It's been about two and a half years since I
proposed the Glutathione Depletion--Methylation Cycle Block hypothesis
for the pathogenesis of CFS, and a simplified treatment approach based
on it. About six months ago, I presented a poster paper proposing that
Lyme disease is a route of entry into CFS for people who are
genomically predisposed to developing a partial methylation cycle
block, based on the observed depletion of glutathione by Borrelia
During the past two and a half years, I estimate
that at least several hundred, and probably now over a thousand PWCs
have tried this treatment. There are several physicians who have added
methylation cycle treatment to their protocols. Dr. Neil Nathan and I
also carried out and reported on an open-label clinical study of the
simplified treatment approach on patients in his practice in Missouri.
There have also been a large number (I don't know how many, but I have
probably personally seen a couple of hundred) methylation pathways
panels run by Vitamin Diagnostics in New Jersey and the European
Laboratory of Nutrients in the Netherlands. For people who have CFS,
nearly all have shown a partial methylation cycle block and/or
glutathione depletion, most showing both.
The treatment used
by itself seems to help about two-thirds of those who try it. When it
is combined with other treatments, it has brought what appears to be
complete recovery to at least a few people, who have been able to
return to full-time work. Some of the other treatments have been
treatments for Lyme disease, mold illness, or toxic metals overload.
Based on all of this experience, I continue to believe that this model
does describe the pathogenesis of CFS for many and perhaps most PWCs.
With regard to viruses or other pathogens, I believe that they are
responsible for the onset of CFS in some cases, especially in the
cluster or epidemic cases, such as the one at Incline Village. These
cases fit within the GD-MCB model, except that the genomic
predisposition aspect does not seem to be as important, or is not
involved at all. But the rest is likely the same, i.e. that the viral
infection depletes glutathione and brings on a partial block in the
methylation cycle. I think the explanation for this is that the virus
in the cluster cases has been particularly virulent, at least until it
mutated and became less so, ending the local epidemic.
far as the pathogenesis model is concerned, I think it is correct and
that it is able to explain essentially all the features of CFS. The
model allows for a variety of routes into this pathogenesis, i.e. a
variety of etiological factors. These include the whole variety of
stressors--physical, chemical, biological and psychological/emotional.
The stressors involved in the onset of each case can be differerent
from those involved in other cases, but they all channel into causing
oxidative stress and a partial methylation cycle block.
most cases the oxidative stress is accompanied by a depletion of
glutathione, but in a minority of cases, there is a genetic
polymorphism in the glutathione peroxidase enzyme. In those cases,
glutathione does not drop, but the effect is the same, because it
cannot be used effectively to counter the oxidative stress without a
functional glutathione peroxidase.
There's still an issue in
the model that is unsolved, and that is how the partial methylation
cycle block interacts with glutathione synthesis to deplete
glutathione. We know that it does, in both autism and CFS, because when
the methylation cycle block is lifted, glutathione comes back up
automatically. But the details of this interaction are still undefined
from a theoretical biochemical standpoint.
Note that the issue
of whether the methylation cycle block is at the root of the
pathogenesis is a separate issue from what is the best way to treat it.
There may be, and likely are, better ways to treat it than the
simplified treatment approach. I proposed that as a simple and
relatively inexpensive, and thus accessible treatment for PWCs, and at
the same time a way to test the model for pathogenesis. I would say
that it has been successful in testing the model, and the model has
survived the test. I think we still have more to learn about treatment,
though the simplified treatment approach has made a significant
contribution, and for some PWCS, has been the last thing they needed to
I don't know if you have been following the
"demonstration project" for treating M.E. patients that is going on in
Ohio, USA, at present, which is updated on the forum called "A New Day," part
of Cort Johnson's forums. The approach to treatment being used there
involves IV nutrition, homeopathic neural therapy, acupuncture,
proliferative therapy, and laser therapy. This is quite an innovative
approach to treatment, and I can't say that I understand how it works
from a fundamental scientific viewpoint. It does, however, so far
appear to be a promising approach, and I am following the updates.?
I don't know the details of what is included in the IVs, and perhaps
there is some B12 and folate involved, which would seem to be important
for lifting the methylation cycle block. On the other hand, perhaps the
other techniques used are able to cause the body to make more effective
use of the resources of B12 and folate that it already has. In any
case, I do think there is good evidence that many or most PWCs have a
methylation cycle block, and to lift this block, the methionine
synthase activity has to be increased, which entails greater functional
use of B12 and folate. So I'm trying to understand how this treatment
intersects with that need.
You asked about treatment
timescale. This seems to vary, depending on a variety of factors. If
the simplified treatment approach is used by itself, the experience is
that improvements usually occur within a couple of months, but full
recovery hasn't happened for many people over a year later, though it
has for a few. Lately I've been studying some of the cases with slow
improvement, and I think that the lack of enough of the cofactors or
enough of the amino acids to feed the methylation cycle and associated
pathways may be the reasons for the slow progress in at least some of
the cases. B-complex vitamins, minerals including zinc, copper,
magnesium and selenium, and amino acids including methionine, serine,
and the precursors for glutathione (glycine and glutamine or glutamate)
are frequently found to be low.
Dysfunction of the gut seems
to be at the basis of the low amino acids. I think that's why the IV
amino acids are an important part of the treatment in Ohio, but for
many PWCs, it may be possible to take free-form amino acids in order to
increase their absorption, even with gut dysbiosis going on.
Beyond this, there are other treatments that may need to be added,
depending on the particular case. These include attention to food
sensitivities, efforts to improve the condition and function of the
gut, support for the adrenal and thyroid axes, treatment of infections,
treatment for mold illness if present, and treatment of heavy metal
toxicity. There are various ways of approaching these issues in
treatment, and physicians differ in their methods, but I think these
are the things that can be required.
So in summary, I think
the theoretical model and the lab test are holding up well, and though
there is more to be learned in treatment, lifting the methylation cycle
block and thereby bringing up glutathione seem to be essential parts of
Rich Van Konynenburg, Ph.D. email@example.com