PHOENIX RISING

Posted to the CFS Experimental Yahoo Group on 7/04/07

The simplified treatment approach for lifting the methylation block appears to be working strikingly well for a large number of people with chronic fatigue syndrome, and I think it is time to make the CFS community aware of this so that more people can be helped sooner, even though controlled testing of this treatment approach has not been done.

A Review. In view of this, I would like to review the current status of pilot hypothesis testing of the Glutathione Depletion—Methylation Cycle Block (GD-MCB) hypothesis for the pathogenesis of chronic fatigue syndrome.

As some readers will probably be aware, I presented a poster paper on this model at the most recent IACFS conference in Florida last January. It can be found on the internet at this url:

http://phoenix-cfs.org/GSH% 20Methylation% 20Van%20Konynenburg.htm  

 Treatment Basis. The main bases for this hypothesis were the wide prevalence of glutathione depletion in CFS, as first reported by Dr. Paul Cheney in 1999, and the work published by S. Jill James et al. in late 2004 that showed that in autism there is also glutathione depletion, and that it is associated with a block in the methylation cycle. Further study suggested to me that the same or very similar genetic and biochemical issues are present in CFS as in autism, and this paper grew out of that study.

The Past Year. The past year or more, I have been encouraging clinicians as well as people with chronic fatigue syndrome (PWCs) (with the cooperation of their doctors if possible) to try treatments based on this hypothesis. Initially, I suggested that they try the treatments that were being used by the Defeat Autism Now! project to treat autism, focusing on the methylation cycle. While some benefits were observed from this, it did not seem to be an effective approach long term, at least in the way I was applying it. I then learned of the work of Dr. Amy Yasko, N.D., Ph.D. in autism, and decided to emphasize her approach after some study of it. An important feature of her work is her effort to tie the genetics of individuals to the biochemistry and to do tailored treatment based on genetics, again directed toward correcting the methylation cycle block, but also incorporating support for a variety of body systems and organs.

Quite a few PWCs acted on my suggestion, and are currently continuing the full Yasko treatment approach. Most of this group are in the first step of this treatment approach, and they are generally reporting that this treatment is producing considerable detoxification of their bodies. The full Yasko treatment approach involves considerable genetic and biochemical testing, and is rather expensive and complex. While some PWCs are in a position to pursue this treatment and are doing so successfully, it appears to me that there are many others for whom this approach is beyond their reach, either for economic or cognitive reasons or both. Practicing physicians also find this treatment to be somewhat problematic to incorporate in their practices because of the complexity and the considerable time required to tailor the treatment to each individual patient.

A Simplified Approach. In response to these problems, and in response to a request from Dr. David Bell for a discussion of treatment based on this hypothesis, I went on to suggest a simplified treatment approach that incorporates the core of Dr. Yasko's so-called "step 2." This is the step in her treatment program that involves actually lifting the block in the methylation cycle. When I proposed this approach, I was not sure how many PWCs would be able to tolerate the resulting detox and die-off of pathogens that would result from the consequent ramp-up of the detox system and the immune system after they had been dysfunctional for such long times during the long illness duration of many PWCs, but I thought it was worth a try, since the existing approach did not appear to have the characteristics necessary for wide use. With the help of a woman (name omitted to protect her privacy) who is currently doing the full Yasko treatment on herself, I selected a basic set of seven supplements from Dr. Yasko's step 2.

I published this simplified approach on the internet, and another woman (name omitted to protect privacy) decided to try it. As a result of benefits that she experienced almost immediately, she reported her experience on the ImmuneSupport.com CFS discussion board. In response to her reports, others began to try this approach. This began last February and the number of people on this treatment has continued to grow, the longest duration of treatment now being in the neighborhood of four months, with some as short as a few days. At this point, over 50 PWCs have reported to me that they are trying this treatment. Most are reporting in periodically to that board. I think I have heard from only one who has decided to
stop the treatment completely, though some have found that they need to take a break for various reasons, and are planning to resume later.

Results. The response to this treatment has involved a combination of improvements in CFS symptoms, together with the appearance of a variety of symptoms that appear to result from increased
detoxification and immune system attack on infections. The former are most welcome, and appear to be what continues to motivate the people on this treatment, in the face of the detox and die-off symptoms, which are unpleasant but appear to be inevitable, given the large body burdens of toxins and infections that many PWCs have accumulated during their illness, lacking adequate detox capability and cell-mediated immune response during that time.

While the pilot testing of this treatment approach is not being carried on in a controlled way, and while not all the PWCs trying it are using the complete suggested complement of supplements (which has currently been decreased to only five, at a cost slightly higher than two U.S. dollars per day), it is nevertheless possible to state that the treatment appears to be working for quite a few PWCs, though perhaps not all.

The following symptoms of CFS have been reported to be corrected by various PWCs on this treatment. Note that these are gathered from reports from several PWCs, so that not all have been reported by a single person, and I may have left some out inadvertently, since the email traffic has been very heavy:

Improvements

1. Improvement in sleep (though a few have reported increased difficulty in sleeping initially).
2. Thyroid hormone supplementation no longer necessary or tolerated.
3. Excessive urination stopped. Night-time urination stopped.
4. Restoration of normal body temperature from lower values.
5. Restoration of normal blood pressure from lower values.
6. Immune system attacking longstanding infections
7. Increased energy and ability to carry on higher levels of
activity without post-exertional fatigue or malaise. Crashing has
stopped.
8. Brain fog lifting, higher cognitive ability, memories coming back
9. Relief from hypoglycemia symptoms
10. Alcohol tolerance improving
11. Decrease in pain (though some have experienced increases in pain
temporarily, as well as increased headaches, presumably as a result
of detoxing).
12. Friends and therapists noticing and remarking on improvements in
the PWC's condition.
13. Necessity to adjust relationship with spouse, because not as much
caregiving needed. Need to come to a more balanced responsibilities
in relationship in view of improved health and improved ability to be
assertive.
14. Ability to read and retain what has been read has come back.
15. Ability to take a shower standing up again.
16. Ability to sit up for long times has returned.
17. Ability to drive for long distances has returned.
18. Ability to tolerate heat is much better.
18. Feeling unusually calm.
19. Feeling "more normal and part of the world."
20. Able to get off hormone support without experiencing problems
from doing it.

Anecdotal Results. I want to emphasize again that this is nothing like a controlled clinical trial. It is only pilot scale hypothesis testing in an uncontrolled way. There are many questions remaining to be answered, such as: For what fraction of the entire PWC population will this treatment be beneficial? Are there PWCs who are too debilitated to be able to tolerate the detoxing and die-off processes that result from this treatment? Will this treatment actually lead to continuing improvements over longer times, all the way to cured cases? Will this treatment be effective in cases of "pure fibromyalgia" as it appears to be in many cases of CFS? And many more. However, I think the results to date are very encouraging, and I don't want to delay in getting the word out, because it appears that many PWCs can be helped by this treatment.

I also want to emphasize again that it is best that this treatment be done in cooperation with a physician, to make sure that if there are individual issues that arise, they can be taken care of. The treatment itself consists only of nonprescription supplements that are normally found in the body and are necessary for normal biochemistry to take place, so it appears fairly benign on its surface, but the resulting detox and die-off can be very challenging in some cases. I also recommend for this reason that caution be used in trying this treatment on PWCs who are very debilitated. I want to remind you that I am not a licensed physician, but a researcher. I am hopeful that clinicians will be able to utilize this treatment approach in a practical way in their practices.

I think the results so far are supporting the validity of the GD-MCB hypothesis, since the treatment based on this hypothesis appears to be correcting the root cause issue in many cases of CFS, so that the many downstream issues in the pathophysiology are being corrected, and the predictions of the hypothesis are being confirmed. So far I have not published this hypothesis in the peer-reviewed literature, but it is my intention to do so.

If any PWCs or physicians who read this decide to try this treatment approach, I hope you will let me know how it goes for you. I may not be able to answer all the emails I receive, since the volume of the email traffic continues to grow.

Below I have pasted a discussion of the details of this treatment approach:

Simplified Treatment Approach--Current Version 05/22/07 09:58 AM

Here is the current version of the simplified treatment approach based on the glutathione depletion--methylat ion cycle block hypothesis.

All the supplements can be obtained from the holisticheal. com site, or you can obtain all but the Complete Vitamin and Neurological Health Formula elsewhere.

These supplements and dosages have been selected by Dr. Amy Yasko as part of her complete treatment approach, as described in her book "The Puzzle of Autism." Substitutions or changes in dosages may not have the same effect as the combination of supplements and dosages suggested, although some people do better if they start with smaller dosages than those given below. It's important to "listen to your body" when doing this treatment. If the detox becomes too intense to tolerate, or if you begin to have significant cardiac or respiratory symptoms, back off on the dosages or take a break for a while. It would be best to do this treatment in cooperation with your doctor, just so that any individual issues you have can be taken care of.

Die-off Symptoms: This treatment will produce die-off and detox symptoms as your immune system and detox system come back to normal operation and begin ridding your body of accumulated infections and toxins. This is inevitable, and has to be endured. However, while you experience detox symptoms, you should also experience improvement in your CFS symptoms over time. You can control the intensity of the detox symptoms by adjusting the dosages.

Please resist the temptation to try to get better faster by increasing the suggested dosages. In particular, do not exceed the suggested dosages for the FolaPro and the Intrinsi/B12/ folate
supplements, at least until you have been detoxing for several weeks. Some who have done this have experienced very unpleasant levels of detox symptoms that had momentum and did not decrease rapidly when the supplements were stopped.

Prescription Medications. As far as I know, there are no negative interactions between these supplements and the prescription medications used by physicians in treating CFS. However, I urge you to discuss this issue with your doctor if you are taking prescription medications.

If you are taking prescription medications, I expect that you will need them less and less as you are on this treatment. However, be sure to consult with your doctor before stopping the use of
prescription medications. Some of them can cause serious withdrawal symptoms if stopped too abruptly.

Several people have reported that they no longer needed thyroid hormone supplementation shortly after starting this treatment. If you are taking thyroid hormones, be alert to the possibility that you may experience HYPER thyroid symptoms after starting this treatment, such
as palpitations and sweats. Consult with your doctor about decreasing thyroid supplementation if this occurs.

The Five Supplements:

1. one-quarter tablet (200 micrograms) Folapro (Metagenics)

2. one-quarter tablet Intrinsi/B12/ folate (Metagenics)

3. (up to) 2 tablets (It's best to start with ¼ tablet and work up as
tolerated) Complete vitamin and antioxidant neurological health
formula (Holistic Health Consultants)

4. one softgel capsule Phosphatidyl Serine Complex

5. one sublingual lozenge Perque B12

The first two supplement tablets can be difficult to break into quarters. An alternative is to crush them into powders, mix the powders together, and divide the powders into quarters using a knife and a flat surface. The powders can be taken orally with water, with or without food, and do not taste bad.

Some people have asked what time of the day to take the supplements. A few have reported that the supplements make them sleepy, so they take them at bedtime. If they don't make you sleepy, I don't think it matters when you take them.

Rationale - Since some questions have been asked about what ingredients are essential, and since some of the people appear to be taking augmented versions of the simplified GD-MCB treatment approach that I wrote about in my January treatment paper, I want to give you some comments about that to help you with your own choices about what to take.

FolaPro--This is in there because a lot of PWCs have a SNP in their MTHFR enzyme that affects the production of 5-methyltetrahydrof olate, which is the same as FolaPro. This form of folate is the one used by the methionine synthase enzyme, and that's the enzyme that appears to be blocked in many or most cases of CFS. If a person had their genetics characterized, as in the full Yasko approach, they would know for sure whether they needed this one, but in the simplified approach we just suggest giving to everyone.

Intrinsi/B12/ folate--This one has 3 forms of folate--FolaPro, folinic acid and folic acid. It also has some cyano-B12 and some intrinsic factor as well as some other things. The folinic is helpful because some people can't use ordinary folic acid well, as a result of genetic issues. Also, this helps to supply forms of folate that will make up for the low tetrahydrofolate resulting from the block in methionine synthase. This enzyme normally converts 5-methytetrahydrofola te to tetrahydrofolate, which is needed in other reactions. This supplement also has some intrinsic factor and some ordinary cyano-B12 supplement to help those who have a type of pernicious anemia that results from low production of intrinsic factor in the stomach and which prevents them from absorbing B12 in the gut. B12 is also needed by methionine synthase, in the form of methylcobalamin, but this supplement has cyanocobalamin, which must be converted in the body by glutathione and SAMe to form methylcobalamin. As glutathione and SAMe come up, this should become more effective.

Complete vitamin and ultra-antioxidant (now called the General Vitamin Neurological Health Formula)--This is Amy Yasko's basic high-potency general nutritional supplement. This is kind of a foundation for the biochemistry in general. However, I think it's better for PWCs than other general supplements, because it has particular things needed for dealing with a methylation cycle block, including some TMG and sulfur metabolism supplements as well as nucleotides. It is also high on magnesium and low on calcium, and has no iron or copper. So I don't think other general supplements do everything this one does, and I think it's important in the treatment. The TMG helps to get the shortcut pathway in the methylation cycle going, and that helps to build SAMe, which is needed to get the methionine synthase reaction going. The nucleotides will help to supply RNA and DNA for new cells until the folate cycle is working right again.

Phosphatidylserine complex--This has various phosphatidyls in it, which will help repair damaged membranes, including those in cells of the brain and nervous system. It should help with the cortisol response. It also has some choline, which can be converted to TMG (betaine) in the body, to help start the shortcut pathway.

Perque B12--This is a hefty dose of sublingual hydroxocobalamin. As I said above, B12 is needed to get methionine synthase going. Methylcobalamin is actually the form needed, but some people cannot tolerate it for genetic reasons, and I'm also concerned that people with high body burdens of mercuric mercury could move mercury into the brain if they take too much methylcobalamin. Methylcobalamin is the only substance in biological systems that can methylate mercury, and methylmercury can cross the blood-brain barrier. This supplement is sublingual to compensate for poor B12 absorption in the gut of many people.

An Earlier Version There are also two others that were in the earlier version of the simplified approach:

SAMe--This is normally part of the methylation cycle. Depending on genetic variations (SNPs or polymorphisms) some people can't tolerate much of this, and some need more. The dosage is a compromise. If people can't tolerate this, they should leave it out, because stimulating the shortcut pathway, using TMG and choline in the other supplements) will probably make enough for them.

Methylation Support Nutriswitch Formula--This is a mixture of RNAs that is designed to help the methylation cycle. It is somewhat expensive, and is not essential, but is helpful and worthwhile if people can afford it.

I do think that the forms of folate and B12 are probably essential, because they go after the basic problem in CFS, in my opinion. I think the General supplement is important, and, and I think that some way to stimulate the shortcut is important, also. SAMe will help some people but perhaps not be tolerated by others, and if not, can be left out. The Methylation Support formula is helpful, but could be left out.

I don't think there is a problem with taking other supplements together with these basic supplements, for the most part. One exception is that I would not recommend taking additional folate beyond what is suggested above, since the various forms of folate compete with each other for absorption, and it is important to get enough of the active forms into the body. Also, it is important not to take too much folate, because this can cause the detox to develop a momentum, so that it will take some time to slow it down if you want to do that.

I would also not recommend taking additional trimethylglycine (TMG, also called betaine) or additional forms of choline, such as phosphatidylcholine or lecithin, since that will speed up the BHMT pathway too much at the expense of the methionine synthase pathway.

The betaine-HCl used to augment stomach acid is something you may have to drop while doing this treatment, too, since it will contribute to this problem.

Adding glutathione support will help some people, as will adding molybdenum. As more things are added, though, we are moving toward the full Yasko approach, which is fine, but it is more complicated and expensive, too. Maybe we should view this simplified approach as the front door to the full Yasko approach. It might work fine by itself for some people, but for others, maybe they should look at The Puzzle of Autism, sold on Amazon.com, to see what else there might help them. If the simplified approach seems to help to some degree, and it catches your attention for that reason, but it still doesn't do the whole job for you, then you could look further at the full Yasko treatment. At least then you would have some reason to dig into it. Otherwise, it looks pretty daunting to a lot of PWCs.

Rich Van Konynenburg, Ph.D.
Independent Researcher and Consultant
richvank@aol. com