Tuesday, March 29, 2011

Proposed Biochemical Cause and Remedy for Crohn's Disease and Ulcerative Colitis

When I first proposed these remedies, only people with Crohn’s Disease tried them. However, since then some people with ulcerative colitis have tried them and found them to be equally effective. You can find responses to this on my original web page where there is additional information. The original paper was written in 1998.

I am not a medical doctor and thus do not attempt to treat people; but, in an effort to help a new friend, Barbara, who suffers from Crohn's Disease (CD), I performed a literature search, and thought deeply about the disease. Within this process I identified two new potential approaches that I thought might be helpful. Neither approach had been used for CD before. I provided Barbara with the results of my search along with my first theory about how CD might be remedied. She discussed it with her physician. She told me that he said that he didn't see how trying it would do her any harm. She had abdominal pain, which had lasted for more than three months with varying degrees of severity, even though she was under a doctor's care and her disease was in partial remission. Barbara decided to try the suggested remedy. She was working half days because of the inflammation, went home at noon as usual, purchased the material at a health food store at minimal cost and applied it. Her abdominal pain was reduced to a mild sensitivity within an hour. That was in February 1995. She was able to return to work full time shortly thereafter. Her disease has been under control ever since then without other medications being required. She gradually recovered her full physical strength and general health, and has noticed no ill side effects from the remedy. She said that before this time she rarely had one good day a month. Shortly after starting the "treatment" she said she felt terrific and rarely had one bad day a month. Her disease management cost changed from approximately $5,000 per year (covered by insurance) with conventional medications, which did not work very well and had substantial negative side effects, to approximately $50.00 per year (no insurance coverage needed) with far better control of the disease and absolutely no negative side effects.

Since that time more than twenty other people with Crohn's Disease and several with Ulcerative Colitis (UC) have chosen to try it. It seems to work equally well with both diseases. They purchased and applied their own material. Their reported success rate has been better than 90%. They have been able to discontinue other medications and enjoy freedom from abdominal pain and intestinal inflammation. Once it works for an individual, there are no cases of a person becoming desensitized to its benefits. It continues to work, with additional applications as needed, indefinitely. According to my theory, the remedy does not just block the pain, it stops both diseases by stopping the common process that causes the degeneration of the intestine.

The time span between my first learning about Barbara's disease (I had never heard of Crohn's Disease before) to my identification of the first projected remedy was three days. She tried it the next day and to my amazement she said it took effect within an hour. This relatively brief time to effectiveness has been repeated many times with many people. I have been told of pain relief time ranging from 20 minutes to four hours.

I should make it clear that I am not selling anything and have no financial interest in the remedies. My motivation is strictly humanitarian. I would simply like to contribute what I can to help eliminate the horrible suffering associated with these diseases.

I. Dimethyl Sulfoxide (DMSO) as a Remedy for Crohn's Disease

In order to appreciate the profoundness of the remedy, which is deceptively trivial in appearance, I believe it is important not only to present the results, but also to take the reader through the technical reasoning I employed. I have a formal education in chemistry and chemical engineering and am now retired after spending more than 30 years performing research at a national laboratory. During that time I developed a personal fascination with the potential of nutritional supplements for helping a broad range of physical and mental problems. It started when I was on the board of directors of a youth home with 70 problem children (wards of the court) and wanted to explore possible approaches for helping the children. This gradually led me into making a serious study of nutrition, biochemistry, medical physiology and psychology and the interrelation between them. I was deep into studying textbooks and performing literature searches on Medline (on the Internet) when I first met Barbara. She was the secretary for the new group I had joined at the national laboratory. I found her to be an exceptionally pleasant person with an exceptionally serious, disabling illness. So, I told her that I would use the capabilities I had developed to try to find something that might help her. I was proud and shocked when the first suggestion I made, derived from my first technical analysis of the cause of Crohn's Disease, was totally successful.

Upon starting the literature search I quickly discovered that the conventional treatment for CD used steroids or sulfa drugs with only moderate success. Failure of the steroids frequently resulted in the need for surgeries removing the damaged part of the intestine. Multiple surgeries eventually end with the need for an ileostomy or a colostomy where excretion of the feces is diverted through the abdominal wall and is collected externally in a bag for disposal. Many other treatments had been tried with little success. The attempts at different treatments seemed almost random, possibly because there was no clear understanding of the cause of the disease. Some believed it was an autoimmune disease, but the evidence for that was not conclusive.

I decided to take a more logically tight, systematic approach, as I would do with one of my typical research projects. This involved first postulating a damage mechanism, checking it against the literature to see if it survives, and designing what should be a logically tight treatment based on the assumed mechanism. In order for me to have any chance of success with my extremely limited access to almost anything sophisticated, I knew I had to approach the problem with a very different thought process than the elaborate research facilities had. The first thing I did was to mentally separate the primary, complex cause of the disease from the damage mechanism, which I hoped may not be so complex. I then focused on the damage mechanism, which I hoped would be more amenable to a simple solution. I reasoned that the damage mechanism was very likely hydroxyl radical attack on the intestinal cells. From reading the medical literature, I discovered that there was considerable evidence that this mechanism might be a primary cause of colon cancer. They are well known to have the capability of destroying cells through oxidative attack and I thought Crohn's Disease might be another expression of their damage. A literature search identified more than 15 publications in the last five years in which the authors also felt this might be true.

In a previous Medline literature search I had done on DMSO, focused on evaluating its toxicity, I discovered not only a lack of toxicity but also that it had been measured to be a powerful antioxidant. The search over the previous five years of medical publications yielded 1117 abstracts describing instances where DMSO was used. Many of the abstracts openly stated that DMSO was a well-tolerated material, and there were no publications indicating any level of toxicity. DMSO had been used in a variety of medical applications, but never for Crohn's Disease. One paper presenting results for a number of materials being tested for antioxidant activity, listed the compounds in order of antioxidant effectiveness and then added the statement that none of them were as effective as DMSO.

DMSO has another very important feature that distinguishes it from commonly used vitamin antioxidants. It will rapidly diffuse through the skin into the blood stream. (There is no need or advantage to taking it orally.) According to my initial theory, this is not just an application convenience, but an essential feature that would make it more effective in the treatment of CD than other antioxidants.

I reasoned that if the damaging hydroxyl radicals are generated inside the intestinal cells, the antioxidants will have to penetrate the cell membranes to get at them. Vitamin antioxidants can have a difficult time penetrating the membranes, which may explain why they are ineffective for treating CD. However, DMSO cannot be stopped by any membrane. That is why it can rapidly diffuse directly through the skin. Thus, only DMSO (and now a second material with a slightly different mechanism, Melatonin, which I will discuss below) would be able to penetrate the cell membranes rapidly and quickly enough to deactivate damaging hydroxyl radicals generated inside the cells before they do damage. I postulated that because of this very unique penetrating characteristic, only DMSO, and now Melatonin, might be effective in reducing the intestinal damage associated with Crohn's Disease. If my theory is true, treatment with DMSO would also serve to illuminate the biochemical cause of CD.

With these thoughts in mind, I thought DMSO had a reasonable chance of helping Barbara with her CD. When I talked to her about it, she told me that she had owned horses for many years and was quite familiar with DMSOs frequent use in veterinary medicine. She felt it would be a safe thing to try, in small amounts, even though she was aware that its use for application to humans had been approved by the FDA only for the treatment of interstitial cystitis. She consulted her physician and he thought it could safely be applied topically. When Barbara started using DMSO she was working half days because she was trying to recover from repair surgery and the deterioration caused by a major relapse of her disease. She went home at noon, as usual, and bought some DMSO at a health food store. She applied "about a teaspoon full or less" to her abdomen. (The body location is not important!) She then went to an afternoon movie. An hour into the movie Barbara noticed that something was missing. Most of her abdominal pain was gone!

Shortly thereafter Barbara was able to return to work full time and was feeling "wonderful". After this success, I am amazed at how many people then called me to find out about it. I discovered that this horribly painful, commonly fatal disease is very prevalent. I am thus compelled to write this paper in an attempt to get this information into the Crohn's Disease and Ulcerative Colitis community so it can be further evaluated, and hopefully provide near-term, safe help.

If my theory is correct, DMSO does not stop the primary cause of Crohn's Disease. It only stops the damage mechanism, very rapidly. Thus, DMSO may have to be used on a continuing basis. The people using it so far apply it only when they feel the onset of abdominal pain. The DMSO quickly stops the pain (and the intestinal damage process) commonly in less than one hour but it can take up to a few days of repeated application. One of the benefits of its rapid action is that it does not have to be taken in a preventive mode, and there are no withdrawal problems. This is in contrast to the steroid treatment, which takes several weeks to take effect and thus often has to be taken in a preventive mode, and where withdrawal must be done with great care. The natural course of Crohn's Disease is to cycle between active and remissive states. The DMSO appears to prevent damage during the active state, and may be required sporadically during remission. It appears to be an extremely affordable remedy that a person can live with comfortably. I recently talked to Barbara and she said it continues to control her CD when it becomes active, but she had to use it only twice in the last year

II. Melatonin as a Remedy for Crohn's Disease

Melatonin is well known as an effective, nonprescription sleeping pill. In the book "Melatonin" by Ray Sahelian, M.D., he references research done by Hardeland, et al. that states "Melatonin has been found to be the most potent physiological scavenger of hydroxyl radicals ever detected. Melatonin stops damage immediately and is more effective as an antioxidant than even vitamins C and E." He also states that Melatonin has the advantage of being able to freely enter and permeate all parts of a cell.

Given the experience with DMSO helping Crohn's Disease, upon reading this, it seemed reasonable to me that Melatonin might be another likely remedy for C.D. I brought this to the attention of Barbara and discovered that she had just started taking Melatonin to help her sleeping problems. She decided to stop using DMSO and see if the Melatonin would control her C.D. It seemed to work for approximately two months when she started to get a recurrence of abdominal pain. At this point she returned to using DMSO, which controlled the pain in its characteristic short time.

Since Barbara's experience, many people have tried both DMSO and Melatonin and both have worked quite well. It is difficult to say if they would both work quite well on the same person because different individuals seem to have chosen one or the other approach and remained with it once it worked. There seemed to be one significant difference in that it appears that DMSO seems to take effect within an hour while Melatonin might take a week or so.

At this point approximately half of those trying this are happy with Melatonin and half with DMSO. It is difficult to say in advance whether DMSO or Melatonin will be the best approach for any particular individual. One of the most interesting points is that once an approach does work for an individual, it does not become ineffectual with time.

I want to remind people that this write-up is for information only and is not a recommendation for treatment. I strongly recommend that you discuss this with your physician and read the large amount of information that has been published about both DMSO and Melatonin before taking any action.

Proposed Biochemical Mechanisms for DMSO Mitigating Crohn's Disease

The Proposed Biochemical Cause of Crohn's Disease

I propose that the cause of Crohn's Disease is oxidative attack on the intestine, and not an autoimmune attack. Specifically, the attack follows the Haber-Weiss reaction where ferrous ions catalyze the dissociation of biochemically-produced hydrogen peroxide into highly reactive hydroxyl radicals. The excessively high production rate of hydroxyl radicals then produces cellular damage in the intestine. The reaction goes as follows:

H2O2 + Fe(+2) = Fe(+3) + OH- + HO

hydrogen peroxide + ferrous ions
react to produce
ferric ions + hydroxyl ions + hydroxyl free radicals

This reaction is always taking place in normal cells and can play a constructive metabolic role by helping with the initial oxidation of fats in the peroxisomes. However, for people with Crohn's Disease, it takes place to excess.

The Proposed Mitigation Mechanisms for Melatonin and DMSO

Melatonin

In the book "Melatonin" by Ray Sahelian he states that Reiter, one of the most active researchers on Melatonin, believes that it stimulates the enzyme glutathione peroxidase, one of the body's most powerful antioxidants. The details of how this enzyme operates to remove hydrogen peroxide are discussed in many books on biochemistry, and won't be reproduced here.

DMSO


Mechanism 1: DMSO can be readily oxidized to dimethyl sulfone. DMSO has one oxygen atom and dimethyl sulfone has two. In the presence of hydrogen peroxide it can be oxidized, picking up one oxygen atom, converting the hydrogen peroxide to water.

Mechanism 2: In the process of carrying out literature searches, I discovered a paper in which it was reported that DMSO increased the number of transferrin receptor sites displayed on the outer membranes of two standard cell cultures with a response time of approximately ten minutes. ("A Rapid Redistribution of the Transferrin Receptor to the Cell Surface of HL-60 Cells and K562 Cells upon Treatment with Dimethyl Sulfoxide Due to Slowing of Endocytosis" D. Vestal et. al., Archives of Biochemistry and Biophysics, Vol. 276, No. 1, Jan. 1990, PP. 278-284) This opens up the possibility of a surprise mechanism for DMSO mitigating Crohn's Disease. Transferrin transports iron in the blood. It picks it up from the intestine and brings it to all the cells in the body that need it.

If we postulate that this same effect occurs when DMSO is applied to the body, it will increase the rate of transport of iron out of the intestine and to other cells in the body. The immediate effect will be to lower the iron concentration in the intestine, and thus lower the rate of production of hydroxyl radicals in the intestine via the Haber-Weiss reaction (catalyzed by iron) discussed above.

It is interesting to note that the measured response time of the cells is fully consistent with the rapid response CD people observe for DMSO mitigating their abdominal pain.

It is also possible to postulate additional, downstream effects.

1) The increased transport of iron will specifically increase its transport to the bone marrow. This could increase production of hemoglobin, reducing any anemia that might exist, which is common with people experiencing a CD inflammation.

2) In normal people, the absorption of iron into the blood from the intestine is actively controlled. If this active control mechanism is sensing on anemia or the lack of it, then (in its simplest conceptual form) the existence of anemia would result in increased iron absorption in the intestinal cells, and the reduction of anemia would have a corresponding reduction of iron absorption. Thus, if the application of DMSO resulted in reduced anemia, it would reduce the rate of absorption of iron (from food) into the intestinal cells while increasing its rate of removal from the intestinal cells by transferrin in the blood, resulting in a two-pronged approach to reducing the Haber-Weiss reaction.

The actual control mechanism for iron absorption is complex and only partly understood. One mechanism that has been demonstrated to regulate the transfer of iron across the mucosal-capillary interface is the synthesis of apoferritin by the mucosal cells. When the host requires little iron, a large amount of apoferritin is synthesized to trap the iron within the mucosal cells and prevent transfer to the capillary bed. As the cells turn over (within a week), their contents are extruded into the intestinal lumen without absorption occurring, thus excreting unneeded iron. When there is a iron deficiency, virtually no apoferritin is synthesized so as not to compete against the transfer of iron to the deficient host. Considering this mechanism, one could postulate that the existence of anemia may prevent the formation of apoferritin. This would result in an increase in free (active) iron ions in the mucosal cells. If this is combined with an ineffectual removal of them into the blood by insufficient transferrin transport capacity, these free iron ions could then be very active in the Haber-Weiss reaction, producing excess hydroxyl radicals, and resulting in cellular damage. DMSO would cause increased transferrin transport capacity, reducing anemia, resulting in increased production of apoferritin in the mucosal cells, reducing free iron ion concentration, and thus reducing the activity of the Haber-Weiss reaction and cellular damage.

A Research Effort to Carry Out Needed Controlled Studies

I would like to strongly encourage the performance of controlled studies to evaluate the DMSO/Melatonin approach to mitigating Crohn's Disease and Ulcerative Colitis so as to place it on a sounder technical basis. The ultimate goal would be to satisfy FDA requirements to qualify one or both of them as approved treatments.