Re: Histamine and the Glutathione Depletion--Methylation Cycle Block Hypothesis

[Guest guest]

Hi Rich,

Allergies were never a serious problem for me until I became

suddenly, severely ill in the Fall of 1975, although older members of

my family suffered from allergies (mother, grandfather, aunts,

uncles). After I became ill, it was a friend who suggested that I

might have allergies and should try an allergist. I had never

considered allergies a serious problem before then. I was tested for

allergies, and I did have a lot of them, but they were mostly mild, a

few moderate. I started taking allergy shots, but over the years, my

allergies worsened.

My allergy doctors (5 of them) always said, however, that my level of

eosinophils and allergy tests were not high enough to be causing my

severe allergy symptoms. The one exception was mold allergy (ERIC

will find that interesting.) I was diagnosed with allergic

tension/fatigue syndrome.

I found that when I avoided one group of allergens, I would develop

another. For example, I would test positive (IgE)for about a dozen

foods. Then I would discontinue those foods and start eating others.

When I was tested again in a year or two, some of my allergies to the

first group of foods would be negative, but I would be allergic to a

lot of the new foods I had started eating. So I slowly became

allergic to just about everything.

By the time I heard about a rotation diet, my allergies were just too

severe for me to tolerate a rotation diet. I tried for about 5 years

to follow one.

I will not go into details about how each of my problems was

diagnosed by different doctors over the years (mitral valve prolapse,

hypothyroidism, adrenal problems, ovarian cyst disease, fainting and

dizzy spells, PMS, GM1 autoantibodies, Rheumatoid factor antibodies,

connective tissue problems, uterine fibroids, demyelinating

neuropathy (but not MS), very low suppressor cells relative to helper

cells, extremely low natural killer cells, anaphylactic shock

reaction, elevated titers and/or cyclical reactivation of Herpes 1

and 2, Epstein Barr, CMV, Rubella, cognitive problems, brain fog,

muscle and joint pain, headaches, IBS, diverticulitus, colitis,

Multiple Chemical Sensitivity, yeast problems, arterosclerosis, Lyme

disease, worse yeast problems... I was not diagnosed with CFS until

2000.

I hope that helps. I would think blocked methylation affects just

about everything (DNA expression, for example), but one of the worst

effects is reducing glutathione, which creates the vicious cycles,

oxidative stress, detox problems, glial cell problems leading to

inflammation in the brain, etc. Everything is interconnected, a

spider web, a nonlinear, self-organizing system. But I guess

demonstrating the links and exactly how all of it works is the

problem.

Wishing you inspiration and great success!!!

Vickie

>

> Hi, all.

>

> I want to bounce something off of you.

>

> As you may be aware, there have been several studies that have

> found that IgE-type allergies are not more common in PWCs than in

> the general public. However, PWCs report having big problems with

> allergies, and they also report worsening of allergies they had

> before developing CFS.

>

> I think I now have something new to add to this topic. I am in the

> process of writing a poster paper for the IACFS meeting coming up

> next month. This one is about the Glutathione Depletion-

> -Methylation Cycle Block Hypothesis for the Pathogenesis of CFS.

> It's based on my past work on glutathione depletion in CFS, and also

> on what's going on in autism research, where Jill and

> coworkers have found that glutathione depletion there is linked to a

> block in the methylation cycle. As I've mentioned before, it looks

> to me as though the same thing is going on in at least a major

> subset of PWCs.

>

> So what I've been doing today is to try to figure out what the

> effects of a blocked methylation cycle are, and to see if these are

> things that show up in CFS. One of the several things I've come

> upon is the fact that the deactivation of histamine requires

> methylation reactions. Thus, if a person has a blocked methylation

> cycle and thus decreased capacity for methylation (because the ratio

> of S-adenosylmethionine to S-adenosylhomocysteine drops, and this

> blocks the methyltransferase enzymes), then I think we should expect

> that if they have an allergic reaction to something, the histamine

> will rise higher and stay up longer than it would in a person with

> normal methylation capacity. Therefore, the allergic reaction would

> be expected to be more severe.

>

> This would explain why, even though the prevalence of IgE allergies

> in PWCs is not significantly different from that in the general

> population, the PWCs would experience more severe reactions when

> they did get them. It would also explain why allergies they had

> prior to developing CFS were observed to get worse after their CFS

> onset.

>

> So what do you think about this?

>

> My experience with this overall hypothesis continues to be that the

> pieces keep falling into place. I've never had an experience like

> this before, in about 40 years of working in science.

>

> Another thing that is really a mind-blower is this: research in

> secretory protein synthesis is showing that glutathione is necessary

> in the process of putting disulfide bonds (into those secretory

> proteins that are supposed to have them) correctly to establish

> their tertiary structure (folding) before they are secreted from

the

> cell.

>

> I've pondered what would happen if the cells that secrete them do

not

> have enough glutathione. They end up not being able to secrete the

> proteins properly, and there will likely be misfolding. (Recall

> that Jim Baraniuk et al. reported widespread misfolding of proteins

> in the spinal fluid in CFS.) O.K., here's the mind-blower: this

> cuts right across the symptoms of CFS. It can explain the low

> perforin production and thus the low cytotoxic activity of natural

> killer (NK) cells, one of the cardinal immunological features of

> CFS. It can also explain low production of ACTH, leading to the

> well-known observed blunting of the HPA axis. It can also explain

> why both oxytocin and antidiuretic hormone are low, the latter

> producing the diabetes insipidus, with its excessive urination,

> constant thirst, and low blood volume. The story just goes on and

> on. This is really a sweeping hypothesis, and I don't know if the

> community will believe it or not. In my view, too many things keep

> coming out right for there not to be some truth in this thing.

>

> Take care, and I wish you all the best in this season, however you

> celebrate it.

>

> Rich

>

[Guest guest]

Hi again, Rich,

Have you reviewed the speeches at the DAN Washington DC and Wisconsin

conferences lately? You might find some new clues in some of that. I

have been watching them this week (since I can't sleep at night).

There is so much good data about methylation.

Vickie

>

> Hi, all.

>

> I want to bounce something off of you.

>

> As you may be aware, there have been several studies that have

> found that IgE-type allergies are not more common in PWCs than in

> the general public. However, PWCs report having big problems with

> allergies, and they also report worsening of allergies they had

> before developing CFS.

>

> I think I now have something new to add to this topic. I am in the

> process of writing a poster paper for the IACFS meeting coming up

> next month. This one is about the Glutathione Depletion-

> -Methylation Cycle Block Hypothesis for the Pathogenesis of CFS.

> It's based on my past work on glutathione depletion in CFS, and also

> on what's going on in autism research, where Jill and

> coworkers have found that glutathione depletion there is linked to a

> block in the methylation cycle. As I've mentioned before, it looks

> to me as though the same thing is going on in at least a major

> subset of PWCs.

>

> So what I've been doing today is to try to figure out what the

> effects of a blocked methylation cycle are, and to see if these are

> things that show up in CFS. One of the several things I've come

> upon is the fact that the deactivation of histamine requires

> methylation reactions. Thus, if a person has a blocked methylation

> cycle and thus decreased capacity for methylation (because the ratio

> of S-adenosylmethionine to S-adenosylhomocysteine drops, and this

> blocks the methyltransferase enzymes), then I think we should expect

> that if they have an allergic reaction to something, the histamine

> will rise higher and stay up longer than it would in a person with

> normal methylation capacity. Therefore, the allergic reaction would

> be expected to be more severe.

>

> This would explain why, even though the prevalence of IgE allergies

> in PWCs is not significantly different from that in the general

> population, the PWCs would experience more severe reactions when

> they did get them. It would also explain why allergies they had

> prior to developing CFS were observed to get worse after their CFS

> onset.

>

> So what do you think about this?

>

> My experience with this overall hypothesis continues to be that the

> pieces keep falling into place. I've never had an experience like

> this before, in about 40 years of working in science.

>

> Another thing that is really a mind-blower is this: research in

> secretory protein synthesis is showing that glutathione is necessary

> in the process of putting disulfide bonds (into those secretory

> proteins that are supposed to have them) correctly to establish

> their tertiary structure (folding) before they are secreted from

the

> cell.

>

> I've pondered what would happen if the cells that secrete them do

not

> have enough glutathione. They end up not being able to secrete the

> proteins properly, and there will likely be misfolding. (Recall

> that Jim Baraniuk et al. reported widespread misfolding of proteins

> in the spinal fluid in CFS.) O.K., here's the mind-blower: this

> cuts right across the symptoms of CFS. It can explain the low

> perforin production and thus the low cytotoxic activity of natural

> killer (NK) cells, one of the cardinal immunological features of

> CFS. It can also explain low production of ACTH, leading to the

> well-known observed blunting of the HPA axis. It can also explain

> why both oxytocin and antidiuretic hormone are low, the latter

> producing the diabetes insipidus, with its excessive urination,

> constant thirst, and low blood volume. The story just goes on and

> on. This is really a sweeping hypothesis, and I don't know if the

> community will believe it or not. In my view, too many things keep

> coming out right for there not to be some truth in this thing.

>

> Take care, and I wish you all the best in this season, however you

> celebrate it.

>

> Rich

>

[Guest guest]

No allergies here, but increasing chemical sensitivities, if that's relevant.

Have you seen this website:

http://www.goodshape.net/

It discusses a home-made transdermal histamine treatment for people with M.S. I

wonder

if it would benefit PWC as well, and may try it.

Thanks for your post, and I look forward to hearing more about this histamine

connection.

>

> Hi, all.

>

> I want to bounce something off of you.

>

> As you may be aware, there have been several studies that have

> found that IgE-type allergies are not more common in PWCs than in

> the general public. However, PWCs report having big problems with

> allergies, and they also report worsening of allergies they had

> before developing CFS.

>

> I think I now have something new to add to this topic. I am in the

> process of writing a poster paper for the IACFS meeting coming up

> next month. This one is about the Glutathione Depletion-

> -Methylation Cycle Block Hypothesis for the Pathogenesis of CFS.

> It's based on my past work on glutathione depletion in CFS, and also

> on what's going on in autism research, where Jill and

> coworkers have found that glutathione depletion there is linked to a

> block in the methylation cycle. As I've mentioned before, it looks

> to me as though the same thing is going on in at least a major

> subset of PWCs.

>

> So what I've been doing today is to try to figure out what the

> effects of a blocked methylation cycle are, and to see if these are

> things that show up in CFS. One of the several things I've come

> upon is the fact that the deactivation of histamine requires

> methylation reactions. Thus, if a person has a blocked methylation

> cycle and thus decreased capacity for methylation (because the ratio

> of S-adenosylmethionine to S-adenosylhomocysteine drops, and this

> blocks the methyltransferase enzymes), then I think we should expect

> that if they have an allergic reaction to something, the histamine

> will rise higher and stay up longer than it would in a person with

> normal methylation capacity. Therefore, the allergic reaction would

> be expected to be more severe.

>

> This would explain why, even though the prevalence of IgE allergies

> in PWCs is not significantly different from that in the general

> population, the PWCs would experience more severe reactions when

> they did get them. It would also explain why allergies they had

> prior to developing CFS were observed to get worse after their CFS

> onset.

>

> So what do you think about this?

>

> My experience with this overall hypothesis continues to be that the

> pieces keep falling into place. I've never had an experience like

> this before, in about 40 years of working in science.

>

> Another thing that is really a mind-blower is this: research in

> secretory protein synthesis is showing that glutathione is necessary

> in the process of putting disulfide bonds (into those secretory

> proteins that are supposed to have them) correctly to establish

> their tertiary structure (folding) before they are secreted from the

> cell.

>

> I've pondered what would happen if the cells that secrete them do not

> have enough glutathione. They end up not being able to secrete the

> proteins properly, and there will likely be misfolding. (Recall

> that Jim Baraniuk et al. reported widespread misfolding of proteins

> in the spinal fluid in CFS.) O.K., here's the mind-blower: this

> cuts right across the symptoms of CFS. It can explain the low

> perforin production and thus the low cytotoxic activity of natural

> killer (NK) cells, one of the cardinal immunological features of

> CFS. It can also explain low production of ACTH, leading to the

> well-known observed blunting of the HPA axis. It can also explain

> why both oxytocin and antidiuretic hormone are low, the latter

> producing the diabetes insipidus, with its excessive urination,

> constant thirst, and low blood volume. The story just goes on and

> on. This is really a sweeping hypothesis, and I don't know if the

> community will believe it or not. In my view, too many things keep

> coming out right for there not to be some truth in this thing.

>

> Take care, and I wish you all the best in this season, however you

> celebrate it.

>

> Rich

>

[Guest guest]

Hi Rich

This had crossed my mind, too. I developed a sensitivity to sticking

plasters sometime after coming down with M.E. I now become rather

fetchingly red and blotchy around the plaster if I have it on for more

than a couple of hours.

Sue

rvankonynen wrote:

> As you may be aware, there have been several studies that have

> found that IgE-type allergies are not more common in PWCs than in

> the general public. However, PWCs report having big problems with

> allergies, and they also report worsening of allergies they had

> before developing CFS.

[Guest guest]

Hi Rich,

as far as my case goes it completely fits into your scenario. I had a

few allergies before CFS which were none of a problem. After the

onset of CFS I experienced a dramatical rise of allergies and

sensitivities. I don't tolerate 90% of all foods now. It's a

catastrophy. There are son many PWCs with allergies here I really

wonder if that study about alelrgies and CFS should be repeated.

I hope your knowledge can soon be converted into a treatment approach.

At the end of the DVD Dr. Cheney speaks about Glutathione and says

that you can take as much supplements for the production of

glutathione as you want, as long as there is not enough energy you

only will produce the oxidised form of it and this form won't be much

of a help. What is your opinion about it?

I'll always be politically incorrect: Happy Christmas!

>

> Hi, all.

>

> I want to bounce something off of you.

>

> As you may be aware, there have been several studies that have

> found that IgE-type allergies are not more common in PWCs than in

> the general public. However, PWCs report having big problems with

> allergies, and they also report worsening of allergies they had

> before developing CFS.

>

> I think I now have something new to add to this topic. I am in the

> process of writing a poster paper for the IACFS meeting coming up

> next month. This one is about the Glutathione Depletion-

> -Methylation Cycle Block Hypothesis for the Pathogenesis of CFS.

> It's based on my past work on glutathione depletion in CFS, and also

> on what's going on in autism research, where Jill and

> coworkers have found that glutathione depletion there is linked to a

> block in the methylation cycle. As I've mentioned before, it looks

> to me as though the same thing is going on in at least a major

> subset of PWCs.

>

> So what I've been doing today is to try to figure out what the

> effects of a blocked methylation cycle are, and to see if these are

> things that show up in CFS. One of the several things I've come

> upon is the fact that the deactivation of histamine requires

> methylation reactions. Thus, if a person has a blocked methylation

> cycle and thus decreased capacity for methylation (because the ratio

> of S-adenosylmethionine to S-adenosylhomocysteine drops, and this

> blocks the methyltransferase enzymes), then I think we should expect

> that if they have an allergic reaction to something, the histamine

> will rise higher and stay up longer than it would in a person with

> normal methylation capacity. Therefore, the allergic reaction would

> be expected to be more severe.

>

> This would explain why, even though the prevalence of IgE allergies

> in PWCs is not significantly different from that in the general

> population, the PWCs would experience more severe reactions when

> they did get them. It would also explain why allergies they had

> prior to developing CFS were observed to get worse after their CFS

> onset.

>

> So what do you think about this?

>

> My experience with this overall hypothesis continues to be that the

> pieces keep falling into place. I've never had an experience like

> this before, in about 40 years of working in science.

>

> Another thing that is really a mind-blower is this: research in

> secretory protein synthesis is showing that glutathione is necessary

> in the process of putting disulfide bonds (into those secretory

> proteins that are supposed to have them) correctly to establish

> their tertiary structure (folding) before they are secreted from

the

> cell.

>

> I've pondered what would happen if the cells that secrete them do

not

> have enough glutathione. They end up not being able to secrete the

> proteins properly, and there will likely be misfolding. (Recall

> that Jim Baraniuk et al. reported widespread misfolding of proteins

> in the spinal fluid in CFS.) O.K., here's the mind-blower: this

> cuts right across the symptoms of CFS. It can explain the low

> perforin production and thus the low cytotoxic activity of natural

> killer (NK) cells, one of the cardinal immunological features of

> CFS. It can also explain low production of ACTH, leading to the

> well-known observed blunting of the HPA axis. It can also explain

> why both oxytocin and antidiuretic hormone are low, the latter

> producing the diabetes insipidus, with its excessive urination,

> constant thirst, and low blood volume. The story just goes on and

> on. This is really a sweeping hypothesis, and I don't know if the

> community will believe it or not. In my view, too many things keep

> coming out right for there not to be some truth in this thing.

>

> Take care, and I wish you all the best in this season, however you

> celebrate it.

>

> Rich

>

[Guest guest]

>

> Hi, all.

>

> I want to bounce something off of you.

>

> As you may be aware, there have been several studies that have

> found that IgE-type allergies are not more common in PWCs than in

> the general public. However, PWCs report having big problems with

> allergies, and they also report worsening of allergies they had

> before developing CFS.

>

> I think I now have something new to add to this topic. I am in the

> process of writing a poster paper for the IACFS meeting coming up

> next month. This one is about the Glutathione Depletion-

> -Methylation Cycle Block Hypothesis for the Pathogenesis of CFS.

> It's based on my past work on glutathione depletion in CFS, and also

> on what's going on in autism research, where Jill and

> coworkers have found that glutathione depletion there is linked to a

> block in the methylation cycle. As I've mentioned before, it looks

> to me as though the same thing is going on in at least a major

> subset of PWCs.

>

> So what I've been doing today is to try to figure out what the

> effects of a blocked methylation cycle are, and to see if these are

> things that show up in CFS. One of the several things I've come

> upon is the fact that the deactivation of histamine requires

> methylation reactions. Thus, if a person has a blocked methylation

> cycle and thus decreased capacity for methylation (because the ratio

> of S-adenosylmethionine to S-adenosylhomocysteine drops, and this

> blocks the methyltransferase enzymes), then I think we should expect

> that if they have an allergic reaction to something, the histamine

> will rise higher and stay up longer than it would in a person with

> normal methylation capacity. Therefore, the allergic reaction would

> be expected to be more severe.

>

> This would explain why, even though the prevalence of IgE allergies

> in PWCs is not significantly different from that in the general

> population, the PWCs would experience more severe reactions when

> they did get them. It would also explain why allergies they had

> prior to developing CFS were observed to get worse after their CFS

> onset.

>

> So what do you think about this?

>

> My experience with this overall hypothesis continues to be that the

> pieces keep falling into place. I've never had an experience like

> this before, in about 40 years of working in science.

>

> Another thing that is really a mind-blower is this: research in

> secretory protein synthesis is showing that glutathione is necessary

> in the process of putting disulfide bonds (into those secretory

> proteins that are supposed to have them) correctly to establish

> their tertiary structure (folding) before they are secreted from

the

> cell.

>

> I've pondered what would happen if the cells that secrete them do

not

> have enough glutathione. They end up not being able to secrete the

> proteins properly, and there will likely be misfolding. (Recall

> that Jim Baraniuk et al. reported widespread misfolding of proteins

> in the spinal fluid in CFS.) O.K., here's the mind-blower: this

> cuts right across the symptoms of CFS. It can explain the low

> perforin production and thus the low cytotoxic activity of natural

> killer (NK) cells, one of the cardinal immunological features of

> CFS. It can also explain low production of ACTH, leading to the

> well-known observed blunting of the HPA axis. It can also explain

> why both oxytocin and antidiuretic hormone are low, the latter

> producing the diabetes insipidus, with its excessive urination,

> constant thirst, and low blood volume. The story just goes on and

> on. This is really a sweeping hypothesis, and I don't know if the

> community will believe it or not. In my view, too many things keep

> coming out right for there not to be some truth in this thing.

>

> Take care, and I wish you all the best in this season, however you

> celebrate it.

>

> Rich

>

Hi Rich

I have only briefly read your post but would like to respond to the

info you give about high histamine. From my point of view it looks

like you are spot on again.

In 1998 I was sent to a Consultant at a local hospital to test for

allergies to milk, wheat etc. He gave me lots of pin pricks but said

to me

" You are a very unusual person in that you appear to have a very high

level of histamine BECAUSE YOU ARE REACTING TO EVERYTHING EVEN THE

PIN PRICK. " He thought it likely that even my waist would leave

marks where clothes sit and he was right. Because of this he said

all my tests were invalid and he did blood tests,which showed I was

indeed allergic to horses, dogs, cats and mites.

He mentioned that antihistamines might help me which they do during

the pollen season.

When I had live blood anaylsis done 2 years ago the doctor thought my

white blood cells were very lazy and just didn't move as they should

(cannot remember which white blood cells though).

Have a lovely holiday and thanks again for working on our behalf

Pam

[Guest guest]

Rich

I had my histamine value checked as asked at Dr. Pfeiffer's approach and it

was just above top limit.Don't know if that means anything for you.

bw

Nil

Histamine and the Glutathione

Depletion--Methylation Cycle Block Hypothesis

> Hi, all.

>

> I want to bounce something off of you.

>

> As you may be aware, there have been several studies that have

> found that IgE-type allergies are not more common in PWCs than in

> the general public. However, PWCs report having big problems with

>

[Guest guest]

Hi, all.

Thanks to all of you who gave me comments on the histamine thing.

I want to make a distinction between types of allergies or

sensitivities. There's a thing called the Gell Coombs

classification of sensitivities. Within this are three types. The

first type is the IgE--histamine type, which is the one I am

referring to. This one tends to last a long time, even all your

life. It responds fast, within a few minutes of exposure, and it

gives you symptoms such as hay fever-type things, or reddening of

the skin. This is what has been traditionally called allergy or

atopy.

Some food allergies are indeed of this type. However, in CFS, I

think most of the food sensitivities are of other types. These are

the ones that come and go depending on what one eats. If you avoid

a food for a couple of weeks, these tend to go away. They are the

delayed sensitivities, and they don't involve histamine. I think

they are often due to leaky gut, which is a consequence of other

mechanisms in CFS.

So PWCs have both types, but I am focussing on the IgE or Type 1

allergies with this hypothesis.

Thanks again, and I hope today is a relatively good day for all of

you.

Rich

[Guest guest]

Dear Rich, thank you for your theories about glutathione. I am

diagnosed with CFS, MCS, and lyme. I am on the far end of the scale

as far as chemically sensitive (extremely sensitive) and have many

food allergies. It seems that any food that I eat on a routine

basis, I become allergic to over time. I have rotated foods formally

for lengthy periods, but even that is no guarantee. I have tried

allergy treatments, but at this point, they are unable to find a

desensitizing formula--one that helps instead of making me feel more

ill.

In my opinion, it has to be something other than allergies--some

other reason the histamine levels are so high and I am so reactive.

Allergies just don't make sense. Treating the allergies by drops or

shots doesn't make sense as there is no way I could treat

everything. I have thought of just treating inhalant allergies, so

Spring is not such a load, but have held back from even that.

I have been getting large dosages of IV glutathione 3-4 times weekly

since June, 2005. There is no question the glutathione has saved my

life. Over time, I am becoming stronger and I am able to withstand

chemical, food, and inhalant allergies and sensitivities more. I am

no where near to being normal, but am much improved. The glutathione

is such a blessing to me.

I see you mentioned protein. I don't quite understand the context of

your comments, but have noticed something lately about the

glutathione and protein. When I dose with glutathione in the

morning, I need much more protein (which I always crave but which is

hard to take in as meat is a bit repulsive to me--can't tolerate

dairy, soy). Anyway, why is it that I need more protein when I take

glutathione? Yesterday is an example--took glutathione just after

breakfast with protein. Felt like I needed more protein but didn't

eat more as I had just eaten. I had a major crash, not knowing what

was going on around me, unable to sit up, etc. What does this mean

to you?

Anyway, I'm waiting for you to get it all figured out. Ha!

Merry Christmas to all. Blessings. Janine

[Guest guest]

Hi, Rich.

" rvankonynen " <richvank@...> wrote:

>

> Hi, all.

>

> Thanks to all of you who gave me comments on the histamine thing.

>

> I want to make a distinction between types of allergies or

> sensitivities. There's a thing called the Gell Coombs

> classification of sensitivities. Within this are three types. The

> first type is the IgE--histamine type, which is the one I am

> referring to. This one tends to last a long time, even all your

> life. It responds fast, within a few minutes of exposure, and it

> gives you symptoms such as hay fever-type things, or reddening of

> the skin. This is what has been traditionally called allergy or

> atopy.

>

> Some food allergies are indeed of this type. However, in CFS, I

> think most of the food sensitivities are of other types. These are

> the ones that come and go depending on what one eats. If you avoid

> a food for a couple of weeks, these tend to go away. They are the

> delayed sensitivities, and they don't involve histamine. I think

> they are often due to leaky gut, which is a consequence of other

> mechanisms in CFS.

>

> So PWCs have both types, but I am focussing on the IgE or Type 1

> allergies with this hypothesis.

>

> Thanks again, and I hope today is a relatively good day for all of

> you.

>

> Rich

***Ah yes, this fits the allergy to nickel I've had which manifests most

obviously when my

left hand touches or handles metals known to have nickel as part of its

composition. My

hand turns beat red and swells a bit with a burning/itchy quality in just a

matter of a

minute or so after exposure.

***I suspect this very clear allergic reaction that most pointedly happens in my

left hand is

connected via the contralateral nerve path to my right brain motor cortex area

known to

control the left hand. My heavy metal tests have consistently shown nickel as

abnormally

high, these metals do get into the brain, and the right motor cortex is

immediately

integrated with the right side dorsal lateral prefrontal cortex(rDLPFC), which

is the area

Dr Goldstein hypthesized is most dysfunctioned-responsible for creating symptoms

in

PWCs.

***Also, the right side brain motor cortex, particularly the region that is most

juxtaposed/

integrated with the rDLPFC, is predicted by Brain Typing(BTI) at

http://www.braintypes.com to be the least efficient area of brain function in

those having

the INFJ-BCAL and ENFJ-FCAL brain types, genetically derived cerebral brain

traits. Kurt

Riley's poll at this list a few months back found that these two brain types

combined

showed they have CFS at 20Xs the rate of the other 14, which is surprising given

these two

together at most comprise no more than 8% of the human population.

***I think what BTI means by areas of brain efficiency and inefficiency may

correlate with

methylation capacity, which may explain why some neurological conditions

involving

methylation issues may look very different to CFS though methylation problems

may be

central to all. Your sweeping hypothesis is looking strong for CFS and the

effective

communication of it to those less immersed in this conversation requiring

thoughtful

consideration before you leap!

[Guest guest]

Hi, .

Thank you for your comments.

Concerning Dr. Cheney's current views about glutathione in CFS, let me

say first that I am deeply indebted to him for observing the low

glutathione status of PWCs and for reporting it back in 1999. That is

what started me on the study of glutathione and its depletion in CFS.

I, too, watched the DVD of his most recent talk in Texas last

September, and I heard his current thinking on glutathione in CFS.

I would suggest that both the level of intracellular reduced

glutathione and the level of total intracellular glutathione (reduced

plus oxidized) are low in CFS, based on reports of measurements I have

seen. (This also corresponds to what S. Jill et al. have found

in autism, and I think there is more and more reason to believe that

the same mechanism is going on in many cases of CFS.) One thing that

should be pointed out is that when a cell cannot maintain its level of

reduced glutathione, it exports oxidized glutathione in an effort to

keep the oxidation potential, which depends on the ratio of the square

of the concentration of reduced glutathione to the concentration of

oxidized glutathione, at the level where it should be to maintain the

proper biochemistry inside the cells. So Dr. Cheney's statement about

the rise in oxidized glutathione inside cells is not quite correct.

I agree with Dr. Cheney that just adding glutathione doesn't usually

solve the problem in CFS, but my views on why this is true differ from

his views, at least as expressed on the DVD of his talk. In my view,

the problem is that the level of glutathione is being held down by a

block in the methylation cycle, which forms a vicious circle mechanism

with the depletion of glutathione. Dr. Cheney's explanation of the

inability to raise the level of reduced glutathione is not clear to

me. He refers to a cellular energy problem, and I agree that there is

one, but I believe that it is caused by glutathione depletion, rather

than being the cause of it. It is known that glutathione depletion

will allow superoxide to rise, and it is known that this will block

the Krebs cycle at aconitase. I think this is what accounts for the

elevatation of citrate and the drop in alpha ketoglutarate (2-ox0-

glutarate), which I also first heard about from Dr. Cheney.

In my view, Dr. Cheney has almost all the pieces needed to explain the

pathogenesis of CFS, but he has not yet put them together in the

correct cause-and-effect tree. I think that the things he is

observing in the heart function of PWCs can be explained by the

belated drop in glutathione levels in the heart muscle cells. This

gives rise to diastolic dysfunction because of the drop in the ATP

production rate, and the diastolic dysfunction either causes

structural changes in or pressure differences across the wall dividing

the right and left atria, or both, which opens up the foramen ovale.

Dr. Cheney continues to cite Prof. Marty Pall's peroxynitrite

hypothesis for the pathogenesis of CFS, but, as I've told Marty

several times, I think he has it backwards, too. He thinks elevation

of peroxynitrite causes the glutathione depletion. I believe the

evidence supports the explanation that it is the other way around.

Glutathione depletion comes first, as a result of some combination of

a variety of stressors that is different in each case, but there is a

common list of possible ones, including physical, chemical, biological

and psychological/emotional factors, which I discussed in my 2004

poster paper. The low glutathione gives rise to a methylation cycle

block in people who have the genetic predisposition for it, as in

autism. This produces a vicious circle, and the person is trapped in

it. Everything else in CFS stems from this vicious circle. There is

a host of manifestations of glutathione depletion, annother host of

manisfestations of decreased methylation capacity, additional effects

from the folate cycle block, which is intimately connected with the

methylation cycle block at methionine synthase, and other effects

caused by the other features of this vicious circle. The totality of

effects of this vicious circle constitutes the multifaceted and

variagated syndrome of CFS. As I continue to look at the individual

pieces, I am able to explain more and more of the features of CFS at

the detailed biochemical and physiological level. I think we are

finally close to the rock-bottom mechanisms in the etiology,

pathogenesis and pathophysiology of CFS.

Rich

> At the end of the DVD Dr. Cheney speaks about Glutathione and says

> that you can take as much supplements for the production of

> glutathione as you want, as long as there is not enough energy you

> only will produce the oxidised form of it and this form won't be

much

> of a help. What is your opinion about it?

>

>

> I'll always be politically incorrect: Happy Christmas!

[Guest guest]

" rvankonynen " <richvank@...> wrote:

> In my view, Dr. Cheney has almost all the pieces needed to explain

the pathogenesis of CFS, but he has not yet put them together in the

correct cause-and-effect tree.

Rich, is it possible that your meaning of CFS refers to the

immunological " roots " of the tree, while Dr Cheney might continue to

think of CFS as the overt clinical postviral illness which blossomed

from an offshoot?

Much as we have come to think of the distinction between " HIV "

infection and its result of AIDS?

And this could be why his cause-effect order appears to be incorrect?

-

[Guest guest]

In my view,

Glutathione depletion comes first, as a result of some combination of a

variety of stressors that is different in each case, but there is a

common list of possible ones, including physical, chemical, biological

and psychological/emotional factors, which I discussed in my 2004

poster paper. The low glutathione gives rise to a methylation cycle

block in people who have the genetic predisposition for it, as in

autism. This produces a vicious circle, and the person is trapped in

it. Everything else in CFS stems from this vicious circle.

So low glutathione causes a person to not be able to produce

glutathione?

[Guest guest]

Hi, j.

Yes, that's what I believe. The initial lowering of glutathione

causes inhibition of redox-sensitive enzymes in the methylation

cycle, and that decreases the flow through that cycle and through

the transsulfuration pathway it feeds, which decreases the

production of cysteine and thus of glutathione. So it's a vicious

circle. I also suspect that the vicious circle gets cemented into

place by the rise of mercury, which happens because there is not

enough glutathione to take it out as fast as it is coming in. It

doesn't take much mercury to block the synthesis of methylcobalamin,

according to Prof. Deth's work. Once that happens, I think the

vicious circle is locked in, until measures are taken to bypass the

problems and get things going again in the sulfur metabolism.

Rich

>

> In my view,

>

> Glutathione depletion comes first, as a result of some combination

of a

> variety of stressors that is different in each case, but there is

a

> common list of possible ones, including physical, chemical,

biological

> and psychological/emotional factors, which I discussed in my 2004

> poster paper. The low glutathione gives rise to a methylation

cycle

> block in people who have the genetic predisposition for it, as in

> autism. This produces a vicious circle, and the person is trapped

in

> it. Everything else in CFS stems from this vicious circle.

>

>

>

> So low glutathione causes a person to not be able to produce

> glutathione?

>

[Guest guest]

Hi, .

I can't speak for Dr. Cheney. I do think he focuses on

pathophysiology, while I focus on pathogenesis, and that could

certainly affect how we look at this disorder.

I think it's true that clinicians in general tend to focus on

pathophysiology, because that relates to symptoms, which they see

clinically. The question of how the person got to where they are is

pathogenesis, and I think clinicians generally view that as somewhat

interesting, but more removed from what they have to deal with daily.

My view is that unless you get the pathogenesis of a chronic illness

figured out, you will always be dealing with downstream issues, much

as conventional doctors tend to treat the symptoms of chronic

illnesses rather than getting at the root causes and bringing about

a cure.

Rich

> > In my view, Dr. Cheney has almost all the pieces needed to

explain

> the pathogenesis of CFS, but he has not yet put them together in

the

> correct cause-and-effect tree.

>

> Rich, is it possible that your meaning of CFS refers to the

> immunological " roots " of the tree, while Dr Cheney might continue

to

> think of CFS as the overt clinical postviral illness which

blossomed

> from an offshoot?

> Much as we have come to think of the distinction between " HIV "

> infection and its result of AIDS?

> And this could be why his cause-effect order appears to be

incorrect?

> -

>

[Guest guest]

Rich, I'm certain that Dr Cheney is working hard on identifying the

pathogenesis by following the clues backwards from the measurable

pathophysiology to find " whatever " .

It has been clear from the beginning of Dr Cheney's investigation

that he is loathe to propose a definite " whatever " , and this is often

interpreted as being overly focused on " downstream " issues.

I've always been impressed by Dr Cheney's methodology, which is

markedly different from the vast majority of researchers, who were so

eager to present a " cause " , that they were willing to disregard all

the evidence which points away.

No accumulation or intensity of the various " whatever " s that are

often implicated have had any known history of resulting in the

particular phenomeon that Dr Cheney is looking at.

It strikes me as particularly interesting that while most

researchers try to emulate the methodology that was initially brought

to bear upon the emergence of AIDS - by cooking up a " pathogen stew "

of total burden of known infections, exposures, behaviors... Dr

Cheney has done the EXACT OPPOSITE.

He went out of his way to locate people with the fewest infections,

least degree of possible exposures, and of course, he saw from the

outset that " whatever " didn't much care about anyone's mental state -

so that is excluded.

As I've pointed out before, it's easy to see in retrospect

that " subsetting " the people who made up the AIDS epidemic didn't

logically lead to HIV. Rather, it simply points at a number of groups

all succumbing to various things that have one major feature in

common:

All of these implicated " whatevers " are well-known to have no history

of causing AIDS.

Until one excludes the differences that CREATED the subsets and

focuses on what they all have in common, there is no inducement to

look for that common denominator of HIV.

My point was that although the ultimate source of the dysregulation

that branched off to CFS may be at the root of autism and other

illnesses, it may be that Dr Cheney is simply not calling this

potential state " CFS " until someone winds up in that particular neck

of the woods - just as we are learning not to call HIV by its result

until it happens.

So far, what I have seen in Dr Cheney's method suggests that is

following the trail in a scientific manner that is as direct as our

technology allows - without being diverted in the same way that the

initial research toward AIDS was misguided by focusing on all the

pathogens which suddenly started acting in an unexpected and

unfamiliar way.

-

" rvankonynen " <richvank@...> wrote:

>

> Hi, .

> I can't speak for Dr. Cheney. I do think he focuses on

> pathophysiology, while I focus on pathogenesis, and that could

> certainly affect how we look at this disorder.

>

> I think it's true that clinicians in general tend to focus on

> pathophysiology, because that relates to symptoms, which they see

> clinically. The question of how the person got to where they are

is pathogenesis, and I think clinicians generally view that as

somewhat interesting, but more removed from what they have to deal

with daily.

>

> My view is that unless you get the pathogenesis of a chronic

illness figured out, you will always be dealing with downstream

issues, much as conventional doctors tend to treat the symptoms of

chronic illnesses rather than getting at the root causes and

bringing about a cure.

>

> Rich