Declaring independence from CFS--the methylation block treatment is working!

[Guest guest]

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.

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

The main bases for this hypothesis were the wide prevalence of

glutathione depletion in CFS, as first reported by Dr. Cheney in

1999, and the work published by S. Jill 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.

For 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.

In response to these problems, and in response to a request from Dr.

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.

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 inadvertantly, since the

email traffic has been very heavy:

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.

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--methylation 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.

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.

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.

Here are 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.

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-methyltetrahydrofolate,

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-

methytetrahydrofolate 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.

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@...