***Hi, Don.
A possible explanation, in my opinion, for the lack of response or even worsening in some patients is that the low levels of glutathione are beneficial and the result of a beneficial oxidation reaction.
changes in the red-ox potential is a regulatory mechanism, and as such it may be beneficial or detrimental depending on the circumstances.
The same is true for methylation.
***I understand your point. This is the main issue between Dr. Cheney and myself concerning the treatment of ME/CFS, and has been for several years. It's certainly true that the body has built-in mechanisms for dealing with its problems by itself, and in many cases is able to heal itself. However, there are limits to what the body can deal with, as evidenced by chronic illnesses and death. The challenge is to determine whether something that is going on in the body is a built-in mechanism that is actually beneficial and is involved in healing or is a response to a disease that is helping to preserve life, but is not helping to achieve recovery. I agree that it is not always easy to tell, and that's why I have tried to develop a comprehensive hypothesis that encompasses what appear to be the causes as well as how the disorder develops and how the symptoms are produced. I think that if one has a thoroughgoing hypothesis that includes all of this, one has a better chance to understand what is a beneficial effect and what is not. But I agree that we need to intervene at the root cause and not downstream in the pathophysiology only. I do think that if we are treating at the root cause, downstream support in addition to this can be helpful, but the downstream support by itself will likely not bring recovery, and as you point out, can sometimes make things worse instead of better.
Many excellent theories and even some which showed promising results in cell cultures , were eventually found to be too simplistic. The main reason for that is the complexity of the human body and regulation mechanisms, which involve complex and interlaced biochemical reactions that are orchestrated in a fascinating spatial and timely manner.
***I agree. I think that developing a comprehensive hypothesis that starts at the beginning, matches all the observables and is logically self-consistent and consistent with known biochemistry and physiology is the best way to make sure that we are not "coming in at the middle of the movie" so to speak.
Also, many times in medicine, correcting an abnormality without understanding the underlying mechanism, can have unwanted effects.
***True.
An excellent example is TTP (thrombotic thrombocytopenic purpra).
Patients with this disease may present with severe bleeding and their blood tests will show very low platelet counts. Yet, if you correct this by giving them platelets (as you would intuitively do) you are going to make them much worse. The reason for that is that their platelets are low because they have too much clotting (and not too little) so by giving them platelets you add fuel to the fire.
***Definitely bad news.
That being said, many effective and even curative treatments were found empirically or with partial understanding of their mechanism.
***True, but I prefer trying to understand the whole picture before figuring out how to treat, rather than just hoping to get lucky. Of course, that's not easy.
Possibly your (no doubt interesting) theory is correct in some patients, but not in others.
***I think that's true. That's why I recommend that people run the methylation pathways panel before trying the treatment, to see if the GD-MCB hypothesis does in fact fit their case.
So far, for people who meet the case definitions for ME/CFS, very few turn out not to have a partial methylation cycle block and glutathione depletion.
The major questions regarding your treatment approach (as is true for every medical intervention) is how many patients benefit from it, how many are harmed from it, how significant is the benefit and does it justify the potential harm, is there any way in which you can know (or prevent/correct) the harm. And those answers in my opinion can only be given in some form of clinical trial (which could possibly be patient initiated).
***Very true. We have been able to do only a simple open-label clnical trial so far. The report on it is here:
http://www.mecfs-vic.org.au/sites/w...Article-2009VanKonynenburg-TrtMethylStudy.pdf
***It would of course be wonderful to have the results of a full-blown randomized, double-blind, placebo-controlled, statistically significant clinical trial with objective outcome measures, but that costs money and needs the right setting. In the meantime, about two-thirds of the people in the small clinical trial did report significant benefit, and the lab testing indicated that the treatment did improve the status of methylation and glutathione.
I believe that the main reason for the lack of significant progress, as yet, in the understanding of CFS is the complex nature of this disease, the large clinical variability (which probably also reflects biological variability) and abnormalities that are not usually seen (or at least not routinely tested for) in other diseases that are well known and relatively easy to diagnose.
***These definitely do make it challenging!
This combined with the (very wrong assumption) of many clinicians that normal or non-specific tests rule out a serious illness. And the other (very wrong assumption) that what we can not explain by our current understanding and knowledge, is due to "emotional problems". (which is a very poorly defined entity, that basically requires that a person would have emotions, in order to fit into it).
***Yes, these do muddy the waters!
I personally think that a better and more accurate clinical definition (and possibly sub-classification) of the disease and a development of a reliable clinical severity index score combined with a definition of clinical response is the first step.
***I agree that better definition would help. I have suggested that the methylation pathways panel be used as a diagnostic. I agree that objective measures of clinical response would also help a lot (such as actimetry, cardiopulmonary exercise testing (though it's kind of brutal for PWMEs), sleep monitoring with a pulse oximeter, dolimetry for pain threshold monitoring, neuropsychological testing for brain function, immune system testing, such as by cytokine measurements, and HPA axis testing, such as 24-hour saliva cortisol testing).
***I don't know if you would be interested in looking into the GD-MCB hypothesis in more detail, but if so, there is a video and a set of slides (blue print below the video) available here:
http://iaomt.media.fnf.nu/2/skovde_2011_me_kroniskt_trotthetssyndrom/$%7Bweburl%7D
***Thank you for your comments.
***Best regards,
***Rich
-) (We also prayed a lot!)
