Re: Article on GD-MCB Hypothesis published in the IACFS/ME Bulletin

[Guest guest]

I have one question about the MCB hypothesis.

When various biological abnormalities found in CFS are brought up, it

is always possible to 'swim upstream' and have low glutathione be a

possible culprit, since it is such a fundamental biochemical process.

However, if it were indeed the case that there was a MCB, then why

are only certain systems comprimised? Why do routine, and even

relatively in-depth laboratory investigations almost always come back

normal? Since glutathione is such a fundamental component of so many

basic bodily processes, then why are there not more abnormalities

when basic measurements are taken? It almost seems like cherry

picking, when abnormalities that are there are blamed on low

glutathione, but what about all the abnormalities that aren't there?

>

> Hi, all.

>

> I'm happy to note that I was invited a few weeks ago to write an

> article for the IACFS/ME Bulletin, and the article was published in

> the 2008 Summer edition today. I just posted the article in the

> files section of the cfs-yasko group's website. The editors asked

me

> not to get too specific in this article about treatment, because

> there have not yet been controlled clinical trials. Nevertheless,

I

> was able to discuss the main aspects of the hypothesis and

> implications for treatment.

>

> It will be interesting to see what sort of response this article

> stimulates. The IACFS/ME is a pretty conservative organization,

> composed mostly of mainline-type physicians. As you know, I am

> trying to recruit more physicians to try this type of treatment in

> their practices. I hope this article will help to do that.

>

> In the same issue of the bulletin there was a review by mund

> Vallings of the recent conference at Cambridge University in the

UK,

> at which Dr. Enlander gave an invited talk, also discussing

> methylation cycle treatment.

>

> In their Editorial in this issue, the Editorial Advisory Board

> characterized the GD-MCB hypothesis as " a most intriguing

hypothesis. "

>

> Best regards,

>

> Rich

>

[Guest guest]

Hi, j.

I think this is an excellent question, and I have pondered it

myself. The fact is that if you " swim downstream " in the

biochemistry starting with a methylation cycle block and glutathione

depletion, and identify all the functions of methylation and

glutathione that are known, you end up with what looks like a roll

call of those things that are not being done well in CFS.

Furthermore, these things don't intersect significantly with the

parameters that are routinely measured in conventional medical lab

tests. This is a more legitimate way to approach the problem than

the " upstream " reasoning approach, which would leave out a lot of

things. At the same time, if you make a list of parameters that

would be expected to be affected by a methylation cycle block and

glutathione depletion, and you measure those, you do find lots of

abnormalities. But they are not the parameters on routine standard

medical lab tests. Why not?

I think your question can be addressed at two levels. At the surface

level, I would say that the answer is that the conventional medical

lab tests have been chosen by a combination of cost considerations

and by their ability to reveal disease processes that can be serious,

even life threatening, which if treated early can be either cured or

headed off to some degree. This list of lab tests was not selected

to detect CFS, which was not even known when most of the selection of

routine lab tests was done, years ago. They are just not looking at

the right parameters.

At a deeper level, I think you are asking why isn't there at least

some intersection between the many parameters that are impacted by

the methylation cycle block and glutathione depletion on the one

hand, and the large number of parameters that are routinely measured,

on the other. You might expect at least some interaction, just on

the basis of chance. This is a much tougher question, and I think to

answer it completely, one would have to go down the list of routine

measurements and see why there are no intersections.

Let's start with the complete blood count. The fact is that you can

see some abnormalities here in PWCs sometimes, but they aren't very

large, and often don't show up until the person is pretty far into

CFS. For example, the white cell count. In a lot of PWCs, it runs a

little low, either because of the block in the folate system that is

associated with the partial methylation cycle block, which hinders

the production of new DNA and RNA to make new blood cells, or because

of viral infections, which tend to lower white cell counts, or both.

But the drop usually isn't very large, and low white cell count is

kind of nonspecific, so the doctors usually ignore it.

How about the red cells? Well, if a person has had B12 and folate

problems for a long time (as associated with methylation and folate

cycle block), you will start to see a drop in the red blood cell

count and a rise in the mean corpuscular volume, signaling the onset

of a macrocytic anemia. However, again, usually these changes aren't

too big in CFS, and they are usually ignored. By the time they are

detected, the person is probably going to be in pretty serious

trouble.

Another place where something might show up is in the creatinine in

the blood chemistry panel. Creatinine comes from the nonenzymatic

breakdown of creatine phosphate, and creatine synthesis is one of

main two demands on methylation. I think I have seen some drops in

creatinine, but because of the fact that the creatinine level depends

on lean body mass, which varies from one person to another, I don't

think the doctors pay much attention to the absolute concentration.

They are more focused on looking at the ratio between blood and urine

creatinine, to see if the kidneys are filtering it out of the blood

properly. It's a good measure of kidney function.

Here's something I think is important: Generally speaking, the

levels of the parameters in the routine blood chemistry panel and the

routine urinalysis are controlled by vital organs, including the

liver, the pancreas and the kidneys. It so happens that these are

among the six organs in the body that have a complete

transsulfuration pathway (the others being the intestine, the lens of

the eye, and to a much lesser extent, the brain). The significance of

this is that these organs are able to convert methionine into

cysteine, which is the rate-limiting amino acid for synthesizing

glutathione. So when cysteine and glutathione become depleted system-

wide, these organs are able to protect their supplies of glutathione

well enough to preserve life, while organs such as the skeletal

muscles become very depleted in glutathione, as do the cells of the

immune system and to a large extent, the brain, because it has low

activity in the transsulfuration pathway. Whether you believe in

design or evolution, the reason for this is probably to maintain life

during tough times, when nutrition is compromised. If the vital

organs are not protected from deficiencies, the person will die. So

perhaps this is the deeper reason for this seemingly strange

observation. Thanks for raising this issue, which forced me to think

about it some more.

Best regards,

Rich

>

> I have one question about the MCB hypothesis.

>

> When various biological abnormalities found in CFS are brought up,

it

> is always possible to 'swim upstream' and have low glutathione be a

> possible culprit, since it is such a fundamental biochemical

process.

>

> However, if it were indeed the case that there was a MCB, then why

> are only certain systems comprimised? Why do routine, and even

> relatively in-depth laboratory investigations almost always come

back

> normal? Since glutathione is such a fundamental component of so many

> basic bodily processes, then why are there not more abnormalities

> when basic measurements are taken? It almost seems like cherry

> picking, when abnormalities that are there are blamed on low

> glutathione, but what about all the abnormalities that aren't there?