Possible explanation for increased acetylcholine sensitivity

[Guest guest]

Hi, all.

As many of you are aware, the group at the University of Dundee in

Scotland (Vance Spence et al.) have recently published papers

reporting on their measurements of increased acetylcholine

sensitivity in dilating the arterioles in the skin of the forearms

of PWCs, compared to normal healthy controls.

By way of background, acetylcholine is the neurotransmitter that the

autonomic nervous system uses to control the dilation of the

arterioles supplying most of the skin on the body (not including the

hands and feet and part of the head). This affects the skin surface

temperature, and thus the rate of heat loss from the body.

The Dundee group has developed an electrochemical method for

injecting a precise amount of acetylcholine through the skin on the

forearm, and then monitoring blood flow noninvasively by a laser

Doppler technique. They have found that PWCs are significantly more

sensitive to this acetylcholine than are normal, healthy controls,

in terms of experiencing greater increase in blood flow, and for a

longer period of time. They have suggested that their results may

mean that there is a lower production of acetylcholinesterase in

this tissue in PWCs than in healthy normal people.

Acetylcholinesterase is the enzyme that the body uses to break down

acetylcholine, so as to control the amount present and its duration

of action.

I would like to suggest an explanation for these observations. As I

have noted in the past, many (or most) PWCs have a lower average

metabolic rate in their skeletal muscles than do normal, healthy

people. This is what produces the lower peripheral body

temperature, such as is measured in the armpit, in many PWCs (Some

have a hypothyroid condition, but I have suggested that most suffer

from partial blockades in the Krebs cycles and possibly also the

respiratory chains of their skeletal muscle cells. I believe that

this results from elevated peroxynitrite (as Prof. Pall has

published), which I believe results in turn from depletion of

glutathione in these cells.)

I suggest that because of this low metabolic rate, the autonomic

nervous system more or less constantly shuts down the blood flow to

the skin in PWCs to conserve heat, thus maintaining the core body

temperature for proper function of the vital organs in order to

preserve life. This entails maintaining a low average output of

acetylcholine by the cells responsible for controlling blood flow to

the skin.

I suggest that these cells adapt to their long-term low average

acetylcholine output by decreasing the production of

acetylcholinesterase. Since the level of acetylcholine is below

normal, not as much acetylcholinesterase is needed to control it as

in a normal, healthy person.

Now, when the experimenters suddenly inject a controlled amount of

acetylcholine into the forearm, because there is less

acetylcholinesterase present, the acetylcholine rises to a higher

concentration than normal, and lasts for a longer time. This

produces greater dilation of the arterioles and also a longer

duration of dilation. I think this would explain their observations.

In the past, I have also discussed the action of norepinephrine in

shutting down the blood flow in the skin. Norepinephrine is used to

shut down blood flow for all the skin of the body. Acetylcholine is

used to actively produce dilation and hence increased blood flow on

all the skin except for that on the hands and feet and part of the

head. For those specific areas, dilation occurs spontaneously when

norepinephrine secretion is cut back. Therefore, I think this

explanation is still consistent with my earlier suggestion that in

PWCs there is an elevated average production of norepinephrine in

the skin to restrict blood flow there.

Rich Van Konynenburg

[Guest guest]

Mr. Rich Van Konynenburg:

I have read your posting with utmost interest.

I have been trying to trace down all the informatios about acetylcholine

abnormalities in CFS, since I believe its a key point in its pathogenesis.

I would like to ask you what information you have, or your impresssions about

possible treatment for cholinergic abnormalities (reported as your sure know not

only by the group of Dundee but also by the group of Glasgow O. Behan).

I have also read a successful three case report from Japan treatment with

pyridostigmine, half a dose (30 mg.), a cholinergic agonist, I understand.

What about acetyl-L-carnitine?, because of its acetyl radical? or choline?

I am new in this group.

Sorry for my English, its not my native language.

Greeting to all from Peru.

Guido Toro

rvankonynen <richvank@...> wrote:

Hi, all.

As many of you are aware, the group at the University of Dundee in

Scotland (Vance Spence et al.) have recently published papers

reporting on their measurements of increased acetylcholine

sensitivity in dilating the arterioles in the skin of the forearms

of PWCs, compared to normal healthy controls.

By way of background, acetylcholine is the neurotransmitter that the

autonomic nervous system uses to control the dilation of the

arterioles supplying most of the skin on the body (not including the

hands and feet and part of the head). This affects the skin surface

temperature, and thus the rate of heat loss from the body.

The Dundee group has developed an electrochemical method for

injecting a precise amount of acetylcholine through the skin on the

forearm, and then monitoring blood flow noninvasively by a laser

Doppler technique. They have found that PWCs are significantly more

sensitive to this acetylcholine than are normal, healthy controls,

in terms of experiencing greater increase in blood flow, and for a

longer period of time. They have suggested that their results may

mean that there is a lower production of acetylcholinesterase in

this tissue in PWCs than in healthy normal people.

Acetylcholinesterase is the enzyme that the body uses to break down

acetylcholine, so as to control the amount present and its duration

of action.

I would like to suggest an explanation for these observations. As I

have noted in the past, many (or most) PWCs have a lower average

metabolic rate in their skeletal muscles than do normal, healthy

people. This is what produces the lower peripheral body

temperature, such as is measured in the armpit, in many PWCs (Some

have a hypothyroid condition, but I have suggested that most suffer

from partial blockades in the Krebs cycles and possibly also the

respiratory chains of their skeletal muscle cells. I believe that

this results from elevated peroxynitrite (as Prof. Pall has

published), which I believe results in turn from depletion of

glutathione in these cells.)

I suggest that because of this low metabolic rate, the autonomic

nervous system more or less constantly shuts down the blood flow to

the skin in PWCs to conserve heat, thus maintaining the core body

temperature for proper function of the vital organs in order to

preserve life. This entails maintaining a low average output of

acetylcholine by the cells responsible for controlling blood flow to

the skin.

I suggest that these cells adapt to their long-term low average

acetylcholine output by decreasing the production of

acetylcholinesterase. Since the level of acetylcholine is below

normal, not as much acetylcholinesterase is needed to control it as

in a normal, healthy person.

Now, when the experimenters suddenly inject a controlled amount of

acetylcholine into the forearm, because there is less

acetylcholinesterase present, the acetylcholine rises to a higher

concentration than normal, and lasts for a longer time. This

produces greater dilation of the arterioles and also a longer

duration of dilation. I think this would explain their observations.

In the past, I have also discussed the action of norepinephrine in

shutting down the blood flow in the skin. Norepinephrine is used to

shut down blood flow for all the skin of the body. Acetylcholine is

used to actively produce dilation and hence increased blood flow on

all the skin except for that on the hands and feet and part of the

head. For those specific areas, dilation occurs spontaneously when

norepinephrine secretion is cut back. Therefore, I think this

explanation is still consistent with my earlier suggestion that in

PWCs there is an elevated average production of norepinephrine in

the skin to restrict blood flow there.

Rich Van Konynenburg

This list is intended for patients to share personal experiences with each

other, not to give medical advice. If you are interested in any treatment

discussed here, please consult your doctor.

[Guest guest]

> Hi, all.

> By way of background, acetylcholine is the neurotransmitter that

the autonomic nervous system uses to control the dilation of the

> arterioles supplying most of the skin on the body

Rich,

I feel I should know this, but I don't. I am taking lecithin granules

for the phosphatidylcholine as I understand the brain uses this as

does a man's orgasm. Are there any connection between the two

cholines?

Bob

[Guest guest]

Every time someone posts about treatment of CFIDS with pyridostigmine, aka

Mestinon, I am so concerned. After all, PB pills (pyridostigmine bromide, which

IS Mestinon) have been implicated by many researchers, particularly

Haley, as a possible co-factor in the development of Gulf War Syndrome, due to

the way they interacted with pesticides to cause brain injury. What these

researchers found was a simple enough combination that could happen to anyone

taking Mestinon, particularly during spraying season (which is now). Pesticides

are sprayed along roadsides, on lawns, on crops, on pets, on people, in stores,

and in almost every hospital and many medical facilities. Taking Mestinon is

playing with fire.

Peggy

<<I have also read a successful three case report from Japan treatment with

pyridostigmine, half a dose (30 mg.), a cholinergic agonist, I understand.>>

[Guest guest]

Hi Peggy:

In efect, that´s a very good point. How can you use a treatment -pyridostigmine-

that might have had a role in the development of Gulf War Syndrome?

By the way, does anyone know which the dose of pyridostigmine was in the case of

Gulf War Veterans?

In any case, if pyridostigmine is not useful or even dangerous, the question

still remains. What would be the best treatment option for the proved

acetylcholine deficiencies in CFS? : nicotine, acetyl-l-carnitine, acetyl

choline agonists other than pyridostigmine?

Guido

Every time someone posts about treatment of CFIDS with pyridostigmine, aka

Mestinon, I am so concerned. After all, PB pills (pyridostigmine bromide, which

IS Mestinon) have been implicated by many researchers, particularly

Haley, as a possible co-factor in the development of Gulf War Syndrome, due to

the way they interacted with pesticides to cause brain injury. What these

researchers found was a simple enough combination that could happen to anyone

taking Mestinon, particularly during spraying season (which is now). Pesticides

are sprayed along roadsides, on lawns, on crops, on pets, on people, in stores,

and in almost every hospital and many medical facilities. Taking Mestinon is

playing with fire.

Peggy

<<I have also read a successful three case report from Japan treatment with

pyridostigmine, half a dose (30 mg.), a cholinergic agonist, I understand.>>

This list is intended for patients to share personal experiences with each

other, not to give medical advice. If you are interested in any treatment

discussed here, please consult your doctor.

[Guest guest]

Bob,

Yes, both molecules contain the same choline. When you ingest

phosphatidylcholine, some is used intact, and some is broken down so

that individual choline molecules are freed. These can be used to

synthesize acetylcholine. Phosphatidylcholine is considered a

delivery form for choline.

Rich

> > Hi, all.

> > By way of background, acetylcholine is the neurotransmitter that

> the autonomic nervous system uses to control the dilation of the

> > arterioles supplying most of the skin on the body

>

> Rich,

>

> I feel I should know this, but I don't. I am taking lecithin

granules

> for the phosphatidylcholine as I understand the brain uses this as

> does a man's orgasm. Are there any connection between the two

> cholines?

>

> Bob

[Guest guest]

Hi, Guido.

Thank you for your response.

I am aware of two significant choline-containing substances in the

body: phosphatidylcholine and acetylcholine. Phosphatidylcholine

is found mainly in the phospholipid membranes of cells, and is

important for cells in the brain as well as other organs.

Acetylcholine is a neurotransmitter, responsible for communication

between some of the neurons in the brain, also serving as the

neurotransmitter of the parasympathetic nervous system, and also

acting as the neurotransmitter between the nervous system and the

muscles to stimulate muscle contraction.

In CFS, I am aware of several magnetic resonance spectroscopy

studies that have found elevated levels of free choline in certain

parts of the brain, suggesting that there may be a disturbance in

phospholipid metabolism in CFS. I am also aware of the work of the

University of Dundee group showing enhanced sensitivity of forearm

blood flow to injected acetylcholine, and as you know, I have

suggested an explanation for this observation.

I'm also aware of a Japanese paper reporting that in CFS there are

autoantibodies against muscarinic cholinergic receptors, and of the

other Japanese paper you mentioned, in which the use of

pyridostigmine was reported for three cases of CFS.

I'm not aware of work by the Glasgow group on cholinergic

abnormalities. Can you give me references for that?

Concerning the use of pyridostigmine in CFS, I am not enthusiastic

about this. As you probably know, pyridostigmine is an inhibitor of

acetylcholinesterase. If the work of the Dundee group is indeed

explained by low acetylcholinesterase in the cells in the skin of

the forearm as an adaptation to low acetylcholine secretion there,

secondary to an abnormally low metabolic rate and an effort to

restrict blood flow to the skin to conserve body heat, as I have

suggested, then it would seem that use of pyridostigmine would not

be getting at the root cause, but would be treating a symptom.

In addition, as Peggy mentioned, use of pyridostigmine bromide in

the Gulf War has been implicated as a possible contributor to the

development of Gulf War illnesses.

I don't have an explanation of the Japanese work. As you may know,

pyridostigmine is used in the treatment of myasthenia gravis, which

is an autoimmune disorder involving attack on acetylcholine

receptors. The Japanese paper describing similar attack in CFS was

probably the rationale for the other Japanese paper in which

pyridostigmine treatment was attempted. I think this subject needs

more study.

Concerning use of acetyl-L-carnitine, I think this supplement can

have benefit for some PWCs, but I don't think the benefit involves

acetylcholine. As I understand it, the route for synthesizing

acetylcholine is the reaction between choline and acetyl CoA. The

acetyl CoA, in turn, is produced from pyruvate by the pyruvate

dehydrogenase complex.

There is a lot that I don't understand about all of this, so if you

have some insights, I would appreciate reading them.

Rich

> Hi, all.

>

> As many of you are aware, the group at the University of Dundee in

> Scotland (Vance Spence et al.) have recently published papers

> reporting on their measurements of increased acetylcholine

> sensitivity in dilating the arterioles in the skin of the forearms

> of PWCs, compared to normal healthy controls.

>

> By way of background, acetylcholine is the neurotransmitter that

the

> autonomic nervous system uses to control the dilation of the

> arterioles supplying most of the skin on the body (not including

the

> hands and feet and part of the head). This affects the skin

surface

> temperature, and thus the rate of heat loss from the body.

>

> The Dundee group has developed an electrochemical method for

> injecting a precise amount of acetylcholine through the skin on

the

> forearm, and then monitoring blood flow noninvasively by a laser

> Doppler technique. They have found that PWCs are significantly

more

> sensitive to this acetylcholine than are normal, healthy controls,

> in terms of experiencing greater increase in blood flow, and for a

> longer period of time. They have suggested that their results may

> mean that there is a lower production of acetylcholinesterase in

> this tissue in PWCs than in healthy normal people.

> Acetylcholinesterase is the enzyme that the body uses to break

down

> acetylcholine, so as to control the amount present and its

duration

> of action.

>

> I would like to suggest an explanation for these observations. As

I

> have noted in the past, many (or most) PWCs have a lower average

> metabolic rate in their skeletal muscles than do normal, healthy

> people. This is what produces the lower peripheral body

> temperature, such as is measured in the armpit, in many PWCs

(Some

> have a hypothyroid condition, but I have suggested that most

suffer

> from partial blockades in the Krebs cycles and possibly also the

> respiratory chains of their skeletal muscle cells. I believe that

> this results from elevated peroxynitrite (as Prof. Pall has

> published), which I believe results in turn from depletion of

> glutathione in these cells.)

>

> I suggest that because of this low metabolic rate, the autonomic

> nervous system more or less constantly shuts down the blood flow

to

> the skin in PWCs to conserve heat, thus maintaining the core body

> temperature for proper function of the vital organs in order to

> preserve life. This entails maintaining a low average output of

> acetylcholine by the cells responsible for controlling blood flow

to

> the skin.

>

> I suggest that these cells adapt to their long-term low average

> acetylcholine output by decreasing the production of

> acetylcholinesterase. Since the level of acetylcholine is below

> normal, not as much acetylcholinesterase is needed to control it

as

> in a normal, healthy person.

>

> Now, when the experimenters suddenly inject a controlled amount of

> acetylcholine into the forearm, because there is less

> acetylcholinesterase present, the acetylcholine rises to a higher

> concentration than normal, and lasts for a longer time. This

> produces greater dilation of the arterioles and also a longer

> duration of dilation. I think this would explain their

observations.

>

> In the past, I have also discussed the action of norepinephrine in

> shutting down the blood flow in the skin. Norepinephrine is used

to

> shut down blood flow for all the skin of the body. Acetylcholine

is

> used to actively produce dilation and hence increased blood flow

on

> all the skin except for that on the hands and feet and part of the

> head. For those specific areas, dilation occurs spontaneously

when

> norepinephrine secretion is cut back. Therefore, I think this

> explanation is still consistent with my earlier suggestion that in

> PWCs there is an elevated average production of norepinephrine in

> the skin to restrict blood flow there.

>

> Rich Van Konynenburg

>

>

>

>

>

>

>

> This list is intended for patients to share personal experiences

with each other, not to give medical advice. If you are interested

in any treatment discussed here, please consult your doctor.

>

>

>

[Guest guest]

Hi Rich:

The reference I mentioned to you as the paper by the Group of Glasgow is

" Chronic Fatigue Syndrome: a disorder of central cholinergic transmission " , that

appeared in the Journal of Chronic Fatigue Syndrome, 1997, N° 3, pgs. 3-16.

Guido

rvankonynen <richvank@...> wrote:

Hi, Guido.

Thank you for your response.

I am aware of two significant choline-containing substances in the

body: phosphatidylcholine and acetylcholine. Phosphatidylcholine

is found mainly in the phospholipid membranes of cells, and is

important for cells in the brain as well as other organs.

Acetylcholine is a neurotransmitter, responsible for communication

between some of the neurons in the brain, also serving as the

neurotransmitter of the parasympathetic nervous system, and also

acting as the neurotransmitter between the nervous system and the

muscles to stimulate muscle contraction.

In CFS, I am aware of several magnetic resonance spectroscopy

studies that have found elevated levels of free choline in certain

parts of the brain, suggesting that there may be a disturbance in

phospholipid metabolism in CFS. I am also aware of the work of the

University of Dundee group showing enhanced sensitivity of forearm

blood flow to injected acetylcholine, and as you know, I have

suggested an explanation for this observation.

I'm also aware of a Japanese paper reporting that in CFS there are

autoantibodies against muscarinic cholinergic receptors, and of the

other Japanese paper you mentioned, in which the use of

pyridostigmine was reported for three cases of CFS.

I'm not aware of work by the Glasgow group on cholinergic

abnormalities. Can you give me references for that?

Concerning the use of pyridostigmine in CFS, I am not enthusiastic

about this. As you probably know, pyridostigmine is an inhibitor of

acetylcholinesterase. If the work of the Dundee group is indeed

explained by low acetylcholinesterase in the cells in the skin of

the forearm as an adaptation to low acetylcholine secretion there,

secondary to an abnormally low metabolic rate and an effort to

restrict blood flow to the skin to conserve body heat, as I have

suggested, then it would seem that use of pyridostigmine would not

be getting at the root cause, but would be treating a symptom.

In addition, as Peggy mentioned, use of pyridostigmine bromide in

the Gulf War has been implicated as a possible contributor to the

development of Gulf War illnesses.

I don't have an explanation of the Japanese work. As you may know,

pyridostigmine is used in the treatment of myasthenia gravis, which

is an autoimmune disorder involving attack on acetylcholine

receptors. The Japanese paper describing similar attack in CFS was

probably the rationale for the other Japanese paper in which

pyridostigmine treatment was attempted. I think this subject needs

more study.

Concerning use of acetyl-L-carnitine, I think this supplement can

have benefit for some PWCs, but I don't think the benefit involves

acetylcholine. As I understand it, the route for synthesizing

acetylcholine is the reaction between choline and acetyl CoA. The

acetyl CoA, in turn, is produced from pyruvate by the pyruvate

dehydrogenase complex.

There is a lot that I don't understand about all of this, so if you

have some insights, I would appreciate reading them.

Rich

---------------------------------

[Guest guest]

Rick,

What is your view of supplementing Phospatidylcholine and

acethyl-L-Carnitine.

When I do them I find a great improvement. But I must stop them

because i expereience a sharp increase in general anxiety with

A=L-C. This comes with feelings of hypoglycemia.

PC causes a general reduction in coping with anxiety after a few

doses. But the first day it feels great. But had to stop it too.

> > Hi, all.

> >

> > As many of you are aware, the group at the University of Dundee

in

> > Scotland (Vance Spence et al.) have recently published papers

> > reporting on their measurements of increased acetylcholine

> > sensitivity in dilating the arterioles in the skin of the

forearms

> > of PWCs, compared to normal healthy controls.

> >

> > By way of background, acetylcholine is the neurotransmitter that

> the

> > autonomic nervous system uses to control the dilation of the

> > arterioles supplying most of the skin on the body (not including

> the

> > hands and feet and part of the head). This affects the skin

> surface

> > temperature, and thus the rate of heat loss from the body.

> >

> > The Dundee group has developed an electrochemical method for

> > injecting a precise amount of acetylcholine through the skin on

> the

> > forearm, and then monitoring blood flow noninvasively by a laser

> > Doppler technique. They have found that PWCs are significantly

> more

> > sensitive to this acetylcholine than are normal, healthy

controls,

> > in terms of experiencing greater increase in blood flow, and for

a

> > longer period of time. They have suggested that their results

may

> > mean that there is a lower production of acetylcholinesterase in

> > this tissue in PWCs than in healthy normal people.

> > Acetylcholinesterase is the enzyme that the body uses to break

> down

> > acetylcholine, so as to control the amount present and its

> duration

> > of action.

> >

> > I would like to suggest an explanation for these observations.

As

> I

> > have noted in the past, many (or most) PWCs have a lower average

> > metabolic rate in their skeletal muscles than do normal, healthy

> > people. This is what produces the lower peripheral body

> > temperature, such as is measured in the armpit, in many PWCs

> (Some

> > have a hypothyroid condition, but I have suggested that most

> suffer

> > from partial blockades in the Krebs cycles and possibly also the

> > respiratory chains of their skeletal muscle cells. I believe

that

> > this results from elevated peroxynitrite (as Prof. Pall

has

> > published), which I believe results in turn from depletion of

> > glutathione in these cells.)

> >

> > I suggest that because of this low metabolic rate, the autonomic

> > nervous system more or less constantly shuts down the blood flow

> to

> > the skin in PWCs to conserve heat, thus maintaining the core body

> > temperature for proper function of the vital organs in order to

> > preserve life. This entails maintaining a low average output of

> > acetylcholine by the cells responsible for controlling blood flow

> to

> > the skin.

> >

> > I suggest that these cells adapt to their long-term low average

> > acetylcholine output by decreasing the production of

> > acetylcholinesterase. Since the level of acetylcholine is below

> > normal, not as much acetylcholinesterase is needed to control it

> as

> > in a normal, healthy person.

> >

> > Now, when the experimenters suddenly inject a controlled amount

of

> > acetylcholine into the forearm, because there is less

> > acetylcholinesterase present, the acetylcholine rises to a higher

> > concentration than normal, and lasts for a longer time. This

> > produces greater dilation of the arterioles and also a longer

> > duration of dilation. I think this would explain their

> observations.

> >

> > In the past, I have also discussed the action of norepinephrine

in

> > shutting down the blood flow in the skin. Norepinephrine is used

> to

> > shut down blood flow for all the skin of the body. Acetylcholine

> is

> > used to actively produce dilation and hence increased blood flow

> on

> > all the skin except for that on the hands and feet and part of

the

> > head. For those specific areas, dilation occurs spontaneously

> when

> > norepinephrine secretion is cut back. Therefore, I think this

> > explanation is still consistent with my earlier suggestion that

in

> > PWCs there is an elevated average production of norepinephrine in

> > the skin to restrict blood flow there.

> >

> > Rich Van Konynenburg

> >

> >

> >

> >

> >

> >

> >

> > This list is intended for patients to share personal experiences

> with each other, not to give medical advice. If you are interested

> in any treatment discussed here, please consult your doctor.

> >

> >

> >

[Guest guest]

PC may make you feel worse as it is known to lower cortisol levels, known to

generally be lowered in CFS. You may experience adrenal insufficiency, of

which anxiety is a symptom.

Regards, Blake Graham

Re: Possible explanation for increased

acetylcholine sensitivity

Rick,

What is your view of supplementing Phospatidylcholine and

acethyl-L-Carnitine.

When I do them I find a great improvement. But I must stop them

because i expereience a sharp increase in general anxiety with

A=L-C. This comes with feelings of hypoglycemia.

PC causes a general reduction in coping with anxiety after a few

doses. But the first day it feels great. But had to stop it too.

> > Hi, all.

> >

> > As many of you are aware, the group at the University of Dundee

in

> > Scotland (Vance Spence et al.) have recently published papers

> > reporting on their measurements of increased acetylcholine

> > sensitivity in dilating the arterioles in the skin of the

forearms

> > of PWCs, compared to normal healthy controls.

> >

> > By way of background, acetylcholine is the neurotransmitter that

> the

> > autonomic nervous system uses to control the dilation of the

> > arterioles supplying most of the skin on the body (not including

> the

> > hands and feet and part of the head). This affects the skin

> surface

> > temperature, and thus the rate of heat loss from the body.

> >

> > The Dundee group has developed an electrochemical method for

> > injecting a precise amount of acetylcholine through the skin on

> the

> > forearm, and then monitoring blood flow noninvasively by a laser

> > Doppler technique. They have found that PWCs are significantly

> more

> > sensitive to this acetylcholine than are normal, healthy

controls,

> > in terms of experiencing greater increase in blood flow, and for

a

> > longer period of time. They have suggested that their results

may

> > mean that there is a lower production of acetylcholinesterase in

> > this tissue in PWCs than in healthy normal people.

> > Acetylcholinesterase is the enzyme that the body uses to break

> down

> > acetylcholine, so as to control the amount present and its

> duration

> > of action.

> >

> > I would like to suggest an explanation for these observations.

As

> I

> > have noted in the past, many (or most) PWCs have a lower average

> > metabolic rate in their skeletal muscles than do normal, healthy

> > people. This is what produces the lower peripheral body

> > temperature, such as is measured in the armpit, in many PWCs

> (Some

> > have a hypothyroid condition, but I have suggested that most

> suffer

> > from partial blockades in the Krebs cycles and possibly also the

> > respiratory chains of their skeletal muscle cells. I believe

that

> > this results from elevated peroxynitrite (as Prof. Pall

has

> > published), which I believe results in turn from depletion of

> > glutathione in these cells.)

> >

> > I suggest that because of this low metabolic rate, the autonomic

> > nervous system more or less constantly shuts down the blood flow

> to

> > the skin in PWCs to conserve heat, thus maintaining the core body

> > temperature for proper function of the vital organs in order to

> > preserve life. This entails maintaining a low average output of

> > acetylcholine by the cells responsible for controlling blood flow

> to

> > the skin.

> >

> > I suggest that these cells adapt to their long-term low average

> > acetylcholine output by decreasing the production of

> > acetylcholinesterase. Since the level of acetylcholine is below

> > normal, not as much acetylcholinesterase is needed to control it

> as

> > in a normal, healthy person.

> >

> > Now, when the experimenters suddenly inject a controlled amount

of

> > acetylcholine into the forearm, because there is less

> > acetylcholinesterase present, the acetylcholine rises to a higher

> > concentration than normal, and lasts for a longer time. This

> > produces greater dilation of the arterioles and also a longer

> > duration of dilation. I think this would explain their

> observations.

> >

> > In the past, I have also discussed the action of norepinephrine

in

> > shutting down the blood flow in the skin. Norepinephrine is used

> to

> > shut down blood flow for all the skin of the body. Acetylcholine

> is

> > used to actively produce dilation and hence increased blood flow

> on

> > all the skin except for that on the hands and feet and part of

the

> > head. For those specific areas, dilation occurs spontaneously

> when

> > norepinephrine secretion is cut back. Therefore, I think this

> > explanation is still consistent with my earlier suggestion that

in

> > PWCs there is an elevated average production of norepinephrine in

> > the skin to restrict blood flow there.

> >

> > Rich Van Konynenburg

> >

> >

> >

> >

> >

> >

> >

> > This list is intended for patients to share personal experiences

> with each other, not to give medical advice. If you are interested

> in any treatment discussed here, please consult your doctor.

> >

> >

> >

[Guest guest]

Mr. Graham,

I thought PS (PhosphatidylSerine) lowers cortisol. I did not know

that PC lowers cortisol. I dont think Dr.Kane mentions that PC lowers

cortisol in her " Detoxx book " book.

If time and energy permits, I would greatly appreciate if you would

provide some reference for this.

Thanks,

Gayathri.

> PC may make you feel worse as it is known to lower cortisol levels,

known to

> generally be lowered in CFS. You may experience adrenal

insufficiency, of

> which anxiety is a symptom.

>

> Regards, Blake Graham

>

[Guest guest]

> Mr. Graham,

>

> I thought PS (PhosphatidylSerine) lowers cortisol.

gayu, I asked Rich this question but I didn't get a reply and maybe

you know. I take lecithin for the Phosphatidyline, is this PS good or

bad for PWC's?

Bob H.

[Guest guest]

Hi Bob,

Dr.Poesnecker recommends PS (PhosphatidylSerine) to lower one's

cortisol. I was taking Seriphos at night to lower my night cortisol

(It was high at night as per my ASI test).

Then I read in The Detoxx book that PS (PhosphatidylSerine) is not

recommended due to teh following reasons:

" There were numerous findings from research (Majumder 2002, et al)

that pointed that PS is implicated in thrombosis on platelet-derived

membranes containing surface-exposed PS. Also, it can trigger

activation of key down-stream steps in blood coagulation via exposure

of otherwise buried PS. "

At the end, they state in the book that

" In light of above research which does not support the use of PS for

memory enhancement, along with the role of PS in thrombosis and

apoptotic signaling, phosphatidylserine may be inappropriate for

patients with neurological or immune conditions. "

So, I has stopped taking Seriphos.

But I dont know of any bad effects of PC (Phosphatidylcholine) so far.

I dont think Dr.kane ever has mentioned that lecithin is bad. I think

her take is that one needs to take a lot of lecithin to get the

required amount of Phosphatidylcholine.

As you can see, PS(PhosphatidylSerine) and PC(Phosphatidylcholine)

are two different things. In your question you ask about

Phosphatidyline. I dont know much about Phosphatidyline.

I hope I have not confused you.

Thanks,

Gayathri.

> > Mr. Graham,

> >

> > I thought PS (PhosphatidylSerine) lowers cortisol.

>

> gayu, I asked Rich this question but I didn't get a reply and maybe

> you know. I take lecithin for the Phosphatidyline, is this PS good

or

> bad for PWC's?

>

> Bob H.

[Guest guest]

Gayathri,,

My mistake. I was thinking of PS.

Blake Graham

Re: Possible explanation for increased

acetylcholine sensitivity

> Mr. Graham,

>

> I thought PS (PhosphatidylSerine) lowers cortisol. I did not know

> that PC lowers cortisol. I dont think Dr.Kane mentions that PC lowers

> cortisol in her " Detoxx book " book.

>

> If time and energy permits, I would greatly appreciate if you would

> provide some reference for this.

>

> Thanks,

> Gayathri.

>

> > PC may make you feel worse as it is known to lower cortisol levels,

> known to

> > generally be lowered in CFS. You may experience adrenal

> insufficiency, of

> > which anxiety is a symptom.

> >

> > Regards, Blake Graham

> >

>

>

>

>

>

> This list is intended for patients to share personal experiences with each

other, not to give medical advice. If you are interested in any treatment

discussed here, please consult your doctor.

>

[Guest guest]

Hi, .

I suspect that these supplements raised the concentration of

acetylcholine too high in your brain, and caused the anxiety

problems. Acetylcholine is a neurotransmitter in the brain, and if

it goes too high, it may disturb the balance in the nervous system.

It is known that acetyl-L-carnitine will supply an acetyl group to

form acetylcholine, and it is also known that phosphatidylcholine

will supply choline to form acetylcholine.

Rich

> > > Hi, all.

> > >

> > > As many of you are aware, the group at the University of

Dundee

> in

> > > Scotland (Vance Spence et al.) have recently published papers

> > > reporting on their measurements of increased acetylcholine

> > > sensitivity in dilating the arterioles in the skin of the

> forearms

> > > of PWCs, compared to normal healthy controls.

> > >

> > > By way of background, acetylcholine is the neurotransmitter

that

> > the

> > > autonomic nervous system uses to control the dilation of the

> > > arterioles supplying most of the skin on the body (not

including

> > the

> > > hands and feet and part of the head). This affects the skin

> > surface

> > > temperature, and thus the rate of heat loss from the body.

> > >

> > > The Dundee group has developed an electrochemical method for

> > > injecting a precise amount of acetylcholine through the skin

on

> > the

> > > forearm, and then monitoring blood flow noninvasively by a

laser

> > > Doppler technique. They have found that PWCs are

significantly

> > more

> > > sensitive to this acetylcholine than are normal, healthy

> controls,

> > > in terms of experiencing greater increase in blood flow, and

for

> a

> > > longer period of time. They have suggested that their results

> may

> > > mean that there is a lower production of acetylcholinesterase

in

> > > this tissue in PWCs than in healthy normal people.

> > > Acetylcholinesterase is the enzyme that the body uses to break

> > down

> > > acetylcholine, so as to control the amount present and its

> > duration

> > > of action.

> > >

> > > I would like to suggest an explanation for these

observations.

> As

> > I

> > > have noted in the past, many (or most) PWCs have a lower

average

> > > metabolic rate in their skeletal muscles than do normal,

healthy

> > > people. This is what produces the lower peripheral body

> > > temperature, such as is measured in the armpit, in many PWCs

> > (Some

> > > have a hypothyroid condition, but I have suggested that most

> > suffer

> > > from partial blockades in the Krebs cycles and possibly also

the

> > > respiratory chains of their skeletal muscle cells. I believe

> that

> > > this results from elevated peroxynitrite (as Prof. Pall

> has

> > > published), which I believe results in turn from depletion of

> > > glutathione in these cells.)

> > >

> > > I suggest that because of this low metabolic rate, the

autonomic

> > > nervous system more or less constantly shuts down the blood

flow

> > to

> > > the skin in PWCs to conserve heat, thus maintaining the core

body

> > > temperature for proper function of the vital organs in order

to

> > > preserve life. This entails maintaining a low average output

of

> > > acetylcholine by the cells responsible for controlling blood

flow

> > to

> > > the skin.

> > >

> > > I suggest that these cells adapt to their long-term low

average

> > > acetylcholine output by decreasing the production of

> > > acetylcholinesterase. Since the level of acetylcholine is

below

> > > normal, not as much acetylcholinesterase is needed to control

it

> > as

> > > in a normal, healthy person.

> > >

> > > Now, when the experimenters suddenly inject a controlled

amount

> of

> > > acetylcholine into the forearm, because there is less

> > > acetylcholinesterase present, the acetylcholine rises to a

higher

> > > concentration than normal, and lasts for a longer time. This

> > > produces greater dilation of the arterioles and also a longer

> > > duration of dilation. I think this would explain their

> > observations.

> > >

> > > In the past, I have also discussed the action of

norepinephrine

> in

> > > shutting down the blood flow in the skin. Norepinephrine is

used

> > to

> > > shut down blood flow for all the skin of the body.

Acetylcholine

> > is

> > > used to actively produce dilation and hence increased blood

flow

> > on

> > > all the skin except for that on the hands and feet and part of

> the

> > > head. For those specific areas, dilation occurs spontaneously

> > when

> > > norepinephrine secretion is cut back. Therefore, I think this

> > > explanation is still consistent with my earlier suggestion

that

> in

> > > PWCs there is an elevated average production of norepinephrine

in

> > > the skin to restrict blood flow there.

> > >

> > > Rich Van Konynenburg

> > >

> > >

> > >

> > >

> > >

> > >

> > >

> > > This list is intended for patients to share personal

experiences

> > with each other, not to give medical advice. If you are

interested

> > in any treatment discussed here, please consult your doctor.

> > >

> > >

> > >

[Guest guest]

Bob wrote: I take lecithin for the Phosphatidyline, is this PS good

or bad for PWC's?

bg responds: Bob, my understanding is that Phosphatidylcholine (PC)

in Lecithin, not Phosphatidyserine (PS). They are two different

things. I am also taking Lecithin Granules (1 T. stirred into my

yogurt 3 times a day) until I get on the PhosChol program. There is

not nearly as much PC in Lecithin as in the PhosChol capsules.

I was taking PS because of so many excellent

things I had read about it -- from a Dr. Khalsa in charge of a

university section on Alzheimers, Dementia, Memory, etc. in either

Arizona or New Mexico. I've had the article for several years.

Then I noticed also that Dr. Perlmutter (neurologist of some esteem)

also had mentioned it favorably.

I began taking the PSerine in Jan 2004 as I knew I had

hypercoagulation and I also knew I had had what seemed like not too

good circulation in my head which was noticeable at certain times,

and my memory seemed to have worsened. I have used other

recommended supplements to help with the hypercoagulation. (Because

I had been on liquid flaxseed oil therapy for several years when the

Hemex tests were done, my physician said that was the reason that

one of the four tests are within normal range. Otherwise, he told

me, all of them would have been bad. This was 2-3 years ago. (By

the way, flaxseed oil is one of the recommended Omega 3's in the

Detoxx protocols, I later learned.)

I felt worse all the time, even after I had begun the PS -- was

thinking it was my condition just naturally worsening, and didn't

associate it with the PS. About 4 months later and feeling worse,

my physician had

many tests drawn to see what was going on. At a second visit

they tried to drawn 3 vials of blood for a Killer Cell Test and my

blood literally would not come out; it took 3 draws to accomplish

this. This was a startling thing, as

usually I had not had this problem in spite of the

hypercoagulation.

Just a couple of days later, I decided that I needed to read " The

Detoxx Book Physicians Guide " which I had ordered, as it appeared I

had a really big problem and puzzle to solve. I was amazed to read

a chapter or so into the book that Phosphatidylserine was not

recommended as it was considered a coagulant! Imagine that! And my

taking it for 4 months. I did a search on PS and these attributes,

and what I found was that for some people with Anti-Phospholipid

Antibody problems it can have a negative effect. (I'm afraid to

leave this post to find the article now, as I'm on the Group site

and I'll lose it. But will post the information on this if anyone

is interested.)

Naturally, I got off of the PS immediately. After studying the

problem, it appeared a quality Gingko Biloba product was in order,

and the Enzymatic Therapy brand was the one I chose, and I take one

three times a day. I'm not back to where I want to be, of course,

but I am doing better than I was when I was on the PS. There is no

warning on the PS bottle. I called the 800 listed on the bottle to

suggest this be looked into and a warning posted. They were

defensive; so guess that won't go anywhere. I also sent an e-mail

to a contact on Dr. Perlmutter's site (he recommends PS) to make him

aware of my experience and to get his feedback, but have not heard

anything. I was not making anyone responsible for anything, just

wanted a warning for others who might take this product and be

harmed. (And I certainly don't want the FDA getting involved in our

right to purchase supplements.)

Phosphatidylcholine (PC) on the other hand is considered very

helpful in detoxing the liver of sludge and other toxins/neurotoxins

that have built up and helping the body function better. Add Lipid

Replacement Therapy to this and the cells and membranes and brain

are restored -- that's what the Detoxx literature says (search

for " The Detoxx System " on www.mercola.com), as well as the book I

mentioned above, as well as many who are receiving this therapy.

The book and other articles I've read state that IV PhosChol

followed by Fast IV Push of Glutathione are very effective, along

with appropriate diet changes and Lipid Replacement; however, an

oral program using PhosChol supplements, Butyrex, and the lipid

replacement, and other helpful protocols listed in the book will

also get the job done, albeit just takes longer.

Hope this will be of help to you.

bg

>

> > Mr. Graham,

> >

> > I thought PS (PhosphatidylSerine) lowers cortisol.

>

> gayu, I asked Rich this question but I didn't get a reply and

maybe

> you know. I take lecithin for the Phosphatidyline, is this PS good

or

> bad for PWC's?

>

> Bob H.