Kill Cancer Cells The life and death of cancer cells

PROPOSED COMMON CAUSE AND CURE FOR ALL FORMS OF CANCER: ITEMS 22-32 (SECTION 3)

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 22-32 (Section 3)

22. Two Forms of Programmed Cell Death
23. Cell Aging—A Primary Cause of Genetic Damage Leading to Cancer
24. Nutrition Prevention of Genetic Damage, Its Propagation, and Cancer
25. Poor Circulation and Cancer
26. Nutrition and Chemotherapy Synergism
27. Oxygen Supply Inhibits Angiogenesis & Thus Tumor Growth
28. "The Antioxidant Miracle" by Packer & Coleman (John Wiley & Sons, Inc. 1999)
29. Cancer, Schizophrenia, Abram Hoffer, Linus Pauling and This Cancer Theory
30. "Vitamin C & Cancer" by Dr. Abram Hoffer, PhD, MD, FRCPS with Dr. Linus Pauling, PhD, Nobel Laureate, Chemistry and Peace, Quarry Health Books
31. Three Separate Paths for NADH Synthesis Involving Niacin, Niacinamide, Vitamin B6 & Tryptophan
32. The Megadose Application of Vitamin C and Niacin



22. Two Forms of Programmed Cell Death
Programmed cell death has the characteristic of no longer needed cells committing suicide for the benefit of the whole. To be sure there may be external encouragement (catalysts) such as hormone signals from neighboring cells, but the chemical changes that lead to the demise of the cells occurs within the cells themselves. Once encouraged, they implement the rest themselves. This process of an orderly elimination of damaged or no longer needed cells is absolutely vital to survival of our bodies. I am proposing that the body has introduced redundancy into this process to better insure its success. It can take place via two quite different processes. If the primary one fails, the other can serve as a backup.

Apoptosis: Apoptosis is the commonly recognized, primary mode of programmed cell death. In this mode, the cell produces/releases enzymes within itself which proceed to dissolve the cell from within. The resulting basic nutrients reenter the blood and can be recycled.

Immune/macrophage attack/dissolution: I propose there is a second mode of programmed cell death, which at first glance appears to be an uninvited external attack by the immune system. It involves the immune system in the form of macrophages attacking, engulfing and dissolving the errant cells. This basic process is well know to happen as a mechanism for disposing not just of foreign pathogens (bacteria) but also of damaged cells. I am proposing that in some cases, there is a deliberate action by the cell to encourage the attack. Let us postulate that a cell that has experienced genetic damage can, in most cases, recognize the need for its removal and trigger programmed cell death. Apoptosis is the primary mode. However, let us suppose this mechanism fails. Then, I propose, that the cell has a second option to achieve the same result. It can deliberately display proteins on its surface that will make it look like a foreign body to the immune system and trigger an attack by macrophages. Thus, this is programmed cell death as much as apoptosis even though it depends on the immune system to complete the task.

Relevance to Cancer: With the billions of cells in the body constantly dividing and being exposed to potentially damaging chemicals, it is highly likely that millions are produced every day with the right type of genetic damage to produce cancer. However in the vast majority of these cases the cells have sufficiently functioning cell chemistry to trigger one of these forms of programmed cell death. If this is successful, the potentially cancerous cells self-destruct and the cancer never develops. For apoptosis we are depending solely on the chemistry within the cell itself. However, for the second, backup, mode we depend on the cell signaling the immune system and the immune system being able to finish the task. Because of this second system, it can be seen how a strong immune system can play a vital role in preventing these cells from progressing into the unchecked growth of cancer. I am unaware of any solid observations that apoptosis occurs to new cancer cells. This would happen quickly and would be difficult to observe. However, there are numerous reported observations of the immune system attacking and destroying cancer cells. This would support the existence of the second proposed mode of programmed cell death.

Cancer: We then have the cells that have the genetic damage for cancer and are unable to initiate either form of programmed cell death, apoptosis or immune system attack. These are the ones that develop in to unchecked cancer. The immune system is totally ineffective as a defense because the cells are not recognized as foreign cells. This explains the apparent paradox of why some cancer cells have been observed to be attacked and destroyed by the immune system while cancers that continue to develop are almost unaffected by the immune system. The first class of cells have been programmed for cell death by displaying the appropriate immune system, signaling proteins on their surfaces, and second class display no such signaling proteins.


23. Cell Aging - A Primary Cause of Genetic Damage Leading to Cancer
All cancers start with genetic damage. All forms of genetic damage do not lead to cancer. It has been proposed above that specific genetic damage causing the cell to become anaerobic is required. What causes this damage. It has been clearly demonstrated the many toxic chemicals, called carcinogens, can cause the genetic damage that results in cancer. Some viruses have also been implicated. Recent biochemical discoveries would indicate that the process of cellular aging alone may be a primary cause. Human cells can divide approximately sixty times before they can no longer divide and die. In contrast, cancer cells have no such counting mechanism and divide indefinitely without ever dying. Normal human cells have a counting mechanism that is handled by an extension/tail on the chromosomes named a telomere. This telomere grows shorter with each division until after the last division it no longer exists and the cell dies. However, as the telomere shortens, the cells not only have fewer divisions left, but they also act like older and weaker cells. Consistent with this, as telomere grows shorter, the cell gets weaker and divisions are not so well regulated (controlled). The checking mechanism that is supposed to assure perfect divisions with no genetic alterations starts to operate imperfectly and cells with genetic damage results from an ever-increasing fraction of cell divisions. Dr. Richard Lerner and his team at the Scripps Research Institute in La Jolla compared the effects of aging on 6,000 genes and found that 61 key genes went through dramatic changes from age 9 to 90. There are checkpoint genes that assert quality control over cell division. When the checkpoint genes fail, mistakes in genes are perpetuated into the new cells and their daughter cells. Given this observation of genetic damage with age, it is reasonable to postulate that a fraction of these imperfect divisions result in genetic damage that produce cancer cells. Most of these are eliminated by the two-programmed cell death mechanism described above. However, eventually some survive, as discussed in 22 above, and develop into cancer. Thus, cellular aging alone can be a primary cause of genetic damage leading to cancer, and probably explains the onset of most cancers that occur increasingly with age.

Conclusion? Different organs in the body probably age at somewhat different rates. Once an organ reaches the age where divisions are more likely to produce cancer cells, the continued creation of new cancer cells is likely to continue, even after all existing cancer cells have been destroyed (chemotherapy or radiation) or removed (surgery). In theory this can be avoided by the removal of the entire organ (breast, prostate, etc.) if you can live without it.

Lung and Skin Cancer: I would like to propose considering a cellular aging connection between smoking and lung cancer. The smoke can damage or kill lung cells, making cellular divisions take place more rapidly, in order to provide the replacement cells. Thus, the lung cells age more rapidly. The aging then causes the cancer. This would also explain why some people can smoke while young, quit, and still get smoking related lung cancer many years later. It doesn't make any difference when you smoke. It still ages the cells faster, and there is a memory of this in the cells for life. The same logic would apply to the exposure of skin to ultraviolet light (too much sun exposure).


24. Nutrition Prevention of Genetic Damage, its Propagation, and Cancer
Briefly, there are a number of ways that proper nutrition (diet and dietary supplements) can prevent the onset of cancer.

Reduction of Cellular Division Rate and Thus Cellular Aging: Cells divide to provide new cells to replace old, warn out, damaged cells. To the extent that optimum nutrition can extend the useful life of existing cells, the need for their replacement slows and so does the aging/replacement process.

Reduction in Genetic Damage due to Imperfect Cellular Division: Optimum nutrition should increase the energy available to the cells and thus help the checkpoint genes do their job of assuring adequate quality control over cell division, minimizing the production of daughter cells with genetic damage due to faulty divisions.

Elimination of Genetically Damaged Cells: Optimum nutrition should help damaged cells retain enough energy to activate either form of program cell death discussed in 21 above. The cell with genetic damage that can produce cancer then has the option/energy to institute programmed cell death, eliminated the potentially cancerous cell.

Supporting Evidence: Diet and dietary supplement prevention of the onset of cancer is not a new concept. There have been a very large number of studies of diets and dietary supplements reducing cancer rates by factors as much as 50% In some cases the studies involved tracking the diet of thousands of people over tens of years, while in others it involved double-blind studies of a smaller group, taking specific dietary supplements over shorter periods of time. I won't attempt to present a review of the studies here. The reader can do that. I am simply supporting the assertion that proper diet/nutrition can prevent the onset of cancer, which provides reasonable support for the mechanism proposed here.


25. Poor Circulation and Cancer
If inadequate cellular nutrition can make cancer more probable, as discussed in 24, then inadequate blood circulation could contribute also. Good circulation is required to deliver adequate nutrition to the cells. There could be a number of causes for poor circulation, one of which is arteriosclerosis. Thus, one would expect arteriosclerosis could be a contributing factor to cancer. Since it usually increases with age, it correlates well with increasing cancer rates with age. In particular, it may contribute significantly to breast and prostate cancer, where circulation is low.

Lysine, Vitamin C & Argenine: It has been reported that a combination of lysine and vitamin C can reverse/prevent arteriosclerosis. Argenine is known to be a precursor to the production of NO, which can help to dilate blood vessels. It has been reported to help with heart disease. Both of these approaches would contribute to enhancing circulation and thus are promising candidates for preventing cancer.

Exercise: There is nothing more important than exercise to enhance circulation.


26. Nutrition and Chemotherapy Synergism
It would appear that nutritional therapy should greatly enhance the effectiveness of chemotherapy in a surprising way, beyond simply enhancing general health.

To illustrate, I would like to take a specific example and then generalize. Taxol is a commonly used chemotherapy agent. It is reported to work by interfering with the transport of protein molecules along the cytoskeleton filaments in the cancer cells. This is the major transport path required for many aspects of the cell chemistry, including the ability to divide and make new cells. The interference not only stops the cancer cells from dividing but also eventually results in cell death. This can control the cancer for some time, but experience has shown that the cancer eventually "mutates" and a creates a version of the same cancer that is resistant to the Taxol. The cancer then starts to grow again and continues to progress unless another chemotherapy agent can be found to stop it again.

The mechanism that the resistant cancer cells use for defense is fascinating. It has been found that they have developed a capability to pump the Taxol out of the cell where it can do no harm.

The fact that the anaerobic cancer cells, which already lack sufficient energy to perform normal cell functions, would still have enough energy to invent and deploy this novel defense, a sophisticated Taxol pumping system, seemed inconsistent to me. After being bothered by this for a number of days, I suddenly realized how it might have happened. The cancer cells didn't develop the Taxol pumping system. Normal, non-cancer cells did. When they became cancerous, via the ongoing, age-related, defective divisions discussed in Item 23 above, they retained this capability as they divided to form cancer cells.

It is reasonable to presume that the normal cells have developed this pumping defense because Taxol was chosen because of its ability to preferentially kill cancer cells and be far less toxic to normal cells. Why is the Taxol not so toxic to normal cells? It is reasonable to postulate it is because the normal cells quickly develop this Taxol pumping capability.

If this is true, then the key to successfully treating with Taxol is to prevent normal cells, resistant to Taxol, from undergoing faulty divisions forming Taxol resistant cancer cells. The key to accomplishing this is proper nutrition as discussed in Item 24 above. Thus, combining nutritional treatment along with treatment with Taxol should be more effective than treatment with Taxol alone. It is also possible that nutritional treatment alone would not be as effective as using it in combination with Taxol. The Taxol may kill existing cancer cells more effectively than the nutritional-programmed cell death approach. It is thus reasonable to conclude that the combination would be more effective than either used alone. However, this points out a clear need to establish the most effective protocol.

This basic theory should apply to many forms of chemotherapy where it is commonly observed that the chemotherapy ceases to be effective against the cancer with time, and a resistant variation appears. It is logical that one would expect this because chemotherapy agents are chosen because they are far more toxic to cancer cells than normal cells. This is likely to be true because the normal cells can rapidly develop a defense. It is not much of a stretch to presume that this defense, whatever it might be, could then be carried along when this normal cell undergoes a faulty division that produces a cancer cell. It is also likely that some form of pumping mechanism keeping the chemotherapy agent out of the cell is the basis of most of the defense mechanisms.

Conclusion: All forms of chemotherapy could be made more effective by combining them with nutritional therapy, using the chemotherapy agent to kill existing cancer cells and nutritional therapy to prevent new, chemotherapy resistant cancer cells from being created.


27. Oxygen Supply Inhibits Angiogenesis & Thus Tumor Growth
It appears that oxygen supply inhibits the formation of the vascular network that that is required for tumor growth. Conversely, an oxygen deficiency promotes the production of vascular endothelial growth factor (VEGF), which plays a key role in angiogenesis (the formation of the tumor supporting vascular-blood supply-network).

This was reported in "FOCUS", the newsletter from Harvard Medical, Dental and Public Health Schools, May 19, 2000. The article summarized work reported in the May 11, 2000 issue of Nature: "Growth Factor Expands Tumor Cell Networks" by Rakesh Jain, Gabriel Helmlinger, Mit Endo, Lynn Hlatky and Napoleone Ferrara.

Summary: Vascular endothelial growth factor (VEGF) promotes angiogenesis and thus the growth of tumors. Oxygen starvation promotes the production of VEGF and thus promotes angiogenesis. They showed that well-nourished and oxygenated cells near the edges of a tumor maintained their normal form, while the starving cells near the center began branching and forming vascular networks within a few hours. They observed a gradient of VEGF expression that was inversely correlated with, and apparently induced by, the oxygen gradient.

I believe this is exciting news because it presents an additional mechanism where promoting oxygen transport to the tumors will inhibit their growth.


28. "The Antioxidant Miracle" by Packer & Coleman (John Wiley & Sons, Inc. 1999)
This is a wonderful book which summarizes the many years of research performed by Lester Packer, Ph.D., Director of the Packer Lab., University of California at Berkeley. It presents a large amount of valuable information, far too much to attempt to summarize here. I would like to limit myself to interpreting a main thread into the context of the cancer theory presented here. His primary focus is to identify five antioxidants (and only five) that appear to form an antioxidant network, they work together. The five are Vitamin C, Vitamin E, Glutathione, Alpha Lipoic Acid and Coenzyme Q10 (CoQ10). The roles of Vitamin C and CoQ10 in the context of this theory has already been addressed (Items 6&11). However, at this point I would like to limit my comments to the mechanisms of the special synergism between Vitamin C and Vitamin E and then the special characteristics of Alpha Lipoic Acid and Coenzyme Q10 as applied to this theory. These are mechanisms I am proposing, not ones presented in the book. It would appear that this particular set of molecules work together to transport oxygen to the cells, and the mitochondria within the cells, and prepare the mitochondria to receive the oxidation potential in a way that it can be used in aerobic metabolism.

Vitamin C & Vitamin E Special Synergism: As discussed in Item 6, Vitamin C has an oxidized and reduced state in equilibrium in solution that can serve as an oxygen transport system. The same is also true of Vitamin E. Vitamin C is soluble in the aqueous phase (cell cytoplasm) an Vitamin E is soluble in the oil phase (cell membranes). In order to transport oxidation potential to the mitochondria starting at the lungs, it will be necessary to transport it across cell cytoplasm as well as cell membranes. Vitamin C and Vitamin E become partners in this process. Briefly, oxidized vitamin C diffuses up to a cell membrane and delivers it to Vitamin E in the cell membrane. The resulting oxidized Vitamin E carries it across the cell membrane and delivers it to reduced vitamin C in the cytoplasm on the other side. The newly oxidized Vitamin C then diffuses to the mitochondria and delivers the oxidation potential to the metabolic system, oxidizing food and becoming reduced in the process. The reduced Vitamin C then diffuses back to the cell membrane to become oxidized again by the oxidized Vitamin E in the membrane. And, the cycle continues. Thus, in this way, Vitamin C and Vitamin E become partners in the oxygen transport stage of aerobic metabolism. Far more Vitamin C would be needed than Vitamin E because the volume of the cytoplasm is far greater than the volume of the cell membrane. Thus megadoses of Vitamin C may be helpful while far lower doses of Vitamin E would be optimum.

This mechanism would also predict that megadoses of Vitamin C would not only assist in transporting oxygen potential from the lungs to the cells, but also would assist in the transport of oxygen potential within any given cell.

Alpha Lipoic Acid (ALA): Packer presents a multitude of benefits for ALA but I will limit myself to addressing one that applies to the cancer theory presented here which is not explained/ addressed in the book. ALA also has an oxidized and reduced state and thus can transport oxidation potential in a similar way to Vitamins C & E. However, it is unique in that it is soluble in both aqueous and oil phases. Thus, it can substitute for either or both Vitamin C and Vitamin E in the oxygen transport system. This versatility makes it an exceptionally valuable nutrient. It can substitute for deficiencies in either. This is partially supported by an experiment discussed in the book where animals made deficient in Vitamin E would not suffer from the deficiency if they were supplemented with Alpha Lipoic Acid.

Toxic Metal Elimination: Alpha Lipoic Acid promotes the synthesis of glutathione in the body. In addition to their oxygen transport capability, they both have the capability to chelate toxic heavy metals and thus assist their elimination from the body.

Coenzyme Q10 (CoQ10): The purpose of oxygen transport is to transport it to the inner membrane of the mitochondria where it can be reacted with hydrogen to make water, while using the chemical energy to produce ATP, the energy-carrying molecule in all cells. Thus, once the oxygen gets there, the membrane must be able to accept in a manner where it can be used for this process. CoQ10 is the molecule in the membrane that accepts the oxidation potential and enables it to be used in this stage of aerobic metabolism.


29. Cancer, Schizophrenia, Abram Hoffer, Linus Pauling and This Cancer Theory
Dr. Abram Hoffer is commonly credited with being the principal founder of the alternative health movement using nutritional or orthomolecular treatment methods. During his practice, extending more than 40 years, he has treated thousands of patients primarily for cancer and schizophrenia, authoring many journal articles and books. As part of this effort he collaborated with Dr. Linus Pauling, two-time Nobel Prize winner, in his focus on utilizing vitamin C (with other nutrients) for the treatment of cancer. One unexpected result was that he discovered that very similar treatment approaches were effective for treating both cancer and schizophrenia. As will be seen, it appears that his treatment approaches are fully consistent with this cancer theory. If true, it provides a vast amount of experimental results that verify this theory and indicates it applies to serious illnesses beyond cancer.

Dr. Hoffer phoned me on 5/10/01 at the recommendation of a mutual friend, Bernie Rimland, Director of the Autism Research Institute in San Diego. Bernie had related to him a success a friend of mine had with reversing stage-four lung cancer following a nutritional treatment approach dictated by the cancer theory presented here and Dr. Hoffer has a close family member with lung cancer. During our phone conversation I first outlined the theory and he said it made sense to him. In fact he could think of a lot of published results that would support it. He also mentioned that strangely enough, he had found that schizophrenics rarely get cancer. However, he had not read this web page on cancer. I gave him the web page address and he said he would take the time to read it. We agreed to continue communication by email. The sequence of emails is as follows (with Dr. Hoffer's permission):


Hoffer Email 1

Sent: 5/12/01 11:53 PM
From: A Hoffer, hoffer@islandnet.com
To: krysalis@krysalis.net

Dear Dr Gregg:

I have now read your proposed common cause and cure of cancer and I agree with your overall hypothesis. I knew about Warburg’s early work when I started many years ago and have followed his idea in developing the nutrients that I use which includes the ones you described with the exception of MSM and DMSO which I have not used. I do agree that it is important to maintain respiratory oxygenation and have depended on maintaining blood flow, which one can do with niacin to dilate the capillaries and with vitamin B-12 that decreases the size of the red cells and permits more efficient distribution of blood through the capillaries. Niacin also ensures proper function of the pyridine nucleotide cycle. I will look at MSM as it is very difficult to get DMSO in Canada.

I think your ideas are sound and deserve to be explored fully but I am not convinced that it is the only answer . I am sure you are not convinced as well and I do think that decreasing the ravages of excess oxidation also plays a role. What we need is a thorough examination of these ideas, which perhaps may come with the new liberation of idea in this field as the alternative complementarity ideas take hold. Thanks for letting me know about your work. I am ordering MSM immediately. MY wife is already following the rest of your program with the exception of exercise, which is very difficult for her because of severe osteoporosis which gradually crept up on her but which is not progressing any further. So far her lesion is not growing but I will not know until we have several more x ray examinations.

A. Hoffer


For information about orthomolecular treatment for schizophrenia see
http://orthomolecularvitamincentre.com/a_hoffer_schizophrenia.php

For more information about treatment with vitamins look up
http://doctoryourself.com/hoffer_niacin.html

For information about orthomolecular treatment and heart disease see
http://doctoryourself.com/hoffer_cardio.html

For information about the orthomolecular treatment of cancer see
http://orthomolecularvitamincentre.com/a_hoffer_cancer.php

Dr. Hoffer's Autobiography
http://www.orthomolecular.org/history/hoffer/index.shtml

Vitamin B-3 and Schizophrenia and Vitamin C and Cancer both by A. Hoffer, Quarry Health Books, Box 1061, Kingston, Ontario, K7L 4Y5, www.quarrypress.com 1998

(Reading Dr. Hoffer's referenced web pages is an absolute must for one to appreciate the magnitude of his accomplishments with cancer and schizophrenia.)


My Response

Dr. Hoffer,

Thank you very much for your reply and taking the time to read my attempts to analyze cancer. I plan to read all your web pages referenced and purchase whatever of your books that are still in print. I am still puzzling over your statement that schizophrenics don't get cancer. Could you give me a reference that I could read. I know you have a theory. I don't want to take too much of your time, but could you briefly outline it to me again. I wonder if I can connect it to the cancer theory I have presented, or whether it involves something quite different. I would like to put some time into it and see if I can identify some useful new insights. It is a fascinating challenge.

David Gregg


Hoffer Email 2

Sent: 5/14/01 5:43 PM
From: A Hoffer, hoffer@islandnet.com
To: David Gregg, krysalis@value.net

The references to the relationship in the literature are few and not very convincing although they do suggest that schizophrenia do not get cancer nearly as often. A study in the mental hospital in New York showed that even the heavy smoker patients got lung cancer much less frequently. My study is based upon 6000 schizophrenics I have seen and nearly 1200 cancer patients. Ten patients had both. The ten schizophrenics all recovered on standard treatment . I have seen no deaths. They also recovered from their schizophrenia. The relationship is not as strong for first order relatives but is still very significant. I have 300 families with the index case schizophrenia and 300 families with the index cases cancer. The cancer families seldom have schizophrenia and vice versa. I use only first order relatives. The theory I am pursuing is based on the adrenochrome hypothesis, which is that schizophrenia is caused by an increased production of adrenochrome and similar oxidized derivatives of the catecholamines. A recent report by Japanese scientists showed that schizophrenics lack the gene that is responsible for helping eliminate adrenochrome. This is the first time a direct relationship has been found. An adrenochrome derivative is used in Japan as a treatment for cancer.

Adrenochrome is a potent anti mitotic. This was first found over fifty years ago. It is also hallucinogenic. For information read my book The Hallucinogens, Academic Press 1967. This book contains a petty good description of our adrenochrome hypothesis. When there is enough adrenochrome to cause schizophrenia there is too much to permit cancer. If there is not enough to cause the psychosis there is not enough to prevent cancer. I consider schizophrenia an evolutionary advance with adrenochrome as one of the main factors controlling cancer. Adrenochrome if formed from adrenaline in white cells and in heart muscle. Too much in cardiac muscle causes atrial fibrillation. I do not know what too much does in white blood cells.

Adrenochrome is irreversibly formed from adrenaline but in turn is rapidly reduced to adrenolutin. Aerobic metabolism must be involved. It is probably stored in tissues that do not divide like red blood cells , white cells. and cardiac cells.

A. Hoffer

Recently the first item of empirical evidence supporting the adrenochrome hypothesis has been presented by Harada et al. (2001). Catecholamine o-quinones (including adrenochrome) are, in part, detoxified by 5-conjugation with glutathione. This reaction is promoted by glutathione S-transferases 1 and 2 (GTM 1& 2). Harada et al. (2001) studied DNA samples from 87 schizophrenics and 176 normal controls. They found an increased frequency of deletion of this gene (frequency of the GSTM1*O allele) in the schizophrenic group (p=0.0075) and an even higher rate in the subgroup of disorganized schizophrenics (p=0.0008). They suggested that the GSTM1 gene deletion may constitute a risk factor for schizophrenia associated with an increased toxic action of catecholamine o-quinones, including possibly adrenochrome, in the brain.

Ref: Harada S, Tachikawa H, Kawanishi Y. (2001) Glutathione S-transferase M1 gene deletion may be associated with susceptibility to certain forms of schizophrenia. Biochem.Biophys.Res.Comm. 281, 267-271.


My Response

Dear Dr. Hoffer,

Thank you very much for your emails. You got me started taking a closer look at Schizophrenia, its connection to cancer, your (and Linus Pauling's) exciting results for both, and the connection of both to my theory for cancer. I read your web pages that you referenced in your email and purchased the only two of your books carried by our local Barnes & Nobel Bookstore, "Vitamin C & Cancer" and "Dr. Hoffer's ABC of Natural Nutrition for Children". I also had the book "Natural Healing for Schizophrenia" by Eva Edelman (foreword by Abram Hoffer) in my library, which I finally took the time to read. It is a good start and I have not yet finished reading the books. I will attempt to get more of your books when I have finished these.

Even though I am just starting to read of your work, you have stimulated a flood of thoughts that I would like to relate. My primary problem is to keep it brief so I will present them in itemized, "bullet" form. I can expand on them later as appropriate.
 
1. I am shocked by the magnitude of work and accomplishments you have made with both Schizophrenia and Cancer and my lack of awareness of it in any detail. I knew you were highly respected for your work with applying nutrition to both, but it is the specifics that make it so profound.

2. It appears that it is appropriate to assign the majority of vitamin B3 discoveries to you and the vitamin C discoveries to Linus Pauling. It must have been exciting for both of you to have enjoyed the experience of collaborating.

3. Both sets of discoveries fit very nicely into the "umbrella" theory of anaerobic vs. aerobic metabolism I have proposed for cancer. (It also seems to apply to Schizophrenia and other degenerative diseases.) We know that all vitamins address essential roles, but why do vitamins C and B3 stand out so much above the rest as having such a broad ranging benefit to almost every illness? We know they have a multitude of biochemical uses, but what are the primary functions that make them so universally powerful?

Thinking in the context of aerobic metabolism:

Vitamin C has oxidized and reduced forms, which are in equilibrium with the distribution depending on the oxidation potential of the solution it is in. When this solution moves in the blood to the lungs it shifts towards the oxidized form and when it then moves to the cells (mitochondria) it delivers that oxidation potential, shifting towards the reduced state. In this way megadoses of vitamin C serve as an oxygen transport system supplementing hemoglobin. Increased oxygen transport allows increased aerobic metabolism resulting in increased cellular energy. The cells with more energy can do more to defend themselves and a person's health. Since oxygen transport is so fundamentally required for aerobic metabolism, one might expect megadoses of vitamin C, enhancing oxygen transport and thus cellular energy in all cells, to have the truly broad ranging benefits that are observed.

Vitamin B3 can promote oxygen and nutrient transport by improving circulation due to dilation of blood vessels, but I do not believe this is its pivotal role that makes it so generally powerful. It is required for the production of NADH, (B3 being a precursor to the production of NADH) which is absolutely essential for the operation of almost all aspects of both the citric acid cycle as well as the respiratory chain, the two key steps in aerobic metabolism. No B3 would stop all aerobic metabolisms and low levels of B3 would restrict - set a limit on the amount of aerobic metabolism that could take place. The cells would then function only as well as the restricted availability of energy would allow. This function is as general as the need for oxygen. I believe this is the reason supplementing with megadoses of B3 exhibits broad ranging benefits similar to that of vitamin C.

It is thus obvious that vitamin C and vitamin B3, promoting key sequential stages of aerobic metabolism, should be good partners in any treatment protocol.4. Why the same treatment works for both cancer and schizophrenia: Both are caused by the cells not having enough energy to operate their extremely complex biochemistry (& utilize nutrients and operate all the control mechanisms), so they can function normally as designed. I have a chart on my wall that takes a stab at outlining all the biochemical paths in a cell. To say it is extremely complex is an understatement. It involves as many as 4,000 enzymes, their products and all the interactions. This system has to operate in a well-organized, orderly way, as designed, or there is no hope. At this point you can invoke a fundamental thermodynamic argument, high degrees of order require high energy. Low energy results in disorder and high entropy. Cellular energy is the starting point for all organized cellular function. For cancer, aerobic metabolism is eliminated, dramatically restricting allowable cellular function to only what anaerobic metabolism will support, while for schizophrenia aerobic metabolism is simply reduced below the minimum amount needed for the cells to function to full capacity. For cancer it appears that the block can be in either or both the oxygen transport mechanism as well as the operation of the citric acid cycle and the respiratory chain. However, for schizophrenia the blockage appears to be dominantly in the citric acid cycle and respiratory chain.

5. The Adrenochrome Hypothesis: I will attempt to connect this to the aerobic metabolism theory. If the cell fluids have a high oxidation potential they are more likely to produce more adrenochrome and low oxidation potential the reverse. In the case of schizophrenia we assume the aerobic metabolism blockage is in the citric acid cycle & respiratory chain and not in the oxygen transport system. Thus, oxygen is transported to the cell from the lungs where it cannot be consumed by reaction with food (glucose) and thus stacks up — maximizing the oxidation potential in the cell fluids. This could be a contributing factor for increased adrenochrome in schizophrenics (in addition to the lack of the gene helping to eliminate adrenochrome). Thus the restricted aerobic metabolism at the citric acid stage could cause schizophrenia by two paths, reduced cellular energy and increased production of adrenochrome, a toxic causal agent. If high adrenochrome concentrations are required to have schizophrenia, it would follow that aerobic metabolism must be blocked at the citric acid cycle and not at the oxygen transport stage in order to have schizophrenia.

It makes sense that if adrenochrome is toxic/inhibiting to cancers that high concentrations would result in lower cancer rates. However, to couple to the aerobic metabolism theory, if the cancer's anaerobic metabolism is caused primarily by a block at the oxygen transport stage and not so much a block of the citric acid cycle, the small amount of oxygen getting to the cell would be consumed, resulting in a low oxidation potential in the cell fluids and thus a low production rate of adrenochrome. With this mechanism one would expect low adenochrome levels correlated with cancer, but it would not be a factor in causing the cancer.

If this analysis is correct, and if adrenochrome is a primary causal agent for schizophrenia, one might expect that treatment of schizophrenia with megadoses of vitamin C alone would increase schizophrenia. It could only have a beneficial effect if used in conjunction with even greater amounts of vitamin B3 so that the combination increased aerobic metabolism without increasing the production of adrenochrome.

Have you observed this?

6. You have stated that it is your personal observation that schizophrenics have a significantly lower rate of cancer. Beyond the adrenochrome theory, could this also be because the schizophrenics you have contact with are so often supplementing with vitamins B3 and C that would mitigate both schizophrenia and cancer? I wonder if you think this is a significant factor.

7. I want to draw your attention to a discovery I made about five years ago, which I put on my web page and have had many reports back. It is now being used by thousands of people with dramatic results. It is more immediately powerful than anything else I have discovered and I personally have little doubt it will have equally dramatic beneficial effects for schizophrenics. I discuss it in two places on my web page Health Notes Anemia and Health Notes Vitamin B12. I first dissolved vitamin B12 into DMSO and applied it to my skin (bringing it in transdermally) with striking results for me, mostly in the form of increased mental clarity (general improved mood and increased energy). I then modified the solution by adding folic acid in slightly larger amounts to the B12 solution since the two should always be used together. This seemed to have a greater benefit for me. I then got a multivitamin-multimineral gel cap, opened the gel cap and added the powdered contents to the solution. The benefits got even greater. I suspect that for schizophrenics you might want to try boosting it further with B3. Specifically I got a 2oz brown glass eyedropper bottle, added 10 — 1000mcg tablets of B12, 20 — 800mcg tablets of folic acid, the powdered contents of 2 — multivitamin-multimineral capsules and filled the bottle with 99.9% DMSO. It took a couple of days for the pills to fall apart, with periodic shaking. There is always an undissolved sludge at the bottom, which you don't want to use. You can filter it out or simply let it settle out and use only the clear liquid above it. I then apply an eyedropper load to the outside of an arm (insensitive skin) and spread it around. It will cover the entire outside of the arm. If you are deficient, you will start to feel very good and a significantly increased mental clarity within one hour. This will last for many days. It also has a dramatic anti-depressant effect. If you try to apply this again the next day, there will not be such a dramatic effect because you are saturated with B12, etc. However, if you wait approximately a month, you will have become depleted again and the benefit will become noticeable again. I personally use it about once a month.

You might have to make a trip to the States to get some DMSO. It would be worth the trip. I get it at my local health food store. A small investment in one or two bottles will give you a several year supply. Some have also found they can order it from sources on the Internet.

One of the conditions for using this seems to be to use it only in combination with a full ranging multivitamin, multimineral supplement. One person reported a dramatic benefit that then vanished after using it for a few months. That person was not using such a diverse supplement in combination with it. Vitamins work in subtle combinations and a focus on taking one alone can deplete others. When the others get depleted the benefits of the one being taken vanish. Also, the depletion of another risks a negative effect. Taking my supplement "Sparx" along with this approach seems to avoid this problem.

WHERE FROM HERE?
I am pleased that my theory seems to be consistent with your very exciting results. It gives me personal intellectual satisfaction. However, in order for such a theory to be important it has to predict modifications that will result in improved benefits. They are obvious and you have already addressed them to some extent. You would want to add a broad multivitamin, multimineral supplement powder that is taken with a diversity of juices (providing essential diversity of phytochemicals). The purpose would be to enhance all steps of aerobic metabolism while continuing to peak on the main players, Vitamin B3 and Vitamin C. For schizophrenia you may want to peak with vitamin B3 with vitamin C being restricted to adequate amounts as a part of the "baseline" supplement formula. However, for cancer you would probably want to peak with both vitamin B3 and vitamin C added to the baseline formula. I have spent the past 5 years attempting to perfect such a baseline formula, which I have named "Sparx". I am far more of a scientist than a businessman and saw this as more of a technical challenge than a business one. Also, it seemed to fill a void in what was available to people. My goal has been to perfect the best such formula that can be made at a very affordable price. This doesn't just involve identifying essential components, but also involves identifying often-costly components that are promoted but do not make an important contribution. The philosophy is to rely on the juice to provide a cost-effective source of phytochemicals, which would otherwise be very costly if provided in pill form. As an engineer at heart, I had to have solid data for the benefits of each component before I would include it. Even at that, I ended up with approximately 60 components. It turned out to be the most complex formulation my manufacturer had ever made. However, I found a sole mate in him and he did his best to help in every way, including drawing from his many years of experience in the field. The first miracle was that there wasn't any component that he could not find a source for. When I progressed to a certain point in my analysis of cancer I decided to have him produce another powder, "Aerobic Boost" to supplement Sparx for the treatment of cancer. It was designed without minerals so individuals could significantly increase the dose without risking going toxic on the minerals. I would design it with a greater emphasis on vitamin B3 now since I have learned of your work. However, it would not be advisable to add megadoses of vitamin B3 or vitamin C to this formula. Those doses should always be adjusted separately and thus independently.

You have reported that you have already used a similar product, Multijet, with a similar approach. How did that work out? I wonder how it compares with my formulation for Sparx given on my product web page www.krysalis.net I also wonder how the price compares. I would obviously be delighted to find out if Sparx or Sparx + Aerobic Boost would be effective in such a baseline supplement role. However, I don't treat patients and thus have no means to test it. If you are interested in exploring this further please let me know.

David Gregg


Hoffer Email 3

Sent: 5/17/01 12:23 PM
From: A Hoffer, hoffer@islandnet.com
To: David Gregg, krysalis@value.net

Dear Mr. Gregg:

I cannot take credit for all the research in which I participated. I was Director of Psychiatric Research for Saskatchewan from 1950 to 1967 and by 1960 had about 30 scientists and a budget of about one million at the University Hospital in the Province. Dr Osmond and I were the key figures of this group. All the -3 studies used in large doses came from our studies. Linus was aware of them after reading our book How To Live with Schizophrenia in about 1960 or 61. But I had nothing to do with the vitamin C studies and the credit goes entirely to Pauling who was stimulated to enter the field by Dr Irvine Stone.

Your anaerobic aerobic theory does make a lot of sense. And if one scans the literature there is ample evidence to support it. Thus, for example, schizophrenics do tend to have decreased levels of oxygenation in their frontal lobes. Circulation studies have shown than this appears to be the case. Following Karl Menninger who first stated this I have the feeling that the schizophrenic is not full awake, is in a dream like state and this would explain their hallucinations since visions and voices are not uncommon in dreams. Normally our frontal lobes call for less oxygen during sleep and more when awake but in schizophrenia there is little difference awake and asleep. Niacin may awaken them since it does increase brain circulation.

Neurons are so finally differentiated that they do not form cancers. When they become anaerobic I believe they cause Alzheimer disease/ i.e. fully differentiated cells will not form cancer even when anaerobic, they simply become quiescent. I know of one case of Alzheimer treated by chelation that recovered. I spoke to him and he had absolutely no memory of his previous condition.

I agree that the main vitamin for cancer is C with moderate amounts of B-3 while with schizophrenia it is just the opposite. In 1952 I treated a woman with beat cancer who had a mastectomy. She became infected and psychotic at the same time. I gave her 1 grams of vitamin C every hour and in 45 hours she was no longer psychotic and her ulcerated lesion began to heal. I sent her home mentally normal but had no idea that the vitamin might be helpful o her disease. She died 6 months later menially normal. But exactly where the oxidation reduction process goes wrong is open conjecture. I hope that as the adrenochrome hypothesis is resurrected scientists will enter this field and fill in the gaps that are so wide today.

I did read about your use of DMSO and B-12 in your web site and was very impressed by it. I will try it out at the first opportunity. It could be very helpful also for chronic fatigue states where injecting of B-12 has been very helpful.

Your idea why schizophrenic patients get less cancer is sound had not occurred to me before i.e. that having placed my patients on B-3 and C that this might have prevented some of them from getting cancer. It is not the only factors as I have seen many other patients on vitamins get cancer but generally they have a better prognosis when treated. It is also true that my schizophrenic population was a younger population to begin with compared to my cancer population on. The families of cancer and schizophrenic patients also showed the same pattern but it was not as clear-cut. Thanks for the suggestion.

I have not used a single multi preparation but have used a vitamin spectrum make up of single vitamins combined with the usual B-complex preparations on the market.

Sincerely, A. Hoffer


30. "Vitamin C & Cancer" by Dr. Abram Hoffer, PhD, MD, FRCPS with Dr. Linus Pauling, PhD, Nobel Laureate, Chemistry and Peace, Quarry Health Books
This excellent book presents a summary of the outstanding work by both Dr. Hoffer and Dr. Pauling investigating the use of Vitamin C + other nutrients for the treatment of cancer. I will make no attempt to summarize it here. I would recommend it strongly for anyone attempting to learn more about the nutritional treatment/prevention of cancer. I would like to present a few of my impressions.

1. It would appear that essentially all the positive results presented in the book are fully consistent with the cancer theory presented here, that there is a single common cause for all cancers, anaerobic metabolism (caused by genetic damage), and a corresponding common cure, nutritionally reversing the cellular metabolism back to aerobic metabolism. The cells then become normal followed by normal programmed cell death eliminating them (along with their genetic damage). It is my opinion that the theory contributes greatly to the understanding of their profound results. To that extent it enhances credibility in both directions. It should also be possible to use it as a guide to further improve treatment.

2. As related to importance, I was taken by one statement (pg 27) "Most of the evidence discussed in this book relates to the effectiveness of megavitamins in the treatment of patients with advanced cancer. Our conclusion is that about 50 percent of these patients with advanced cancer can be "cured" (survival for over five years). We surmise that if the megavitamin regimen were to be started at the time of first diagnosis of cancer, as an adjunct to appropriate conventional therapy, the cancer death rate could be reduced to 25 percent of its present value, and moreover, if, in the course of time, a reasonable megavitamin regimen were to be followed regularly by every person, as a way of improving the health and decreasing the incidence of cancer and other diseases, the cancer death rate would fall to one eighth of its present value." I was also impressed by the long list of types of cancer that were treated. The treatment approach appeared to be effective for all forms of cancer tested. This is also consistent with the theory presented here. As stated in the beginning, it should apply to all forms of cancer.

3. Point: (pg. 58): "In a study by V. Noto, either vitamin C or E inhibited the growth of breast carcinoma, epidermoid carcinoma, and endometrial adenocarcinoma in vitro, but when both were combined, there was a pronounced synergistic effect. Ten to 50 times lower concentrations were as effective." This special synergism is fully consistent with the oxygen transport part of the theory presented here, addressed in more detail in Items 6 and 28. It is one specific example of how this theory can greatly help in understanding such observations.

4. Point: (pg. 45) One study found that increasing the daily intake of vitamin C to megadose levels did not increase the amount found in the blood in a straight line relationship. It increased to a point and then did not increase much further. This led the investigator to conclude that megadoses are of no clinical value and daily doses of 200 milligrams were sufficient. Let us assume that the blood measurements were accurate, and so are the numerous observations that megadoses of vitamin C can be very helpful (presented in this book and elsewhere). What is happening? Where is the vitamin C going (it has to be going somewhere) and why does it continue to be ever more beneficial to cancer treatment at increasing megadose levels? Is it consistent with the theory presented here? I would like to suggest an answer. Initially, at the low doses, the vitamin C concentration in the blood increased as expected with increasing dose of vitamin C. This increases oxygen transport from the lungs to the cells as already discussed (Item 6). However, what was not measured, as the vitamin C dose was increased further, the transport rate of it out of the blood into every cell in the body then accelerates in a nonlinear way with further increases in blood concentration. This second stage would involve a far larger mass of cells than the blood and would consume a far larger amount of vitamin C without a corresponding increase in concentration. At this point, the further increases in vitamin C dose would increases oxygen transport within each cell while oxygen transport in the blood is maintained at an enhanced level by the already enhanced levels of vitamin C in the blood. This cellular mechanism is described in Item 28. According to the cancer theory presented here, the resulting increase in oxygen transport within each cell would be an essential step towards further enhancing its contribution to reversing/preventing cancer.

5. Point: (pg 73) "We concluded that while vitamin C alone led to about 10 percent excellent responders, the addition of the other nutrients increased this to about 40 percent." This is fully consistent with the theory presented here. According to the theory one would want to use a set of supplements that stimulate all the steps of aerobic metabolism together. That is what the additional nutrients added.


31. Three Separate Paths for NADH Synthesis Involving Niacin, Niacinamide, Vitamin B6 and Tryptophan
According to two of my biochemistry books, "Harper's Biochemistry" twenty fourth edition (pg 602) and "Textbook of Biochemistry", Thomas M Devlin, editor, Third Edition (pg 560) there are three separate paths for the synthesis of NADH. One starts with niacin, another with niacinamide, and a third involves the conversion of tryptophan to NADH catalyzed by vitamin B6. There appears to be some confusion about this in Eva Edelman's book "Natural Healing for Schizophrenia" where she shows vitamin B6 catalyzing the conversion of niacin to NADH. It does catalyze the formation of NADH, but by catalyzing the conversion of tryptophan, not niacin, to NADH. 

Abram Hoffer found that megadoses of niacin or niacinamide could both be used (along with supporting nutrients) to treat schizophrenia (and cancer along with vitamin C). Carl Pfeiffer in his book "mental and Elemental Nutrients" found that megadoses of vitamin B6 (along with supporting nutrients) were very effective in treating schizophrenia. If production of NADH was the key mechanism for reversing schizophrenia, then this is what would be expected. They are two separate paths to the same goal. Bernie Rimland, of the Autism Research Institute in San Diego also found that megadoses of vitamin B6 (along with supporting nutrients) were effective in treating autism. Since the proposed mechanism, the production of NADH, was not recognized, neither Carl Pfeiffer nor Bernie Rimland tried adding a tryptophan supplement to the mega-vitamin B6 treatment. They thus were limited by the amount of tryptophan existing in the diet of the patients. I would predict that adding a significant amount of tryptophan, as a supplement to the B6 treatment would greatly enhance the results. (Are we looking at a very general cause and cure for many mental and physical problems?)

Each of these paths involves a number of steps, each requiring their own set of enzymes. If there is a block restricting the synthesis of NADH, it would be quite difficult to determine which enzymes might be missing and thus which paths are blocked. I would thus conclude that the best approach would be to enhance all three paths at the same time. This would involve supplementing with niacin, niacinamide, vitamin B6 and tryptophan at the same time (along with supporting nutrients). I could only guess as to the right distribution between these, but I would expect that by combining them, far less would be needed than the megadoses for niacin (up to 3g/day) or B6 (up to 1.2g/day) that were used by Hoffer (niacin) and Pfeiffer (vitamin B6).


32. The Megadose Application of Vitamin C and Niacin
Dr. Hoffer, in his book "Vitamin C & Cancer" demonstrated the importance of large doses of only two vitamins, vitamin C and niacin (or niacinamide), for the treatment of cancer. Of these two, Hoffer found Vitamin C to play a greater role for treating cancer (while niacin played a greater role for treating schizophrenia). Other nutrients were added also, but more at elevated levels, not at megadose levels. I would like to make some comments about taking such large doses of these vitamins.

1. Vitamin C, Overcoming the Bowel Tolerance Limitation: Dr. Hoffer commonly prescribed 12 grams/day of vitamin C to his patients, taken in 4-gram doses three times a day. This was in combination with niacin (up to 3 grams/day) and other supplements at elevated levels but not in megadose levels. At this dose he seemed to experience more success than at lower doses. There were also some patients that increased this to 40 grams/day with what seemed to be even more success (with cancer). However, when attempting such large doses, most people experience the onset of diarrhea at considerably lower levels. Thus, as is common in the community of people advocating large doses of vitamin C, it is suggested that one take up to the "bowel tolerance level", which is the dose rate just below that which causes the onset of diarrhea. It appeared that the bowel limitation was limiting the oral intake of vitamin C to a level that was less than optimum for the treatment of cancer, at least in some people. I decided to take a look at what was causing this diarrhea limitation and came up with a logic for both the cause and how it could be removed as a treatment limitation, while retaining oral intake.

The cause of the bowel limitation: When food leaves the stomach it enters the duodenum as an acidic chime. When the duodenum senses the acidity, it releases secretin to the blood. The secretin then stimulates the pancreas to release a bicarbonate flush into the duodenum, which neutralizes the acid and sweeps in the digestive enzymes. If this does not happen, the acidity can damage the intestine. Now lets introduce large doses of vitamin C. Vitamin C is very acidic. It increases the acid load in the stomach. Above a certain point, the volume of acid entering the duodenum exceeds the ability of the pancreas to neutralize it. The acid then starts to damage the intestine and the intestine responds with diarrhea in order to flush the acid out. Thus you have the bowel limit for vitamin C. It will vary from one individual to the next because everyone will have a somewhat different capacity for a bicarbonate flush to neutralize the acid.

The solution: The solution is very simple, neutralize the vitamin C before taking it. You can purchase the sodium salt of vitamin C (or another salt of it) but more simply you can neutralize the vitamin C yourself. I have done this many times. I simply fill a glass of water about 1/4 full and add a teaspoon full of vitamin C powder, which dissolves. If you taste the solution at this point it will be very sour (acidic). I then sprinkle in some baking soda. This results in a lot of foaming (releasing carbon dioxide) while forming the sodium salt of the vitamin C in the water phase. I taste the solution and watch the foaming as I slowly add the baking soda. When the foam stops forming, the sour taste is gone and I can hardly taste anything except a slight taste of the baking soda. The vitamin C is still there and should be just as effective for the treatment of cancer, but will no longer add to the acidity of the stomach and should no longer cause diarrhea at large doses. Thus, the vitamin C can now be added to the optimum level for the treatment of the cancer without being concerned with a bowel tolerance limitation. I have tried this on myself and found it to be quite effective for me - eliminating diarrhea. (I don't have cancer.) Some others have found it to be effective also. However, every individual is different and it may not work for everyone.

2. Niacin, Overcoming the Niacin Flush Limitation: As Dr. Hoffer has discussed in his book; many people cannot tolerate the flush that goes with his maximum recommended dose of 3 grams/day. His remedy is niacinamide, at lower levels, which does not cause a flush. However, as I have discussed in Item 31 above, I would think it would be even better to replace it with a combination of niacin (at a much lower, flush tolerable dose), niacinamide, vitamin B6 and tryptophan. This will eliminate the flush limitation while stimulating all three paths for the formation of NADH, not just one. It should result in a more effective method of producing NADH at lower doses of each, without a serious flush limitation.

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