Townsend Letter for Doctors and Patients, Oct, 2006 by Richard A. Van Konynenburg
For the past ten years I have been studying chronic fatigue syndrome (CFS) as an independent researcher. Over the course of several years, I developed a hypothesis for the pathogenesis of this disorder that prominently featured the depletion of glutathione. I presented a paper on this hypothesis at the AACFS (now the International Association for Chronic Fatigue Syndrome) 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 with CFS who acted upon my hypothesis 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 I wrote my poster paper, I was aware of these anecdotal outcomes, and I acknowledged in the conclusions of the paper that there appeared to be factors blocking the raising of glutathione in CFS. At that time, I was not sure specifically what those factors might be. 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.
Shortly thereafter, I became aware of the work of S. Jill James et al. in autism (American Journal of Clinical Nutrition. 2004 Dec; 80(6):1611-7). The authors of that study found that glutathione was also depleted in autistic children, that this depletion was associated with a partial block in the methylation cycle (also called the methionine cycle), that this partial block was associated with genetic variations in the genes for certain enzymes and other proteins associated with the sulfur metabolism, and that it interfered with the synthesis of glutathione. The authors also found that by using certain supplements (methylcobalamin, folinic acid, and trimethylglycine), they could lift the block in the methylation cycle and restore the glutathione level.
Upon learning of this work, I became very interested in possible parallels between chronic fatigue syndrome and autism. I attended the conference of the Defeat Autism Now! (DAN!) project in Long Beach, California in October 2005, sponsored by the Autism Research Institute, headed by Dr. Bernard Rimland. As a result, I became convinced that the genetic predisposition found in autism must be the same or similar to that in a major subset of CFS, 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 US and the UK in genomic aspects of CFS.
There are obviously major differences between CFS and autism. I believe that these differences 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, many similarities exist in the biochemistry and symptoms 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. Although this subject remains controversial, there appears to be substantial evidence that vaccinations (containing either a mercury-based preservative or live viruses, many given within a short period of time) were responsible for triggering many of the cases of autism in genetically susceptible children (D. Geier and M.R. Geier. International Journal of Toxicology. 2004 Nov-Dec; 23(6):369-76; and A.J. Wakefield, several publications beginning in 1997). In CFS, a variety of triggering factors (physical, chemical, biological, or psychological/emotional) have been found to be involved in various cases, as reviewed in my poster paper, cited above. All these factors have a demand on glutathione in common.
It appears that genetically susceptible persons are unable to maintain normal glutathione levels when the total demand is high, and that once glutathione drops sufficiently in a genetically susceptible person, the sulfur metabolism becomes disrupted. In many cases, the methylation cycle (part of the sulfur metabolism) becomes partially blocked, and the result can be a depletion of some or all of several important sulfur-containing metabolites, including S-adeno-sylmethionine (SAMe), cysteine, glutathione, taurine, and sulfate. A vicious circle is thus formed, and the depletion in these metabolites causes an avalanche of pathogenesis, since they all perform important functions in the body. I think that much of this pathogenesis is common between autism and CFS. In autism, the loss of methylation capacity because of the drop in SAMe appears to be responsible for much of the interference with normal brain development.
There is also a major difference in the sex ratio between autism and CFS. In Autism: Effective Biomedical Treatments, author Dr. Jon Pangborn discusses possible reasons why autism is more prevalent in boys. In the paper I presented to the AACFS, I suggested a hypothesis to explain the female dominance in the prevalence of CFS in adults. 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 a similar genetic predisposition) is that fewer vaccinations were required when these patients were children. The schedule of vaccinations required for children in the US has grown substantially over the past two or three decades, as has the incidence of autism. This is also true in the UK.
Shortly after attending the DAN! conference, I also learned of the work of Dr. Amy Yasko, primarily in autism but extending to a number of other disorders as well. Working independently of the DAN! project, Dr. Yasko develops her treatment recommendations by analyzing the specific gene variations in each patient. In addition to studying effects on the methylation cycle, Dr. Yasko has considered the effects on associated biochemistry, including folate metabolism, biopterin, the urea cycle, and the synthesis of neurotransmitters.
My main message here is that ... the CFS community would benefit greatly by looking carefully at the conclusions reached both by Dr. Yasko and the autism researchers and clinicians associated with the Defeat Autism Now! project. The doctors associated with the DAN! project treat autism with nutritional supplements that compensate for genetic mutations in the sulfur metabolism. These include such supplements like magnesium sulfate, taurine, molybdenum, vitamin B6 and its active form P5P, magnesium, methylcobalamin, folinic acid, trimethylglycine, and dimethylglycine. These practitioners also use certain diets, and they perform chelation treatments to remove heavy metals. The results in many autistic children have been astounding. (Visit http://www.danwebcast.com to view interviews with children undergoing this treatment.) Dr. Yasko, in cooperation with Dr. Garry Gordon, also uses many of the same supplements used by the DAN! project doctors as well as some additional ones, including RNA supplements, and she is also reporting great success.
Although I have been suggesting consideration of the DAN! treatments and the Yasko testing to people with CFS for only a short time (and it is too soon to draw conclusions), early feedback is very encouraging. Of course, we should all keep in mind that, within the current case definition of CFS, we have a heterogeneous population, and the autism treatments will very likely not help everyone who has CFS. Nonetheless, I am convinced that these treatments could help a substantial subset, and I want to strongly encourage everyone who has an interest in CFS to look at the work of the DAN! project and Dr. Amy Yasko. Their work and treatment protocols could provide answers for many CFS patients.
Richard Van Konynenburg, PhD
To view videos of the talks given at the latest two DAN! conferences on the internet, go to http://www.danwebcast.com. You can choose the more recent Long Beach conference or the earlier Boston conference. Both conferences cover much of the same material, but both are worth watching. If you want to see and hear a good explanation of the methylation cycle research, go to the Boston meeting first; 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. You will be emailed a password right away, and then you can choose a talk to watch.
Autism: Effective Biomedical Treatments by Jon Pangborn, PhD and Sydney Baker, MD, a biochemist and an autism clinician, respectively. Available on Amazon.com for people within the US; outside the US, the book can be purchased through http://www.autismresearchinstitute.com ($30 US). This is an excellent reference book, full of good information and good science, explained clearly. This book deals with developing a practical treatment program for an individual child. I think that most of it will turn out to apply directly to adults with CFS as well.
Genetic ByPass by Amy Yasko, available at http://www.longevityplus-rna.com/store/product.php?productid=49 as part of the "Nutrigenomics Educational Starter Packet" ($49.95). This is an excellent book that discusses treatments specifically tailored to the particular combinations of genetic variations found in different patients.
I think these two books complement each other. I would recommend reading the Pangborn and Baker book first, as it provides a good basis for understanding the technical aspects of the genetics found in the Yasko book.
Note: The author has no financial interest in any book, product, or service recommended in this article.
by Richard A. Van Konynenburg, PhD