Re: Glutathione/methylation/monoamine metabolism.

[Guest guest]

Hi, Blake.

Thanks for this response. I'm going to ponder it when I've had some

sleep. It may take me a while to get back to you, as I'm leaving

for Baja in the morning, and it's past midnight here, now. It

sounds interesting, though.

Rich

>

> >Hi, Blake.

> >

> >Thanks for the comments.

> >

> >I was aware that Dr. Perlmutter has had good success using

> >I.V. glutathione for Parkinson's, but I didn't know that he had

> >figured out the mechanism to explain it. I guess I should read

his

> >book.

> >

> >The evidence on serotonin activity in CFS is indirect.

> >The urls for the papers I was referring to are as follows:

> >

> >http://www.findarticles.com/p/articles/mi_m0FDN/is_1_6/ai_71948209

> >

> >and

> >

>

>http://www.findarticles.com/cf_0/m0ISW/2001_Nov/79757264/print.jhtml

> >

> >I don't know if one could get direct evidence about serotonin

> >activity in the brain without doing a brain biopsy. Probably

hard

> >to get volunteers!

> >

> >That's a good point about the SAMe. I think that people who are

> >depleted in glutathione are also low in SAMe. The reason I think

> >that is that I read somewhere that the enzyme methionine

> >adenosyltransferase, which converts methionine to SAMe in the

liver,

> >has cysteine residues in it. If the glutathione level in the

liver

> >drops too low, these residues oxidize to cystine, and the enzyme

is

> >inhibited. Thus, these people are not able to use methionine to

> >make SAMe (or cysteine or glutathione, which are farther along

the

> >methylation-transulfuration pathway) very well, as normal,

healthy

> >people do. This really cuts down on their ability to get

cysteine

> >to make glutathione, so it constitutes another vicious circle

that

> >goes on when glutathione gets too low. I think this is one of

the

> >reasons why people who have serious glutathione depletion must

> >ingest cysteine, either as nondenatured whey protein, which has

> >cysteine residues, or as N-acetylcysteine in order to climb back

out

> >of this hole. Once their glutathione status improves, they can

> >start using methionine to make SAMe and glutathione again, and

that

> >should really help.

> >

> >In a normal, healthy person, essentially all the methionine

> >eventually goes this route, but in people with severe glutathione

> >depletion, I think this route is blocked. I haven't checked, but

it

> >would seem that methionine would build up in these people.

> >

> >Taking SAMe would probably help mood in these cases. Thanks for

> >raising the subject of SAMe.

> >

> >Rich

> >

> >

[Guest guest]

Rich,

Ideal would be cerebro-spinal fluid neurotransmitter studies (which can

be done although is very invasive) of CFS patients. Some research in the

last few years has indicated that platelet monamine levels correlate

closely with CSF levels and obviously are a lot less invasive. This test

is offered by some U.S. labs and is used by some in the nutritional

mental health field. I was under the impression that some studies have

shown small benefits of SSRI's in CFS which would be inconsistent with

the elevated serotonin theory. I have not really looked into this

research myself, do you know?

I recall one of the papers by the Newcastle, Australian CFS research

group, documented elevated urinary methionine excretion in ~11/20 of

subjects tested. Maybe this is due to the mechanism described.

Interestingly magnesium (often deficient in CFS/FMS) is needed to

convert methionine into SAMe. If methylation is disturbed in CFS this

could be a significant part of it process as methylation is required for

glutathione synthesis, lecithin synthesis, neurotransmitter synthesis,

melatonin synthesis, DNA/RNA metabolism - gene expression, histamine

breakdown, some aspects of endocrine metabolism, liver detoxification.

Looking back at this past sentence, many of these things are already

known to be abnormal in CFS, maybe we have stumbled onto something

important? SAMe has tested positively with FMS although I don't believe

it has been tested with CFS.

Regards, Blake

rvankonynen wrote:

>Hi, Blake.

>

>Thanks for the comments.

>

>I was aware that Dr. Perlmutter has had good success using

>I.V. glutathione for Parkinson's, but I didn't know that he had

>figured out the mechanism to explain it. I guess I should read his

>book.

>

>The evidence on serotonin activity in CFS is indirect.

>The urls for the papers I was referring to are as follows:

>

>http://www.findarticles.com/p/articles/mi_m0FDN/is_1_6/ai_71948209

>

>and

>

>http://www.findarticles.com/cf_0/m0ISW/2001_Nov/79757264/print.jhtml

>

>I don't know if one could get direct evidence about serotonin

>activity in the brain without doing a brain biopsy. Probably hard

>to get volunteers!

>

>That's a good point about the SAMe. I think that people who are

>depleted in glutathione are also low in SAMe. The reason I think

>that is that I read somewhere that the enzyme methionine

>adenosyltransferase, which converts methionine to SAMe in the liver,

>has cysteine residues in it. If the glutathione level in the liver

>drops too low, these residues oxidize to cystine, and the enzyme is

>inhibited. Thus, these people are not able to use methionine to

>make SAMe (or cysteine or glutathione, which are farther along the

>methylation-transulfuration pathway) very well, as normal, healthy

>people do. This really cuts down on their ability to get cysteine

>to make glutathione, so it constitutes another vicious circle that

>goes on when glutathione gets too low. I think this is one of the

>reasons why people who have serious glutathione depletion must

>ingest cysteine, either as nondenatured whey protein, which has

>cysteine residues, or as N-acetylcysteine in order to climb back out

>of this hole. Once their glutathione status improves, they can

>start using methionine to make SAMe and glutathione again, and that

>should really help.

>

>In a normal, healthy person, essentially all the methionine

>eventually goes this route, but in people with severe glutathione

>depletion, I think this route is blocked. I haven't checked, but it

>would seem that methionine would build up in these people.

>

>Taking SAMe would probably help mood in these cases. Thanks for

>raising the subject of SAMe.

>

>Rich

>

>

[Guest guest]

Hi, Blake (and the group).

I'm back from Baja, and had a great time. Glad to see that things

are still perking along on the list!

Getting back to the things we were talking about, Blake, I wasn't

aware of the platelet monoamine analyses. That sounds like a much

better approach than brain biopsy!

As far as I know, the SSRIs have not been helpful for most PWCs. I

see that Dr. Teitelbaum has some of them on his treatment protocol

list under the category " Antidepressants-helps pain & brain fog-even

if not depressed, " but most of the PWCs I've heard from have not

found them to help.

Thanks for the info on methionine secretion from the U. of Newcastle

group. I hadn't remembered that. That would be consistent with

inhibition of methionine adenosyltransferase.

I agree that low SAMe levels could be important in CFS. You're

right, there hasn't been a published study of SAMe supplementation

in CFS, though there have been several in FM that showed good

results. In Chapter 27 of the Handbook of Chronic Fatigue Syndrome,

p. 635, I summarized the SAMe section by writing, " There appears to

be good evidence that SAMe is useful in the treatment of FM. It

should also be tested for CFS. " In Table 27.1 (pp. 592-593), I

suggested 200 mg IM/day and 400 mg orally, 2 times per day, for a 6-

week trial, based on the FM work.

Probably the Italians would be the ones most motivated to do such a

test, since they control the supply of high-quality SAMe. Three of

the four studies in FM that I reviewed were Italian studies.

According to the latest issue of the Life Extension magazine,

recently lower quality SAMe has started coming out of India.

Rich

>

> >Hi, Blake.

> >

> >Thanks for the comments.

> >

> >I was aware that Dr. Perlmutter has had good success using

> >I.V. glutathione for Parkinson's, but I didn't know that he had

> >figured out the mechanism to explain it. I guess I should read

his

> >book.

> >

> >The evidence on serotonin activity in CFS is indirect.

> >The urls for the papers I was referring to are as follows:

> >

> >http://www.findarticles.com/p/articles/mi_m0FDN/is_1_6/ai_71948209

> >

> >and

> >

>

>http://www.findarticles.com/cf_0/m0ISW/2001_Nov/79757264/print.jhtml

> >

> >I don't know if one could get direct evidence about serotonin

> >activity in the brain without doing a brain biopsy. Probably

hard

> >to get volunteers!

> >

> >That's a good point about the SAMe. I think that people who are

> >depleted in glutathione are also low in SAMe. The reason I think

> >that is that I read somewhere that the enzyme methionine

> >adenosyltransferase, which converts methionine to SAMe in the

liver,

> >has cysteine residues in it. If the glutathione level in the

liver

> >drops too low, these residues oxidize to cystine, and the enzyme

is

> >inhibited. Thus, these people are not able to use methionine to

> >make SAMe (or cysteine or glutathione, which are farther along

the

> >methylation-transulfuration pathway) very well, as normal,

healthy

> >people do. This really cuts down on their ability to get

cysteine

> >to make glutathione, so it constitutes another vicious circle

that

> >goes on when glutathione gets too low. I think this is one of

the

> >reasons why people who have serious glutathione depletion must

> >ingest cysteine, either as nondenatured whey protein, which has

> >cysteine residues, or as N-acetylcysteine in order to climb back

out

> >of this hole. Once their glutathione status improves, they can

> >start using methionine to make SAMe and glutathione again, and

that

> >should really help.

> >

> >In a normal, healthy person, essentially all the methionine

> >eventually goes this route, but in people with severe glutathione

> >depletion, I think this route is blocked. I haven't checked, but

it

> >would seem that methionine would build up in these people.

> >

> >Taking SAMe would probably help mood in these cases. Thanks for

> >raising the subject of SAMe.

> >

> >Rich

> >

> >

[Guest guest]

Hi Rich,

The trial idea sounds good. Dr. Walsh writes in relation to

depression, after a 2 week trial of SAMe most people will know if it's

doing them good or harm. He also writes that monomine synthesis is

largely dictated by the methyl/folate ratio - in other words excess

folate has a negative effect. Hopefully the price of SAMe will come down

in the coming years.

Blake

rvankonynen wrote:

>Hi, Blake (and the group).

>

>I'm back from Baja, and had a great time. Glad to see that things

>are still perking along on the list!

>

>Getting back to the things we were talking about, Blake, I wasn't

>aware of the platelet monoamine analyses. That sounds like a much

>better approach than brain biopsy!

>

>As far as I know, the SSRIs have not been helpful for most PWCs. I

>see that Dr. Teitelbaum has some of them on his treatment protocol

>list under the category " Antidepressants-helps pain & brain fog-even

>if not depressed, " but most of the PWCs I've heard from have not

>found them to help.

>

>Thanks for the info on methionine secretion from the U. of Newcastle

>group. I hadn't remembered that. That would be consistent with

>inhibition of methionine adenosyltransferase.

>

>I agree that low SAMe levels could be important in CFS. You're

>right, there hasn't been a published study of SAMe supplementation

>in CFS, though there have been several in FM that showed good

>results. In Chapter 27 of the Handbook of Chronic Fatigue Syndrome,

>p. 635, I summarized the SAMe section by writing, " There appears to

>be good evidence that SAMe is useful in the treatment of FM. It

>should also be tested for CFS. " In Table 27.1 (pp. 592-593), I

>suggested 200 mg IM/day and 400 mg orally, 2 times per day, for a 6-

>week trial, based on the FM work.

>

>Probably the Italians would be the ones most motivated to do such a

>test, since they control the supply of high-quality SAMe. Three of

>the four studies in FM that I reviewed were Italian studies.

>According to the latest issue of the Life Extension magazine,

>recently lower quality SAMe has started coming out of India.

>

>Rich

>