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Question from a new guy...

Big

Messages
15
HI everyone, I'm new to this board and am reading through all these threads one after another...I'm actually somewhat researched in methylation issues from some other forums I read.

My question is this...is anyone doing remarkably better or "cured" by taking the right methylation supplements?

Everything I read on CFS seems to point to methylation blocks and I read people taking large amounts of b12 and methyl donors etc. but I rarely see them report dramatic improvement.

It would seem for example, that if the issues were primarily methylation then taking something like SAM-e would result in rapid improvement.

My primary symptom outside of terrible fatigue is orthostatic intolerance and pounding heartbeat. I would love to fix this.

Is anyone "cured" by fixing these methylation issues or taking things like SAM-e etc.?
 

caledonia

Senior Member
At least one person in Rich's six month study was able to go back to work. Others seemed to have gradual but definite improvement. There are some people who have been on the protocol for 2 years. The person I'm thinking of (of course, can't remember her name) is still seeing gradual improvement. There was someone who tried for 2 years, didn't see any improvement and discontinued. I think you could tell long before then if it was going to work for you or not.

I've had a small improvement with one year on just a tiny amount of Folapro. I'm going to be adding in some other supps and increasing Folapro soon. I have to go very gradually because the detox can make me feel worse.
I recently got back my Vitamin Diagnostics lab which shows a classic CFS pattern and partial methylation block.

This might be a good time to round up reports from everyone who's tried it over the past few years, and see where we're at with this therapy. Maybe a poll would be a good way to do this.

Ken Lassessen from CFSFMExperimental sets up his protocol effectiveness polls like this:

Question: I have tried the XYZ Protocol and the result was:
Choices:
Went to 100% remission
Went to 80%
Went to 60%
Went to 40%
Went to 20%
No Change
Lost ground
Major adverse reaction or side effects
 

gracenote

All shall be well . . .
Messages
1,537
Location
Santa Rosa, CA
Good idea caledonia.

I've only been on the Simplified Yasko for about a month. (I stopped and started again and worked up to these amounts.) So far I've noticed No Change.

A big welcome to Big. Glad to have you here.
 

Sunday

Senior Member
Messages
733
Hi, Big. That is a good question, and I agree with Kim and Grace, this is a good idea for a thread.

I have as yet had only some success with methylation protocol, but I am convinced that it is fundamental at least for a lot of us. Why? Because things that didn't work for me before are now starting to have an effect. It's as if my body is finally able to respond, at least a little, to food, VERY mild small amounts of exercise, and supplements. A lot of this is my intuition speaking. I'd be curious to know what other people's reactions are.

I've been doing Freddd's "Hidden Story" protocol for about 6 months. I've also been reading whatever I can grasp of what RichvanK writes. His simplified protocol is a revision of Yasko's, which is similar to Freddd's with some significant differences. Rich specializes in the biochemistry of it all and I think we're very lucky to have his perspective and Freddd's, as well as some of the other knowledgeable people on that thread. It gets hot and heavy over there sometimes, but I guess that's what it's like when you're doing cutting-edge science!

Of course, saying you're doing this protocol can mean any number of things, as there are basics everyone does but we all have to kind of mix and match our b12 and methylfolate dosages, and our cofactors.

I have noticed gradual changes for the better in the months I have been working on the basics and upping my b12/methylfolate. Although I should say I also went through 2 months of symptom hell, where pretty much everything acted up the worst I've had it. This is what Freddd calls startup. I hung through it, because I felt this protocol had the most hope of any I'd seen. Freddd's story itself is pretty dramatic, and he claims hundreds have been helped by his protocol on another website. I've been to that site (I think it's wrongdiagnostics, but I'm not sure and can't remember, sorry; if you PM Freddd I'm sure he would tell you). It's a huge thread, so I didn't read it all, but I did see some dramatic changes there as well as some less dramatic ones.

What has happened with me is that many of my symptoms have lessened: brain fog, OI, fatigue, nausea, insomnia, weird neuropathies, balance, skin sensation, and a bunch of other things.

What was disappointing, until recently, was that I still wasn't very functional - although the quality of my crashes was way up and I did have some good functional periods. But I may have found the missing co-factor that completes my picture: CoQ10. It's too early to say, of course, but I took a 10-day free sample, and at the end of that found myself significantly more functional.

I found myself reading long complicated books in a day, and not being completely tanked by my trip to visit family (which included a drive to and from the airport, about an hour and a half). These are significant markers for me, and now I'm back on CoQ10 again, I'm gradually feeling better in the brainfog and fatigue departments.

Time will tell. As Freddd says, there are a lot of ways to get a cake recipe wrong. He contributes valuable and very particular information about ingredients, but it's clear that we each have to find which constellation works for us individually. I suspect that, while methylation is vital, we may need other protocols along with it, especially those who've had this illness for a long time and have secondary troubles as a result of it.
 

Sunday

Senior Member
Messages
733
Sorry, Caledonia, I see that that was you and not Kim who put up that useful comment - something in your avatars reminds me of each other.

Guess that's proof my brain fog still needs work...think I'll go take some CoQ10 and vinpocetine, now.
 

Wayne

Senior Member
Messages
4,298
Location
Ashland, Oregon
Methylation - Vinpocetine

Guess that's proof my brain fog still needs work...think I'll go take some CoQ10 and vinpocetine, now.

Hi Sunday,

I was wondering if you've posted about your experiences with vinpocetine. I use piracetam occasionally, and find it helpful (can't tolerate very much however). Seems I saw a reference recently to two people reversing Alzheimer's using vinpocetine.

I've also been reading whatever I can grasp of what RichvanK writes.
You mean you don't grasp EVERYTHING Rich writes about? :D

Hi Big,

Welcome to the forum. I've been doing some of the supplements to support the methylation cycle for almost three years now, and consider them an important part of my health protocol. I started out doing some B-12, and some Folate, which eventually seemed to lose some effectiveness for me.

But when I started with some SAM-e earlier this year, some of the benefits I'd experienced earlier kicked in again. I believe supporting the methylation cycle is just one of many "layers" of dysfunction that needs to be addressed in ME/CFS.

I might mention that I noticed an immediate reaction (detox symptoms) as soon as I began to experiment with the methylation supplements. That told me right off that my methylation cycle was parftially blocked, and I needed to pay attention to this.

I may get some more in-depth testing done at some point to pinpoint more of what I may need to tailor my supplements to my own genetic profile. In the mean time, I believe my current methylation program is responsible for as much as 1/4 of my functionality, perhaps more. I would recommend doing some simple trials to see whether you can get a pretty quick take on whether this might work for you.

Best, Wayne
 

heapsreal

iherb 10% discount code OPA989,
Messages
10,086
Location
australia (brisbane)
hi big, i use to use b12 injections at high doses regularly, they helped abit but not a great deal, every so often when feeling a bit worse then normal have have a shot and it does help some. I also did the b12 sublingual thing with folic acid etc and to be honest it didnt do alot, but in saying that it has helped others, so its worth a try, its all trial and error. I have found that sublingual NADH at 20mg gives me abit of a lift for awhile
http://www.iherb.com/Co-E1-mojo-Plus-Enada-20-mg-30-Tablets/9292?at=0. I think the main thing wrong with treating cfs is that there arent alot of tests done to show us whats going wrong, maybe find an intergrative doc who does alot of testing for vitamins, aminos,hormones etc.

good luck mate
 

richvank

Senior Member
Messages
2,732
HI everyone, I'm new to this board and am reading through all these threads one after another...I'm actually somewhat researched in methylation issues from some other forums I read.

My question is this...is anyone doing remarkably better or "cured" by taking the right methylation supplements?

Everything I read on CFS seems to point to methylation blocks and I read people taking large amounts of b12 and methyl donors etc. but I rarely see them report dramatic improvement.

It would seem for example, that if the issues were primarily methylation then taking something like SAM-e would result in rapid improvement.

My primary symptom outside of terrible fatigue is orthostatic intolerance and pounding heartbeat. I would love to fix this.

Is anyone "cured" by fixing these methylation issues or taking things like SAM-e etc.?

Hi, Big.

I think you've asked a very good question! When I first suggested the so-called Simplified Treatment Approach (extracted from Amy Yasko's full treatment program with the help of a person on that program) in January, 2007, I wasn't sure whether it would work for very many PWCs. Then, when several people started reporting favorable responses, I became hopeful that it would be the "silver bullet" that could be used in a "cookie cutter" approach to help all PWCs! Well, as time has gone on, the evidence seems to be that it really is the silver bullet for a few, while for about two-thirds it is a help, and maybe gives something like a 30% improvement, while about one-third don't seem to respond.

When I say that it has been the "silver bullet" for a few PWCs, I mean that they became well enough to go back to work full-time if they wanted to, or were able to go on foreign travel with friends or do other fairly demanding leisure activities if they didn't need or want to go back to work. In my hypothesis, a genetic predisposition is part of the reason a person develops CFS, and this treatment of course doesn't change the person's genetics. So I guess it's debatable whether that can be called a "cure," but at least unless these people are exposed again to a sufficiently high level of stressors (physical, chemical, biological and/or emotional/psychological), I think they will be free of symptoms and can live their lives more or less normally. Of course, it's been only three years since we started, and I would say that most of the people who get well don't check back in regularly and tell me how they are doing. They really want to put CFS behind them and forget about it, I think, and I certainly don't blame them for that.

The best documentation we have is from a treatment study on 30 women that lasted 9 months. The first 6 months of it were reported in a poster paper at the most recent conference of the IACFS/ME. You can find it at www.cfsresearch.org by clicking on M.E./CFS and then on my name. Cort also has it on his site, and it's also in the files section of the Yahoo cfs_yasko group. Some case studies and some data plots from that study that go out to nine months are also in the files section of the cfs_yasko group. Beyond this study, there is quite a lot of anecdotal experience that has been posted to the ProHealth fibromyalgia and CFS board and the cfs_yasko group over the past 3 years.

As was mentioned, Ken Lassesen has conducted a couple of polls on the methylation-type treatment in the Yahoo CFSFMExperimental group. I think these are interesting, and they do give some kind of an impression, but they are uncontrolled in the sense that there are no objective measures of improvement, and the actual treatment the various people have followed can vary quite a bit in terms of supplements, dosages and duration, and how steadily they followed it. But at least it's a way to get some idea about what's going on with the people. I'm always in favor of finding out how people are faring on this treatment. I do think that the polls may under-report the more successful outcomes, though, because those people may be out "having a life" as some of them have put it. Those of you who are Bible scholars may recall the story of Jesus and the ten lepers (Luke 17: 11-19). Let me be clear: Please don't misunderstand me. I'm not comparing myself to Jesus!!! I just think the very human response described in this story is timeless.

Another source of information I have is very occasional reports from physicians who have incorporated this treatment into their practices. They don't report very often (usually only if I solicit reports!), but generally speaking, the feedback I have received is that the methylation cycle block treatment is an important part of their protocols, but it is not the whole thing needed to help most of their patients to fully recover. Of course, I wish it were otherwise, but that is the hard fact. One told me that it was the last thing he needed to bring some patients to recovery whom he had treated for several other aspects of the disorder, but were still not well. So it seems to be an essential piece of the treatment puzzle for at least quite a few patients.

I'm continuing to study individual cases and to try to understand what needs to be done to bring more people "across the finish line." Below is something I posted recently to the cfs_yasko group in response to questions from a person there. It sort of summarizes my current view of this treatment, and also comments briefly on variants of the methylation block treatment that are advocated by others.


1. I think it is well established now that many and probably most cases of both
autism and CFS have a partial methylation cycle block at the root of their
biochemical abnormalities.

I realize that most of the people in the research and clinical
communities involved in these two disorders are not (yet!) on board with this
concept, but I believe that careful study of the available research results and
attention to the results of treatment based on this concept do bear it out.

2. While a knowledge of the normal biochemistry of the methylation cycle and
related pathways points in a general way toward the types of treatment that are
likely to be effective, it does not uniquely identify the optimum treatment for
either autism or CFS.

For one thing, we humans all differ in terms of our particular sets of genomic
polymorphisms, so that the same treatment is likely not optimum for all people
who have autism or CFS.

For another thing, a person who has one of these disorders does not have
normally functioning physiology and biochemistry. The best path back to normal
will probably have to be determined experimentally by each person, because
normal biochemistry is not enough to tell us the best path back to normal.
Because of this, I don't think that anyone can claim that a particular protocol
is the "best" for use by everyone who has autism or CFS.

3. What we can say on the basis of biochemical testing is that in autism and CFS
there is a partial block of the enzyme methionine synthase, which is found in
every cell of the body.

We also know that this enzyme requires the reactants homocysteine and 5-methyl
tetrahydrofolate, that it requires methylcobalamin (a biochemically active form
of vitamin B12) as a coenzyme, and that the reaction it catalyzes produces
methionine and tetrahydrofolate.

We also know that in the liver and kidneys there is an alternate pathway that
converts homocysteine to methionine, which is called the BHMT (betaine
homocysteine methyltransferase) pathway.

Both these reactions produce methionine, and a second reaction in the
methylation cycle converts methionine to S-adenosylmethionine, which is the main
source of methyl groups for methylation reactions in the body, of which there
are a very large number.

While the BHMT reaction does convert homocysteine to methionine, it does not
involve the folate metabolism, and thus does not convert 5-methyl
tetrahydrofolate to tetrahydrofolate, as the methionine synthase reaction does.

Since the folate metabolism is important for other aspects of the overall
biochemistry (including the synthesis of DNA and RNA to make new cells), and
since the methionine synthase pathway is the only pathway that closes the
methylation cycle in organs, tissues and cells beside the liver and kidneys, it
is not sufficient to support only the BHMT pathway.

4. Based on this, the main goal of treatment of autism and CFS must be to
restore methionine synthase to normal operation. Since there is usually not a
shortage of homocysteine, the substances that need to be raised in their levels
in the body to stimulate the activity of methionine synthase are 5-methyl
tetrahydrofolate and methylcobalamin.

5. In addition to stimulating methionine synthase, there are other things that
are needed by the methylation cycle and associated biochemical pathways for
their operation.

Other cofactors that are needed are other B vitamins (which are included in
B-complex vitamin supplements), some minerals (including zinc, magnesium,
manganese, copper and selenium). In addition, certain amino acids are needed to
feed this part of the biochemistry. These include methionine, serine, cysteine,
glutamine and glycine.

Whether or not these additional substances will need to be supplemented in
treating a particular person will depend on the nutritional status of that
person.

6. Some of the toxic heavy metals, including mercury, are capable of blocking
the activity of various enzymes in this part of the biochemistry. If the levels
of these toxic metals are too high, they may prevent operation of the
methylation cycle or associated biochemical pathways unless treatment is
specifically used to lower their levels. Whether this is necessary for a
particular person will depend on that person's body burdens of toxic metals.

7. Getting back to the substances the levels of which need to raised to
stimulate the activity of methionine synthase, there are various ways in which
the levels of 5-methyl tetrahydrofolate and methylcobalamin can be raised.
Possibilities to consider start from supplying the most common commercial
supplemental forms of folate and B12, which are folic acid and cyanocobalamin.
These are the least expensive and have the longest shelf lives.

8. Folic acid is not a natural form of folate, and must be chemically reduced in
the body before it can be used. People vary by a factor of five in their
ability to do this, so that some people cannot utilize folic acid very well as a
source of usable folate.

One solution is to raise the dosage, so that more of the folic acid will be
reacted by the DHFR enzyme to produce tetrahydrofolate, which can be converted
by the cells to other forms of folate, including 5-methyl tetrahydrofolate.

However, four sequential biochemical reactions are needed to convert folic acid
to 5-methyl tetrahydrofolate, including two DHFR reactions, the SHMT reaction,
and the MTHFR reaction. If a person has genomic polymorphisms in any of these
enzymes that slow their resepective reactions, this will interfere with the
formation of 5-methyl THF from folic acid.

If the folic acid dosage is increased in order to raise the amount of 5-methyl
THF that is produced in the bodies of these people, the level of unreacted folic
acid in their blood streams will rise. There have been some suggestions that
this can increase the risk of cancer, but this is not well established at this
time.

I do not advocate using folic acid as the main source of folate in treatment to
lift the methylation cycle block because it is an unnatural form of folate,
because many people cannot use it readily because of their genomics, and because
there is at least some evidence suggesting that high dosages of it can raise the
risk of cancer. Also, I have seen in test results that many people with CFS
have "normal" levels of folic acid in their blood, while their levels of
5-methyl THF are low.

Nevertheless, high enough dosages of folic acid will likely work as the source
of folate for many people who have partial blocks of methionine synthase, and I
realize that this form of folate has been advocated and used with some success
by Dr. Vinitsky. I think that the reason he uses such large dosages is that
they are needed to overcome the problems I have discussed. I view this as a
rather inefficient approach to raising 5-methyl THF, though if and when it
works, I can't argue with success.

9. If folinic acid is used, this will bypass the need for the DHFR reaction,
which is slow in many people. Folinic acid is a natural form of folate, found
in natural foods. It can be converted by the cells to the various coenzyme
forms of folate, including 5-methyl THF.
Three sequential reactions are needed to convert folinic acid to 5-methyl THF,
including the MTHFR reaction. If genomic polymorphisms are present that will
slow these reactions, the conversion to 5-methyl THF will be hindered. This can
be compensated to some degree by raising the dosage of folinic acid. In spite
of some claims, formaldehyde is not involved in the folinic acid reactions. Dr.
Jon Pangborn has been a proponent of using folinic acid in the treatment of
autism, and it is used to a considerable extent by the DAN! (Defeat Autism Now!)
doctors. Dr. Amy Yasko has included folinic acid in her treatment as well.

I think that one advantage of including folinic acid in the treatment of CFS is
that it can be used by the cells to supply other forms of folate, especially
initially, before the methionine synthase reaction is producing enough
tetrahydrofolate to supply these needs. Thus, this should be able to help
support the synthesis of DNA and RNA for making new cells, such as in the gut
and the bone marrow, before the methylation cycle block has been fully lifted.

10. The most direct approach to raising the level of 5-methyl THF is to take it
directly. The correct chiral form for use by the body is sold as Metafolin or
FolaPro or Deplin and comes from a manufacturing process that has been patented
by Merck-Germany. There are other 5-methyl THF products that are made in
different ways, and some of them may be racemic mixtures, which include forms
that are not usable by the body, but I don't know about this in detail.
Metafolin is the Merck trademark, which has been licensed to some suppliers.
FolaPro is a Metagenics trademark, but the form of folate in it is the same as
in Metafolin. Deplin is a "medical food" produced by PamLab under license from
Merck-Germany. It has gone through FDA-approved testing as a treatment for
depression. The dosage in Deplin is 7.5 milligrams (7,500 micrograms), which is
much larger than the dosages in which Metafolin and FolaPro are sold (800
micrograms). Note also that I (following the lead of Dr. Yasko) have recommended
a dosage that is one-quarter of that, or 200 micrograms, in addition to a
smaller amount of 5-methyl THF in the Actifolate combined-folate supplement. So
the dosage in Deplin is quite large compared to what I have suggested for use in
treating CFS.

Dr. Amy Yasko has been a proponent of using 5-methyl THF in the treatment of
autism and other neurological disorders, and I have adopted it in the Simplified
Treatment Approach for treating CFS, also.

Dr. Jon Pangborn has argued against its use on the grounds that it is a
"dead-end" form of folate that can be used only by the methionine synthase
reaction. However, this is the reaction that needs to be stimulated in autism
and CFS.

In addition, it has been reported by Antoniades et al. that 5-methyl THF also
reacts with peroxynitrite, which may be an additional advantage in CFS, and
Prof. Martin Pall argues that this is the main role of 5-methyl THF in the
treatment of CFS and related disorders, on the basis of his NO-ONOO theory.

In my view, Dr. Yasko has the right approach, in using both folinic acid and
5-methyl THF. She also uses some folic acid, and I included that when I adopted
the combined supplements she was using, though I don't think it is a necessary
part of the treatment, and may be better omitted.

11. There is also the question of which route should be used to supplement
folate. Most people seem to be able to absorb folate if it is taken orally, and
that is what I have recommended, but sublingual and injection routes may be
necessary for some, if their digestive problems are severe.

12. Moving on to the possible supplemental forms of vitamin B12 that can be
used, they are cyanocobalamin, hydroxocobalamin (which is in equilibrium with
aquocobalamin in the body)adenosylcobalamin (also known as dibencozide) and
methylcobalamin.

13. Cyanocobalamin is the least expensive and has the longest shelf life.
However, in the cell, the cyanide group must be removed from the molecule before
it can be converted to methylcobalamin, and this cyanide must be disposed of so
that it does not rise to toxic levels, which can be life-threatening.

The body has four ways of detoxing cyanide, and for low dosages (in the
micrograms per day range), these usually do the job, except perhaps in people
who have the rare Leber's hereditary optic neuropathy.

However, in the larger dosages used for treating autism and CFS (several
milligrams per day), detoxing the cyanide can be a concern, and I know of one
case of CFS in which use of large dosages of cyanocobalamin led to cyanide
toxicity.

So I don't recommend using cyanocobalamin in milligram-level dosages by itself.
If there is enough hydroxocobalamin used with it, that can help to protect
against cyanide toxicity, but I still think it is better not to take large
dosages of cyanocobalamin.

14. Hydroxocobalamin must be converted by the cells into methylcobalamin before
it can be used by methionine synthase.

Unless a person has an inborn error of metabolism that involves the
intracellular cobalamin processing enzymes, which is rare, their cells should be
able to do this conversion, and this has the advantage that the cells can
control how much methylcobalamin they make and retain so that they do not
overdrive the methylation cycle.

The cells can normally also convert this form to adenosylcobalamin, the other
coenzyme form of B12 that they use (in the mitochondria).

Hydroxocobalamin is the form of B12 that I favor for treating CFS. Dr. Amy
Yasko also uses this form for treating some cases of autism, depending on the
person's particular COMT and VDR polymorphisms.

"Freddd," who posts to the aboutMECFS forum and the wrongdiagnosis forum, does
not advocate use of hydroxocobalamin on the grounds that it is an "inactive"
form of B12. It's true that it is not one of the coenzyme forms of B12, and
must be converted to become one of these forms, but in all but a very few
people, it is "active," in sense that the cells are equipped to use it
effectively. Freddd himself has reported that he has a genetic mutation in his
intracellular cobalamin processing enzymes.

15. Methylcobalamin can be supplemented directly. At relatively low dosages,
the cells will initially remove the methyl group from the molecule, and then
will reform methylcobalamin and adenosylcobalamin as needed.

At very high dosages (several milligrams per day) taken either sublingually or
by injection, some methylcobalamin is apparently able to diffuse into cells and
bypass the normal cobalamin processing enzymes, to supply itself to the
methionine synthase enzyme directly.

This is the approach advocated by freddd, and it seems to be helping some people
with CFS. However, I have three concerns about this approach.

One is that methylcobalamin is chemically able to react with inorganic mercury
to produce methylmercury, which can readily enter the brain, where mercury acts
as a potent neurotoxin. Many PWCs have high body burdens of inorganic mercury as
a result of inhaling mercury vapor from amalgam fillings over extended periods
in which their glutathione was depleted, so that they could not detox it well.

I don't have proof that methylation of mercury occurs in CFS patients, though
two or three anecdotal reports have suggested that it might, and guinea pig
experiments have found that this can occur in them.

Second, many PWCs have fairly high body burdens of a variety of toxins, and high
dosages may cause rapid mobilization of these toxins, producing symptoms that
are intolerable.

Third, I have seen a couple of cases in which such high dosages of
methylcobalamin, together with high dosages of 5-methyl THF, have apparently
overdriven the methylation cycle, which I believe will prevent glutathione from
coming up to normal as soon as it otherwise would.

So while I think that methylcobalamin can be helpful, particularly in cases in
which the person is low in methyl groups, I recommend caution with using
multi-milligram dosages of methylcobalamin by sublingual or injection routes.

Dr. James Neubrander has advocated use of subcutaneously injected
methylcobalamin at a dosage of about 60 micrograms per kilogram of body weight
every three days for the treatment of autism, and it is widely used by the DAN!
doctors. Subcutaneous injection gives a slower release to the blood stream.

16. Adenosylcobalamin (dibencozide) can also be used. This is the other
coenzyme form of B12 used by the cells. In small dosages taken orally, this
passes to the cells and the adenosyl group is first removed, and then both
methyl- and adenosylcobalamin are made as needed by the cells.

If taken in larger dosages (several milligrams per day) by the sublingual or
injection routes, some adenosylcobalamin is apparently able to diffuse into the
cells and be used directly.

Dr. Amy Yasko recommends use of this form in addition to others by some people
with autism and other disorders.

Freddd advocates use of large dosages of this form sublingually.

I haven't recommended use of this form, but it may be helpful in CFS.

17. The question of what dosages of folate and B12 forms should be used to treat
CFS is one that is not easy to resolve, and I think it varies with the
individual PWCs.

I have suggested some dosages based on Dr. Yasko's use in autism. Some people
have found them to be too high, at least initially, and have had to start with
lower dosages in order to be able to tolerate what appear to be detox and/or
die-off related symptoms. Others have found that they need larger dosages.

Freddd has advocated continuing with larger dosages and "pushing through" what
he calls the "start-up" symptoms. I have advocated what I think is the cautious
approach of backing off on the dosages until the symptoms are tolerable, and
working up from there, as tolerated. Freddd's view is that that only delays the
recovery.
I don't have proof of which of these approaches is the best.

18. I want to acknowledge Trina's help in choosing the initial supplements for
the Simplified Treatment Approach back in January, 2007.

19. I think there is still a lot more to be learned about how best to treat CFS.
Basic treatment directed at lifting the methylation cycle block clearly seems to
me to be an important aspect, but it does not appear to do the whole job for
many PWCs. For those who receive limited help or no help at all from this
treatment, I suggest considering the issues discussed in sections 5 and 6 above.
If this still doesn't bring recovery, then I would suggest considering direct
efforts to treat problems of the digestive system as well as exploring whether
there are comorbid conditions, such as tick-borne diseases or mold illness, if
this has not already been done.
As always, I recommend working closely with a physician when doing treatment to
lift a partial methylation cycle block.

I hope this addresses the issues you raised.

Best regards,

Rich