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So what exactly lowers ammonia levels? I used to know, but my brain is really

mushy

these days...I think the arginine/orthinine amino acid combo is one...

???

d

>

> HI All,

>

> If you have a CBS upregulation, NOS or SUOX +/- genetic mutation and

> you continue to use sulfur and protein, you drive up ammonia. If

> ammonia is high, then what happpens to all your methylation

> support??? What happens to MB12, SAMe and the whole list of methyl

> groups you are taking and in your body??

>

> If you have the CBS, the door is open and what should be methylation

> turns into a toxic substance, ammonia and others. So you don't

> methylate properly. If you don't methylate properly, you also don't

> detox properly. If your body is using up everything you've got to

> get rid of excess ammonia, there is nothing left for detoxing for

> methylating or RNA, DNA synthesis.

>

> And around and round we go! So your've got to get the ammonia down

> so your body will methylate. This is why genetics points to why some

> people have stayed sick when they have tried everything yet, they

> are still sick.

>

> Its a vicious cycle. Methylation helps at first, but if their is the

> CBS, NOS or SUOX mutation, methylation stopes working, then ammonia

> rises, the more methylation and glutationie for detox--the higher

> the ammonia goes as well as taurine sometimes and the sicker the

> person gets or stays. They are stuck.

>

> Janet

>

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Hi - Can you post any studies which show that the SNPs that you mention,

would actually increase serum ammonia levels? (Btw, urinary ammonia is

not a good indicator of the free ammonia in the body that could cause

damage).

Also, the SNPs you refer to are not mutations, as mutations are

considered to be rare forms of genes (i.e. <1% of the populations).

Anything more common is considered a polymorphism.

Most of the ammonia in the body, is produced by orgaisms in the

intestinal tract which breakdown protein.

Since high protein diets can greatly increase ammonia production, and

since ammonia is toxic, a normal healthy liver has the ability of

metabolizing lots of ammonia. For a good article, see:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Retrieve & dop\

t=AbstractPlus & list_uids=15494874 & query_hl=29 & itool=pubmed_DocSum

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Retrieve & do\

pt=AbstractPlus & list_uids=15494874 & query_hl=29 & itool=pubmed_DocSum>

" Ammonia, normally produced from catabolism of amino acids, is a deadly

neurotoxin. As such, the concentration of free ammonia in the blood is

very tightly regulated and is exceeded by two orders of magnitude by its

physiologic derivative, urea. The normal capacity for urea production

far exceeds the rate of free ammonia production by protein catabolism

under normal circumstances, such that any increase in free blood ammonia

concentration is a reflection of either biochemical or pharmacologic

impairment of urea cycle function or fairly extensive hepatic damage. "

You mentioned CBS. I have argued in a previous post that there is

little support for the CBS SNPs to significantly affect CBS production.

Several studies have not confirmed it. If you have know of any further

studies, please email me so that I can update my information.

Even so, CBS activity would increase production of taurine and

glutathione, both of which protect the CNS from ammonia effects. See:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Retrieve & dop\

t=AbstractPlus & list_uids=16382336 & query_hl=41 & itool=pubmed_docsum

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Retrieve & do\

pt=AbstractPlus & list_uids=16382336 & query_hl=41 & itool=pubmed_docsum>

So any extra ammonia that is produced, would be offset by these

substances. Thus, the body has several ways to protect and remove

ammonia from the body.

- Mark

>

> HI All,

>

> If you have a CBS upregulation, NOS or SUOX +/- genetic mutation and

> you continue to use sulfur and protein, you drive up ammonia. If

> ammonia is high, then what happpens to all your methylation

> support??? What happens to MB12, SAMe and the whole list of methyl

> groups you are taking and in your body??

>

> If you have the CBS, the door is open and what should be methylation

> turns into a toxic substance, ammonia and others. So you don't

> methylate properly. If you don't methylate properly, you also don't

> detox properly. If your body is using up everything you've got to

> get rid of excess ammonia, there is nothing left for detoxing for

> methylating or RNA, DNA synthesis.

>

> And around and round we go! So your've got to get the ammonia down

> so your body will methylate. This is why genetics points to why some

> people have stayed sick when they have tried everything yet, they

> are still sick.

>

> Its a vicious cycle. Methylation helps at first, but if their is the

> CBS, NOS or SUOX mutation, methylation stopes working, then ammonia

> rises, the more methylation and glutationie for detox--the higher

> the ammonia goes as well as taurine sometimes and the sicker the

> person gets or stays. They are stuck.

>

> Janet

>

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So, in laymans terms, you're saying that ammonia isn't a problem?

> >

> > HI All,

> >

> > If you have a CBS upregulation, NOS or SUOX +/- genetic mutation and

> > you continue to use sulfur and protein, you drive up ammonia. If

> > ammonia is high, then what happpens to all your methylation

> > support??? What happens to MB12, SAMe and the whole list of methyl

> > groups you are taking and in your body??

> >

> > If you have the CBS, the door is open and what should be methylation

> > turns into a toxic substance, ammonia and others. So you don't

> > methylate properly. If you don't methylate properly, you also don't

> > detox properly. If your body is using up everything you've got to

> > get rid of excess ammonia, there is nothing left for detoxing for

> > methylating or RNA, DNA synthesis.

> >

> > And around and round we go! So your've got to get the ammonia down

> > so your body will methylate. This is why genetics points to why some

> > people have stayed sick when they have tried everything yet, they

> > are still sick.

> >

> > Its a vicious cycle. Methylation helps at first, but if their is the

> > CBS, NOS or SUOX mutation, methylation stopes working, then ammonia

> > rises, the more methylation and glutationie for detox--the higher

> > the ammonia goes as well as taurine sometimes and the sicker the

> > person gets or stays. They are stuck.

> >

> > Janet

> >

>

>

>

>

>

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I don't see how taking MB12 would cause a methylation substance to turn

into a toxic substance. MB12 should initially pull homocysteine away

from the transulfuration cycle which may have otherwise gone down it.

It may eventually go down the transulfuration cycle eventually but

taking MB12 should delay it. I can see SAMe being a problem. I know

Dr. Yasko has said taking B12, folic, SAMe etc will cause more

intermediates to go through the transulfuraiton pathway but I would

think only new intermediates added would do that.

HI All,

If you have a CBS upregulation, NOS or SUOX +/- genetic mutation and

you continue to use sulfur and protein, you drive up ammonia. If

ammonia is high, then what happpens to all your methylation

support??? What happens to MB12, SAMe and the whole list of methyl

groups you are taking and in your body??

If you have the CBS, the door is open and what should be methylation

turns into a toxic substance, ammonia and others. So you don't

methylate properly. If you don't methylate properly, you also don't

detox properly. If your body is using up everything you've got to

get rid of excess ammonia, there is nothing left for detoxing for

methylating or RNA, DNA synthesis.

And around and round we go! So your've got to get the ammonia down

so your body will methylate. This is why genetics points to why some

people have stayed sick when they have tried everything yet, they

are still sick.

Its a vicious cycle. Methylation helps at first, but if their is the

CBS, NOS or SUOX mutation, methylation stopes working, then ammonia

rises, the more methylation and glutationie for detox--the higher

the ammonia goes as well as taurine sometimes and the sicker the

person gets or stays. They are stuck.

Janet

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Mark, you submit these questions in a form that suits you for Rich to

ask Amy at the end of October. Those individuals who are ill and

studying her program are not going to give you answers, I don't think.

> >

> > HI All,

> >

> > If you have a CBS upregulation, NOS or SUOX +/- genetic mutation and

> > you continue to use sulfur and protein, you drive up ammonia. If

> > ammonia is high, then what happpens to all your methylation

> > support??? What happens to MB12, SAMe and the whole list of methyl

> > groups you are taking and in your body??

> >

> > If you have the CBS, the door is open and what should be methylation

> > turns into a toxic substance, ammonia and others. So you don't

> > methylate properly. If you don't methylate properly, you also don't

> > detox properly. If your body is using up everything you've got to

> > get rid of excess ammonia, there is nothing left for detoxing for

> > methylating or RNA, DNA synthesis.

> >

> > And around and round we go! So your've got to get the ammonia down

> > so your body will methylate. This is why genetics points to why some

> > people have stayed sick when they have tried everything yet, they

> > are still sick.

> >

> > Its a vicious cycle. Methylation helps at first, but if their is the

> > CBS, NOS or SUOX mutation, methylation stopes working, then ammonia

> > rises, the more methylation and glutationie for detox--the higher

> > the ammonia goes as well as taurine sometimes and the sicker the

> > person gets or stays. They are stuck.

> >

> > Janet

> >

>

>

>

>

>

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Jill,

If someone instructs the list about something so specific and detailed, and

someone else asks questions, maybe the poster would like to answer.

Katrina

> > >

> > > HI All,

> > >

> > > If you have a CBS upregulation, NOS or SUOX +/- genetic mutation and

> > > you continue to use sulfur and protein, you drive up ammonia. If

> > > ammonia is high, then what happpens to all your methylation

> > > support??? What happens to MB12, SAMe and the whole list of methyl

> > > groups you are taking and in your body??

> > >

> > > If you have the CBS, the door is open and what should be methylation

> > > turns into a toxic substance, ammonia and others. So you don't

> > > methylate properly. If you don't methylate properly, you also don't

> > > detox properly. If your body is using up everything you've got to

> > > get rid of excess ammonia, there is nothing left for detoxing for

> > > methylating or RNA, DNA synthesis.

> > >

> > > And around and round we go! So your've got to get the ammonia down

> > > so your body will methylate. This is why genetics points to why some

> > > people have stayed sick when they have tried everything yet, they

> > > are still sick.

> > >

> > > Its a vicious cycle. Methylation helps at first, but if their is the

> > > CBS, NOS or SUOX mutation, methylation stopes working, then ammonia

> > > rises, the more methylation and glutationie for detox--the higher

> > > the ammonia goes as well as taurine sometimes and the sicker the

> > > person gets or stays. They are stuck.

> > >

> > > Janet

> > >

> >

> >

> >

> >

> >

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Katrina, maybe I would like to state my opinion, which I did. He

should form the question for Rich to ask Amy, who is the source of

this information. Last time he posted on similar issues regarding CBS

upregulation etc, and concluded that the data were sparse for the

conclusions being drawn although the supplements themselves might be

helpful, there were no answers of any substance, at least that I recall.

>

>

> Jill,

>

> If someone instructs the list about something so specific and

detailed, and someone else asks questions, maybe the poster would like

to answer.

>

> Katrina

>

>

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Hi, .

There's a lot I don't understand about this yet, and I haven't had

time to do a good job of studying it yet because of a load of other

stuff I need to do now, but I think the key to this is that the

methylation cycle has both a feed and a drain. The feed is at

methionine. If the cycle is blocked, I think it's difficult for more

methionine to come into it, so then there is less homocysteine

available to go down the transsulfuration pathway. On the other hand,

if methionine synthase is functioning normally and the cycle is

unblocked, then more methionine can enter the cycle, and more

homocysteine can go down the transsulfuration pathway. The operation

of methionine synthase is rather complex. I wouldn't be surprised if

it cooperates in some way with the CBS enzyme, shuttling some

homocysteine to methionine and some to the transsulfuration pathway

when it is operating correctly. But as I say, I still have a lot to

learn about this. At this point, I'm still operating to a degree on

faith that Dr. Yasko has done correlations between the SNPs and the

biochemical testing in a lot of autistic kids, and has inferred things

from that, even though the peer-reviewed scientific literature may

still not contain the controlled research that explains the operation

of these pathways in detail. I wish I could do better than that, but

right now, I can't.

Rich

>

> I don't see how taking MB12 would cause a methylation substance to

turn

> into a toxic substance. MB12 should initially pull homocysteine away

> from the transulfuration cycle which may have otherwise gone down it.

> It may eventually go down the transulfuration cycle eventually but

> taking MB12 should delay it. I can see SAMe being a problem. I know

> Dr. Yasko has said taking B12, folic, SAMe etc will cause more

> intermediates to go through the transulfuraiton pathway but I would

> think only new intermediates added would do that.

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Hi, Mark.

I think you're raising important issues here, and I wish I could

address them satisfactorily, but right now, I can't. I do have

individual data from one person, I think, who showed both elevated

urine ammonia and elevated serum ammonia.

As I think I've suggested before, I think Dr. Yasko is making her

treatment decisions partly on the basis of her own database from a

large number of autistic children. I think she correlates findings

on the genetic panel with test results from the biochemical testing,

mostly in urine, and that is what she uses to decide what is likely

to be going on. I realize that this is somewhat unorthodox from the

scientific research point of view, and it makes it difficult for the

rest of us to check the path she has followed, but she may still be

reaching valid conclusions. There certainly seems to be a body of

autism parents who testify that her methods are working on their

kids, when other approaches failed.

I'm looking forward to what she will say at her next series of

seminars in Boston in early October. I'm not planning to attend,

but perhaps others here are, and I expect there will be DVDs. I

think she is planning to draw some conclusions from her database to

report then. I'm willing to give her some slack on the lack of

scientific research orthodoxy for now, because I think she is

basically on the right track, and so far the outcomes are sounding

good. I don't think the research has caught up yet in the areas

where we are trying to do treatment.

Rich

I note that Dr. Cheney operates in somewhat a similar fashion, and

though he isn't always right, I think he has made very important

contributions to our understanding of CFS.

-- In , " Mark London " <mrl@...>

wrote:

>

>

> Hi - Can you post any studies which show that the SNPs that you

mention,

> would actually increase serum ammonia levels? (Btw, urinary

ammonia is

> not a good indicator of the free ammonia in the body that could

cause

> damage).

>

> Also, the SNPs you refer to are not mutations, as mutations are

> considered to be rare forms of genes (i.e. <1% of the

populations).

> Anything more common is considered a polymorphism.

>

> Most of the ammonia in the body, is produced by orgaisms in the

> intestinal tract which breakdown protein.

>

> Since high protein diets can greatly increase ammonia production,

and

> since ammonia is toxic, a normal healthy liver has the ability of

> metabolizing lots of ammonia. For a good article, see:

>

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

db=pubmed & cmd=Retrieve & dop\

> t=AbstractPlus & list_uids=15494874 & query_hl=29 & itool=pubmed_DocSum

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

db=pubmed & cmd=Retrieve & do\

> pt=AbstractPlus & list_uids=15494874 & query_hl=29 & itool=pubmed_DocSum>

>

> " Ammonia, normally produced from catabolism of amino acids, is a

deadly

> neurotoxin. As such, the concentration of free ammonia in the

blood is

> very tightly regulated and is exceeded by two orders of magnitude

by its

> physiologic derivative, urea. The normal capacity for urea

production

> far exceeds the rate of free ammonia production by protein

catabolism

> under normal circumstances, such that any increase in free blood

ammonia

> concentration is a reflection of either biochemical or

pharmacologic

> impairment of urea cycle function or fairly extensive hepatic

damage. "

>

> You mentioned CBS. I have argued in a previous post that there is

> little support for the CBS SNPs to significantly affect CBS

production.

> Several studies have not confirmed it. If you have know of any

further

> studies, please email me so that I can update my information.

>

> Even so, CBS activity would increase production of taurine and

> glutathione, both of which protect the CNS from ammonia effects.

See:

>

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

db=pubmed & cmd=Retrieve & dop\

> t=AbstractPlus & list_uids=16382336 & query_hl=41 & itool=pubmed_docsum

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

db=pubmed & cmd=Retrieve & do\

> pt=AbstractPlus & list_uids=16382336 & query_hl=41 & itool=pubmed_docsum>

>

> So any extra ammonia that is produced, would be offset by these

> substances. Thus, the body has several ways to protect and remove

> ammonia from the body.

>

> - Mark

>

>

> >

> > HI All,

> >

> > If you have a CBS upregulation, NOS or SUOX +/- genetic mutation

and

> > you continue to use sulfur and protein, you drive up ammonia. If

> > ammonia is high, then what happpens to all your methylation

> > support??? What happens to MB12, SAMe and the whole list of

methyl

> > groups you are taking and in your body??

> >

> > If you have the CBS, the door is open and what should be

methylation

> > turns into a toxic substance, ammonia and others. So you don't

> > methylate properly. If you don't methylate properly, you also

don't

> > detox properly. If your body is using up everything you've got to

> > get rid of excess ammonia, there is nothing left for detoxing for

> > methylating or RNA, DNA synthesis.

> >

> > And around and round we go! So your've got to get the ammonia

down

> > so your body will methylate. This is why genetics points to why

some

> > people have stayed sick when they have tried everything yet, they

> > are still sick.

> >

> > Its a vicious cycle. Methylation helps at first, but if their is

the

> > CBS, NOS or SUOX mutation, methylation stopes working, then

ammonia

> > rises, the more methylation and glutationie for detox--the higher

> > the ammonia goes as well as taurine sometimes and the sicker the

> > person gets or stays. They are stuck.

> >

> > Janet

> >

>

>

>

>

>

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I asked the question about urinary ammonia, because I know someone

who was given just the urinary test, and not serum. That person had

elevated urinary ammonia. However, the kidneys converts certain

amino acids to ammonia. Glutamine is the most well known. " The

kidney takes up glutamine and metabolizes it to ammonia. This

process is sensitive to pH and serves to maintain acid-base

homeostasis and to excrete nitrogen. " But glycine can also produce

ammonia in the kidneys. This person that I know, just happened to

have been taking magnesium glycinate, and this could have been a

factor in the increased urinary ammonia. Thus, there are several

different factors that can may be the cause of elevated ammonia, and

is not thus not used for determining systematic elevated ammonia. -

Mark

> > >

> > > HI All,

> > >

> > > If you have a CBS upregulation, NOS or SUOX +/- genetic

mutation

> and

> > > you continue to use sulfur and protein, you drive up ammonia.

If

> > > ammonia is high, then what happpens to all your methylation

> > > support??? What happens to MB12, SAMe and the whole list of

> methyl

> > > groups you are taking and in your body??

> > >

> > > If you have the CBS, the door is open and what should be

> methylation

> > > turns into a toxic substance, ammonia and others. So you don't

> > > methylate properly. If you don't methylate properly, you also

> don't

> > > detox properly. If your body is using up everything you've got

to

> > > get rid of excess ammonia, there is nothing left for detoxing

for

> > > methylating or RNA, DNA synthesis.

> > >

> > > And around and round we go! So your've got to get the ammonia

> down

> > > so your body will methylate. This is why genetics points to

why

> some

> > > people have stayed sick when they have tried everything yet,

they

> > > are still sick.

> > >

> > > Its a vicious cycle. Methylation helps at first, but if their

is

> the

> > > CBS, NOS or SUOX mutation, methylation stopes working, then

> ammonia

> > > rises, the more methylation and glutationie for detox--the

higher

> > > the ammonia goes as well as taurine sometimes and the sicker

the

> > > person gets or stays. They are stuck.

> > >

> > > Janet

> > >

> >

> >

> >

> >

> >

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Hi,

I was asking about sulfur/sulfate a while back, and while I think I

got my answer, I'm not sure.

Would raising sulfate have a positive, negative, or neutral effect

on sulfur buildup, one of the theories behind whey protein not

working past a certain point?

Thanks.

> > > >

> > > > HI All,

> > > >

> > > > If you have a CBS upregulation, NOS or SUOX +/- genetic

> mutation

> > and

> > > > you continue to use sulfur and protein, you drive up

ammonia.

> If

> > > > ammonia is high, then what happpens to all your methylation

> > > > support??? What happens to MB12, SAMe and the whole list of

> > methyl

> > > > groups you are taking and in your body??

> > > >

> > > > If you have the CBS, the door is open and what should be

> > methylation

> > > > turns into a toxic substance, ammonia and others. So you

don't

> > > > methylate properly. If you don't methylate properly, you

also

> > don't

> > > > detox properly. If your body is using up everything you've

got

> to

> > > > get rid of excess ammonia, there is nothing left for

detoxing

> for

> > > > methylating or RNA, DNA synthesis.

> > > >

> > > > And around and round we go! So your've got to get the

ammonia

> > down

> > > > so your body will methylate. This is why genetics points to

> why

> > some

> > > > people have stayed sick when they have tried everything yet,

> they

> > > > are still sick.

> > > >

> > > > Its a vicious cycle. Methylation helps at first, but if

their

> is

> > the

> > > > CBS, NOS or SUOX mutation, methylation stopes working, then

> > ammonia

> > > > rises, the more methylation and glutationie for detox--the

> higher

> > > > the ammonia goes as well as taurine sometimes and the sicker

> the

> > > > person gets or stays. They are stuck.

> > > >

> > > > Janet

> > > >

> > >

> > >

> > >

> > >

> > >

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