy, considerably more than either did alone.
8. Inositol Hexaphosphate (IP6)
A search on Medline yielded numerous publications that indicated that IP6 held considerable promise for treating some forms of cancer. How does it function biochemically? It has been found in the blood of birds where its function is to facilitate the release of oxygen from hemoglobin. Therefore, the treatment with IP6 would logically work to compensate for the lack of carbon dioxide in the cancer cells and promote the availability of oxygen from hemoglobin. (There is some evidence that it may also act as an oxygen transporter independent of hemoglobin.) It is most interesting to note that its effect on cancer is not to kill the cells, but rather to cause them to revert back to normal cells, as this theory would predict.
9. Synthetic Blood
The research directed at finding effective forms of synthetic blood has included the identification of molecules that would be nontoxic and effective at transporting oxygen. If my theory is correct, all of these molecules would have potential for treating cancer although I don't know of any attempts made to investigate the use of synthetic blood for this purpose.
10. Oxygen Transport Summary
It appears that enhancing oxygen transport to the mitochondria of cancer cells could promote their reverting back to normal cells. This can be done either by enhancing the release of oxygen from hemoglobin, compensating for the lack of carbon dioxide (Inositol Hexaphosphate) or by providing a supplemental system of oxygen transport that does not depend on hemoglobin (DMSO-MSM system, Vitamin C, Synthetic Blood). Undoubtedly there are systems that I have not thought of, but the consequences of all such systems should be the same. They should all help to promote cancer cells to return to aerobic metabolism and thus return to being normal cells by the same basic mechanism. However, if my theory is correct, this is only part of the solution. It will work for some cancers that need the lack of carbon dioxide to stabilize their cancerous state. If the aerobic metabolism of the cell is totally blocked earlier in the aerobic metabolic sequence, providing oxygen at the end will not help. For such cancers it will be necessary to provide an external source of the missing enzymes necessary for the earlier steps. As was discussed earlier, a vegetable diet might achieve this. In such cases, a supplemental oxygen transport system in combination with a vegetable diet might be more effective than the diet alone.
There is a very reasonable concern that if one chooses to employ only one of the possible oxygen transport systems you will reach a toxic level (for the whole body) before you have adequately treated the cancer. Thought should be given to combinations (blends) of them. At first glance it would appear that their transport mechanisms would supplement each other without much interference. Thus it may be feasible to greatly enhance this mechanism with combinations while remaining below a toxic level for any one. I can only hope that those who are entitled to do cancer research will explore this.
11. Coenzyme Q10 (CoQ10)
We now move from oxygen transport to the mitochondria to the specific part of the mitochondria where it is used. Oxygen must be transported to the inner membrane of the mitochondria where the respiratory chain takes place. For this membrane to function, it is vital for it to contain the electron carrier CoQ10. In fact the CoQ10 was discovered when the treatment of isolated mitochondria with an organic solvent such as isooctane completely stopped aerobic metabolism, and when the material extracted was added back, aerobic metabolism was completely restored. In time, the essential material was identified and named CoQ10 (also called ubiquitone).
Application to cancer: If this theory is correct, one would expect the lack of CoQ10 could cause cancer, and replenishing it should cause the cancer cells to return to normal (if this was the only cause).I would like to refer to the results presented in a paper by Lockwood K, Moesgaard S, & Folkers: "Partial and complete regression of breast cancer in patients in relation to dosage of coenzyme Q10" (Biochem Biophys Res Commun 1994 Mar 30;199(3):1504-8 ). Pharma Nord, Vejle, Denmark. In this paper it is stated that "in a clinical protocol, 32 patients having -"high-risk"-breast cancer were treated with antioxidants, fatty acids, and 90 mg. of CoQ10. Six of the 32 patients showed partial tumor regression. In one of these 6 cases, the dosage of CoQ10 was increased to 390 mg. In one month, the tumor was no longer palpable and in another month, mammography confirmed the absence of tumor. Encouraged, another case having a verified breast tumor, after non-radical surgery and with verified residual tumor in the tumor bed was then treated with 300 mg. CoQ10. After 3 months, the patient was in excellent clinical condition and there was no residual tumor tissue."
These results are dramatic and are fully consistent with the theory presented here, which would conclude the anaerobic metabolism causing the breast cancer was caused by a lack of CoQ10, and when it was replenished, aerobic metabolism was restarted and the cancer cells turned back into normal cells.
12. Vitamin B12 and Folic Acid
It is well known that the combination of vitamin B12 and folic acid (both essential) are partners in the production of the heme molecule, which is essential for the production of hemoglobin. A deficiency of either will result in anemia. The combination will contribute to the production of hemoglobin and thus the transport of oxygen in the blood. It the above proposed mechanism for cancer is correct is, this mechanism alone would make one expect that the combination would be helpful in the treatment of cancer, if an oxygen release mechanism is present, such as IP6. However, the immediate focus is on the inner membrane of the mitochondria. As was discussed in 11 above, CoQ10 plays an important role. However, the inner membrane also has a series of "cytochromes" which provide the rest of the active roles. All of these cytochromes on iron incorporated in a heme molecule to function. Thus, the production of the heme molecule not only plays an essential role in oxygen transport, but also plays an essential role in the inner membrane of the mitochondria, and thus the respiratory chain. One would expect a deficiency in the production of the heme molecule would diminish aerobic metabolism from two directions, lowered oxygen transport in the hemoglobin, and reduced capability of the inner membrane of the mitochondria to carry out the respiratory chain even if the oxygen gets there.
As would be expected from the above cancer theory, a Medline search identified numerous publications that indicate an inadequate absorption of vitamin B12 or inadequate dietary folate are closely associated with increased cancer risk.
13. The Inner Membrane of the Mitochondria
As discussed in 11 and 12 above, the respiratory chain takes place at the inner membrane of the mitochondria and carries out the process called "oxidative phosphorylation" where ADP is converted back to ATP, the energy currency of the cell. This process is discussed in essentially all books on biochemistry. The investigative work that has been done is truly beautiful, with one exception. I believe one fundamental error has been made which is present in all the books, and which has major implications. The respiratory chain operates much like a fuel cell. We manufacture fuel cells to produce electricity. They are well know for their exceptional efficiency as well as the requirement to use simple, pure reactants, such as oxygen and hydrogen and not anything so complicated as gasoline instead of hydrogen. The respiratory chain seems to have similar characteristics. The processes entering the Kreb's cycle and the Kreb's cycle itself proceed in a way that produces two very simple forms of hydrogen, NADH and FADH2. They are then reacted with oxygen to yield electrons in the inner membrane, which then carry out the work of oxidative phosphorylation with the help of CoQ10 and the cytochromes. However, there is one problem with the descriptions. They show the oxygen and the fuel, NADH and FADH2 in solution on the same side of the membrane. Any fuel cell engineer knows that you must keep the oxygen and the fuel (hydrogen) in solution on opposite sides of the semi-permeable membrane (the inner membrane of the mitochondria). Otherwise they will react directly in the solution, producing heat but no electrons, and thus producing no useful work. There is nothing more fundamental to the design of a fuel cell than this. To assume that nature violates this fundamental design requirement, which would greatly reduce efficiency at best, is to assume that the great designer in the sky is not as intelligent as the average fuel cell engineer. Frankly, I think She might resent that. This erroneous assumption has resulted in a number of downstream distortions in mechanisms that need correction. However, I won't attempt to accomplish all of them. I will only address what is important to the cancer theory presented here.
I won't reproduce the mechanism presented in the biochemical books. You can get one and read it there. I will simply state what I believe must the be correct process.
1) The fuel produced from the Kreb's cycle, such as NADH diffuses to the inner wall of the inner membrane of the mitochondria and gives up two electrons forming NAD+ and H+, which remain in solution. 2) The electrons move through the membrane attached to CoQ10 and cytochrome molecules, doing the work required to produce ATP from ADP. 3) When the electrons (negative charges) finally reach the outer surface of the membrane they combine with two hydrogen ions (2H+) to make two hydrogen atoms (2H) attached in some way to the surface. 4) These hydrogen atoms then react with oxygen to form water (at the outer surface of the membrane). 5) It is the chemical energy of this reaction that creates the electrical potential in the membrane that allows the electrons to do the work on the CoQ10 and cytochromes needed to produce ATP from ADP. 6) The positive electric charge that is produced on the inside of the membrane due to the loss of electrons is neutralized by the diffusion of negatively charged phosphate ions across the membrane, into the matrix (along with ADP). These phosphate ions, along with the hydrogen ions that have been produced are needed to react with ADP to make ATP. The newly created ATP diffuses out of the mitochondria and is used for energy throughout the cell, creating ADP, a phosphate ion, and a hydrogen ion. The ADP and phosphate ion then pass back though the membrane, but the hydrogen ion doesn't . It is consumed at the outer surface of the membrane to make water by the mechanism just discussed.
The importance of understanding this change in mechanism is that it shows that the oxidizing species, (O2, etc.) does not have to diffuse across this relatively impermeable inner membrane to carry out its task at the inner surface. It does it at the outer surface of the membrane. One of the added benefits is that this allows the process to be more flexible in its ability to utilize different oxidizing species. If they all had to cross this low permeability membrane to the inner surface, each would probably have to have its own specialized protein transporter embedded in the membrane. Such specialized transporters are not known to be there and would not be expected to be there if my model is correct. There are simply too many different molecules that have been found to carry oxygen potential in the blood for my model to be incorrect. Specifically, it explains why MSM and vitamin C can be effective. The oxidizing species simply have to be able to react with hydrogen to form a reduced species, delivering the energy of reaction to the oxidative phosphorylation process.
Normal cells die on a regular and planned basis, and their component molecules are metabolized and thus recycled. This planned (sometimes called programmed) cell death is called apoptosis. The life span of a particular cell can vary from a few hours to many years. However, the majority of the cells die and are replaced every few days. ("Textbook of Biochemistry with Clinical Correlations" Thomas M. Devlin, Editor, Fourth Edition, 1997) This normal process is essential for maintaining the health of the organism. One of the distinguishing features between cancer cells and normal cells is that cancer cells do not exhibit apoptosis. The live and multiply indefinitely.
How does this relate to cancer and the approach proposed here. One of the critical features distinguishing cancer cells from normal cells is that cancer cells do not undergo apoptosis. They continue to multiply unchecked, growing in number until the host is destroyed. However, if the cancer cells can be caused to revert back to normal functioning cells, the natural process of apoptosis can then proceed and the "normalized" cancer cells will gradually die. This will not be due to a chemical attack, as with chemotherapy, but rather through normalizing cell function. With luck, the remission of the cancer could take place within a matter of a few weeks. However, this depends on the cancer cells exercising their apoptosis option. If every cell chose apoptosis at the same time, we would obviously die. We want the "normalized" cancer cells to preferentially recognize their need to commit apoptosis to preserve the health of the organism. How this selection can be made to be preferential for cancer is not understood. However, there are some experimental measurements that have identified some molecules that appear to promote this. One of these is DMSO, which is discussed, in the same book referenced in Item 1 above. Others have also been identified. However, one would expect that any approach that promotes cancer cells to revert back to normal cells would result in an increase in the rate of apoptosis, and this alone could explain how some "nutrients" can induce apoptosis of cancer cells.
15. The Citric Acid (Kreb's) Cycle
The anaerobic stage of metabolism produces pyruvate from glucose when the aerobic metabolism sequence is operational. Pyruvate is then oxidized to acetyl-CoA, which enters the Krebs cycle (A nine step cycle). (This is also called the citric acid cycle.) The combination of pyruvate oxidation and the Krebs cycle converts one molecule of glucose into 6 carbon dioxides, 10 NADH's, 2 FADH2's and 4 ATP's. The ATP molecules are then used for cellular energy. When the 10 NADH's and the 2 FADH2's are then fed into the respiratory chain already discussed, they are oxidized to produce an additional 34 ATP's. It can thus be seen that the primary task of the Krebs cycle is to produce NADH and FADH2 as feed for the respiratory chain, along with the release of the carbons as carbon dioxide.
Kreb's cycle vital to both cellular energy and primary biochemicals for biosynthesis: The Kreb's cycle is critical not just for the production of energy (the feed of NADH and FADH2 to the respiratory chain). It also produces key biochemical feedstocks required for the further synthesis of a wide variety of biochemicals essential for cellular function. As an example, the forth step produces a-ketoglutarate. This is then used by the cell to produce at least sixteen additional essential biochemicals. The ninth step produces oxaloacetate, which the cell uses to produce an additional eight essential biochemicals. These are just some of the ones that have been identified. There are probably many others. When the Kreb's cycle shuts down, it not only removes a vital source of energy, but it also removes a key source of biochemicals essential to a broad range of cellular function. Thus, even if the energy function was replaced (I don't know how) the cell would still cease to function normally.
Each step of this sequence requires its own special enzymes both to catalyze the reactions as well as those that control the rate of each reaction so that they operate in a coordinated manner. If any one of the steps is blocked due to a lack of an essential enzyme, the entire sequence could shut down, stopping all of aerobic metabolism.
It is my belief that most cancers probably start with an interruption of the Kreb's cycle, which arrests aerobic metabolism and forces the cell to revert to anaerobic metabolism. The 100 or more identified oncogenes are genes that formerly produced essential enzymes for the Kreb's cycle, but have become damaged and no longer do so. Suppressor genes are genes that compensate in some way for the damaged genes that are now oncogenes. It is likely they produce enzymes that provide an alternative path that allows the Kreb's cycle to continue to operate. However, it would be difficult to distinguish between a shut down caused by a direct interruption of the Kreb's cycle or one that is caused by a shut down of the respiratory chain which in turn would shut down the Kreb's cycle.
It has been estimated that there are as many as 100,000 genes for the entire mammalian genome. If the approximately 100 oncogenes discovered thus far represent a reasonable representation of the complete set, this would indicate that cancer is initiated/controlled by a rather small part of the complete biochemistry of the cell. Such a conclusion would be consistent with the theory of cancer presented here.
It should also be pointed out that there are two separate sets of genes in every cell. There is the set in the nucleus, derived from both the mother and the father, which is the one that we commonly think about. However, the mitochondria have there own set of genes that are derived exclusively from the mother. An oncogene that disrupts the Kreb's cycle would have its origin in the mitochondria. An oncogene that disrupts oxygen transport would have its origin in the cell nucleus. If the origin of the oncogene was known, this would give some indication as to how it operates. There is another important difference. There is only one nucleus and thus one set of nuclear genes in a cell, but there are many mitochondria and thus sets of mitochondria genes. In fact, mitochondria can divide and thus multiply, changing the numbers in a cell in response to cellular (energy) needs. How can an oncogene in one mitochondria propagate to many mitochondria? Is it by reproduction of the mitochondria in the cell? Can you have damaged and undamaged mitochondria in the same cell and how will this affect cancer? These are some of the challenging questions I don't have answers to.
16. Fruits, Vegetables & Herbs
There are numerous reports that many fruits, vegetables and herbs can inhibit the onset and progression of cancer. How can this be explained within the context of the theory presented here? We have to assume that the fruits, vegetables and/or herbs contain essential cellular nutrients/biochemicals that the cancer cells can no longer produce for themselves and the consumption of the appropriate set allows them to be digested, enter the blood stream, get to the cancer cells where they are absorbed, resulting in the biochemistry of the cells returning to normal. This could happen either by the providing the missing enzymes (or coenzymes) no longer produced in the cells due to damaged genes, or by providing the end point biochemicals the missing enzymes are responsible for producing. Examples of end point biochemicals would be those that have been identified as derived from the Krebs cycle, which is not operating in the cancer cells.
One Recent Review Paper: (Craig WJ, "Phytochemicals: guardians of our health" J Am Diet Assoc 1997 Oct; 97(10 Suppl 2): S199-204) "The foods and herbs with the highest anticancer activity include garlic, soybeans, cabbage, ginger, licorice, and the umbelliferous vegetables (caraway, carrots, celery, dill, parsley). Citrus, in addition to providing an ample supply of vitamin C, folic acid, potassium, and pectin, contains a host of active phytochemicals. The phytochemicals in grains reduce the risk of cardiovascular disease and cancer."
This should be considered a guide giving the best demonstrated effective foods and herbs, but not something that should be limiting. Other fruits, vegetables and herbs may be less effective but still helpful. This may also vary significantly between individuals. It brings to mind one lady I know who discovered that cherries, including the dried ones sold at her grocery store, greatly alleviated her arthritis. When she ate them daily, her arthritic pain went away and when she stopped, it returned in a couple of weeks. This was repeated enough to where she was convinced of the connection. I have never hear of this working for anyone else. It appears that cherries contain some specific phytochemical that addresses her individual deficiency. Thus, observe you own reactions to different variations, and trust your observations.
Garlic is a particularly interesting case because it seems to be the most effective (anticancer agent) of the vegetables or fruits, and the active ingredients have been identified. . Diallyl sulfide, a major volatile thioether present in garlic is believed to be the active ingredient most responsible for garlic's anticancer properties. In addition, ajoene, another major compound of garlic has been shown to induce apoptosis in human leukemic cells.
Diallyl sulfide: I find it very interesting to note the similarity between diallyl sulfide and dimethylsulfide. They both consist of one sulfur with two organic molecules attached. In the case of dimethylsulfide two methyl groups (CH3) are attached, in the case of diallyl sulfide, to allyl goups (C3H5) are attached. In the health note "DMSO" it was pointed out that there is an equilibrium established between dimethylsulfide (no oxygen attached), DMSO (one oxygen attached to the sulfur) and MSM (two oxygen's attached to the sulfur). Because of this equilibrium, this set of molecules can act as an effective oxygen transport system. Since diallyl sulfide is a very similar molecule and the same bonding sites are available on the sulfur, one would expect it to behave in a similar manner, and it seems to.
Consistent with the discussion on DMSO, this would suggest that one of the major anticancer contributions of diallyl sulfide (and thus garlic) is to enhance oxygen transport to the cancer cells.
Ajoene: Ajoene (C9H14OS3) is a major compound of garlic that has been shown to induce apoptosis in human leukemic cells (Dirsch VM et al, "Ajoene, a compound of garlic, induces apoptosis in human promyeloleukemic cells" Mol Pharmacol 1998 Mar, 53(3): 402-7). It is a linear carbon-sulfur chain containing nine carbons and three sulfurs (with two bonds each). This means that each sulfur has sufficient extra bonding sites to attach two oxygen's. Thus, a maximum of six oxygen's could be attached - if oxygen saturated. Thus, it too could function as an oxygen transport agent with even greater oxygen carrying capacity than DMSO or diallyl sulfide. There is some evidence that it stimulates peroxide production, which would be consistent with this interpretation.
The assumption would then be that ajoene helps the cancer cells to revert back to normal cells by enhancing oxygen transport (turning on aerobic metabolism) and once the cells become normal they go through the normal process of apoptosis.
18. Glutamine and Glucose – Cancer Foods
As has been discussed, anaerobic metabolism primarily consumes glucose. Since it is so inefficient compared to aerobic metabolism, cancers have a voracious appetite for glucose to sustain themselves. This is why excess consumption of sugars tends to promote cancer growth. It is less well known that cancers have an equally voracious appetite for glutamine. ("Glutamine and Cancer" Wiley W. Souba M.D., Sc.D., Annals of Surgery, Vol. 218, No. 6, 715-728) Briefly, glutamine is the most important "nitrogen shuttle" in the blood. It brings the organic nitrogen to the cancer cells so they can use it to make the essential amino acids and thus proteins required to make more cancer cells. As the glutamine supply goes to zero, tumor growth goes to zero. A rich dietary source of glutamine is red meats. This is why excess consumption of red meats and other concentrated sources of protein tend to promote tumor growth. Since normal cells also require both glucose and glutamine, reducing the intake of either to zero would have an undesirable outcome. Consumption in moderation (small quantities), along with fruits and vegetables seems to be the best approach.
As was discussed in item 18, cancer tumors require glutamine to grow. So do your muscles. Body builders supplement with glutamine to help develop larger muscles. Muscles not only consume glutamine in order to grow, but in the times of insufficient dietary glutamine, muscles can serve as a source of glutamine (for the blood) and diminish is size by doing so. This is why as cancer tumors grow, there is usually a wasting away (diminishing in size) of muscle structure. As the tumor (s) extract the glutamine from the blood, the body tries to resupply it by obtaining it from the muscles (that which hasn't been supplied by diet.)
Postulation: The tumor-glutamine-muscle degeneration connection is a reversible chemical reaction. Essentially all chemical reactions are reversible even though the degree of reversibility can vary widely. As was already discussed, the process of forming muscle tissue using glutamine from the blood, is reversible in that the muscle tissue can resupply glutamine to the blood as needed by the body. The same is most likely true for cancer tumors, even though the reversal process where the tumor wastes away by resupplying glutamine to the blood does not appear to take place as easily as for muscles. The big question is can this reverse process be made to happen for tumors and how can it be maximized? I propose that this might be achievable by exercising in a manner that promotes the building of muscle. Aerobic exercise is obviously beneficial, but body builders know full well that weight-bearing exercise is far more beneficial for building muscle. I thus propose: Exercise that builds muscle in combination with a diet that minimizes the intake of glutamine has a good chance of reversing the glutamine reaction in the tumor, causing it to degenerate to supply glutamine to the blood, thus building muscle at the expense of tumor mass. Exercising in such a manner in combination with the rest of the dietary approaches discussed in this health note should have a good chance of inhibiting the onset or progression of cancer and with luck it could even reverse its progress. However, you are attempting to force a chemical reaction to go in a direction that is less preferred. Thus, we are talking about a committed, serious exercise program. I suspect you should anticipate needing at least 2-4 hours of exercise every day. Possible even more. Mimic serious body builders.
This presents a reasonable biochemical explanation for Lance Armstrong's dramatic recovery from cancer. Lance Armstrong is the only American ever to have won the Tour de France riding for an American team (The U.S. Postal Service Team). He won it in 1999 just two-and-a-half years after being diagnosed with advanced testicular cancer. It had spread throughout his body. He received conventional treatments, and trained intensely for racing in the Tour at the same time. He credits his commitment to an exceptionally vigorous training program to have played a key role in his recovery from cancer. The French newspaper L'Equipe called his win "the comeback of the century" and Armstrong's response: "If you ever get a second chance in life, you have got to go all the way".
This opens up the question as to whether some of the supplements, other than glutamine, that are used by body builders to build muscle, will enhance this tumor wasting, muscle building process. I could even envision that some of these that might risk promoting cancer growth without a coupled exercise program may become highly beneficial when, and only when combined with a muscle building program. I suspect some of them will, and I hope research will be done to evaluate this possibility.
Unfortunately, people suffering from cancer frequently have highly diminished energy. This makes this exercise option even more difficult. Thus, in reality, there may be only a limited fraction of cancer patients who will be able to explore it.
A second argument for exercise. As was pointed out in item 18, cancers have a voracious appetite for glucose due to their inefficient extraction of energy from glucose. This is an unavoidable consequence of their anaerobic metabolism. Normal aerobic cells with aerobic metabolism can obtain almost 20 times more energy from a molecule of glucose. An excess of glucose (sugar) in the diet will promote the progression of the cancer. However, aerobic (any) exercise causes the muscles to consume glucose. As the glucose is consumed during exercise its availability diminishes. This should inhibit the progression of the cancer. Exercise should also help to compensate for excess sugar in the diet (if done soon enough). Sometimes excess dietary sugar is unavoidable. During the exercise there is a competition between the cancer cells and normal cells for the glucose. As glucose levels in the blood diminish, one would expect the cancer cells to suffer the most first. Normal cells should continue to function to much lower levels due to their far more efficient use of the glucose. Conclusion: Exercise of any type should inhibit the progression of cancers.
21. Mental Exercise-Glucose
Your brain, through mental activity, consumes considerably more than 50% of the glucose in your body, far more than any other organ or activity. Mental activity is your most efficient method for consuming glucose. Thus, to consume excess glucose I would suggest you curl up with a book that seriously challenges your brain, such as a physics or biochemistry text. If you find yourself falling asleep, this is probably due to greatly lowered glucose in your blood.
It has occurred to me that this same approach might help diabetics achieve some control of high blood sugar with reduced requirement for insulin.
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