Hypothesis for diabetes insipidus link to glutathione depletion

[Guest guest]

Hi, all.

As most of you know, I have been working for several years on a

pathogenesis hypothesis for CFS that features glutathione depletion

as a major aspect.

As you probably also know, many people were not able to raise their

glutathione by direct approaches, and I suspected that there were

one or more vicious circles operating that tended to prevent it.

With the progress by others in understanding the biochemistry of

autism and the observed glutathione depletion there as well, which

was associated with genetically-influenced blocks earlier in the

sulfur metabolism, I came to believe that the same mechanisms were

responsible for a vicious circle holding down the glutathione in

CFS.

A few PWCs have begun to get their genetic variations

(polymorphisms) characterized, and so far the results seem to be

fitting into this new paradigm. In addition, there have started to

be some papers published that report on polymorphisms that are more

frequent in CFS, and so far I think they support the hypothesized

glutathione depletion-methylation cycle block model for CFS. I'm

hoping that more work will be done in this area, because I think it

will lead us to a better understanding of the root causes of CFS.

So I would say that many of the pieces seem to have fallen into

place for this model. However, there are still some loose pieces

out there, in terms of aspects commonly found in CFS for which I do

not yet have biochemical mechanisms that would connect them to the

glutathione depletion and methylation cycle block (which also

includes the disruption of folate metabolism, the biopterin cycle,

the neurotransmitters, nitric oxide synthase and the urea cycle,

which are all linked together. For these latter connections, I am

indebted to the work of the DAN! project and also Dr. Amy Yasko in

autism.)

Well, yesterday another idea occurred to me. Some of you may

remember that a while back Dr. Baraniuk at town

University and colleagues published a paper on the proteins they

found in the spinal fluid of PWCs, and one of their conclusions was

that there was a protein folding problem. I wrote to Jim, and

suggested that glutathione depletion might be responsible, because

protein folding depends on the formation of disulfide bonds between

cysteine residues in the proteins, and this is a redox-dependent

process, which must involve glutathione, because it regulates the

redox potential in the cells. He said he thought that was a good

possibility and would look into it.

O.K., as you know, , here on the list, observed that his

diabetes insipidus went away when he was able to raise his

glutathione. This caused me to start thinking about what the link

might be. Well, here's what I've come up with: central diabetes

insipidus, which is the type observed in CFS, is caused by

insufficient secretion of the hormone arginine vasopressin (AVP),

also known as antidiuretic hormone. This hormone is made inside

neurons in the preoptic nucleus, which is located in the anterior

hypothalamus of the brain. The AVP molecule has one disulfide bond.

In order for this molecule to be synthesized in the organelle in

these neurons called the rough endoplasmic reticulum, the redox

condition must be maintained sufficiently reducing to keep the

sulfur atoms in the sulfhydryl state until the molecule has been

assembled to the appropriate stage for the sulfur atoms to be

oxidized by a special molecule in order to form the disulfide bond.

What I suggest is going on in CFS is that these neurons do not have

enough glutathione to maintain this reducing environment properly,

and as a result they are not able to make enough AVP. This, then,

produces the diabetes insipidus. If the body's overall glutathione

status is restored to normal, these neurons will be able to resume

their synthesis of AVP, and that accounts for 's relief from

this part of the syndrome of CFS.

Well, now I'm on a roll. I think this same mechanism might explain

the deficiency of secretory IgA in CFS, since it depends on lots of

cysteine being in the right oxidation state for its synthesis as

well. In fact, this mechanism might explain a few other aspects of

CFS as well, if they involve what are called secretory proteins.

Secretory proteins are proteins that are made inside cells and are

then secreted to the extracellular region. Many of these proteins

have disulfide bonds, and they must be precisely formed inside the

cells, which depends on having enough glutathione there. These

secretory proteins with disulfide bonds include quite a few of the

other peptide hormones (such as oxytocin, for example), as well as

plasma proteins and digestive enzymes. Most of the plasma proteins

are made in the liver, and I suspect that the liver, being normally

the main glutathione producer, and having first access to the amino

acids coming in from the gut, probably maintains a sufficient

glutathione supply to be able to keep making plasma proteins.

That's probably why we don't generally see problems with them in

CFS. The digestive enzymes and insulin are made in the pancreas.

Usually we don't hear of problems with insulin in CFS (which would

amount to diabetes mellitis), so I suspect that the pancreatic beta

cells must be able to maintain a reasonable glutathione status as

well. I don't know about the digestive enzymes, which are made in

different cells in the pancreas. Maybe there is some deficiency

there. There certainly are a lot of G.I. issues in CFS, so maybe a

digestive enzyme deficit could be part of that.

I also don't know what to think about the other immunoglobulins

(antibodies). They have double bonds holding them together, and

they are made in the plasma cells, which are derived from B

lymphocytes, which are in the blood and the lymph, and I do think

the lymphocytes are depleted in glutathione in CFS. I don't think

there is a shortage of antibodies in CFS, especially since there is

often a shift to Th2, which particularly involves antibodies, so

this part doesn't appear to fit very well. I'll have to look into

how the antibodies are formed, and maybe there's something special

about that, which would enable them to be synthesized even if there

is a depletion in glutathione. There are always a lot of wrinkles

in these things. What a complex machine the body is!

Well, I need to look into some of these other possibilities, also,

but wanted to share this insight, for what it's worth.

Rich

[Guest guest]

Hi Rich,

I find your hypothesis very interesting. Glutathione seems to be

a " master regulator " of body systems, sort of like the idea of

a " strange attractor " in fractals that keeps the fractal

organized. " Perturbations " from outside the system cause disturbances

that weaken the organization.

Glutathione seems to be the master regulator of the immune system,

but since the connections are nonlinear (chemical and electrical

feedback mechanisms), glutathione is affected by and modified by

feedback from the system.

I don't know where that came from! I don't know that much about

fractals or the science of self-organizing systems, and my brain is

pretty fuzzy on what I did know about fractals and self-organizing

systems theory.

I think the pancreas is one of the organs most affected by CFS. I

know many CFSers who have insulin resistance, which causes a lot of

insulin to be released, as I recall. I know that my ability to

produce digestive enzymes has decreased over time, and one of the

things that helps me the most is taking digestive enzymes.

Just the ramblings of an amateur.

Vickie

>

> Hi, all.

>

> As most of you know, I have been working for several years on a

> pathogenesis hypothesis for CFS that features glutathione depletion

> as a major aspect.

>

> As you probably also know, many people were not able to raise their

> glutathione by direct approaches, and I suspected that there were

> one or more vicious circles operating that tended to prevent it.

>

> With the progress by others in understanding the biochemistry of

> autism and the observed glutathione depletion there as well, which

> was associated with genetically-influenced blocks earlier in the

> sulfur metabolism, I came to believe that the same mechanisms were

> responsible for a vicious circle holding down the glutathione in

> CFS.

>

> A few PWCs have begun to get their genetic variations

> (polymorphisms) characterized, and so far the results seem to be

> fitting into this new paradigm. In addition, there have started to

> be some papers published that report on polymorphisms that are more

> frequent in CFS, and so far I think they support the hypothesized

> glutathione depletion-methylation cycle block model for CFS. I'm

> hoping that more work will be done in this area, because I think it

> will lead us to a better understanding of the root causes of CFS.

>

> So I would say that many of the pieces seem to have fallen into

> place for this model. However, there are still some loose pieces

> out there, in terms of aspects commonly found in CFS for which I do

> not yet have biochemical mechanisms that would connect them to the

> glutathione depletion and methylation cycle block (which also

> includes the disruption of folate metabolism, the biopterin cycle,

> the neurotransmitters, nitric oxide synthase and the urea cycle,

> which are all linked together. For these latter connections, I am

> indebted to the work of the DAN! project and also Dr. Amy Yasko in

> autism.)

>

> Well, yesterday another idea occurred to me. Some of you may

> remember that a while back Dr. Baraniuk at town

> University and colleagues published a paper on the proteins they

> found in the spinal fluid of PWCs, and one of their conclusions was

> that there was a protein folding problem. I wrote to Jim, and

> suggested that glutathione depletion might be responsible, because

> protein folding depends on the formation of disulfide bonds between

> cysteine residues in the proteins, and this is a redox-dependent

> process, which must involve glutathione, because it regulates the

> redox potential in the cells. He said he thought that was a good

> possibility and would look into it.

>

> O.K., as you know, , here on the list, observed that his

> diabetes insipidus went away when he was able to raise his

> glutathione. This caused me to start thinking about what the link

> might be. Well, here's what I've come up with: central diabetes

> insipidus, which is the type observed in CFS, is caused by

> insufficient secretion of the hormone arginine vasopressin (AVP),

> also known as antidiuretic hormone. This hormone is made inside

> neurons in the preoptic nucleus, which is located in the anterior

> hypothalamus of the brain. The AVP molecule has one disulfide

bond.

> In order for this molecule to be synthesized in the organelle in

> these neurons called the rough endoplasmic reticulum, the redox

> condition must be maintained sufficiently reducing to keep the

> sulfur atoms in the sulfhydryl state until the molecule has been

> assembled to the appropriate stage for the sulfur atoms to be

> oxidized by a special molecule in order to form the disulfide

bond.

> What I suggest is going on in CFS is that these neurons do not have

> enough glutathione to maintain this reducing environment properly,

> and as a result they are not able to make enough AVP. This, then,

> produces the diabetes insipidus. If the body's overall glutathione

> status is restored to normal, these neurons will be able to resume

> their synthesis of AVP, and that accounts for 's relief from

> this part of the syndrome of CFS.

>

> Well, now I'm on a roll. I think this same mechanism might explain

> the deficiency of secretory IgA in CFS, since it depends on lots of

> cysteine being in the right oxidation state for its synthesis as

> well. In fact, this mechanism might explain a few other aspects of

> CFS as well, if they involve what are called secretory proteins.

> Secretory proteins are proteins that are made inside cells and are

> then secreted to the extracellular region. Many of these proteins

> have disulfide bonds, and they must be precisely formed inside the

> cells, which depends on having enough glutathione there. These

> secretory proteins with disulfide bonds include quite a few of the

> other peptide hormones (such as oxytocin, for example), as well as

> plasma proteins and digestive enzymes. Most of the plasma proteins

> are made in the liver, and I suspect that the liver, being normally

> the main glutathione producer, and having first access to the amino

> acids coming in from the gut, probably maintains a sufficient

> glutathione supply to be able to keep making plasma proteins.

> That's probably why we don't generally see problems with them in

> CFS. The digestive enzymes and insulin are made in the pancreas.

> Usually we don't hear of problems with insulin in CFS (which would

> amount to diabetes mellitis), so I suspect that the pancreatic beta

> cells must be able to maintain a reasonable glutathione status as

> well. I don't know about the digestive enzymes, which are made in

> different cells in the pancreas. Maybe there is some deficiency

> there. There certainly are a lot of G.I. issues in CFS, so maybe a

> digestive enzyme deficit could be part of that.

>

> I also don't know what to think about the other immunoglobulins

> (antibodies). They have double bonds holding them together, and

> they are made in the plasma cells, which are derived from B

> lymphocytes, which are in the blood and the lymph, and I do think

> the lymphocytes are depleted in glutathione in CFS. I don't think

> there is a shortage of antibodies in CFS, especially since there is

> often a shift to Th2, which particularly involves antibodies, so

> this part doesn't appear to fit very well. I'll have to look into

> how the antibodies are formed, and maybe there's something special

> about that, which would enable them to be synthesized even if there

> is a depletion in glutathione. There are always a lot of wrinkles

> in these things. What a complex machine the body is!

>

> Well, I need to look into some of these other possibilities, also,

> but wanted to share this insight, for what it's worth.

>

> Rich

>

[Guest guest]

Hi rich,

If methylation is disordered in CFS, then lower levels of creatine should be

fairly universal. As creatine synthesis requires 70% of the methyl donors it

should be the first thing to drop. Do you know what th literature says about

creatine levels in CFS compared to controls?

Blake

Hypothesis for diabetes insipidus link to

glutathione depletion

Hi, all.

As most of you know, I have been working for several years on a

pathogenesis hypothesis for CFS that features glutathione depletion

as a major aspect.

As you probably also know, many people were not able to raise their

glutathione by direct approaches, and I suspected that there were

one or more vicious circles operating that tended to prevent it.

With the progress by others in understanding the biochemistry of

autism and the observed glutathione depletion there as well, which

was associated with genetically-influenced blocks earlier in the

sulfur metabolism, I came to believe that the same mechanisms were

responsible for a vicious circle holding down the glutathione in

CFS.

A few PWCs have begun to get their genetic variations

(polymorphisms) characterized, and so far the results seem to be

fitting into this new paradigm. In addition, there have started to

be some papers published that report on polymorphisms that are more

frequent in CFS, and so far I think they support the hypothesized

glutathione depletion-methylation cycle block model for CFS. I'm

hoping that more work will be done in this area, because I think it

will lead us to a better understanding of the root causes of CFS.

So I would say that many of the pieces seem to have fallen into

place for this model. However, there are still some loose pieces

out there, in terms of aspects commonly found in CFS for which I do

not yet have biochemical mechanisms that would connect them to the

glutathione depletion and methylation cycle block (which also

includes the disruption of folate metabolism, the biopterin cycle,

the neurotransmitters, nitric oxide synthase and the urea cycle,

which are all linked together. For these latter connections, I am

indebted to the work of the DAN! project and also Dr. Amy Yasko in

autism.)

Well, yesterday another idea occurred to me. Some of you may

remember that a while back Dr. Baraniuk at town

University and colleagues published a paper on the proteins they

found in the spinal fluid of PWCs, and one of their conclusions was

that there was a protein folding problem. I wrote to Jim, and

suggested that glutathione depletion might be responsible, because

protein folding depends on the formation of disulfide bonds between

cysteine residues in the proteins, and this is a redox-dependent

process, which must involve glutathione, because it regulates the

redox potential in the cells. He said he thought that was a good

possibility and would look into it.

O.K., as you know, , here on the list, observed that his

diabetes insipidus went away when he was able to raise his

glutathione. This caused me to start thinking about what the link

might be. Well, here's what I've come up with: central diabetes

insipidus, which is the type observed in CFS, is caused by

insufficient secretion of the hormone arginine vasopressin (AVP),

also known as antidiuretic hormone. This hormone is made inside

neurons in the preoptic nucleus, which is located in the anterior

hypothalamus of the brain. The AVP molecule has one disulfide bond.

In order for this molecule to be synthesized in the organelle in

these neurons called the rough endoplasmic reticulum, the redox

condition must be maintained sufficiently reducing to keep the

sulfur atoms in the sulfhydryl state until the molecule has been

assembled to the appropriate stage for the sulfur atoms to be

oxidized by a special molecule in order to form the disulfide bond.

What I suggest is going on in CFS is that these neurons do not have

enough glutathione to maintain this reducing environment properly,

and as a result they are not able to make enough AVP. This, then,

produces the diabetes insipidus. If the body's overall glutathione

status is restored to normal, these neurons will be able to resume

their synthesis of AVP, and that accounts for 's relief from

this part of the syndrome of CFS.

Well, now I'm on a roll. I think this same mechanism might explain

the deficiency of secretory IgA in CFS, since it depends on lots of

cysteine being in the right oxidation state for its synthesis as

well. In fact, this mechanism might explain a few other aspects of

CFS as well, if they involve what are called secretory proteins.

Secretory proteins are proteins that are made inside cells and are

then secreted to the extracellular region. Many of these proteins

have disulfide bonds, and they must be precisely formed inside the

cells, which depends on having enough glutathione there. These

secretory proteins with disulfide bonds include quite a few of the

other peptide hormones (such as oxytocin, for example), as well as

plasma proteins and digestive enzymes. Most of the plasma proteins

are made in the liver, and I suspect that the liver, being normally

the main glutathione producer, and having first access to the amino

acids coming in from the gut, probably maintains a sufficient

glutathione supply to be able to keep making plasma proteins.

That's probably why we don't generally see problems with them in

CFS. The digestive enzymes and insulin are made in the pancreas.

Usually we don't hear of problems with insulin in CFS (which would

amount to diabetes mellitis), so I suspect that the pancreatic beta

cells must be able to maintain a reasonable glutathione status as

well. I don't know about the digestive enzymes, which are made in

different cells in the pancreas. Maybe there is some deficiency

there. There certainly are a lot of G.I. issues in CFS, so maybe a

digestive enzyme deficit could be part of that.

I also don't know what to think about the other immunoglobulins

(antibodies). They have double bonds holding them together, and

they are made in the plasma cells, which are derived from B

lymphocytes, which are in the blood and the lymph, and I do think

the lymphocytes are depleted in glutathione in CFS. I don't think

there is a shortage of antibodies in CFS, especially since there is

often a shift to Th2, which particularly involves antibodies, so

this part doesn't appear to fit very well. I'll have to look into

how the antibodies are formed, and maybe there's something special

about that, which would enable them to be synthesized even if there

is a depletion in glutathione. There are always a lot of wrinkles

in these things. What a complex machine the body is!

Well, I need to look into some of these other possibilities, also,

but wanted to share this insight, for what it's worth.

Rich

[Guest guest]

Rich,

For those who have a hard time building up glutathione levels, are there

any functional analogs to glutathione that might be a poor-man's

substitute? Another similar antioxidant perhaps? Or maybe a

combination of supplements that will do many of the same things? After

tracking a few people with CFS type symptoms who have had dramatic

improvements on salt/c, for example, I am wondering whether there is a

glutathione-building property of that combination, or some type of

functional glutathione analog in that combination.

Also, might glutathione depletion be down-stream from the primary CFS

problem, and could the primary problem be causing some of the other

pathologies not directly attributable to glutathione shortage?

For example, consider the hypothesis of a mercury load as a possible

primary factor, or at least a major co-factor for CFS in a genetically

susceptible person, similar to Autism. That will certainly block parts

of the methylation cycle for some people, causing the lowered

glutathione production capacity. But additionally, mercury also could

block other systems, digestive enzymes perhaps. If a person also has a

compromised BBB (due to infection, EMF, vascular disease, etc.), then

the blocked digestive enzymes cause a huge problem, as large protein

molecules can get into the brain where they can cause reactions, and

neurological disruption. Just as we see with inadequate processing of

casein molecules in Autism. So in this case the glutathione problem

would not be at the top of the pathology, but one of several result of

the primary factor(s). And maybe this type of situation can explain the

consistent concurrency of the more loosely-related CFS pathologies.

They may all stem from a reliable, common cause.

--Kurt

Hypothesis for diabetes insipidus link to

glutathione depletion

Hi, all.

As most of you know, I have been working for several years on a

pathogenesis hypothesis for CFS that features glutathione depletion

as a major aspect.

As you probably also know, many people were not able to raise their

glutathione by direct approaches, and I suspected that there were

one or more vicious circles operating that tended to prevent it.

With the progress by others in understanding the biochemistry of

autism and the observed glutathione depletion there as well, which

was associated with genetically-influenced blocks earlier in the

sulfur metabolism, I came to believe that the same mechanisms were

responsible for a vicious circle holding down the glutathione in

CFS.

A few PWCs have begun to get their genetic variations

(polymorphisms) characterized, and so far the results seem to be

fitting into this new paradigm. In addition, there have started to

be some papers published that report on polymorphisms that are more

frequent in CFS, and so far I think they support the hypothesized

glutathione depletion-methylation cycle block model for CFS. I'm

hoping that more work will be done in this area, because I think it

will lead us to a better understanding of the root causes of CFS.

So I would say that many of the pieces seem to have fallen into

place for this model. However, there are still some loose pieces

out there, in terms of aspects commonly found in CFS for which I do

not yet have biochemical mechanisms that would connect them to the

glutathione depletion and methylation cycle block (which also

includes the disruption of folate metabolism, the biopterin cycle,

the neurotransmitters, nitric oxide synthase and the urea cycle,

which are all linked together. For these latter connections, I am

indebted to the work of the DAN! project and also Dr. Amy Yasko in

autism.)

Well, yesterday another idea occurred to me. Some of you may

remember that a while back Dr. Baraniuk at town

University and colleagues published a paper on the proteins they

found in the spinal fluid of PWCs, and one of their conclusions was

that there was a protein folding problem. I wrote to Jim, and

suggested that glutathione depletion might be responsible, because

protein folding depends on the formation of disulfide bonds between

cysteine residues in the proteins, and this is a redox-dependent

process, which must involve glutathione, because it regulates the

redox potential in the cells. He said he thought that was a good

possibility and would look into it.

O.K., as you know, , here on the list, observed that his

diabetes insipidus went away when he was able to raise his

glutathione. This caused me to start thinking about what the link

might be. Well, here's what I've come up with: central diabetes

insipidus, which is the type observed in CFS, is caused by

insufficient secretion of the hormone arginine vasopressin (AVP),

also known as antidiuretic hormone. This hormone is made inside

neurons in the preoptic nucleus, which is located in the anterior

hypothalamus of the brain. The AVP molecule has one disulfide bond.

In order for this molecule to be synthesized in the organelle in

these neurons called the rough endoplasmic reticulum, the redox

condition must be maintained sufficiently reducing to keep the

sulfur atoms in the sulfhydryl state until the molecule has been

assembled to the appropriate stage for the sulfur atoms to be

oxidized by a special molecule in order to form the disulfide bond.

What I suggest is going on in CFS is that these neurons do not have

enough glutathione to maintain this reducing environment properly,

and as a result they are not able to make enough AVP. This, then,

produces the diabetes insipidus. If the body's overall glutathione

status is restored to normal, these neurons will be able to resume

their synthesis of AVP, and that accounts for 's relief from

this part of the syndrome of CFS.

Well, now I'm on a roll. I think this same mechanism might explain

the deficiency of secretory IgA in CFS, since it depends on lots of

cysteine being in the right oxidation state for its synthesis as

well. In fact, this mechanism might explain a few other aspects of

CFS as well, if they involve what are called secretory proteins.

Secretory proteins are proteins that are made inside cells and are

then secreted to the extracellular region. Many of these proteins

have disulfide bonds, and they must be precisely formed inside the

cells, which depends on having enough glutathione there. These

secretory proteins with disulfide bonds include quite a few of the

other peptide hormones (such as oxytocin, for example), as well as

plasma proteins and digestive enzymes. Most of the plasma proteins

are made in the liver, and I suspect that the liver, being normally

the main glutathione producer, and having first access to the amino

acids coming in from the gut, probably maintains a sufficient

glutathione supply to be able to keep making plasma proteins.

That's probably why we don't generally see problems with them in

CFS. The digestive enzymes and insulin are made in the pancreas.

Usually we don't hear of problems with insulin in CFS (which would

amount to diabetes mellitis), so I suspect that the pancreatic beta

cells must be able to maintain a reasonable glutathione status as

well. I don't know about the digestive enzymes, which are made in

different cells in the pancreas. Maybe there is some deficiency

there. There certainly are a lot of G.I. issues in CFS, so maybe a

digestive enzyme deficit could be part of that.

I also don't know what to think about the other immunoglobulins

(antibodies). They have double bonds holding them together, and

they are made in the plasma cells, which are derived from B

lymphocytes, which are in the blood and the lymph, and I do think

the lymphocytes are depleted in glutathione in CFS. I don't think

there is a shortage of antibodies in CFS, especially since there is

often a shift to Th2, which particularly involves antibodies, so

this part doesn't appear to fit very well. I'll have to look into

how the antibodies are formed, and maybe there's something special

about that, which would enable them to be synthesized even if there

is a depletion in glutathione. There are always a lot of wrinkles

in these things. What a complex machine the body is!

Well, I need to look into some of these other possibilities, also,

but wanted to share this insight, for what it's worth.

Rich

[Guest guest]

Hi, Kurt.

***Thanks for your comments. My responses are at the asterisks

below:

>

> Rich,

>

> For those who have a hard time building up glutathione levels, are

there

> any functional analogs to glutathione that might be a poor-man's

> substitute? Another similar antioxidant perhaps? Or maybe a

> combination of supplements that will do many of the same things?

After

> tracking a few people with CFS type symptoms who have had dramatic

> improvements on salt/c, for example, I am wondering whether there

is a

> glutathione-building property of that combination, or some type of

> functional glutathione analog in that combination.

***You may have heard of Dr. Cathcart. He practices in Los

Altos, CA, and has a big website on vitamin C. He takes vitamin C

to bowel tolerance himself, and has since he was a teenager (he's

now probably in his 70s). He got mono then, and didn't recover, and

he found that he could function if he took vitamin C to bowel

tolerance, and he's still doing it. (I suspect that he may have a

genetic variation that prevents normal glutathione function, but I

don't know for sure.) He wrote a paper in which he made the point

that whereas at normal physiological levels of glutathione and

vitamin C in the body, glutathione recycles vitamin C. However, if

the concentration of vitamin C is raised to high levels by taking it

to bowel tolerance, then the reaction can be reversed, and vitamin C

will recycle glutathione. I don't know how high the vitamin C

dosage is in people who do the salt/c treatment, but if it is very

high, this may be what is going on.

***I really think that glutathione itself is essential, because I

think so many of the things it does can't be done by other

substances. So I think a person could take a lot of antioxidants,

and they would do part of the jobs that glutathione does, but not

all of them. For example, there's the Phase II detox role of

glutathione. There's also its role in controlling the redox

potential inside the cells. So I think that inherent in Cathcart's

approach is that he is supporting his glutathione.

>

> Also, might glutathione depletion be down-stream from the primary

CFS

> problem, and could the primary problem be causing some of the other

> pathologies not directly attributable to glutathione shortage?

***I've come to believe that the " primary problem " in CFS, at least

after the person has become ill, is that there is a vicious circle

that involves glutathione depletion, but also involves a problem

earlier in the sulfur metabolism that is blocking the methylation

cycle, the folate metabolism, and other aspects of the biochemistry

that are linked to them. And I think you're right. Many of the

pathological effects in CFS are directly due to glutathione

depletion, but others are due to a lack of enough methylation

capacity, or a block in folate metabolism, or a consequent problem

with the biopterin cycle, or a shortage of taurine or sulfate, etc.

I think the irreducible " primary problem " as you call it, is this

vicious circle. How a person gets into this vicious circle in the

first place is another issue. That's pathogenesis, while the other

is pathophysiology. Knowing the pathophysiology doesn't

automatically tell you what the pathogenesis was. I think the

pathogenesis takes place when glutathione drops far enough as a

result of a variety of possible reasons, in a person who has

been " set up " by their particular combination of genetic

variations. I think this is what makes possible the development of

the vicious circle, which traps them. I think that explains why we

are getting more evidence for the genetic predisposition, while we

also have plenty of evidence for a history prior to onset of some

combination of things that present major demands on the supply of

glutathione.

>

> For example, consider the hypothesis of a mercury load as a

possible

> primary factor, or at least a major co-factor for CFS in a

genetically

> susceptible person, similar to Autism. That will certainly block

parts

> of the methylation cycle for some people, causing the lowered

> glutathione production capacity. But additionally, mercury also

could

> block other systems, digestive enzymes perhaps. If a person also

has a

> compromised BBB (due to infection, EMF, vascular disease, etc.),

then

> the blocked digestive enzymes cause a huge problem, as large

protein

> molecules can get into the brain where they can cause reactions,

and

> neurological disruption. Just as we see with inadequate

processing of

> casein molecules in Autism. So in this case the glutathione

problem

> would not be at the top of the pathology, but one of several

result of

> the primary factor(s). And maybe this type of situation can

explain the

> consistent concurrency of the more loosely-related CFS pathologies.

> They may all stem from a reliable, common cause.

***I agree that mercury exposure can be an initial stressor for some

people who develop CFS, and certainly for many who develop autism.

But in order to have toxic effects, the mercury level in the body

must rise to toxic levels. I don't think it's possible to develop a

high body burden of mercury unless the glutathione level drops,

because otherwise the glutathione would take out the mercury and

prevent its rise (assuming that the glutathione transferase enzymes

are O.K., which they are not in some people, and that's another

subset). So these two go together. Do you blame the mercury, or

the lack of glutathione? I do think that glutathione depletion is a

core feature of the pathogenesis in many PWCs. Lots of things can

cause it to become depleted, and if you want to call those the

causes of CFS, that's fine. But those same things don't cause CFS

in most of the population, so I think the genetic predisposition of

PWCs must be included in the root causes. To develop a viable

hypothesis for pathogenesis, you have to start with an apparently

healthy person (albeit one who has some so far innocuous genetic

variations), and move from there to an ill person, and the process

must not have " jumps, " but must be continuous and must be self-

consistent at every stage.

***I think that some of the issues are semantic. For example, in

defining the " cause " or " causes, " do you focus on the underlying

things that make the person vulnerable and set him or her up, or do

you just look at the visible things that went on before they became

ill. I think you have to consider both.

***Once the person becomes ill, the picture gets really tangled,

because there are all sorts of feedbacks, interactions and vicious

circles that get going, and I think there are more as time goes by.

It gets really hard to sort out in a person who is far along. I see

urine organic acids tests from some people in which nearly every one

of the parameters measured is outside its normal range. Where do

you start in trying to unravel one of these cases?

***From an operational point of view, what counts is not so much how

you define things, but where are the levers you can pull to get the

person back out of this. Do you have to do lots of things, or can

you get down to the root of it and do only one or a very few

things. At this point, I'm hoping that if we compensate for the

genetic variations that allow the development of the vicious circle

in the sulfur metabolism, we won't have to do very many other things

to get the person out of the trap, other than continuing to prevent

the vicious circle from reforming. I think the biochemistry and

physiology will take care of the rest, though it seems to take quite

a bit of time. That's what Amy Yasko reports in autism.

> --Kurt

>

***Rich

[Guest guest]

> >

> > Rich,

> >

> > For those who have a hard time building up glutathione levels,

are

> there

> > any functional analogs to glutathione that might be a poor-man's

> > substitute? Another similar antioxidant perhaps? Or maybe a

> > combination of supplements that will do many of the same

things?

> After

> > tracking a few people with CFS type symptoms who have had

dramatic

> > improvements on salt/c, for example, I am wondering whether

there

> is a

> > glutathione-building property of that combination, or some type

of

> > functional glutathione analog in that combination.

>

> ***You may have heard of Dr. Cathcart. He practices in Los

> Altos, CA, and has a big website on vitamin C. He takes vitamin C

> to bowel tolerance himself, and has since he was a teenager (he's

> now probably in his 70s). He got mono then, and didn't recover,

and

> he found that he could function if he took vitamin C to bowel

> tolerance, and he's still doing it. (I suspect that he may have a

> genetic variation that prevents normal glutathione function, but I

> don't know for sure.) He wrote a paper in which he made the point

> that whereas at normal physiological levels of glutathione and

> vitamin C in the body, glutathione recycles vitamin C. However,

if

> the concentration of vitamin C is raised to high levels by taking

it

> to bowel tolerance, then the reaction can be reversed, and vitamin

C

> will recycle glutathione. I don't know how high the vitamin C

> dosage is in people who do the salt/c treatment, but if it is very

> high, this may be what is going on.

>

> ***I really think that glutathione itself is essential, because I

> think so many of the things it does can't be done by other

> substances. So I think a person could take a lot of antioxidants,

> and they would do part of the jobs that glutathione does, but not

> all of them. For example, there's the Phase II detox role of

> glutathione. There's also its role in controlling the redox

> potential inside the cells. So I think that inherent in

Cathcart's

> approach is that he is supporting his glutathione.

> >

> > Also, might glutathione depletion be down-stream from the

primary

> CFS

> > problem, and could the primary problem be causing some of the

other

> > pathologies not directly attributable to glutathione shortage?

>

> ***I've come to believe that the " primary problem " in CFS, at

least

> after the person has become ill, is that there is a vicious circle

> that involves glutathione depletion, but also involves a problem

> earlier in the sulfur metabolism that is blocking the methylation

> cycle, the folate metabolism, and other aspects of the

biochemistry

> that are linked to them. And I think you're right. Many of the

> pathological effects in CFS are directly due to glutathione

> depletion, but others are due to a lack of enough methylation

> capacity, or a block in folate metabolism, or a consequent problem

> with the biopterin cycle, or a shortage of taurine or sulfate,

etc.

> I think the irreducible " primary problem " as you call it, is this

> vicious circle. How a person gets into this vicious circle in the

> first place is another issue. That's pathogenesis, while the

other

> is pathophysiology. Knowing the pathophysiology doesn't

> automatically tell you what the pathogenesis was. I think the

> pathogenesis takes place when glutathione drops far enough as a

> result of a variety of possible reasons, in a person who has

> been " set up " by their particular combination of genetic

> variations. I think this is what makes possible the development

of

> the vicious circle, which traps them. I think that explains why

we

> are getting more evidence for the genetic predisposition, while we

> also have plenty of evidence for a history prior to onset of some

> combination of things that present major demands on the supply of

> glutathione.

> >

> > For example, consider the hypothesis of a mercury load as a

> possible

> > primary factor, or at least a major co-factor for CFS in a

> genetically

> > susceptible person, similar to Autism. That will certainly

block

> parts

> > of the methylation cycle for some people, causing the lowered

> > glutathione production capacity. But additionally, mercury also

> could

> > block other systems, digestive enzymes perhaps. If a person

also

> has a

> > compromised BBB (due to infection, EMF, vascular disease, etc.),

> then

> > the blocked digestive enzymes cause a huge problem, as large

> protein

> > molecules can get into the brain where they can cause reactions,

> and

> > neurological disruption. Just as we see with inadequate

> processing of

> > casein molecules in Autism. So in this case the glutathione

> problem

> > would not be at the top of the pathology, but one of several

> result of

> > the primary factor(s). And maybe this type of situation can

> explain the

> > consistent concurrency of the more loosely-related CFS

pathologies.

> > They may all stem from a reliable, common cause.

>

> ***I agree that mercury exposure can be an initial stressor for

some

> people who develop CFS, and certainly for many who develop

autism.

> But in order to have toxic effects, the mercury level in the body

> must rise to toxic levels. I don't think it's possible to develop

a

> high body burden of mercury unless the glutathione level drops,

> because otherwise the glutathione would take out the mercury and

> prevent its rise (assuming that the glutathione transferase

enzymes

> are O.K., which they are not in some people, and that's another

> subset). So these two go together. Do you blame the mercury, or

> the lack of glutathione? I do think that glutathione depletion is

a

> core feature of the pathogenesis in many PWCs. Lots of things can

> cause it to become depleted, and if you want to call those the

> causes of CFS, that's fine. But those same things don't cause CFS

> in most of the population, so I think the genetic predisposition

of

> PWCs must be included in the root causes. To develop a viable

> hypothesis for pathogenesis, you have to start with an apparently

> healthy person (albeit one who has some so far innocuous genetic

> variations), and move from there to an ill person, and the process

> must not have " jumps, " but must be continuous and must be self-

> consistent at every stage.

>

> ***I think that some of the issues are semantic. For example, in

> defining the " cause " or " causes, " do you focus on the underlying

> things that make the person vulnerable and set him or her up, or

do

> you just look at the visible things that went on before they

became

> ill. I think you have to consider both.

>

> ***Once the person becomes ill, the picture gets really tangled,

> because there are all sorts of feedbacks, interactions and vicious

> circles that get going, and I think there are more as time goes

by.

> It gets really hard to sort out in a person who is far along. I

see

> urine organic acids tests from some people in which nearly every

one

> of the parameters measured is outside its normal range. Where do

> you start in trying to unravel one of these cases?

>

> ***From an operational point of view, what counts is not so much

how

> you define things, but where are the levers you can pull to get

the

> person back out of this. Do you have to do lots of things, or can

> you get down to the root of it and do only one or a very few

> things. At this point, I'm hoping that if we compensate for the

> genetic variations that allow the development of the vicious

circle

> in the sulfur metabolism, we won't have to do very many other

things

> to get the person out of the trap, other than continuing to

prevent

> the vicious circle from reforming. I think the biochemistry and

> physiology will take care of the rest, though it seems to take

quite

> a bit of time. That's what Amy Yasko reports in autism.

>

> > --Kurt

> >

> ***Rich

I am able to do most everyday 'things' now but do suffer daily odd

feeling pains mainly in legs and feet always dull not sharp very

tight skin as if I am making to much muscle now...and it certainly

seems like I am making lactic acid and not making the right use of

it if that makes sense. I was thin 18 months ago and very poorly.

some obvious things happening at the time I could urinate very

little for starters and it felt like my CNS was very very delicate.

I had very bad muscle twitching and my balance was a little like I

was drunk..ok so I do like a glass of the red wine but that was not

the cause..lots of other stuff but todate I have gained too much

weight and stable now but over the normal for me..I urinate far to

much noticabley the past two months. I still have the fasciculations

in the legs that are only annoying nothing more and I seem to

tolerate 5HTP ok amongst other sulfur foods in moderation...but the

urination I feel is over the top somewhat. Just my

tuppenceworth...Dianne

>

[Guest guest]

Hi Rich,

That is interesting that high dose C recycles glutathione. In those of

us with low glutathione, would high dose vitamin C be sufficient or

would we also have to take measures to generate new glutathione ?

Re: Hypothesis for diabetes insipidus link

to glutathione depletion

***You may have heard of Dr. Cathcart. He practices in Los

Altos, CA, and has a big website on vitamin C. He takes vitamin C

to bowel tolerance himself, and has since he was a teenager (he's

now probably in his 70s). He got mono then, and didn't recover, and

he found that he could function if he took vitamin C to bowel

tolerance, and he's still doing it. (I suspect that he may have a

genetic variation that prevents normal glutathione function, but I

don't know for sure.) He wrote a paper in which he made the point

that whereas at normal physiological levels of glutathione and

vitamin C in the body, glutathione recycles vitamin C. However, if

the concentration of vitamin C is raised to high levels by taking it

to bowel tolerance, then the reaction can be reversed, and vitamin C

will recycle glutathione. I don't know how high the vitamin C

dosage is in people who do the salt/c treatment, but if it is very

high, this may be what is going on.

..

<http://geo./serv?s=97359714 & grpId=91574 & grpspId=1600061645 & msg

Id=99515 & stime=1150183854>

[Guest guest]

Rich,

Thanks for the thoughtful responses. I think this idea makes good

sense, that the high-level cause is a fragile detox process itself, and

that the pathogenesis is strain on that fragile system. Then the

progression of the illness would be due to the down-stream effects of

the overwhelmed detox system, which gradually destabilizes other systems

and perhaps also causes secondary vicious circles. Would be nice if it

really becomes this simple, I am growing weary of the ever-increasing

complexity of this illness, and the endless treatments.

But even if this is 'it', we still have a lot of work ahead to find out

how to manage our bio-individuality in dealing with this situation.

Maybe some good decision algorithms would help, and rational, natural,

inexpensive treatment options. Also, is there an ideal order of

operations for treatment, or will this remain individualized? I think

that is an interesting question.

And some of the secondary issues will become primary problems once the

fragile detox system is shored up, I suspect we aren't out of the woods

when we correct the glutathione problem. For example, we probably have

a huge toxin load and need a lot of detox, and liver support to get

through that. Also we may need to correct an acquired immune imbalance

being maintained by a vicious cycle of symbiotic bugs (or should I say a

symbiotic cycle of vicious bugs), and repair vascular and coag damage

(esp. the BBB), safely pull out a high body burden of metals, repair an

exhausted adrenal system, recondition maladapted neuro-immune processes,

support enzymatic processes while the body repairs itself, provide

proper recovery nutrients, and more. And some of us probably have also

acquired disseminated infection loads that can only be eliminated with

outside interventions, and only AFTER the detox system is repaired (such

as Lyme and toxic parasites/Nematodes with a high herx potential).

I appreciate all your efforts on our behalf. I am benefiting from this

personally, I now understand my liver function profile better (my doctor

just read off the lab report to me and did not catch all the subtle

problems that are now evident after studying autism liver problems).

And have added several supplements to boost glutathione, and they are

helping. Also, I am now taking detox much more seriously, and am on a

cleansing program, along with everything else I am doing. So maybe the

fog is starting to clear.

--Kurt

Re: Hypothesis for diabetes insipidus link

to glutathione depletion

Hi, Kurt.

***Thanks for your comments. My responses are at the asterisks

below:

>

> Rich,

>

> For those who have a hard time building up glutathione levels, are

there

> any functional analogs to glutathione that might be a poor-man's

> substitute? Another similar antioxidant perhaps? Or maybe a

> combination of supplements that will do many of the same things?

After

> tracking a few people with CFS type symptoms who have had dramatic

> improvements on salt/c, for example, I am wondering whether there

is a

> glutathione-building property of that combination, or some type of

> functional glutathione analog in that combination.

***You may have heard of Dr. Cathcart. He practices in Los

Altos, CA, and has a big website on vitamin C. He takes vitamin C

to bowel tolerance himself, and has since he was a teenager (he's

now probably in his 70s). He got mono then, and didn't recover, and

he found that he could function if he took vitamin C to bowel

tolerance, and he's still doing it. (I suspect that he may have a

genetic variation that prevents normal glutathione function, but I

don't know for sure.) He wrote a paper in which he made the point

that whereas at normal physiological levels of glutathione and

vitamin C in the body, glutathione recycles vitamin C. However, if

the concentration of vitamin C is raised to high levels by taking it

to bowel tolerance, then the reaction can be reversed, and vitamin C

will recycle glutathione. I don't know how high the vitamin C

dosage is in people who do the salt/c treatment, but if it is very

high, this may be what is going on.

***I really think that glutathione itself is essential, because I

think so many of the things it does can't be done by other

substances. So I think a person could take a lot of antioxidants,

and they would do part of the jobs that glutathione does, but not

all of them. For example, there's the Phase II detox role of

glutathione. There's also its role in controlling the redox

potential inside the cells. So I think that inherent in Cathcart's

approach is that he is supporting his glutathione.

>

> Also, might glutathione depletion be down-stream from the primary

CFS

> problem, and could the primary problem be causing some of the other

> pathologies not directly attributable to glutathione shortage?

***I've come to believe that the " primary problem " in CFS, at least

after the person has become ill, is that there is a vicious circle

that involves glutathione depletion, but also involves a problem

earlier in the sulfur metabolism that is blocking the methylation

cycle, the folate metabolism, and other aspects of the biochemistry

that are linked to them. And I think you're right. Many of the

pathological effects in CFS are directly due to glutathione

depletion, but others are due to a lack of enough methylation

capacity, or a block in folate metabolism, or a consequent problem

with the biopterin cycle, or a shortage of taurine or sulfate, etc.

I think the irreducible " primary problem " as you call it, is this

vicious circle. How a person gets into this vicious circle in the

first place is another issue. That's pathogenesis, while the other

is pathophysiology. Knowing the pathophysiology doesn't

automatically tell you what the pathogenesis was. I think the

pathogenesis takes place when glutathione drops far enough as a

result of a variety of possible reasons, in a person who has

been " set up " by their particular combination of genetic

variations. I think this is what makes possible the development of

the vicious circle, which traps them. I think that explains why we

are getting more evidence for the genetic predisposition, while we

also have plenty of evidence for a history prior to onset of some

combination of things that present major demands on the supply of

glutathione.

>

> For example, consider the hypothesis of a mercury load as a

possible

> primary factor, or at least a major co-factor for CFS in a

genetically

> susceptible person, similar to Autism. That will certainly block

parts

> of the methylation cycle for some people, causing the lowered

> glutathione production capacity. But additionally, mercury also

could

> block other systems, digestive enzymes perhaps. If a person also

has a

> compromised BBB (due to infection, EMF, vascular disease, etc.),

then

> the blocked digestive enzymes cause a huge problem, as large

protein

> molecules can get into the brain where they can cause reactions,

and

> neurological disruption. Just as we see with inadequate

processing of

> casein molecules in Autism. So in this case the glutathione

problem

> would not be at the top of the pathology, but one of several

result of

> the primary factor(s). And maybe this type of situation can

explain the

> consistent concurrency of the more loosely-related CFS pathologies.

> They may all stem from a reliable, common cause.

***I agree that mercury exposure can be an initial stressor for some

people who develop CFS, and certainly for many who develop autism.

But in order to have toxic effects, the mercury level in the body

must rise to toxic levels. I don't think it's possible to develop a

high body burden of mercury unless the glutathione level drops,

because otherwise the glutathione would take out the mercury and

prevent its rise (assuming that the glutathione transferase enzymes

are O.K., which they are not in some people, and that's another

subset). So these two go together. Do you blame the mercury, or

the lack of glutathione? I do think that glutathione depletion is a

core feature of the pathogenesis in many PWCs. Lots of things can

cause it to become depleted, and if you want to call those the

causes of CFS, that's fine. But those same things don't cause CFS

in most of the population, so I think the genetic predisposition of

PWCs must be included in the root causes. To develop a viable

hypothesis for pathogenesis, you have to start with an apparently

healthy person (albeit one who has some so far innocuous genetic

variations), and move from there to an ill person, and the process

must not have " jumps, " but must be continuous and must be self-

consistent at every stage.

***I think that some of the issues are semantic. For example, in

defining the " cause " or " causes, " do you focus on the underlying

things that make the person vulnerable and set him or her up, or do

you just look at the visible things that went on before they became

ill. I think you have to consider both.

***Once the person becomes ill, the picture gets really tangled,

because there are all sorts of feedbacks, interactions and vicious

circles that get going, and I think there are more as time goes by.

It gets really hard to sort out in a person who is far along. I see

urine organic acids tests from some people in which nearly every one

of the parameters measured is outside its normal range. Where do

you start in trying to unravel one of these cases?

***From an operational point of view, what counts is not so much how

you define things, but where are the levers you can pull to get the

person back out of this. Do you have to do lots of things, or can

you get down to the root of it and do only one or a very few

things. At this point, I'm hoping that if we compensate for the

genetic variations that allow the development of the vicious circle

in the sulfur metabolism, we won't have to do very many other things

to get the person out of the trap, other than continuing to prevent

the vicious circle from reforming. I think the biochemistry and

physiology will take care of the rest, though it seems to take quite

a bit of time. That's what Amy Yasko reports in autism.

> --Kurt

>

***Rich

[Guest guest]

On Jun 13, 2006, at 9:21 AM, Kurt R. wrote:

> And some of the secondary issues will become primary problems once the

> fragile detox system is shored up, I suspect we aren't out of the

> woods

> when we correct the glutathione problem. For example, we probably

> have

> a huge toxin load and need a lot of detox, and liver support to get

> through that. Also we may need to correct an acquired immune

> imbalance

> being maintained by a vicious cycle of symbiotic bugs (or should I

> say a

> symbiotic cycle of vicious bugs), and repair vascular and coag damage

> (esp. the BBB), safely pull out a high body burden of metals,

> repair an

> exhausted adrenal system, recondition maladapted neuro-immune

> processes,

> support enzymatic processes while the body repairs itself, provide

> proper recovery nutrients, and more. And some of us probably have

> also

> acquired disseminated infection loads that can only be eliminated with

> outside interventions, and only AFTER the detox system is repaired

> (such

> as Lyme and toxic parasites/Nematodes with a high herx potential).

Many of these issues are also resolved -- or, at least, the

conditions for resolution are created -- by having high enough

glutathione.

For example: Glutathione's main job in the system is detox. It's made

by the liver for that purpose; having enough will greatly support the

liver in this effort. It also balances the immune system,

discouraging the growth of unfriendly bugs. (AIDS patients take GSH

mainly as an immune supporter.)

As the body's master antioxidant, glutathione plays an essential role

in speeding the repair of tissue damage. It is the second-best

mercury chelator known; and second to nothing in moving metals out of

the system once they've been chelated. In fact, that's its other

natural job in the system besides detox.

With glutathione supporting neuro-immune and enzymatic processses (it

also tunes the methylation cycle, which fosters these processes),

recovery improves. Even the infection loads decrease: Lyme and other

parasites have a very hard time getting a toehold in a high-

glutathione environment.

So, yes, it's quite possible that we will be substantially out of the

woods when we correct the glutathione problem. Pretty much every

concern you raise is also affected positively by rising GSH.

Sara

[Guest guest]

Hi, .

That's a good question. I don't have enough experience to give you a

straightforward answer, though.

I recall that there was a woman on the list a while back who found

that taking vitamin C to bowel tolerance did the whole job for her,

and I suspect that it helped to regenerate her glutathione, as well

as serving as an antioxidant to take care of some of the reactive

oxygen species at the same time. The body has a reservoir of the

amino acids needed to make glutathione in the skeletal muscle

protein. If things are working right, it can break down some of

this protein to obtain the raw materials for making glutathione. I

think this is what happened in that woman's body.

But this may not work in people who have a stubborn block in their

methylation cycle. I think it could depend on the genetic

variations a particular person has, involving the methylation

cycle. In some people, it may be possible to break the vicious

circle by forcing the glutathione level back up by the use of heavy

vitamin C alone.

In others, it may be necessary to boost the glutathione more

directly, using the various ways of building glutathione, and that

may be enough to break the vicious circle.

In still others, it may be necessary to compensate directly for the

genetic variations (using such things as methyl B-12, folinic acid,

TMG, B6, magnesium, or others, depending on the particular set of

genetic variations that is present) in order to break the vicious

circle and get the methylation cycle going again.

I think we are going to have to follow some cases of pioneers who

try these various things in order to get a good answer to that

question. The more testing people can do along the way, the more

information we will have about what is going on. Unfortunately,

that can be pretty expensive. I think there's a real benefit in

sharing experiences on the list, so people can benefit from each

other. I appreciate your willingness, and that of so many others,

to share test results, treatments, and outcomes.

Rich

>

> Hi Rich,

>

> That is interesting that high dose C recycles glutathione. In

those of

> us with low glutathione, would high dose vitamin C be sufficient or

> would we also have to take measures to generate new glutathione ?

>

>

>

>

>

>

>

> Re: Hypothesis for diabetes insipidus

link

> to glutathione depletion

>

>

>

> ***You may have heard of Dr. Cathcart. He practices in Los

> Altos, CA, and has a big website on vitamin C. He takes vitamin C

> to bowel tolerance himself, and has since he was a teenager (he's

> now probably in his 70s). He got mono then, and didn't recover,

and

> he found that he could function if he took vitamin C to bowel

> tolerance, and he's still doing it. (I suspect that he may have a

> genetic variation that prevents normal glutathione function, but I

> don't know for sure.) He wrote a paper in which he made the point

> that whereas at normal physiological levels of glutathione and

> vitamin C in the body, glutathione recycles vitamin C. However, if

> the concentration of vitamin C is raised to high levels by taking

it

> to bowel tolerance, then the reaction can be reversed, and vitamin

C

> will recycle glutathione. I don't know how high the vitamin C

> dosage is in people who do the salt/c treatment, but if it is very

> high, this may be what is going on.

>

>

>

> .

>

>

> <http://geo./serv?

s=97359714 & grpId=91574 & grpspId=1600061645 & msg

> Id=99515 & stime=1150183854>

>

>

>

>

>

[Guest guest]

Rich and ,

This is quite anecdotal, but after more than a year of following the

reports of hundreds of people on Salt/C, some of whom may have succeeded

in what Rich is suggesting, restoring glutathione levels by Vit C alone,

my sense is that Rich is right. There are subsets who succeed from this

alone, some who get part-way there, and others who only have marginal

benefits. There must be other significant factors, genetics,

co-infections, etc. If you are lucky enough to be able to recover from

Vit C, the rule of thumb seems to be that a fairly high dose is

required, at least 12g daily, and possibly as much as 24g. Most of the

people reporting near recovery are in that range, and quite a few in the

middle, say 18g of Vit C (and 18g of natural unprocessed sea salt). But

not all can tolerate that dose, the 30 day cyclical herxing can be

tremendous, and seems to follow a schedule (worse every third month).

--Kurt

Re: Hypothesis for diabetes insipidus

link

> to glutathione depletion

>

>

>

> ***You may have heard of Dr. Cathcart. He practices in Los

> Altos, CA, and has a big website on vitamin C. He takes vitamin C

> to bowel tolerance himself, and has since he was a teenager (he's

> now probably in his 70s). He got mono then, and didn't recover,

and

> he found that he could function if he took vitamin C to bowel

> tolerance, and he's still doing it. (I suspect that he may have a

> genetic variation that prevents normal glutathione function, but I

> don't know for sure.) He wrote a paper in which he made the point

> that whereas at normal physiological levels of glutathione and

> vitamin C in the body, glutathione recycles vitamin C. However, if

> the concentration of vitamin C is raised to high levels by taking

it

> to bowel tolerance, then the reaction can be reversed, and vitamin

C

> will recycle glutathione. I don't know how high the vitamin C

> dosage is in people who do the salt/c treatment, but if it is very

> high, this may be what is going on.

>

>

>

> .

>

>

> <http://geo.. <http://geo./serv?> com/serv?

s=97359714 & grpId=91574 & grpspId=1600061645 & msg

> Id=99515 & stime=1150183854>

>

>

>

>

>

[Guest guest]

Hi, Kurt.

>

> Rich,

>

> Thanks for the thoughtful responses. I think this idea makes good

> sense, that the high-level cause is a fragile detox process

itself, and

> that the pathogenesis is strain on that fragile system. Then the

> progression of the illness would be due to the down-stream effects

of

> the overwhelmed detox system, which gradually destabilizes other

systems

> and perhaps also causes secondary vicious circles. Would be nice

if it

> really becomes this simple, I am growing weary of the ever-

increasing

> complexity of this illness, and the endless treatments.

***I think that genetic weakness in the detox system definitely is a

pathway into CFS for many people. For those who suspect this, I

think it's helpful to get the Genovations Detoxi-genomic profile and

the Genova Diagnostics (formerly Great Smokies) Comprehensive

detoxification panel run. I've seen quite a few with SNPs in some

of the important CYP450 enzymes as well as in the glutathione

transferase enzymes and superoxide dismutases. I think these are

clues to the detox system being an important factor in these cases.

>

> But even if this is 'it', we still have a lot of work ahead to

find out

> how to manage our bio-individuality in dealing with this situation.

***I think you're right about this, and I think the reason for it is

that people can have a variety of combinations of the genetic

variations, and this gives them biochemical individuality.

> Maybe some good decision algorithms would help, and rational,

natural,

> inexpensive treatment options.

***This is a goal that I have had for a long time, but I still don't

know enough yet to set it down in cookbook fashion.

Also, is there an ideal order of

> operations for treatment, or will this remain individualized? I

think

> that is an interesting question.

***I do, too! It would be really nice to figure out a

straightforward treatment approach that would work for everyone, but

with these differences in genetics, I'm not sure that will be

possible. I'm hoping, though, that by knowing enough about the

effects of the different genetic variations, we may be able to infer

which ones a person has from other test data (particularly plasma

and urinary amino acids, urinary organic acids, and red blood cell

elements tests) as well as symptoms and history of response to

various foods, chemicals and drugs. Alternatively, hopefully the

characterization of SNPS will get cheaper, as technology is improved

and competition grows among labs. I think a bigger demand will help

this along. It really is nice to know what you're starting with, in

terms of SNPs, rather than having to guess.

>

> And some of the secondary issues will become primary problems once

the

> fragile detox system is shored up, I suspect we aren't out of the

woods

> when we correct the glutathione problem.

***I've suspected this, too, and I actually also wrote it in the

conclusion of my 2004 poster paper on glutathione in CFS.

For example, we probably have

> a huge toxin load and need a lot of detox, and liver support to get

> through that. Also we may need to correct an acquired immune

imbalance

> being maintained by a vicious cycle of symbiotic bugs (or should I

say a

> symbiotic cycle of vicious bugs), and repair vascular and coag

damage

> (esp. the BBB), safely pull out a high body burden of metals,

repair an

> exhausted adrenal system, recondition maladapted neuro-immune

processes,

> support enzymatic processes while the body repairs itself, provide

> proper recovery nutrients, and more. And some of us probably have

also

> acquired disseminated infection loads that can only be eliminated

with

> outside interventions, and only AFTER the detox system is repaired

(such

> as Lyme and toxic parasites/Nematodes with a high herx potential).

***You may be right about all of this. I've been concerned about

many of these things, too, and mentioned some of them in my paper.

One thing that is encouraging though, is that Amy Yasko is finding

that some of the downstream aspects in the pathophysiology of autism

are automatically taken care of when the basic methylation cycle

issues are corrected. So we may not have to deal directly with all

of them in CFS, either.

>

> I appreciate all your efforts on our behalf.

***You're certainly welcome, and I appreciate the thinking that you

bring to the problem as well.

I am benefiting from this

> personally, I now understand my liver function profile better (my

doctor

> just read off the lab report to me and did not catch all the subtle

> problems that are now evident after studying autism liver

problems).

> And have added several supplements to boost glutathione, and they

are

> helping. Also, I am now taking detox much more seriously, and am

on a

> cleansing program, along with everything else I am doing. So

maybe the

> fog is starting to clear.

***This is really good to hear, Kurt, and I certainly hope your

improvement continues!

>

> --Kurt

***Rich

[Guest guest]

Hi, Vickie.

Thanks for the comments. You're right. Glutathione is sort of

a " master regulator. " It regulates the redox potential inside all

the cells. Since the metabolism involves a lot of redox reactions,

and since their rates depend on the redox potential, glutathione

plays a very fundamental and universal chemical role in the cells.

When I first learned that glutathione regulates the redox potential

inside the cells, I " knew " that its reported depletion in CFS (by

Dr. Cheney) had to be a very big deal. I had come out of many years

of studying corrosion chemistry and geochemistry, and in both those

fields the redox potential is extremely important in determining

what goes on. Since redox reactions are also important in

biochemistry, I figured I had better focus on glutathione for a

while to see if it would pay off, and so far I think it has.

Thanks for sharing your experience with digestive enzymes. I think

it's possible that glutathione depletion is taking its toll on

production of these enzymes in the pancreas.

Rich

>

> Hi Rich,

>

> I find your hypothesis very interesting. Glutathione seems to be

> a " master regulator " of body systems, sort of like the idea of

> a " strange attractor " in fractals that keeps the fractal

> organized. " Perturbations " from outside the system cause

disturbances

> that weaken the organization.

>

> Glutathione seems to be the master regulator of the immune system,

> but since the connections are nonlinear (chemical and electrical

> feedback mechanisms), glutathione is affected by and modified by

> feedback from the system.

>

> I don't know where that came from! I don't know that much about

> fractals or the science of self-organizing systems, and my brain

is

> pretty fuzzy on what I did know about fractals and self-organizing

> systems theory.

>

> I think the pancreas is one of the organs most affected by CFS. I

> know many CFSers who have insulin resistance, which causes a lot

of

> insulin to be released, as I recall. I know that my ability to

> produce digestive enzymes has decreased over time, and one of the

> things that helps me the most is taking digestive enzymes.

>

> Just the ramblings of an amateur.

>

> Vickie

[Guest guest]

Hi, Blake.

I agree with you, and I've been looking for 24-hour urine creatinine

levels in tests where it's evaluated. Creatine isn't measured very

often, but creatinine is, and it should be a good indicator of total

creatine present in the body, since the breakdown rate should be

pretty constant. I have seen some low urine creatinine numbers, but

they are usually from spot urine samples, so you can't be sure whether

the low values aren't just due to the diabetes insipidus that many

PWCs have, which dilutes the urine with a lot of excreted water.

I don't think there has been much study of creatine or creatinine in

CFS. In the magnetic resonance spectroscopy studies of the brain,

they use creatine to normalize the other peaks. In urinalysis, they

use creatinine to normalize the other substances. In the phosphorus-

31 nuclear magnetic resonance studies of muscle, they look at the

fraction of creatine that is phosphorylated. I don't think the

medical people are accustomed to looking at the absolute values of

creatine or creatinine. Of course, absolute values are harder to

measure than ratios in just about any experimental technique, because

you have to have absolute calibration, rather than just a stable, more

or less linear response of your measuring technique. But big changes

like this should be easy to see, and it would definitely be a good

think to look for.

Rich

>

> Hi rich,

>

> If methylation is disordered in CFS, then lower levels of creatine

should be fairly universal. As creatine synthesis requires 70% of the

methyl donors it should be the first thing to drop. Do you know what

th literature says about creatine levels in CFS compared to controls?

>

> Blake