Re: Glutathione depletion--methylation block model and sleep problems

[Guest guest]

Rich

I concur 100%. But, I think it also requires enough quality sunlight to

reset the circadian, .rhythm, and maybe also some vitamin D.

Also, the trick for some may be finding the right types and amounts of folic

acid, B6 and B12 to do the job.

mjh

" The Basil Book "

_http://foxhillfarm.us/FireBasil/_ (http://foxhillfarm.us/FireBasil/)

My current view is that it is most likely caused by the disorder in

the serotonin/melatonin metabolism that accompanies a block in the

methylation cycle and problems in the biopterin cycle (which is

linked to the methylation cycle via the folate metabolism).

[Guest guest]

I definitely had a big improvement in my sleep patterns when i started

taking SAMe. That was the best sleep improvment I had seen with any

supplement, although I did also see benefits when taking 5-HTP.

But I find that if I take 200 mg SAMe every day, that I don't really

need to take supplemental 5-HTP.

I have mold-related fatigue.. but at this point, I also get it when I

go into big stores with lots of plastic, so I guess I also have MCS..

I lived in a building that had serious stachy for ten years..

[Guest guest]

Rich, I intuitively disagree with you here or believe it is not the

whole picture.

I think it is a gaba/glutamate problem primarily, and there may be a

skewing of cortisol cycles as well. I think Cheney was right when he

said that klonipin/benzos indirectly quieted the NDMA upregulation in CFS.

I think it is an excitotoxin problem and an excess of glutamate. It's

a wired/tired feeling often accompanied by actual buzzing/vibrating

sensations. I think some of the neuropathies are tied in this way too.

>

> Hi, all.

>

> As you know, one of the aspects of CFS that is most distressing and

> debilitating is the problem of not being able to get a good night's

> sleep. Any valid, comprehensive hypothesis for the pathophysiology

> of CFS must explain what causes this.

>

> My current view is that it is most likely caused by the disorder in

> the serotonin/melatonin metabolism that accompanies a block in the

> methylation cycle and problems in the biopterin cycle (which is

> linked to the methylation cycle via the folate metabolism).

>

> It is known that serotonin (which requires BH4 for its synthesis)

> and melatonin (which is produced from serotonin by a reaction that

> involves methylation) are important for falling asleep and staying

> asleep, so I think that disruption in the serotonin/melatonin

> metabolism is most likely the cause of the sleep problems in CFS,

> and that these problems should resolve when the blocks are removed

> by targeted nutritional supplements, based on a knowledge of the

> genetic polymorphisms in the enzymes impacting the methylation cycle.

>

> Rich

>

[Guest guest]

rvankonynen wrote:

.....I think that disruption in the serotonin/melatonin

> metabolism is most likely the cause of the sleep problems in CFS,

> and that these problems should resolve when the blocks are removed

> by targeted nutritional supplements, based on a knowledge of the

> genetic polymorphisms in the enzymes impacting the methylation cycle.

>

Rich, what would be the targeted nutritional supplements you would

suggest. I'm taking one clonazepam 0.5mg plus one melatonin [3mg]

each night, but I would like to ease off of the clonazepam and use

something else. I'm considering GABA, but maybe there is something

better that you or someone else in the group would suggest. In the

past couple months I have developed daily hand and arm tremors and I

suspect the clonazapam may have something to do with that. I've been

taking it for many years. Maybe my liver can't process it anymore and

it's beginning to affect my nervous system, but I feel as though

tapering off of it may be a good idea. I've had sleep problems

since infancy.

Sandy

[Guest guest]

I just read the Nutritional Support program for Sleep on Dr. Yasko's

website, so I'm assuming that this is the answer to my question

below. For anyone who hasn't seen this page of nutritional programs,

here is the link - click TWICE on each program list to make it

larger.

http://www.holistichealth.com/Programs.html

" Olson " wrote:

> rvankonynen wrote:

> ....I think that disruption in the serotonin/melatonin

> > metabolism is most likely the cause of the sleep problems in

CFS, and that these problems should resolve when the blocks are

removed by targeted nutritional supplements, based on a knowledge of

the genetic polymorphisms in the enzymes impacting the methylation

cycle.

> >

>

> Rich, what would be the targeted nutritional supplements you would

> suggest. I'm taking one clonazepam 0.5mg plus one melatonin [3mg]

> each night, but I would like to ease off of the clonazepam and use

> something else. I'm considering GABA, but maybe there is something

> better that you or someone else in the group would suggest. In the

> past couple months I have developed daily hand and arm tremors and

I

> suspect the clonazapam may have something to do with that. I've

been

> taking it for many years. Maybe my liver can't process it anymore

and

> it's beginning to affect my nervous system, but I feel as though

> tapering off of it may be a good idea. I've had sleep problems

> since infancy.

>

> Sandy

>

[Guest guest]

Hi, Jill.

Thanks for sharing your views. You may be right. I wonder if a

serotonin/melatonin problem could end up giving rise to a

gaba/glutamate problem. I know that Amy Yasko emphasizes dealing with

gaba/glutamate in the first step of her treatment.

I need to learn more about how these things might be tied together. I

know about Cheney's seizure--coma continuum and his argument for

Klonopin. But this may be treating the problem downstream of its

actual biochemical cause.

Rich

>

> Rich, I intuitively disagree with you here or believe it is not the

> whole picture.

>

> I think it is a gaba/glutamate problem primarily, and there may be a

> skewing of cortisol cycles as well. I think Cheney was right when he

> said that klonipin/benzos indirectly quieted the NDMA upregulation

in CFS.

> I think it is an excitotoxin problem and an excess of glutamate. It's

> a wired/tired feeling often accompanied by actual buzzing/vibrating

> sensations. I think some of the neuropathies are tied in this way

too.

[Guest guest]

Yes, I agree, Cheney (and myself with my sleeping pill) are treating

the problem downstream. Of all the things I've intuitively done so far

(magnesium IV, heavy doses of decaffeinated green tea daily [thus,

Yasko's theanine], unsweetened chocolate [flavanoids that I suspect

are anti inflammatory, plus recent research shows are very good for

blood vessel function]) etc etc, the one thing I do with some regret

is take a benzo, and I'm going to try and reduce it soon by water

titration method. However, I have felt that given a bad situation

(lyme) and not knowing a better solution at the moment, that I was

limiting excitotoxin damage. But I do agree its downstream (the

gaba/glutamate).

I'm on DVD #7 now, stress...she just explained the SAH connection with

stress and SAH being antiviral, so fascinating. She is connecting dots

nobody ever connected.

> >

> > Rich, I intuitively disagree with you here or believe it is not the

> > whole picture.

> >

> > I think it is a gaba/glutamate problem primarily, and there may be a

> > skewing of cortisol cycles as well. I think Cheney was right when he

> > said that klonipin/benzos indirectly quieted the NDMA upregulation

> in CFS.

> > I think it is an excitotoxin problem and an excess of glutamate. It's

> > a wired/tired feeling often accompanied by actual buzzing/vibrating

> > sensations. I think some of the neuropathies are tied in this way

> too.

>

[Guest guest]

Hi, Sandy.

I'm sorry about the tremors.

In order to choose the netritional supplements by other than a trial-

and-error approach, it's necessary to know what genetic

polymorphisms you have. Unfortunately, the test for them costs $750

plus shipping (from www.testing4health.com), and more if you order

the analysis report. I think that's the only way to know which

supplements to use, and what the sequence of steps should be.

Having certain genetic polymorphisms might explain why you have had

sleep problems since infancy.

Rich

> Rich, what would be the targeted nutritional supplements you would

> suggest. I'm taking one clonazepam 0.5mg plus one melatonin [3mg]

> each night, but I would like to ease off of the clonazepam and use

> something else. I'm considering GABA, but maybe there is something

> better that you or someone else in the group would suggest. In the

> past couple months I have developed daily hand and arm tremors and

I

> suspect the clonazapam may have something to do with that. I've

been

> taking it for many years. Maybe my liver can't process it anymore

and

> it's beginning to affect my nervous system, but I feel as though

> tapering off of it may be a good idea. I've had sleep problems

> since infancy.

>

> Sandy

>

[Guest guest]

Hi, Sandy.

O.K., I just read the Sleep page (Isn't that a pretty website?) and it

does look like a good thing to try in the absence of knowing the

specific polymorphisms. If you do have them characterized, I think

you can do a better job of targeting the SNPs with particular

nutrients. Also, if a person has a CBS upregulation, I'm not sure

that this general sleep approach would work. So I think it's a

compromise that will work for a lot of people, but probably not all.

Rich

>

> I just read the Nutritional Support program for Sleep on Dr. Yasko's

> website, so I'm assuming that this is the answer to my question

> below. For anyone who hasn't seen this page of nutritional programs,

> here is the link - click TWICE on each program list to make it

> larger.

>

> http://www.holistichealth.com/Programs.html

>

>

[Guest guest]

Hi, Jill and Rich.

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

>

> Hi, Jill.

>

> Thanks for sharing your views. You may be right. I wonder if a

> serotonin/melatonin problem could end up giving rise to a

> gaba/glutamate problem.

***I recall looking at a lot of pubmed articles on glutamates role in the brain

and when it gets upregulated. What I learned is glutamate is the most abundant

neurotransmitter of them all, it is excititory/stimulating and gets upregulated

upon trauma by blunt force, neurotoxic exposure, ischemia as happens with

stroke, and according to Dr Goldenstein in his book, Betral of the Brain, is

upregulated in CFS.

***I learned that increased glutamate necessarily means that gaba output is

down. It's also interesting I found that glutamate activity goes up when

glutathione is down, so perhaps this is the connection to your hypthesis for

CFS, Rich?

***Also, most glutamate activity happens on the right side of the brain and I

suspect because of the larger/overlapping neurons(demanding more of everything)

compared to the left side most of the glutathione needed by the brain happens to

be on the right side as well, which seems to connect to the abnormalright side

hippocampus readings found by MRS in PWCs by Cheney and others.

I know that Amy Yasko emphasizes dealing with

> gaba/glutamate in the first step of her treatment.

>

> I need to learn more about how these things might be tied together. I

> know about Cheney's seizure--coma continuum and his argument for

> Klonopin. But this may be treating the problem downstream of its

> actual biochemical cause.

***I know he agrees with this. He has seen the use of Klonopin as a short term

way to hold down brain cell death until the cause of such a shift toward seizure

in PWCs is clarified.

> Rich

" jill1313 " <jenbooks13@>

> wrote:

I think it is a gaba/glutamate problem primarily, and there may be a

skewing of cortisol cycles as well.

I think Cheney was right when he

said that klonipin/benzos indirectly quieted the NDMA upregulation

in CFS. I think it is an excitotoxin problem and an excess of glutamate. It's a

wired/tired feeling often accompanied by actual buzzing/vibrating

sensations.

***I had this feeling disappear once for literally one day in 20 years of

treatments and though not reproduced since it happened, it was a great

experience of true " normal " . My sleep was perfect this one time and this

experience has convinced me that once the silencing of excitotoxicity in the

brain is mastered, down goes the house of CFIDS permanently!

***Consistent great sleep over days/weeks/months, feeling sustainably

" normal " (for the individual) most of the time, and no worsening of symptoms as a

result of exertion(physical or mental) are the key three elements needed to be

in place to genuinely declare " I'm cured " by the PWC. Actually, I think if the

sleep issue goes, the other two will be a natural by product, making the sleep

issue the real final tipping point out of the CFS hole!

[Guest guest]

Rich,

This is good to know, that there could be a glutathione depletion link

to the sleep problems we have. However, having worked through an 8 year

dependency on drugs for sleep, and solved that personally without yet

correcting my methylation cycle problems, I believe there are other

major, significant factors involved in the sleep problems of PWC. In my

case at least I believe that a disruption in my parasympathetic

responses was the culprit, probably from biotoxins (Lyme, or whatever).

I had to completely re-train my body to sleep, learning how to relax and

fall asleep through the pains and discomforts of CFS/Lyme. I believe

the cause for this disorder in the subset of PWC like myself, is

multi-factorial. In my case I believe that because the sleep response

was learned in early childhood, and because my PWC brain now operates

under different parameters, that old learned response of self-settling

and falling asleep simply can not work. The thresholds have changed.

But that can be re-set, and re-learned, through subconscious

re-programing (I used a type of NLP, and also I believe salt/c helped).

There are still nights when sleep fails, usually around the full moon

(high parasite activity and thus high biotoxin loads), so I do still

need some help on occasion, but most of the time I now sleep quite

naturally. And this was a major personal victory as severe insomnia was

one of my primary early CFS pathologies. I believe in fact that

insomnia probably helped to put me into the vicious circle you talk

about. But that was corrected without fixing the methylation cycle.

--Kurt

Glutathione depletion--methylation block

model and sleep problems

Hi, all.

As you know, one of the aspects of CFS that is most distressing and

debilitating is the problem of not being able to get a good night's

sleep. Any valid, comprehensive hypothesis for the pathophysiology

of CFS must explain what causes this.

My current view is that it is most likely caused by the disorder in

the serotonin/melatonin metabolism that accompanies a block in the

methylation cycle and problems in the biopterin cycle (which is

linked to the methylation cycle via the folate metabolism).

It is known that serotonin (which requires BH4 for its synthesis)

and melatonin (which is produced from serotonin by a reaction that

involves methylation) are important for falling asleep and staying

asleep, so I think that disruption in the serotonin/melatonin

metabolism is most likely the cause of the sleep problems in CFS,

and that these problems should resolve when the blocks are removed

by targeted nutritional supplements, based on a knowledge of the

genetic polymorphisms in the enzymes impacting the methylation cycle.

Rich

[Guest guest]

Hi Kurt,

Could you elaborate on this...

<<There are still nights when sleep fails, usually around the full

moon (high parasite activity and thus high biotoxin loads)>>

please? A URL? An article or something? Level of parasite activity

and biotoxin load in the body varies with the moon?

Thanks ahead of time, again.

in Champaign IL

>

> Rich,

> This is good to know, that there could be a glutathione depletion

link

> to the sleep problems we have. However, having worked through an 8

year

> dependency on drugs for sleep, and solved that personally without

yet

> correcting my methylation cycle problems, I believe there are other

> major, significant factors involved in the sleep problems of PWC.

In my

> case at least I believe that a disruption in my parasympathetic

> responses was the culprit, probably from biotoxins (Lyme, or

whatever).

> I had to completely re-train my body to sleep, learning how to

relax and

> fall asleep through the pains and discomforts of CFS/Lyme. I

believe

> the cause for this disorder in the subset of PWC like myself, is

> multi-factorial. In my case I believe that because the sleep

response

> was learned in early childhood, and because my PWC brain now

operates

> under different parameters, that old learned response of self-

settling

> and falling asleep simply can not work. The thresholds have

changed.

> But that can be re-set, and re-learned, through subconscious

> re-programing (I used a type of NLP, and also I believe salt/c

helped).

> There are still nights when sleep fails, usually around the full

moon

> (high parasite activity and thus high biotoxin loads), so I do still

> need some help on occasion, but most of the time I now sleep quite

> naturally. And this was a major personal victory as severe

insomnia was

> one of my primary early CFS pathologies. I believe in fact that

> insomnia probably helped to put me into the vicious circle you talk

> about. But that was corrected without fixing the methylation cycle.

> --Kurt

>

>

[Guest guest]

,

That URL truncated, so here is the abstract from that study.

--Kurt

Sleepless night, the moon is bright: longitudinal study of lunar phase

and sleep.

Roosli, Juni, Braun-Fahrlander, Brinkhof, Low, Egger

Department of Social and Preventive Medicine, University of Berne,

Berne, Switzerland. roeoesli@...

Popular belief holds that the lunar cycle affects human physiology,

behaviour and health. We examined the influence of moon phase on sleep

duration in a secondary analysis of a feasibility study of mobile

telephone base stations and sleep quality. We studied 31 volunteers (18

women and 13 men, mean age 50 years) from a suburban area of Switzerland

longitudinally over 6 weeks, including two full moons. Subjective sleep

duration was calculated from sleep diary data. Data were analysed using

multiple linear regression models with random effects. Mean sleep

duration was 6 h 49 min. Subjective sleep duration varied with the lunar

cycle, from 6 h 41 min at full moon to 7 h 00 min at new moon (P <

0.001). Average sleep duration was shortened by 68 min during the week

compared with weekends (P < 0.001). Men slept 17 min longer than women

(P < 0.001) and sleep duration decreased with age (P < 0.001). There was

also evidence that rating of fatigue in the morning was associated with

moon phase, with more tiredness (P = 0.027) at full moon. The study was

designed for other purposes and the association between lunar cycle and

sleep duration will need to be confirmed in further studies.

PMID: 16704569 [PubMed - in process]

[Guest guest]

Hi Kurt,

Thank you. I will look at this further.

I'm not sure what the " left-brained " reference means. My head's more

like Swiss cheese lately, so I've forgotten what constitutes left vs.

right brain types of things. My inadequacy again, I'm afraid--I'm

sorry. I feel like somewhere along the way, someone came along and

ripped up all my road maps and left me with only the pieces to put

back together again--but sans any Scotch tape. Sigh.

I have always heard the general global statements made about suicides

and psychiatric events increasing during the full moon, so your

statement about the elevation in toxins during this time jumped out

at me, and I wondered if there was any correlation.

Thanks again for the further info, Kurt.

>

> Hi ,

>

> I had to smile a bit posting that comment to this very left-brained

> list, knew someone would comment. I would estimate that on health

lists

> I subscribe to I have read over 100 posts affirming that people

have had

> insomnia after weeks of sleeping fine, then checked the moon and

sure

> enough it was a full moon. So this is a very clinical observation.

>

> My wife formerly was a Med Tech at a hospital and she worked many

late

> shifts. She commented that the ER was almost always full on a full

> moon, and that this is well known in some ERs. People just seem

more

> agitated and have more health problems in general on a full moon.

But

> some studies have shown that this more a matter of expectation

creating

> a correlation and in fact there is not more ER activity. Maybe it

is

> just the intensity level of the people in the ER during a full moon

that

> is noticeable, hard to say. Studies often miss important details

like

> that, and yet still they make sweeping conclusions (that can later

be

> proven to be embarrassingly wrong).

>

> As far as parasite activity being the explanation, the Borrelia

bacteria

> has a well-known 30 day cycle of activity. People on abx or on

strong

> natural therapies like salt/c seem to have herx-type effects

> approximately every 30 days. This also matches the lunar cycle in

many

> cases.

>

> Is there science behind this? I believe so, but this is a complex

> systemic effect, and right now medical science is very mired in

> reductionistic, patent-medicine-producing research, and there is not

> much data. Here is what I did find, a PubMed-indexed study showing

that

> yes, we get less sleep when there is a full moon:

>

> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed

> <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

db=pubmed & cmd=Retrieve & do

> pt=AbstractPlus & list_uids=16704569 & query_hl=1 & itool=pubmed_docsum>

>

& cmd=Retrieve & dopt=AbstractPlus & list_uids=16704569 & query_hl=1 & itool=pu

bm

> ed_docsum

>

> And an interesting opinion URL with a few speculations about the

reasons

> for this effect:

>

> http://theunexplainedworld.com/afullmoon.htm

>

> There are also many studies showing that there is no effect on

various

> health problems from a full moon and I am sure that is correct in

some

> cases. For instance, one study that I read showed that there are

not

> more epileptic seizures on a full moon. And even Dr. Weil says

there is

> no effect. But I do not believe you can disprove something like

this

> because there may be limited effects, for instance, a certain type

of

> bacteria in a person with certain susceptibilities, and studies may

have

> a hard time ferreting that out.

>

> This was not something I went looking for, just an wierd coincidence

> that has emerged, and experientially I know that there is something

to

> this. Just a curiosity really though, not much one can do except to

> take extra measures to sleep when we notice the full moon, maybe an

> extra Chamomille tea at night, etc.

>

> --Kurt

[Guest guest]

Thanx, Kurt...appreciate it.

>

> ,

> That URL truncated, so here is the abstract from that study.

> --Kurt

[Guest guest]

Thanx, Edy. I appreciate the Scotch tape help!

>

> left brained=logical, mathmatical etc. Right-brained=artistic,

creative. Both is a good combo.

>