Opinion: Chronic Fatigue Syndrome, Glutathione Depletion, and Autism
January 25, 2006
By Rich Van Konynenburg, Ph.D.
Editor's note: Rich Van Konynenburg, Ph.D., has kindly given permission to reprint his post, below, to share with our readers.
"I have been researching chronic fatigue syndrome (CFS) for over eight years. As some readers (of CFSFMExperimental posts) may recall, I had developed a hypothesis for the pathogenesis of chronic fatigue syndrome that prominently featured the depletion of glutathione, and I presented a poster paper on it at the AACFS (now the IACFS) meeting in October, 2004, in Madison, Wisconsin. This paper can be found at http://www.cfsresearch.org/cfs/research/treatment/15.htm
Anecdotal experience of people in the CFSFMExperimental Internet group and others who took my hypothesis seriously and acted upon it, suggested that while some were able to raise their glutathione levels by various means and experienced benefit from doing so, others were not able to do so.
At the time of writing my poster paper, I was aware of this, and I acknowledged in the conclusions of the paper that there appeared to be things that were blocking the raising of glutathione in CFS. At that time, I was not sure specifically what they were. I also knew that there was evidence for a genetic predisposition in CFS, but I did not know the details of the genetic variations involved.
Since then, I became aware of the work of S. Jill James et al. in autism (Am J Clin Nutr. 2004 Dec;80(6):1611-7). They found that glutathione was also depleted in autistic children, that this resulted from a partial block in the methylation (also called methionine) cycle, that this partial block resulted in part from genetic variations in the genes for certain enzymes and proteins associated with the sulfur metabolism (I don't think the genetic part of their research is published yet, but it has been presented at conferences), and that it interfered with the conversion of methionine to cysteine, which is the rate-limiting amino acid for the synthesis of glutathione. They found that by using certain supplements they could lift the block in the methylation cycle and restore the glutathione level.
In response to learning of this work, I became very interested in possible parallels between chronic fatigue syndrome and autism. I went on to attend the conference of the Defeat Autism Now! project in Long Beach, California in October, 2005.
As a result of this experience, I became convinced that the genetic predisposition found in autism must be the same or similar to that in a major subset of chronic fatigue syndrome, and that the resulting biochemical abnormalities were also the same or similar. As far as I know, the genetic variations in people with CFS have not yet been studied in detail or published, but I am optimistic that this will occur soon, because of the rapid advances in the technology for doing so, and the current active interest of at least three groups in the U.S. and the U.K. in genomic aspects of CFS. There are obviously also major differences between chronic fatigue syndrome and autism. I believe that these result primarily from the different ages of onset.
Autistic children experience onset early in life, before their brains are fully developed. I believe that this gives rise to the very different brain-related symptoms seen in autistic children from those seen in adults with CFS. However, there are many similarities in the symptomatology and the biochemistry of these two disorders as well, including oxidative stress, buildup of toxins, immune response shift to Th2, and gut problems, for example. The triggering factors for autism and chronic fatigue syndrome are also largely different.
There appears to be substantial evidence now that vaccinations (containing either a mercury-based preservative or live viruses, many given at the same time) were responsible for triggering many of the cases of autism in genetically-susceptible children.
In CFS, a variety of triggering factors (physical, chemical, biological, or psychological/emotional) have been shown to be involved in various cases. All of these factors have in common the tendency to deplete glutathione.
It appears that once glutathione drops sufficiently in a genetically susceptible person, the methylation cycle goes down, and the result is a depletion of several important metabolites in the sulfur metabolism, including S-adenosylmethionine (SAMe), cysteine, glutathione, taurine and sulfate. The depletion in these metabolites causes an avalanche of pathogenesis, since they all have very important functions in the body, and I think that much of this pathogenesis is common between autism and CFS.
In autism, I think the loss of methylation capacity because of the drop in SAMe is responsible for much of the interference with normal brain development.
There are also differences in the sex ratio in autism and CFS. The former is found most in boys, while the latter is found most in women. The book I mention later in this article discusses possible reasons for the sex ratio in autism. In my poster paper, cited above, I suggested an explanation for the female dominance in the prevalence of CFS. I think that the reason why the people who have developed CFS as adults did not develop autism as children (even though I suspect that they have the same or similar genetic predisposition) is that when they were children, not as many vaccinations were required.
The schedule of vaccinations required for children in the U.S. has grown substantially in the past two or three decades, as has the incidence of autism. I think this is also true in the U.K. My main message is that a great deal has already been worked out in autism by the people in the Defeat Autism Now! project, and that I believe that the CFS community would benefit greatly by looking carefully at what they have already done. They have found supplements that will compensate for the genetic variations and correct these biochemical irregularities. They are also detoxing heavy metals. The results in many autistic children have been astounding.
So I want to encourage everyone who has an interest in CFS to look at the results of the DAN! project in autism. You can view videos of the talks given at the latest two DAN! conferences on the internet at no cost (unless you are paying for the internet time!). Go to this site: http://www.danwebcast.com/. You can choose either the later Long Beach conference or the earlier Boston conference. They cover much of the same material, but both are worthwhile to watch.
If you want to see a good explanation of the methylation cycle research, go to the Boston meeting first, so you will be able to view the talk by Jill James, who did not attend the Long Beach meeting.
After selecting one of the conferences, go to the lower left and register. This is free. They will email a password to you right away, and then you can choose a talk to watch. Beyond this, I also want to recommend a book. This is a new book (Sept. 2005). It is by Jon Pangborn, Ph.D. and Sydney Baker, M.D., a biochemist and an autism clinician, respectively. It is available on Amazon for people within the U.S. For people outside the U.S., it can be obtained from the following website by means of PayPal: http://www.autismresearchinstitute.com
The cost for the book is $30 U.S. This is an excellent book. It is a reference book, full of good information and good science, explained clearly. This book deals very practically with developing a treatment program for an individual child. I think that most of it will turn out to apply directly to adults with CFS as well.
Although I have been suggesting consideration of the DAN! treatments to people with CFS for only about two months, and it is too soon to draw conclusions, early feedback is very encouraging. While I am going out on a limb in announcing this on Co-Cure now [where this post first appeared], I don't want to wait any longer, because I think this could help a lot of people.
Of course, we should all keep in mind that with the current case definition of CFS we have a very heterogeneous population, and the DAN! treatments may not help all PWCs, but I am convinced that they will help a substantial subset. So I want to encourage you to look into this. I think it could be the answer for many of you."
(c) 2006 Rich Van Konynenburg, Ph.D.
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