Re: Amy Yasko - MTHFR and CBS deplete B12 ?

August 21, 2006

I don't know about that, but I should mention that Jill '

research on MTHFR does not show that particular mutation being

meaningful, at this point, in autism.

>

> Hi,

> I'm reading through the messages on www.autismanswer.com. One thing she

> says is that the MTHFR C6777T SNP and the CBS SNP upregulation will

> deplete B12.

> For those of you studying this info, does this make sense ? I can't

> quite grasp why this would occur.

>

August 21, 2006

Hi, .

If she is speaking of the methyl form of B12, I think I can understand

that. First, the forward MTHFR SNP to which you refer will slow the

production of 5-methyl tetrahydrofolate from 5,10 methylene

tetrahydrofolate. Since 5-methyl THF is needed to supply methyl

groups to remethylate B12, a deficiency there would tend to lower the

supply of methyl B12.

With regard to the CBS upregulation SNPs, I think the idea there is

that this upregulation will raise the production of cysteine, and

higher cysteine causes the flow to be diverted through the cysteine

dioxygenase enzyme down to sulfoxidation, rather than through

glutamate cysteine ligase, to make glutathione. So glutathione will

go low. Low glutathione will lower the production of methyl B12 from

either cyano B12 or hydroxo B12, because it, together with SAMe, is

needed to make those conversions.

Rich

>

> Hi,

> I'm reading through the messages on www.autismanswer.com. One thing

she

> says is that the MTHFR C6777T SNP and the CBS SNP upregulation will

> deplete B12.

> For those of you studying this info, does this make sense ? I can't

> quite grasp why this would occur.

>

August 21, 2006

Hi, Jill.

I think that's really interesting. In her paper just published, she

and her coauthors say that there was no significant elevated

frequency of the individual MTHFR SNPs in autism, only a modest

increase of the combined MTHFR SNPs taken as a pair, but there is a

more important interaction between the forward MTHFR SNP and the

reduced folate carrier SNP. Are you speaking of this work, or work

done since the work for this paper was done?

I also think that there are several separate issues here. One is

whether MTHFR SNPs are found at higher frequencies in autistic kids,

either individually or in combination with each other or other

SNPs. A second is whether they are found at higher frequencies in

PWCs in any of these combinations. And the third is whether they

are found in a particular individual with CFS. All of these are

interesting questions. However, regardless of how the first two come

out, if the answer to the third one is yes, then I think it would be

worthwhile for that individual to target the SNP or SNPs with

selected supplements to get the folate metabolism operating better,

because this can impact their methylation cycle and their biopterin

cycle, and those can have big ramifications, including the level of

glutathione.

Rich

> >

> > Hi,

> > I'm reading through the messages on www.autismanswer.com. One

thing she

> > says is that the MTHFR C6777T SNP and the CBS SNP upregulation

will

> > deplete B12.

> > For those of you studying this info, does this make sense ? I

can't

> > quite grasp why this would occur.

> >

>

August 21, 2006

Its exactly as you say. She said that the one concern was the low

folate with that SNP but that the enzyme recovered beautifully when

you restored the folate.

And I think it would be unlikely, given our whole hypothesis here,

that CFS would have significantly different variations than autism.

You're either very right about this or very wrong . Let's hope

you're very right as so much work is being done on methylation stuff

for the autistic kids.

> > >

> > > Hi,

> > > I'm reading through the messages on www.autismanswer.com. One

> thing she

> > > says is that the MTHFR C6777T SNP and the CBS SNP upregulation

> will

> > > deplete B12.

> > > For those of you studying this info, does this make sense ? I

> can't

> > > quite grasp why this would occur.

> > >

> >

>

August 21, 2006

Let me refine this a little. Without going back to my notes at the

moment, there was another mutation with that MTHFR SNP that could be

fixed with low folate--that was the only combo that was significant.

And easily fixed.

That's not having read the journal article yet, and not looking back

at my notes. And it would be nice of course to do a few more such

studies if one could to be sure.

In preparation for embarking on Yasko sometime in Sept when I get my

results back, I am still tapering off my sleeping pill. I'm using a

really cool water titration method which allows me to be very precise

even though its powder in a capsule; but the taper is still AWFUL. I

feel HORRIBLE. Being impatient, and stoical, and mad about the whole

thing (I never would be at this dose if not for my crazy building's

insane or should I say obscene demolition) I've decided that since the

withdrawal is already somewhat hellish, I might as well speed it up.

I'm going to go down 2 milligrams every few days. If I'm really

feeling bad I may not post much. I may just have to rest a lot while

doing this. I figure however that to be on a drug like this is nuts if

I'm going to be trying to restore pathways in my body. So this is

really step one of my journey.

> > > >

> > > > Hi,

> > > > I'm reading through the messages on www.autismanswer.com. One

> > thing she

> > > > says is that the MTHFR C6777T SNP and the CBS SNP upregulation

> > will

> > > > deplete B12.

> > > > For those of you studying this info, does this make sense ? I

> > can't

> > > > quite grasp why this would occur.

> > > >

> > >

> >

>

August 21, 2006

What is this not-so-wonderful drug you are attempting to withdraw from?

Yes, Breckenridge's experiences were really tragic.

mjh

" The Basil Book "

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

Posted by: " rvankonynen " _richvank@... _

(mailto:richvank@...?Subject=

Re:%20Amy%20Yasko%20-%20MTHFR%20and%20CBS%20deplete%20B12%20?)

_rvankonynen _ (rvankonynen)

Mon Aug 21, 2006 12:09 pm (PST)

Hi, Jill.

Please be careful, O.K.? Some of these drugs really bite you if you

go down too fast. Remember .

Rich

> In preparation for embarking on Yasko sometime in Sept when I get

my

> results back, I am still tapering off my sleeping pill. I'm using a

> really cool water titration method which allows me to be very

precise

> even though its powder in a capsule; but the taper is still AWFUL.

I

> feel HORRIBLE. Being impatient, and stoical, and mad about the

whole

> thing (I never would be at this dose if not for my crazy building's

> insane or should I say obscene demolition) I've decided that since

the

> withdrawal is already somewhat hellish, I might as well speed it

up.

> I'm going to go down 2 milligrams every few days. If I'm really

> feeling bad I may not post much. I may just have to rest a lot

while

> doing this. I figure however that to be on a drug like this is

nuts if

> I'm going to be trying to restore pathways in my body. So this is

> really step one of my journey.

August 21, 2006

Jill

Braverman, MD, has a GABA complex on his website that is helpful to me.

_www.pathmed.com_ (http://www.pathmed.com) Madison Ave., NYC.

Also consider SAM-e instead of l-Tryptophan.

Good luck

mjh

" The Basil Book "

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

Posted by: " jill1313 " _jenbooks13@... _

(mailto:jenbooks13@...?Subject=

Re:%20Amy%20Yasko%20-%20MTHFR%20and%20CBS%20deplete%20B12%20?)

_jill1313 _ (jill1313)

Mon Aug 21, 2006 12:40 pm (PST)

Thanx!...I googled but there's not much that really replaces gaba as a

precursor. Gaba and glutamate are so linked, your body can make gaba

from glycine, or from glutatmine, but it can also make glutamate just

as easily!

Hot baths, a heating pad, rest, and a good attitude. I was trying to

'talk' to my body last night and will try to do so more. Letting it

know it needs to start making gaba.

August 21, 2006

Hi, Jill.

Please be careful, O.K.? Some of these drugs really bite you if you

go down too fast. Remember .

Rich

> In preparation for embarking on Yasko sometime in Sept when I get

my

> results back, I am still tapering off my sleeping pill. I'm using a

> really cool water titration method which allows me to be very

precise

> even though its powder in a capsule; but the taper is still AWFUL.

I

> feel HORRIBLE. Being impatient, and stoical, and mad about the

whole

> thing (I never would be at this dose if not for my crazy building's

> insane or should I say obscene demolition) I've decided that since

the

> withdrawal is already somewhat hellish, I might as well speed it

up.

> I'm going to go down 2 milligrams every few days. If I'm really

> feeling bad I may not post much. I may just have to rest a lot

while

> doing this. I figure however that to be on a drug like this is

nuts if

> I'm going to be trying to restore pathways in my body. So this is

> really step one of my journey.

August 21, 2006

Thank you Rich. Its because of I'm going down a few milligrams

at a time, probably twice a week. Probably when I get down to 10

milligrams (from my current dose of 30 milligrams, which is to me a

very high dose considering I never take drugs!!!) I will hold steady

at that dose until I feel 'normal' (ie lymie normal) and then taper

off from that. From the reading I've done, the body suffers the eworst

at the beginning, and then at the end.

By the way, the symptoms for benzodiazapene withdrawal are SO similar

to lyme that I really think that one central aspect of lyme, and/or

CFIDS, is glutamate upregulation and gaba downregulation. That must be

one central pathway by which the bug disrupts you. Everything from

sleep disorders to mood disorders to stiff muscles, tremors,

parasthesias, light and sound sensitivity, a sore scalp--I mean, its

amazing. Everything that was sudden onset for me with my second

tickbite is on the benzo withdrawal symptom list.

>

> Hi, Jill.

>

> Please be careful, O.K.? Some of these drugs really bite you if you

> go down too fast. Remember .

>

> Rich

>

August 21, 2006

Thanx!...I googled but there's not much that really replaces gaba as a

precursor. Gaba and glutamate are so linked, your body can make gaba

from glycine, or from glutatmine, but it can also make glutamate just

as easily!

Hot baths, a heating pad, rest, and a good attitude. I was trying to

'talk' to my body last night and will try to do so more. Letting it

know it needs to start making gaba.

> > > > >

> > > > > Hi,

> > > > > I'm reading through the messages on www.autismanswer.com.

One

> > > thing she

> > > > > says is that the MTHFR C6777T SNP and the CBS SNP

upregulation

> > > will

> > > > > deplete B12.

> > > > > For those of you studying this info, does this make sense

? I

> > > can't

> > > > > quite grasp why this would occur.

> > > > >

> > > >

> > >

> >

>

> 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.

>

August 21, 2006

Hi, Jill.

" ...make haste slowly! " , as the one character in the movie, The Village, said.

I agree, especially given the

bad siezure risk I sense is there, like , with me and many PWCs.

PWCsrvankonynen " <richvank@...> wrote:

>

> Hi, Jill.

>

> Please be careful, O.K.? Some of these drugs really bite you if you

> go down too fast. Remember .

>

> Rich

>

\> <jenbooks13@> wrote:

>

> > In preparation for embarking on Yasko sometime in Sept when I get

> my

> > results back, I am still tapering off my sleeping pill. I'm using a

> > really cool water titration method which allows me to be very

> precise

> > even though its powder in a capsule; but the taper is still AWFUL.

> I

> > feel HORRIBLE. Being impatient, and stoical, and mad about the

> whole

> > thing (I never would be at this dose if not for my crazy building's

> > insane or should I say obscene demolition) I've decided that since

> the

> > withdrawal is already somewhat hellish, I might as well speed it

> up.

> > I'm going to go down 2 milligrams every few days. If I'm really

> > feeling bad I may not post much. I may just have to rest a lot

> while

> > doing this. I figure however that to be on a drug like this is

> nuts if

> > I'm going to be trying to restore pathways in my body. So this is

> > really step one of my journey.

>

August 21, 2006

It is temazepam. From my reading, it seems that though all the benzos

are similar, some bind more tightly to receptors, and have shorter

half-lives. The most difficult to get off, for that reason,

apparently, are klonipin and xanax. The equivalence is strange, too. 6

milligrams of xanax equals 120 milligrams of valium. 30 milligrams of

temazepam equals 15 milligrams of valium. So milligram amounts fool

unsuspecting patients and maybe doctors, I suspect. They might think,

" I'm only on 2 milligrams of this drug " and not realize its power. And

the short half life can be a problem in withdrawal apparently.

I suspect there is a kind of crossover line for every individual,

where the dose gets to a level that causes the body to really

significantly shut down its own production.

I also suspect that the gaba receptors change structure slightly to

accomodate the drug when there is a lot of it around, and may even

develop a greater affinity for that drug than natural gaba.

I also read that the drugs are stored in fatty tissue and release over

many months from the fat.

These all could be reasons it could be hard to get off. Your body has

to realize what's going on and make its own. Your receptors have to

change shape back to 'normal'. All kinds of shifts have to occur to

get you back to where you were.

>

> > In preparation for embarking on Yasko sometime in Sept when I get

> my

> > results back, I am still tapering off my sleeping pill. I'm using a

> > really cool water titration method which allows me to be very

> precise

> > even though its powder in a capsule; but the taper is still AWFUL.

> I

> > feel HORRIBLE. Being impatient, and stoical, and mad about the

> whole

> > thing (I never would be at this dose if not for my crazy building's

> > insane or should I say obscene demolition) I've decided that since

> the

> > withdrawal is already somewhat hellish, I might as well speed it

> up.

> > I'm going to go down 2 milligrams every few days. If I'm really

> > feeling bad I may not post much. I may just have to rest a lot

> while

> > doing this. I figure however that to be on a drug like this is

> nuts if

> > I'm going to be trying to restore pathways in my body. So this is

> > really step one of my journey.

>

August 21, 2006

I tend to think precursors are just fine IF you need them. There could

be a problem with precursors that are what Yasko calls 'fair weather

friends. " That is, say, glycine or gluatamine, can build gaba or

glutamate, depending. Or with precursors that you can't use or that

you break down incorrectly (trytophan breaking down into kynurenic

acid in the presence of chronic infection, rather than building up

serotonin)

> >

> > > In preparation for embarking on Yasko sometime in Sept when I get

> > my

> > > results back, I am still tapering off my sleeping pill. I'm using a

> > > really cool water titration method which allows me to be very

> > precise

> > > even though its powder in a capsule; but the taper is still AWFUL.

> > I

> > > feel HORRIBLE. Being impatient, and stoical, and mad about the

> > whole

> > > thing (I never would be at this dose if not for my crazy building's

> > > insane or should I say obscene demolition) I've decided that since

> > the

> > > withdrawal is already somewhat hellish, I might as well speed it

> > up.

> > > I'm going to go down 2 milligrams every few days. If I'm really

> > > feeling bad I may not post much. I may just have to rest a lot

> > while

> > > doing this. I figure however that to be on a drug like this is

> > nuts if

> > > I'm going to be trying to restore pathways in my body. So this is

> > > really step one of my journey.

> >

August 22, 2006

>

> HI Rich,

>

> So I am confused. I am on step one and Yasko recomends subligual

cyanocobalamine B 12 and sublingual hydroxycobalamine B12. Of course

what I have on hand is methycobalamin. I am CBS upregulated with

MTHFR (A1298C) +/-. Can I take the methylcobalamin now without

distrubing things????

***You could try it, and see if you experience mood swings. If you

do, then switching to the non-methylated forms of B12 may help. I

think Dr. Yasko recommended them in your case because you have COMT

SNPs, and that can cause you to have too many methyl groups

available, because they are not being used by COMT as fast as normal.

>

> Also I don't understand the front way around or the long way

around. Can you explain what cycle she is talking about???? Which

genes are affected by this??? How do I figure out what I need to do

for myself???

***There are two pathways that go from homocysteine to methionine.

One of them requires B12 and 5-methyl tetrahydrofolate. I think she

calls this the long way, because more is required to get it going,

and it takes longer to do that.

***The short way uses trimethylglycine or phosphatidly choline,

phosphatidylserine or phosphatidylethanolamine. In people who have

the CBS upregulation, as you do, she recommends using the short way

first, because you can get it going faster. Then she recommends

building up what's necessary to get the long way going, so that you

can switch to that later on by adding DMG to shut down the short

way. But you have to build up folate and B12 before you can make

that switch, and it takes some time to do that.

>

> As always, thank you for your help,

>

> Janet

***You're welcome.

***Rich

August 22, 2006

Hi, .

The reduced folate carrier SNP is discussed in her new paper, just

published. Here's the abstract of it:

Am J Med Genet B Neuropsychiatr Genet. 2006 Aug 17; [Epub ahead of

print] Links

Metabolic endophenotype and related genotypes are associated with

oxidative stress in children with autism. SJ, Melnyk S,

Jernigan S, Cleves MA, Halsted CH, Wong DH, Cutler P, Bock K, Boris

M, Bradstreet JJ, Baker SM, Gaylor DW.

Department of Pediatrics, University of Arkansas for Medical

Sciences, Arkansas Children's Hospital Research Institute, Little

Rock, Arkansas.

Autism is a behaviorally defined neurodevelopmental disorder usually

diagnosed in early childhood that is characterized by impairment in

reciprocal communication and speech, repetitive behaviors, and

social withdrawal. Although both genetic and environmental factors

are thought to be involved, none have been reproducibly identified.

The metabolic phenotype of an individual reflects the influence of

endogenous and exogenous factors on genotype. As such, it provides a

window through which the interactive impact of genes and environment

may be viewed and relevant susceptibility factors identified.

Although abnormal methionine metabolism has been associated with

other neurologic disorders, these pathways and related polymorphisms

have not been evaluated in autistic children. Plasma levels of

metabolites in methionine transmethylation and transsulfuration

pathways were measured in 80 autistic and 73 control children. In

addition, common polymorphic variants known to modulate these

metabolic pathways were evaluated in 360 autistic children and 205

controls. The metabolic results indicated that plasma methionine and

the ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine

(SAH), an indicator of methylation capacity, were significantly

decreased in the autistic children relative to age-matched controls.

In addition, plasma levels of cysteine, glutathione, and the ratio

of reduced to oxidized glutathione, an indication of antioxidant

capacity and redox homeostasis, were significantly decreased.

Differences in allele frequency and/or significant gene-gene

interactions were found for relevant genes encoding the reduced

folate carrier (RFC 80G > A), transcobalamin II (TCN2 776G > C),

catechol-O-methyltransferase (COMT 472G > A),

methylenetetrahydrofolate reductase (MTHFR 677C > T and 1298A > C),

and glutathione-S-transferase (GST M1). We propose that an increased

vulnerability to oxidative stress (endogenous or environmental) may

contribute to the development and clinical manifestations of autism.

PMID: 16917939 [PubMed - as supplied by publisher]

I don't think she discussed it at the conference in April. She

usually doesn't talk about things publicly until the publication

comes out. This is pretty standard practice among professional

research scientists. It avoids problems of who discovered what

first, which is important to the scientists in terms of their

careers and future funding and to the institutions for which they

work. I worked under that same system for nearly 40 years.

Rich

> >

>

August 22, 2006

Whoops, I guess I was wrong and its already out. I thought it was

about to come out.

> > >

> >

August 22, 2006

It's slated for publication which is why Rich posted the abstract. No

she hasn't discussed it yet.

> >

>

August 22, 2006

Hi, Janet.

I think I have a feel for the theory behind the treatment, but I

don't have experience with the details of it, in terms of timing and

dosages. I would like to be able to help you with these, but I

don't know enough about them to do so.

My impression is that Dr. Yasko prefers using small amounts of

several things for each part of the treatment, so I would follow

what she says about the TMG dosage.

Maybe you can get some advice from her assistants at autismanswer.

I realize that she is off for a couple of weeks herself.

Rich

>

> HI Rich,

>

> Thanks for clearing that up for me. But I am still a bit

confused because when I see her talk about TMG, she says " no more

than what is in the multiple for CBS up regulation. " I will try the

methy B-12 as all my COMT's are +/- and pay attention to how I feel.

>

> I think timing is important, so when do I add in the

phosphatidyl serine, phosphatidy choline and do I add in more TMG???

>

> As always, thank you for your help,

>

> Janet

August 22, 2006

>

> HI Rich,

>

> So I am confused. I am on step one and Yasko recomends subligual

cyanocobalamine B 12 and sublingual hydroxycobalamine B12. Of course

what I have on hand is methycobalamin. I am CBS upregulated with MTHFR

(A1298C) +/-. Can I take the methylcobalamin now without distrubing

things????

>

Janet, I have been studying this some for a friend on Yasko's site.

From what I understand, using the methyl B12 before the CBS problem is

corrected can increase ammonia problems. You might try searching for

Methyl B12 and Ammonia, and see if anything comes up.

Once your ammonia is under control, and other CBS issues are

corrected, then methyl B12 and other methyl donors are added in slowly.

Hope this helps.

August 26, 2006

Hi, .

I may have answered this before. Sorry, I lose track sometimes.

I think the answer here can be found in Professor Deth's talks. He

notes that the methionine synthase enzyme can be booted back up

either by getting a new methyl B12 molecule, having it regenerated

by getting a methyl group via methionine synthase reductase from 5-

methyl tetrahydrofolate, or having it regenerated by SAMe. In the

case of people who don't use as many methyl groups as normal for the

COMT reactions, because they have a slow COMT, then I think there

can be more SAMe available, and I think that's why Dr. Yasko

recommends hydroxocobalamin for these people.

Rich

>

> Hi Rich and Janet,

>

> I have a general comment about using hydroxycobalamine. I read

> Pangborns section on B12 in the Autism: Effective Biomedical

treatments

> book and it says that glutathione is needed to make Mb12 out of

> hydroxycobalamine. I know Dr. Yasko recommends hydroxyB12 for

those

> with extra methyl groups, but I'm wondering if this would be

effective

> if one is low in glutathione ?

>

> -

>

August 27, 2006